PMID:  Molecules. 2019 May 17 ;24(10). Epub 2019 May 17. PMID: 31108834 Abstract Title:  Flower Petal Extract Inhibits Adipogenesis and Lipid Accumulation in 3T3-L1 Preadipocytes by Downregulating Adipogenic Gene Expression. Abstract:  (commonly known as blue pea) flower petal extract (CTE) is used as a natural colorant in a variety of foods and beverages. The objective of study was to determine the inhibitory effect of CTE on adipogenesis in 3T3-L1 preadipocytes. The phytochemical profiles of CTE were analyzed by liquid chromatography and tandem mass spectrometry (LC-MS/MS). Anti-adipogenesis effect of CTE was measured by using Oil Red O staining, intracellular triglyceride assay, quantitative real-time PCR and western blot analysis in 3T3-L1 adipocytes. Cell cycle studies were performed by flow cytometry. Lipolysis experiments were performed using a colorimetric assay kit. In early stages, CTE demonstrated anti-adipogenic effects through inhibition of proliferation and cell cycle retardation by suppressing expression of phospho-Akt and phospho-ERK1/2 signaling pathway. The results also showed that CTE inhibited the late stage of differentiation through diminishing expression of adipogenic transcription factors including PPARand C/EBP. The inhibitory action was subsequently attenuated in downregulation of fatty acid synthase and acetyl-CoA carboxylase, causing the reduction of TG accumulation. In addition, CTE also enhanced catecholamine-induced lipolysis in adipocytes. These results suggest that CTE effectively attenuates adipogenesis by controlling cell cycle progression and downregulating adipogenic gene expression.

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PMID:  Evid Based Complement Alternat Med. 2019 ;2019:2916914. Epub 2019 May 20. PMID: 31236123 Abstract Title:  A Commercial Potential Blue Pea (L.) Flower Extract Incorporated Beverage Having Functional Properties. Abstract:  L. commonly known as 'blue pea' is an underutilized plant in Sri Lanka. The blue coloured flower of this plant is used in medicine in Sri Lankan traditional medical system and also reported to have several health benefits in recent findings at the international level. However, to date scientifically validated value added products from blue pea flower (BPF) is very limited worldwide. In this connection, this study was carried out to develop a commercial potential blue pea flower extract (BFE) incorporated beverage having functional properties. Dried BPFs were extracted into water with varying flower: water ratio, temperature, and time using response surface methodology (RSM) along with Box-Behnken design. A range of BFE incorporated beverages was developed comprising a natural sweetener (Stevia extract) and a flavour (lime). The most acceptable formulation was selected via ranking and hedonic sensory tests. Further, it was evaluated for functional properties in terms of antioxidant activity via total polyphenolic and flavonoid contents, ferric reducing antioxidant power and radical scavenging activities via ORAC; DPPH and ABTSGlycaemic regulatory properties (GCP) were evaluated in terms of antiamylase and antiglucosidase activities. Quality parameters of the developed beverage were evaluated for a period of 28 days at different time intervals and a colour chart was also developed. The optimum conditions for extraction of BPF via RSM were 3 g of powdered BPF/L of water at 59.6C for 37 min. The most acceptable formulation consists of BFE, Stevia extract, and lime at a ratio of 983.25:1.75:15. Further, it had significantly higher (p

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PMID:  Food Res Int. 2020 Feb ;128:108763. Epub 2019 Oct 31. PMID: 31955736 Abstract Title:  Clitoria ternatea L. petal bioactive compounds display antioxidant, antihemolytic and antihypertensive effects, inhibit-amylase and-glucosidase activities and reduce human LDL cholesterol and DNA induced oxidation. Abstract:  The purpose of this study was to use a statistical approach to optimise the experimental conditions regarding the extraction of bioactive compounds, and to analyse the in vitro functional properties of crude lyophilized extracts (CLE) and partially purified (PPE) extracts of Clitoria ternatea petals. The results showed that the factors of temperature and time influenced the extraction of phenolic compounds, antioxidant activity and the physicochemical parameters. Simultaneous optimisation showed that the same levels of bioactive compounds were extracted when using temperatures from 11.7 to 68.3C and times from 8.47 to 51.12min. Principal component analysis revealed the experimental conditions that provided the extraction producing the highest level of phenolic content (40C/30min). The CLE showed antimicrobial activity; protective effect against hemolysis of erythrocytes; inhibition of-amylase,-glucosidase and angiotensin-I-converting (ACE-I) enzymes; and inhibition of lipid peroxidation. The CLE and PPE demonstrated oxygen radical absorption capacity; inhibition of DNA strand scission; inhibition of LDL cholesterol oxidation; intracellular antioxidant activity against reactive oxygen species (>100g/mL); and no cytotoxicity (IC, GIand LC>900g/mL) against A549, HCT8 and IMR90 cell lines.

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PMID:  Neurochem Int. 2020 Oct ;139:104785. Epub 2020 Jul 8. PMID: 32650028 Abstract Title:  The nootropic and anticholinesterase activities of Clitoria ternatea Linn. root extract: Potential treatment for cognitive decline. Abstract:  BACKGROUND: Clitoria ternatea (CT) is an herbal plant that has been used as a memory booster in folk medicine. CT root extract has been proven to restore chronic cerebral hypoperfusion (CCH)-induced memory deficits in a rat model, but the underlying mechanisms and the toxicity profile following repeated exposure have yet to be explored.THE AIM OF THE STUDY: To investigate the effects of the chronic (28 days) oral administration of CT root extract on CCH-induced cognitive impairment, neuronal damage and cholinergic deficit, and its toxicity profile in the CCH rat model.MATERIALS AND METHODS: The permanent bilateral occlusion of common carotid arteries (PBOCCA) surgery method was employed to develop a CCH model in male Sprague Dawley (SD) rats. Then, these rats were given oral administration of CT root extract at doses of 100, 200, and 300 mg/kg, respectively for 28 days and subjected to behavioural tests. At the end of the experiment, the brain was harvested for histological analysis and cholinesterase activities. Then, blood samples were collected and organs such as liver, kidney, lung, heart, and spleen were procured for toxicity assessment.RESULTS: Chronic treatment of CT root extract at doses of 200 and 300 mg/kg, restored memory impairments induced by CCH. CT root extract was also found to diminish CCH-induced neuronal damage in the CA1 region of the hippocampus. High dose (300 mg/kg) of the CT root extract was significantly inhibited the increased acetylcholinesterase (AChE) activity in the frontal cortex and hippocampus of the PBOCCA rats. In toxicity study, repeated doses of CT root extract were found to be safe in PBOCCA rats after 28 days of treatment.CONCLUSIONS: Our findings provided scientific evidence supporting the therapeutic potential of CT root extract in the treatment of vascular dementia (VaD)-related cholinergic abnormalities and subsequent cognitive decline.

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PMID:  Trop Life Sci Res. 2020 Jul ;31(2):1-17. Epub 2020 Aug 6. PMID: 32922666 Abstract Title:  Optimum Extraction Condition ofFlower on Antioxidant Activities, Total Phenolic, Total Flavonoid and Total Anthocyanin Contents. Abstract:  is a herbaceous plant with many health benefits. Extraction is crucial to obtain its bioactive components which contribute to its antioxidant properties. Therefore, this study was conducted to find an optimum extraction condition offlower on total phenolic content (TPC) and antioxidant activity (2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical-scavenging activity) as well as to determine its total flavonoid content (TFC) and anthocyanin content based on the optimum extraction condition generated by Response Surface Methodology (RSM)-Design Expert 7.1.5. TPC, TFC and total anthocyanin ofwere conducted by Folin Ciocalteu (FC), calorimetric assay and pH differential method, respectively. The ranges of selected independent variables were ethanol concentration (30C-90% v/v), time (60-120 min) and temperature (30C-70C). The optimum extraction condition was obtained at 39.62% v/v ethanol concentration, 90 min and 44.24C. However, these values were slightly adjusted according to the convenience of equipment to operate in which ethanol concentration was adjusted to 37% v/v, time remain at 90 min and temperature at 45C. The predicted values of TPC and DPPH radical scavenging activity were 41.60 mg GAE/g dry samples and 68.12% inhibition and were experimentally verified to be 41.170.5 mg GAE/g dry samples and 63.530.95% inhibition of TPC and DPPH radical scavenging activity respectively. This result has showed RSM can optimise TPC and radical scavenging activity of. Upon the optimum condition, the TFC determined was 187.053.18 mg quercetin/g dried sample which was higher than TPC and the total anthocyanin content was 28.600.04 mg/L. Hence, the extractable phenolic, flavonoid and anthocyanin compounds indicated thatis a good source of natural antioxidant.

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PMID:  Chin Herb Med. 2021 Apr ;13(2):243-249. Epub 2020 Dec 1. PMID: 36117501 Abstract Title:  Evaluation of anti-inflammatory and anti-arthritic property of ethanolic extract of. Abstract:  OBJECTIVE: is a well-known bioactive plant used to treat several inflammatory ailments in Ayurvedic system of medicine in India. The present investigation aimed to determine the anti-inflammatory and anti-arthritic activity of ethanolic extract ofroots (EECT) in animal models.METHODS: The anti-inflammatory activity of the EECT was evaluated by carrageenan and histamine-induced paw edema.RESULTS: EECT showed a significant reduction in mean paw edema volume in both carrageenan and histamine-induced inflammation. The efficacy of EECT in rheumatoid arthritis was tested against Freund's complete adjuvant (CFA) induced arthritic model in Wistar rats. The anti-arthritic effect of EECT was determined by systematic scoring of arthritis symptoms and measuring paw edema. A considerable decrease in paw diameter was observed in the EECT (200 and 400 mg/kg) and diclofenac (10 mg/kg) treated groups after day 7. Diclofenac (10 mg/kg) and EECT (400 mg/kg) showed a significant reduction in paw diameter from day 14 compared with CFA control ( 

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PMID:  BMC Complement Med Ther. 2021 Mar 1 ;21(1):80. Epub 2021 Mar 1. PMID: 33648500 Abstract Title:  Protective role of Clitoria ternatea L. flower extract on methylglyoxal-induced protein glycation and oxidative damage to DNA. Abstract:  BACKGROUND: Methylglyoxal (MG) is a highly reactive dicarbonyl precursor for the formation of advanced glycation end products (AGEs) associated with age-related diseases, including diabetes and its complications. Clitoria ternatea L. flower has been reported to possess antioxidant and antiglycating properties. Evidence indicates that the extract of Clitoria ternatea L. flower inhibits fructose-induced protein glycation and oxidative damage to bovine serum albumin (BSA). However, there is no evidence to support the inhibitory effect of CTE against MG-mediated protein glycation and oxidative damage to protein and DNA. Therefore, the aim of the present study was to investigate whether C. ternatea flower extract (CTE) prevents MG-induced protein glycation and oxidative DNA damage.METHODS: The formation of fluorescent AGEs in BSA was evaluated using spectrofluorometer. The protein carbonyl and thiol group content were used for detecting protein oxidation. DNA strand breakage in a glycation model comprising of MG, lysine and Cuor a free radical generator 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH) systems was investigated using gel electrophoresis. Generation of superoxide anions and hydroxyl radicals in the MG/lysine system was assessed by the cytochrome c reduction assay and thiobarbituric acid reactive substances assay, respectively. High performance liquid chromatography (HPLC) was used to measure the MG-trapping ability.RESULTS: In the BSA/MG system, CTE (0.25-1mg/mL) significantly inhibited the formation of fluorescent AGEs and protein oxidation by reducing protein carbonyl content as well as preventing the protein thiol depletion. The concentration of CTE at 0.125-1mg/mL prevented oxidative DNA cleavage in MG/lysine and AAPH systems associated with the inhibition of superoxide anion and hydroxyl radical formation. It also directly trapped MG in a concentration-dependent manner, ranging from 15 to 43%.CONCLUSIONS: The study findings suggest that the direct carbonyl trapping ability and the free radical scavenging activity of CTE are the underlying mechanisms responsible for the prevention of protein glycation and oxidative DNA damage.

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PMID:  Antioxidants (Basel). 2021 Mar 27 ;10(4). Epub 2021 Mar 27. PMID: 33801631 Abstract Title:  Butterfly Pea Flower (Linn.) Extract Ameliorates Cardiovascular Dysfunction and Oxidative Stress in Nitric Oxide-Deficient Hypertensive Rats. Abstract:  In this study, we examine whetherLinn. (CT) can prevent N-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced cardiac and vascular dysfunction in rats. Male Sprague Dawley rats were given L-NAME (40 mg/kg, drinking water) and orally administered with CT extract (300 mg/kg/day) or lisinopril (2.5 mg/kg/day) for 5 weeks. The main phytochemical components of the CT extract were found to be flavonoids. The CT extract alleviated the high blood pressure in rats receiving L-NAME. Decreased vasorelaxation responses to acetylcholine and enhanced contractile responses to sympathetic nerve stimulation in aortic rings and mesenteric vascular beds of L-NAME treated rats were ameliorated by CT extract supplementation. Left ventricular hypertrophy and dysfunction were developed in L-NAME rats, which were partially prevented by CT extract treatment. The CT extract alleviated upregulated endothelial nitric oxide synthase expression, decreased plasma nitrate/nitrite levels, and increased oxidative stress in L-NAME rats. It suppressed high levels of serum angiotensin-converting enzyme activity, plasma angiotensin II, and cardiac angiotensin II type 1 receptor, NADPH oxidases 2, nuclear factor-kappa B, and tumor necrosis factor-alpha expression. The CT extract, therefore, partially prevented L-NAME-induced hypertension and cardiovascular alterations in rats. These effects might be related to a reduction in the oxidative stress and renin-angiotensin system activation due to L-NAME in rats.

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PMID:  J Med Chem. 2021 Jun 10 ;64(11):7422-7433. Epub 2021 May 28. PMID: 34048659 Abstract Title:  Disulfide-Rich Cyclic Peptides fromProtect against-Amyloid Toxicity and Oxidative Stress in Transgenic. Abstract:  Neurotoxic aggregation of-amyloid (A) peptides is a hallmark of Alzheimer's disease and increased reactive oxygen species (ROS) is an associated process. In the present study, we report the neuroprotective effects of disulfide-rich, circular peptides from() (butterfly pea) on A-induced toxicity in transgenic. Cyclotides (30 amino acids long) are a special class of cyclic cysteine knot peptides. We show that cyclotide-rich fractions from different plant tissues delay A-induced paralysis in the transgenic CL4176 strain expressing the human muscle-specific Agene. They also improved A-induced chemotaxis defects in CL2355 strain expressing Ain the neuronal cells. ROS assay suggests that this protection is likely mediated by the inhibition of Aoligomerization. Furthermore, Adeposits were reduced in the CL2006 strain treated with the fractions. The study shows that cyclotides fromcould be a source of a novel pharmacophore scaffold against neurodegenerative diseases.

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PMID:  Ann Anat. 2021 Nov ;238:151783. Epub 2021 Jun 16. PMID: 34144158 Abstract Title:  Clitoria ternatea L. extract prevents kidney damage by suppressing the Ang II/Nox4/oxidative stress cascade in l-NAME-induced hypertension model of rats. Abstract:  Clitoria ternatia L. (CT) has been reported to have anti-inflammatory and antioxidant effects. This study investigated the effect of CT aqueous flower extract on blood pressure and renal alterations in N-nitro-l-arginine methyl ester hydrochloride (l-NAME)-induced hypertensive rats. Male Sprague Dawley rats received l-NAME in drinking water and were treated with CT flower extract or lisinopril. CT aqueous flower extract and lisinopril alleviated l-NAME-induced hypertension (p

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PMID:  Molecules. 2021 Jul 7 ;26(14). Epub 2021 Jul 7. PMID: 34299411 Abstract Title:  Clitorienolactones and Isoflavonoids ofRoots Alleviate Stress-Like Symptoms in a Reserpine-Induced Zebrafish Model. Abstract:  has been used in Ayurvedic medicine as a brain stimulant to treat mental illnesses and mental functional disorders. In this study, the metabolite profiles of cruderoot extract (CTRE), ethyl acetate (EA), and 50% aqueous methanol (50% MeOH) fractions were investigated using ultrahigh-performance liquid chromatography-diode array detector-tandem mass spectrometry (UHPLC-DAD-MS/MS), while their effect on the stress-like behavior of zebrafish, pharmacologically induced with reserpine, was investigated. A total of 32 compounds were putatively identified, among which, a series of norneolignans, clitorienolactones, and various flavonoids (flavone, flavonol, isoflavone, and isoflavanone) was found to comprise the major constituents, particularly in the EA and 50% MeOH fractions. The clitorienolactones, presently unique to the species, were present in both the free and glycosylated forms in the roots. Both the EA and 50% MeOH fractions displayed moderate effects on the stress-induced zebrafish model, significantly decreasing freezing duration and elevating the total distance travelled and average velocity, 72 h post-treatment. The results of the present study provide further evidence that the basis for the use ofroots in traditional medicine to alleviate brain-related conditions, such as stress and depression, is attributable to the presence of clitorienolactones and the isoflavonoidal constituents.

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PMID:  J Sci Food Agric. 2022 Apr ;102(6):2253-2261. Epub 2021 Oct 19. PMID: 34622460 Abstract Title:  Clitoria ternatea (Linn.) flower extract attenuates vascular dysfunction and cardiac hypertrophy via modulation of Ang II/ATR/TGF-1 cascade in hypertensive rats. Abstract:  BACKGROUND: Clitoria ternatea (CT) (the Fabaceae family) has been reported to elicit several biological responses, such as anti-inflammation and anti-depression effects. This study evaluated the effect of CT flower extract on blood pressure, vascular function, and left ventricular hypertrophy in a two-kidney, one-clip (2K-1C) rat model. Hypertensive rats were treated with CT extract at various doses (100, 300, or 500mgkgday) or losartan (10 mgkgday) for 4weeks (n = 8/group).RESULTS: CT extract reduced blood pressure in a dose-dependent manner, and CT extract at a dose of 300mgkgwas an effective concentration (P

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PMID:  Biology (Basel). 2021 Sep 28 ;10(10). Epub 2021 Sep 28. PMID: 34681074 Abstract Title:  Flower Extract Attenuates Postprandial Lipemia and Increases Plasma Antioxidant Status Responses to a High-Fat Meal Challenge in Overweight and Obese Participants. Abstract:  High-fat (HF) meal-induced postprandial lipemia, oxidative stress and low-grade inflammation is exacerbated in overweight and obese individuals. This postprandial dysmetabolism contributes to an increased risk of cardiovascular disease and metabolic disorders.flower extract (CTE) possesses antioxidant potential and carbohydrate and fat digestive enzyme inhibitory activity in vitro. However, no evidence supporting a favorable role of CTE in the modulation of postprandial lipemia, antioxidant status and inflammation in humans presently exists. In the present study, we determine the effect of CTE on changes in postprandial glycemic and lipemic response, antioxidant status and pro-inflammatory markers in overweight and obese men after consumption of an HF meal. Following a randomized design, sixteen participants (age, 23.50.6 years, and BMI, 25.70.7 kg/m) were assigned to three groups that consumed the HF meal, or HF meal supplemented by 1 g and 2 g of CTE. Blood samples were collected at fasting state and then at 30, 60, 90, 120, 180, 240, 300 and 360 min after the meal consumption. No significant differences were observed in the incremental area under the curve (iAUC) for postprandial glucose among the three groups. Furthermore, 2 g of CTE decreased the iAUC for serum triglyceride and attenuated postprandial serum free fatty acids at 360 min after consuming the HF meal. In addition, 2 g of CTE significantly improved the iAUC for plasma antioxidant status, as characterized by increased postprandial plasma FRAP and thiol levels. Postprandial plasma glutathione peroxidase activity was significantly higher at 180 min after the consumption of HF meal with 2 g of CTE. No significant differences in the level of pro-inflammatory cytokines (interleukin-6, interleukin-1and tumor necrosis factor-) were observed at 360 min among the three groups. These findings suggest that CTE can be used as a natural ingredient for reducing postprandial lipemia and improving the antioxidant status in overweight and obese men after consuming HF meals.

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PMID:  Recent Adv Antiinfect Drug Discov. 2023 Feb 22. Epub 2023 Feb 22. PMID: 36815641 Abstract Title:  Effects of Active Compounds of Nigella sativa in COVID-19: A Narrative Review. Abstract:  BACKGROUND: SARS-CoV-2 infection that led to the COVID-19 pandemic has changed human health and the economy globally. SARS CoV-2 is a type of Coronaviruses that has caused pneumonia and its complications with many deaths over the past two years. The use of hydroxychloroquine and chloroquine, accepted as generally safe for patients with autoimmune diseases or malaria, was attempted in many trials for COVID-19 treatment. Nigella sativa (NS) (black caraway, also known as black cumin, nigella or Kalonji) is an annual flowering plant of the Ranunculaceae family, chemically composed of the main constituent natural Thymoquinone (TQ) (30%- 48%) in forms of thymohydroquinone, dithymoquinone (Nigellone) is a native to wider regions, including parts of eastern Europe, west Asia, North of Africa and east of Myanmar. In this review, we explored the Randomized Controlled Trial, Controlled Trial, and Systematic review studies that support Nigella sativa Thymoquinone-targeted SARS-CoV-2 targeting. Therefore, A literature search was performed for publications published on the electronic databases (PubMed, Embase, Scopus, CNKI, and Google Scholar) for Nigella sativa, black seeds, Kalonji, coronavirus, SARS-CoV -2 and COVID-19. This review aimed to find relevant evidence of Nigella sativa preferences as a natural feasible remedy with no side effects in COVID-19. Studies reported the benefits of NS as beneficial, another appropriate remedy for patients with COVID-19. However, all studies have shown limitations, such as limiting clinical symptom outcomes due to regulations imposed by isolation policies and lack of adequate funding. Therefore, the evidence suggests that the chemical contents of NS are a safe and possible treatment for COVID-19 patients that helps to improve COVID-19 infection in patients with no side effects.CONCLUSION: Nigella sativa seeds were one of the well-documented herbal products. Three reviewed randomized controlled trials reported that NS reduced covid-19 risk and could improve immune function. It was also helpful in upper respiratory infections such as asthma and bronchitis, with one RCT showing that honey and NS significantly improved symptoms, viral clearance, and mortality of COVID-19 patients. This review concludes that NS has a positive barrier effect on people at risk of acquiring a COVID-19 infection.

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PMID:  Int J Clin Pract. 2023 ;2023:9917306. Epub 2023 Feb 20. PMID: 36861057 Abstract Title:  Nigelladine A among Selected Compounds fromExhibits Propitious Interaction with Omicron Variant of SARS-CoV-2: An In Silico Study. Abstract:  COVID-19 has been a threat to the entire world for more than two years since its outbreak in December 2019 in Wuhan city of China. SARS-CoV-2, the causative agent, had been reported to mutate over time exposing new variants. To date, no impeccable cure for the disease has been unveiled. This study outlines an extensive in silico approach to scrutinize certain phytochemical compounds of(mainly the black cumin seeds) targeting the spike protein and the main protease (M) enzyme of the Omicron variant of SARS-CoV-2. The objective of this study is to investigate the extracted compounds with a view to developing a potential inhibitor against the concerned SARS-CoV-2 variant. The investigation contemplates drug-likeness analysis, molecular docking study, ADME and toxicity prediction, and molecular dynamics simulation which have been executed to elucidate different phytochemical and pharmacological properties of the tested compounds. Based on drug-likeness parameters, a total of 96 phytochemical compounds fromhave been screened in the study. Interestingly, Nigelladine A among the compounds exhibited the highest docking score with both the targets with the same binding affinity which is -7.8kcal/mol. However, dithymoquinone, kaempferol, Nigelladine B, Nigellidine, and Nigellidine sulphate showed mentionable docking scores. Molecular dynamics up to 100nanoseconds were simulated under GROMOS96 43a1 force field for the protein-ligand complexes exhibiting the top-docking score. The root mean square deviations (RMSD), root mean square fluctuations (RMSF), radius of gyration (Rg), solvent accessible surface area (SASA), and the number of hydrogen bonds have been evaluated during the simulation. From the findings, the present study suggests that Nigelladine A showed the most promising results among the selected molecules. This framework, however, interprets only a group of computational analyses on selected phytochemicals. Further investigations are required to validate the compound as a promising drug against the selected variant of SARS-CoV-2.

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PMID:  Nutr Metab Cardiovasc Dis. 2023 Jan 29. Epub 2023 Jan 29. PMID: 36849317 Abstract Title:  Green tea consumption and the risk of coronary heart disease: A systematic review and meta-analysis of cohort studies. Abstract:  BACKGROUND AND AIMS: Conflicting evidence exists regarding the association between green tea consumption and the risk of coronary heart disease (CHD). We performed a meta-analysis to determine whether an association exists between them in cohort studies.METHODS AND RESULTS: We searched the PubMed and EMBASE databases for studies conducted until September 2022. Prospective cohort studies that provided relative risk (RR) estimates with 95% confidence intervals (CIs) for the association were included. Study-specific risk estimates were combined using a random-effects model. A total of seven studies, with 9211 CHD cases among 772,922 participants, were included. We observed a nonlinear association between green tea consumption and the risk of CHD (P for nonlinearity = 0.0009). Compared with nonconsumers, the RRs (95% CI) of CHD across levels of green tea consumption were 0.89 (0.83, 0.96) for 1 cup/day (1 cup = 300 ml), 0.84 (0.77, 0.93) for 2 cups/day, 0.85 (0.77, 0.92) for 3 cups/day, 0.88 (0.81, 0.96) for 4 cups/day, and 0.92 (0.82, 1.04) for 5 cups/day.CONCLUSIONS: This updated meta-analysis of studies from East Asia suggests that green tea consumption may be associated with a reduced risk of CHD, especially among those with low-to-moderate consumption. Additional cohorts are still needed before we could draw a definitive conclusion.SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022357687.

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PMID:  Anticancer Res. 2023 Mar ;43(3):1025-1030. PMID: 36854509 Abstract Title:  Epigallocatechin Gallate Inhibits Cell Growth and Hedgehog Signalling in Human Rhabdomyosarcoma Cell Lines. Abstract:  BACKGROUND/AIM: Epigallocatechin gallate (EGCG), a major polyphenol of green tea, has been shown to inhibit cancer cell proliferation. In this study the effect of EGCG on cell metabolism and the human hedgehog signalling pathway (HH) in human rhabdomyosarcoma (RMS) cells was investigated.MATERIALS AND METHODS: Two human RMS cell lines (RD and RH30) were incubated with EGCG. To evaluate the effects of EGCG on RMS cells, cell viability, colony formation, cell migration, and alteration of genes related to the HH signalling pathway were investigated.RESULTS: EGCG showed cytostatic effects on RMS cells in a dose-dependent manner. Incubation with 25M EGCG resulted in a significant reduction of cell migration by 70% and downregulation of the HH pathway transcription factor GLI1.CONCLUSION: EGCG inhibits RMS cells in vitro by reducing cell proliferation and downregulating the HH signalling pathway. It may therefore be a promising agent in chemoresistant or advanced RMS in children.

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PMID:  J Nat Med. 2023 Mar 1. Epub 2023 Mar 1. PMID: 36854953 Abstract Title:  Suppressive effect of black tea polyphenol theaflavins in a mouse model of ovalbumin-induced food allergy. Abstract:  Food allergy is recognized as a global medical problem with increasing prevalence in recent years. Currently, the treatment of food allergy mainly involves avoidance of allergens and allergen-specific immunotherapy. Barring the spontaneous resolution of food allergy during the growth process, this disease is difficult to treat fundamentally. In recent years, the use of functional food ingredients derived from natural products has been attracting attention for their prophylactic use in food allergy. Theaflavins, i.e., black tea polyphenols, are potent antioxidants that have inhibitory effects on a variety of diseases. However, little is known about the preventive effect of theaflavins on food allergy. In this study, we designed a mouse model of food allergy and examined the effect of theaflavins using the severity of diarrhea, a symptom of food allergy, as an indicator. The administration of a black tea extract rich in theaflavins or theaflavin 1 (subgroup of theaflavins) to mice reduced the severity of diarrhea when compared with a normal diet. A reduction in malondialdehyde levels, a key marker of lipid peroxidation, was also observed. Overall, these data suggest that theaflavins may potentially inhibit food allergy by alleviating oxidative stress in the colon and can be a potential food material for prevention of food allergy.

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PMID:  Am J Chin Med. 2023 Mar 3:1-17. Epub 2023 Mar 3. PMID: 36867109 Abstract Title:  Epigallocatechin-3-Gallate Decreases Hypoxia-Inducible Factor-1 in Pancreatic Cancer Cells. Abstract:  Hypoxia-inducible factor-1 (HIF-1) is an [Formula: see text]/[Formula: see text] heterodimeric transcription factor. In normal mammalian cells, HIF-1[Formula: see text] is hydroxylated and degraded upon biosynthesis. However, HIF-1[Formula: see text] is frequently expressed in cancer and adds to cancer malignancy. In this study, we investigated whether green tea-derived epigallocatechin-3-gallate (EGCG) decreased HIF-1[Formula: see text] in pancreatic cancer cells. After MiaPaCa-2 and PANC-1 pancreatic cancer cells were exposed to EGCG, we performed a Western blot to determine native and hydroxylated HIF-1[Formula: see text], which was in turn used to assess HIF-1[Formula: see text] production. In order to assess HIF-1[Formula: see text] stability, we determined the HIF-1[Formula: see text] after MiaPaCa-2 and PANC-1 cells were switched from hypoxia to normoxia. We found that EGCG decreased both production and stability of HIF-1[Formula: see text]. Further, the EGCG-induced decrease in HIF-1[Formula: see text] reduced intracellular glucose transporter-1 and glycolytic enzymes and attenuated glycolysis, ATP production, and cell growth. Because EGCG is known to inhibit cancer-induced insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF1R), we created three MiaPaCa-2 sublines whose IR, IGF1R, and HIF-1[Formula: see text] were decreased using RNA interference. From wild-type MiaPaCa-2 cells and these sublines, we found evidence that suggested that the EGCG-induced inhibition of HIF-1[Formula: see text] was both dependent on and independent of IR and IGF1R., we transplanted wild-type MiaPaCa-2 cells in athymic mice and treated the mice with EGCG or vehicle. When the resulting tumors were analyzed, we found that EGCG decreased tumor-induced HIF-1[Formula: see text] and tumor growth. In conclusion, EGCG decreased HIF-1[Formula: see text] in pancreatic cancer cells and sabotaged the cells. The anticancer effects of EGCG were both dependent on and independent of IR and IGF1R.

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PMID:  Inflammopharmacology. 2023 Feb 27:1-20. Epub 2023 Feb 27. PMID: 36849854 Abstract Title:  The effects of vitamin C on respiratory, allergic and immunological diseases: an experimental and clinical-based review. Abstract:  Vitamin C is used in modern medicine supplements for treatment of various disorders associated with oxidative stress, inflammation and immune dysregulation. In this review article, experimental and clinical results regarding the effects of vitamin C on respiratory immunologic, and allergic diseases are reviewed. Various databases and appropriate keywords are used to search the effect of vitamin C on respiratory diseases until the end of May 2022. Books, theses and articles were included. These studies assessed the effects of vitamin C on respiratory disorders including asthma, chronic obstructive pulmonary disease (COPD), lung infection and lung cancer. Vitamin C showed relaxant effect on tracheal smooth muscle via various mechanisms. The preventive effects of vitamin C were mediated by antioxidant, immunomodulatory and anti-inflammatory mechanisms in the experimental animal models of different respiratory diseases. Some clinical studies also indicated the effect of vitamin C on lung cancer and lung infections. Therefore, vitamin C could be used a preventive and/or relieving therapy in respiratory diseases.

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PMID:  J Neuroinflammation. 2023 Mar 1 ;20(1):54. Epub 2023 Mar 1. PMID: 36859349 Abstract Title:  Berberine ameliorates depression-like behaviors in mice via inhibiting NLRP3 inflammasome-mediated neuroinflammation and preventing neuroplasticity disruption. Abstract:  OBJECTIVES: Neuroinflammation has been suggested that affects the processing of depression. There is renewed interest in berberine owing to its anti-inflammatory effects. Herein, we investigated whether berberine attenuate depressive-like behaviors via inhibiting NLRP3 inflammasome activation in mice model of depression.METHODS: Adult male C57BL/6N mice were administrated corticosterone (CORT, 20 mg/kg/day) for 35 days. Two doses (100 mg/kg/day and 200 mg/kg/day) of berberine were orally administrated from day 7 until day 35. Behavioral tests were performed to measure the depression-like behaviors alterations. Differentially expressed gene analysis was performed for RNA-sequencing data in the prefrontal cortex. NLRP3 inflammasome was measured by quantitative reverse transcription polymerase chain reaction, western blotting, and immunofluorescence labeling. The neuroplasticity and synaptic function were measured by immunofluorescence labeling, Golgi-Cox staining, transmission electron microscope, and whole-cell patch-clamp recordings.RESULTS: The results of behavioral tests demonstrated that berberine attenuated the depression-like behaviors induced by CORT. RNA-sequencing identified that NLRP3 was markedly upregulated after long-term CORT exposure. Berberine reversed the concentrations of peripheral and brain cytokines, NLRP3 inflammasome elicited by CORT in the prefrontal cortex and hippocampus were decreased by berberine. In addition, the lower frequency of neuronal excitation as well as the dendritic spine reduction were reversed by berberine treatment. Together, berberine increases hippocampal adult neurogenesis and synaptic plasticity induced by CORT.CONCLUSION: The anti-depressants effects of berberine were accompanied by reduced the neuroinflammatory response via inhibiting the activation of NLRP3 inflammasome and rescued the neuronal deterioration via suppression of impairments in synaptic plasticity and neurogenesis.

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PMID:  Histol Histopathol. 2023 Feb 24:18599. Epub 2023 Feb 24. PMID: 36861878 Abstract Title:  Treatment of berberine alleviates diabetic nephropathy by reducing iron overload and inhibiting oxidative stress. Abstract:  Diabetic nephropathy (DN) has become one of the major fatal factors in diabetic patients. The aim of this study was to elucidate the function and mechanism by which berberine exerts renoprotective effects in DN. In this work, we first demonstrated that urinary iron concentration, serum ferritin and hepcidin levels were increased and total antioxidant capacity was significantly decreased in DN rats, while these changes could be partially reversed by berberine treatment. Berberine treatment also alleviated DN-induced changes in the expression of proteins involved in iron transport or iron uptake. In addition, berberine treatment also partially blocked the expression of renal fibrosis markers induced by DN, including MMP2, MMP9, TIMP3,-arrestin-1, and TGF-1. In conclusion, the results of this study suggest that berberine may exert renoprotective effects by ameliorating iron overload and oxidative stress and reducing DN.

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PMID:  Infect Disord Drug Targets. 2023 Feb 23. Epub 2023 Feb 23. PMID: 36825730 Abstract Title:  Potential of Black Seeds (Nigella Sativa) in the Management of Long COVID or Post-acute Sequelae of COVID-19 (PASC) and Persistent COVID-19 Symptoms - An Insight. Abstract:  BACKGROUND: Some individuals may experience symptoms persisting for many months after the recovery from COVID-19 and patients with Long COVID are managed mainly with symptomatic treatment and supportive care.OBJECTIVE: This review article focuses on the beneficial effects of black seeds (Nigella Sativa) in the management of long COVID and persistent COVID symptoms.METHODS: The literature was searched in databases such as LitCOVID, Web of Science, Google Scholar, bioRxiv, medRxiv, Science Direct, EBSCO, Scopus, Embase, and reference lists to identify studies, which evaluated various effects of black seeds (N. sativa) related to signs and symptoms of Long COVID.RESULTS: Black seeds (N. sativa) have shown potential anti-COVID, antiviral, anti-inflammatory, antioxidant, immunomodulatory, antihypertensive, anti-obesity, antidiabetic, antihyperlipidemic, and antiasthmatic properties in various clinical, animal, in-vitro, in-vivo, and in-silico studies, which would help the patients recovered from COVID to mitigate Long COVID complications.CONCLUSION: Patients experiencing Long COVID may use black seeds (N. sativa) as adjunctive therapy in combination with symptomatic treatment and supportive care to prevent further deterioration and hospitalization. The safety and efficacy of N. sativa in patients with Long-COVID would further be established by future randomized controlled clinical trials.

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PMID:  Antioxidants (Basel). 2023 Feb 9 ;12(2). Epub 2023 Feb 9. PMID: 36829993 Abstract Title:  Antioxidant Thymoquinone and Its Potential in the Treatment of Neurological Diseases. Abstract:  Oxidative stress is one of the main pathogenic factors of neuron damage in neurodegenerative processes; this makes it an important therapeutic target to which the action of neuroprotectors should be directed. One of these drugs is thymoquinone. According to modern data, this substance has a wide range of pharmacological activity, including neuroprotective, which was demonstrated in experimental modeling of various neurodegenerative diseases and pathological conditions of the brain. The neuroprotective effect of thymoquinone is largely due to its antioxidant ability. Currently available data show that thymoquinone is an effective means to reduce the negative consequences of acute and chronic forms of cerebral pathology, leading to the normalization of the content of antioxidant enzymes and preventing an increase in the level of lipid peroxidation products. Antioxidant properties make this substance a promising basis for the development of prototypes of therapeutic agents aimed at the treatment of a number of degenerative diseases of the central nervous system.

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PMID:  BMC Complement Med Ther. 2023 Mar 4 ;23(1):69. Epub 2023 Mar 4. PMID: 36870998 Abstract Title:  Thymoquinone, piperine, and sorafenib combinations attenuate liver and breast cancers progression: epigenetic and molecular docking approaches. Abstract:  BACKGROUND: Traditional herbal medicine has been used for centuries to cure many pathological disorders, including cancer. Thymoquinone (TQ) and piperine (PIP) are major bioactive constituents of the black seed (Nigella sativa) and black pepper (Piper nigrum), respectively. The current study aimed to explore the potential chemo-modulatory effects, mechanisms of action, molecular targets, and binding interactions after TQ and PIP treatments and their combination with sorafenib (SOR) against human triple-negative breast cancer (MDA-MB-231) and liver cancer (HepG2) cells.METHODS: We determined drug cytotoxicity by MTT assay, cell cycle, and death mechanism by flow cytometry. Besides, the potential effect of TQ, PIP, and SOR treatment on genome methylation and acetylation by determination of DNA methyltransferase (DNMT3B), histone deacetylase (HDAC3) and miRNA-29c expression levels. Finally, a molecular docking study was performed to propose potential mechanisms of action and binding affinity of TQ, PIP, and SOR with DNMT3B and HDAC3.RESULTS: Collectively, our data show that combinations of TQ and/or PIP with SOR have significantly enhanced the SOR anti-proliferative and cytotoxic effects depending on the dose and cell line by enhancing G2/M phase arrest, inducing apoptosis, downregulation of DNMT3B and HDAC3 expression and upregulation of the tumor suppressor, miRNA-29c. Finally, the molecular docking study has identified strong interactions between SOR, PIP, and TQ with DNMT3B and HDAC3, inhibiting their normal oncogenic activities and leading to growth arrest and cell death.CONCLUSION: This study reported TQ and PIP as enhancers of the antiproliferative and cytotoxic effects of SOR and addressed the mechanisms, and identified molecular targets involved in their action.

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PMID:  J Med Food. 2022 May ;25(5):529-533. Epub 2022 Mar 24. PMID: 35333621 Abstract Title:  L. Seed Oil: Effect on Cell Viability in Colon Cancer Line Caco2 and Breast Cancer Line MCF7. Abstract:  Cancer is one of the main causes of mortality and morbidity worldwide, which does not have a fully effective medical treatment. Therefore, the objective of this study was to evaluate the effect of lipidically characterized and hydrolyzed chia seed (L.) oil oncolon cancer (Caco2 cell line) and breast cancer cells (MCF7 cell line) cell viability. Cancer cells were treated with different hydrolyzed oil concentrations (12.5-400g/mL) for 48h; then cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. All chia seed oil concentrations significantly reduced cell viability in the Caco2 line, with the best reduction being 23.88% with the 25g/mL concentration. However, in the breast cancer line the highest concentrations (200 and 400g/mL) increased the viability of malignant cells. Chia seed oil significantly reduces the viability of Caco2 cells, although at the higher concentrations it can increase the viability of breast cancer cells.

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PMID:  Food Funct. 2022 Jul 4 ;13(13):7333-7345. Epub 2022 Jul 4. PMID: 35726830 Abstract Title:  L. (chia) seed ameliorates liver injury and oxidative stress by modulating NrF2 and NFB expression in sucrose-rich diet-fed rats. Abstract:  The aim of this study was to analyze the liver injury and oxidative stress in an experimental model of Metabolic Syndrome (MS) induced by chronic administration of a sucrose-rich diet (SRD) and to evaluate the effects of chia seed as a therapeutic strategy. Male Wistar rats were fed with a reference diet (RD) -6 months- or a SRD -3 months. Then, the latter group was randomly divided into two subgroups. One subgroup continued receiving the SRD for up to 6 months and the other was fed with a SRD where whole chia seed was incorporated as a source of dietary fat for the next 3 months (SRD+CHIA). The results showed that rats fed with a SRD for a long period of time developed dyslipidemia, hyperglycemia, hepatic lipid accumulation, liver injury, hepatic lipid peroxidation and oxidative stress. Hepatic NrF2 expression was significantly decreased. In addition, a significant increase in hepatic NFB p65 expression and a positive correlation of this with plasma TNFlevels were found. The administration of chia seed for 3 months reversed dyslipidemia, hyperglycemia, lipid accumulation, liver injury, lipid peroxidation and oxidative stress. In the liver tissue, NrF2 expression was normalized and NFB p65 expression was decreased, the latter was associated with a decrease in plasma TNFlevels. The present study showed new aspects of liver damage, lipid peroxidation and oxidative stress in dyslipidemic insulin resistant rats chronically fed with a sucrose-rich diet. However, we demonstrated new properties and molecular mechanisms associated with the beneficial anti-oxidant effects of chia seed consumption.

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PMID:  Curr Pharm Biotechnol. 2022 Sep 21. Epub 2022 Sep 21. PMID: 36154592 Abstract Title:  Chia seeds oil suppresses the resistance of hepatocellular carcinoma cells to liposomal-doxorubicin and upregulates the tumor suppressor miRNAs. Abstract:  BACKGROUND: Chia seed is an oil-seed of multiple biological activities. Doxorubicin is an effective chemotherapy for liver cancer. Resistance and adverse effects are doxorubicin limitations.OBJECTIVE: This study aimed to investigate the effect of chia seeds oil (CSO) on the resistance of HepG2 cells to liposomal-doxorubicin (DOX).METHODS: The objective were investigated through measuring cytotoxicity, doxorubicin-metabolizing enzyme Cytochrome P450 3A4 (CYP-3A4), multidrug resistance-associated protein (MRP1), and the expression of multiple tumor suppressor microRNAs.RESULTS: The findings indicated that low concentration of CSO increased HepG2 cells sensitivity to DOX as concluded from its higher cytotoxicity. DOX induced mRNAs of CYP-3A4 and MRP1 and their protein levels. CSO inhibited both in DOX-treated cells. CSO induced tumor suppressor miRNAs. Doxorubicin inhibited miR-122 and let-7/b/e expression, while it led to overexpression of let-7a. CSO/DOX upregulated let-7/b/e, miR-34a, and miR-122 (which inhibits MRP1) and downregulated let-7a that may lead to increased apoptosis.CONCLUSION: CSO effectively re-sensitized HepG2 cells to liposomal-doxorubicin via inhibiting MRP1 and CYP-3A4 that may increase in vivo doxorubicin bioavailability and decrease its therapeutic dose to diminish its adverse effects.

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PMID:  Food Funct. 2022 Oct 31 ;13(21):11249-11261. Epub 2022 Oct 31. PMID: 36222595 Abstract Title:  L. (chia) seed improves liver inflammation and endothelial dysfunction in an experimental model of metabolic syndrome. Abstract:  The purposes of the present study were to analyze liver inflammation and endothelial dysfunction in an experimental model of metabolic syndrome (MS) induced by chronic administration of a sucrose-rich diet (SRD) and to evaluate the effects of chia seed as a therapeutic strategy. Male Wistar rats were fed with a reference diet (RD) for 6 months or a SRD for 3 months. Then, the latter group was randomly divided into two subgroups. One subgroup continued receiving the SRD for up to 6 months and the other was fed with a SRD where whole chia seed was incorporated as a source of dietary fat for the next 3 months (SRD + CHIA). Results showed that rats fed a SRD for a long period of time developed dyslipidemia, hyperglycemia, inflammation and endothelial dysfunction. Hepatic NAS, IL-1, NFB p65, PAI-1, and F4-80 expression, as well as MPO activity were significantly increased and IL-10 expression was significantly decreased; this was accompanied by increased plasma IL-6 and TNF-levels in rats fed a SRD. In addition, serum and liver nitric oxide (NO) levels and nitric oxide synthase (NOS) were significantly increased in the SRD group. In addition, a significant increase in hepatic iNOS expression and a positive correlation of this with liver NFB p65 was found. We observed a significant increase in hepatic intercellular adhesion molecule (ICAM), and a negative correlation of this with liver Nrf2 was found. The administration of chia seed for 3 months reversed dyslipidemia, hyperglycemia, inflammation and endothelial dysfunction. In the liver tissue, NAS, IL-1, IL-10, NFB p65, PAI-1, and F4-80 expression and MPO activity were normalized. Serum and liver NO and NOS levels and hepatic iNOS expression were decreased and this last one was associated with a decrease in liver NFB p65 levels. Hepatic ICAM-1 was normalized and negatively correlated with liver NrF2 levels. This study showed new aspects of liver inflammation and endothelial dysfunction in dyslipidemic insulin resistant rats chronically fed with a sucrose-rich diet. In addition, we demonstrated new properties and molecular mechanisms associated with beneficial effects on inflammation and endothelial dysfunction of chia seed as a therapeutic strategy.

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PMID:  Nutrients. 2022 Nov 21 ;14(22). Epub 2022 Nov 21. PMID: 36432610 Abstract Title:  Effect of Chia (L.) Associated with High-Fat Diet on the Intestinal Health ofRats. Abstract:  A direct correlation has been reported between excessive fat intake and the development and progression of various enteropathies. Plant foods may contain bioactive compounds and non-digestible dietary fiber, with potential to improve intestinal health. Chia is a good source of dietary fiber and bioactive compounds. Our study evaluated the role of chia flour associated with a high-fat diet (HFD) on colon histomorphometry, intestinal functionality and intestinal microbiome composition and function inrats. The study used 32 young male rats separated into four groups to receive a standard diet (SD) or HFD, with or without chia, for 35 days. At the end of the study, the cecum, cecal content and duodenum were collected. The consumption of chia increased the production of short-chain fatty acids and improved fecal moisture. Chia consumption improved the circular muscle layer in the SD group. The diversity and abundance of intestinal bacteria were not affected, but increased richness was observed in the microbiome of the SD+chia group. Moreover, chia consumption decreased the expression of proteins involved in intestinal functionality. Chia consumption improved intestinal morphology and functionality in youngrats but was insufficient to promote significant changes in the intestinal microbiome in a short term of 35 days.

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PMID:  Food Sci Nutr. 2023 Jan ;11(1):3-16. Epub 2022 Dec 15. PMID: 36655089 Abstract Title:  Chia seeds (L.): A therapeutic weapon in metabolic disorders. Abstract:  The growth of functional components containing agricultural foods is enhancing because these components aid the human body against different chronic diseases. Currently, chia seeds basically belong to the mint family and are edible seeds of. These seeds are composed of different functional components including fiber, polyphenols, antioxidants, omega-3 fatty acid vitamins, minerals, and peptides. Besides, these seeds are also a good source of vegetable protein, unsaturated fat, carbohydrates, and ash. Chia seed components are helpful in cardiovascular disease (CVD) by reducing blood pressure, platelet aggregation, cholesterol, and oxidation. In GI-tract-related diseases like diabetes and constipation, chia fiber reduces the blood glucose level and provides bulk to stool. However, antioxidants and polyphenols are protected beta cells of the pancreas from inflammation. These components are protected from the cell damage of the different body parts, which can provide help in different types of cancer including breast, colorectal, liver, and pancreatic. Conclusively, some pervious studies approved that chia seed components are played important role in chronic diseases.

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PMID:  Struct Chem. 2022 Jun 16:1-16. Epub 2022 Jun 16. PMID: 35729937 Abstract Title:  Study of nonlinear optical responses of phytochemicals ofby quantum mechanical approach and investigation of their anti-Alzheimer activity with in silico approach. Abstract:  UNLABELLED: is a flowering plant with promising medicinal plants with a wide variety of active phytochemicals. The present study aimed at the computational investigation of the nonlinear optical (NLO) responses of the active phytochemicals of theThe computational investigation of the NLO features was done by using the density functional theory (DFT) by B3LYP/6-311G++(d, p) basis set. The structural parameters, mulliken charge distribution, and molecular electrostatic potential (MEP) surface clearly show the intramolecular charge transfer within Clitorin. The NLO properties were identified by computing the polarizability parameters. As the plant has high medicinal characteristics, the inhibiting properties of its phytochemicals were also investigated to combat Alzheimer disease (AD). The systematic in silico study identifies Clitorin as the most active and inhibiting phytochemicals of the plant. The results obtained from molecular dynamics (MD) simulation tell the stability of the complex and make it a fair selection as a drug-like molecule against AD. The cardio-toxicity analysis done for the Clitorin molecule verifies that it is harmless for the supplementary material available at 10.1007/s11224-022-01981-5.

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PMID:  Access Microbiol. 2022 ;4(4):000343. Epub 2022 Apr 26. PMID: 35812712 Abstract Title:  Antibiofilm properties offlower anthocyanin-rich fraction towards. Abstract:  In Asia,flowers are commonly used as a traditional medicinal herb and as a food colourant. Their bioactive compounds have anti-inflammatory, anti-microbial and anti-biofilm activities.is one of the major pathogens that cause biofilm-associated infections resulting in an increase in antimicrobial resistance. Hence, the aim of this study was to investigate if the anti-biofilm properties of the anthocyanin-rich fraction offlowers were effective against. The effect of the anthocyanin-rich fraction offlowers onbiofilms formed on a polystyrene surface was determined using the crystal violet assay and scanning electron microscopy (SEM). The anthocyanin-rich fraction reduced biofilm formation by fourstrains with a minimum biofilm inhibitory concentration value ranging between 0.625 and 5.0mgml. We further show that the biofilm-inhibiting activity offlowers is not due to the flavonols but is instead attributed to the anthocyanins, which had significant biofilm inhibitory activity (64.01.1%) at 24h in a time-response study. The anthocyanin-rich fraction also significantly reduced bacterial attachment on the polystyrene by 1.1 log c.f.u. cmsurface based on SEM analysis. Hence, anthocyanins fromflowers have potential as an agent to decrease the risk of biofilm-associated infections.

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PMID:  Sci Rep. 2022 Sep 1 ;12(1):14890. Epub 2022 Sep 1. PMID: 36050436 Abstract Title:  Antioxidant, cytotoxic, and antibacterial activities of Clitoria ternatea flower extracts and anthocyanin-rich fraction. Abstract:  Clitoria ternatea flower is a traditional medicinal herb that has been used as a natural food colourant. As there are limited studies on investigating the bioactivities of the anthocyanin-rich fraction of Clitoria ternatea flower, this study aimed to determine an efficient column chromatography method to obtain the anthocyanin-rich fraction from this flower and characterise its composition, antioxidant, antibacterial, and cytotoxic activities. Amberlite XAD-16 column chromatography was more efficient in enriching the total anthocyanin content (TAC) of the fraction with the highest TAC to total phenolic content (TPC) ratio of 1:6 than that using C18-OPN. A total of 11 ternatin anthocyanins were characterised in the anthocyanin-rich fraction by LC-MS analysis. The antioxidant activity of the anthocyanin-rich fraction was more potent in the chemical-based assay with an ICvalue of 0.860.07 mg/mL using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay than cellular antioxidant assay using RAW 264.7 macrophages. In vitro cytotoxicity assay using human embryonic kidney HEK-293 cell line showed the anthocyanin-rich fraction to be more toxic than the crude extracts. The anthocyanin-rich fraction had more potent antibacterial activity than the crude extracts against Bacillus cereus, Bacillus subtilis, and Escherichia coli. The anthocyanin-rich fraction of C. ternatea has the potential to be used and developed as a functional food ingredient or nutraceutical agent.

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PMID:  J Biomol Struct Dyn. 2022 Sep 24:1-10. Epub 2022 Sep 24. PMID: 36153001 Abstract Title:  screening of the phytochemicals present inL. as the inhibitors of snake venom phospholipase A(PLA). Abstract:  Millions of people suffer from snake bite envenomation, and its management is a challenge, even today. Medicinal plants have attracted the researcher's attention for their outstanding advantages in treating many diseases, including snake venom poisoning.L, is a plant popularly known for its various pharmacological effects especially, anti-snake venom property. However, the molecular mechanism behind this is poorly understood. It is reported that snake venom PLAis an extensively studied toxic factor. This study is meant to screen the compound's capability to act as inhibitors of thesnake venom PLAthrough molecular docking and dynamics studies. Our results show that among the 27 compounds taken for the study, only Kaempferol showed good interaction profile with the conserved catalytic active site residues, His48 and Asp49. The pharmacophore features of the compound also demonstrate its exact fitting at the binding pocket. Further RMSD, RMSF, Rg, and hydrogen bond analysis confirmed the stable binding of Kaempferol with PLAthrough molecular dynamic simulations for 100ns. In addition, the MM/PBSA binding free energy calculation of the complex was also affirming the docking results. The binding free energy (BFE) of Kaempferolis better than the reference compound. ADME and Lipinski's rule of five reveals its drug like properties.Communicated by Ramaswamy H. Sarma.

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PMID:  Molecules. 2022 Sep 26 ;27(19). Epub 2022 Sep 26. PMID: 36234873 Abstract Title:  Phytochemical Properties and In Vitro Biological Activities of Phenolic Compounds from Flower ofL. Abstract:  Phenolic compounds from the flower ofL. (PCFCTL) were extracted using a high-speed shearing extraction technique and purified by AB-8 macroporous resins, and the phytochemical composition of the purified phenolic compounds from the flower ofL. (PPCFCTL) was then analyzed. Subsequently, its bioactivities including antioxidant properties, enzyme inhibitory activities, and antiproliferative activities against several tumor cell lines were evaluated. Results indicated that the contents of total phenolics, flavonoids, flavonols, flavanols, and phenolic acids in PPCFCTL were increased by 3.29, 4.11, 2.74, 2.43, and 2.96-fold, respectively, compared with those before being purified by AB-8 macroporous resins. The results showed PPCFCTL have significant antioxidant ability (measured by reducing power, RP, and ferric reducing antioxidant power method, FRAP) and good DPPH, ABTS, and superoxide anion radical scavenging activities. They can also significantly inhibit lipase,-amylase, and-glucosidase. In addition, morphological changes of HeLa, HepG2, and NCI-H460 tumor cells demonstrated the superior antitumor performance of PPCFCTL. However, the acetylcholinesterase inhibitory activity was relatively weak. These findings suggest that PPCFCTL have important potential as natural antioxidant, antilipidemic, anti-glycemic and antineoplastic agents in health-promoting foods.

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PMID:  Front Mol Biosci. 2022 ;9:986704. Epub 2022 Sep 30. PMID: 36250019 Abstract Title:  Effects of a plant cyclotide on conformational dynamics and destabilization of-amyloid fibrils through molecular dynamics simulations. Abstract:  Aggregation of-amyloid (A) peptide is one of the hallmarks of Alzheimer's disease (AD) which results in chronic and progressive neurodegeneration of the brain. A recent study by our group have shown the ability of cyclic disulfide-rich peptides ("cyclotides") isolated from a medicinal plant,, to inhibit the aggregation of Apeptides and reduce oxidative stress caused by reactive oxygen species usingmodels of transgenic. In the present study, through extensive computational docking and multi-ns molecular dynamics (MD) simulation, we evaluated if cyclotides can stably bind to Amolecules and/or destabilize the Afibril by preventing conformational changes from-helical to-sheet rich structures. We demonstrate that cyclotides bind effectively and stably to different forms of Astructureshydrogen bonding and hydrophobic interactions. One of the conserved hydrophobic interface residues, Tyr10 was mutated to Ala and the impact of this virtual mutation was estimated by additional MD simulations for the wild-type (WT) and mutant protein-peptide complexes. A detailed MD simulation analyses revealed that cyclotides form hydrogen bonds with the toxic amyloid assemblies thereby weakening the inter-strand hydrogen bonds between the Apeptide. The-distribution map of residues in the cyclotide binding pocket that ideally adopt-sheet conformation show deviation towards right-handed-helical () conformation. This effect was similar to that observed for the Tyr10Ala mutant and doubly so, for the cyclotide bound form. It is therefore possible to hypothesise that the opening up of amyloid-sheet is due to an unfolding process occurring in the Acaused by cyclotide binding and inhibition. Our current findings provide novel structural insights on the mode of interaction between cyclotides and Afibrils and describe their anti-amyloid aggregation potential. This sheds light on the future of cyclotide-based drug design against protein aggregation, a hallmark event in many neurodegenerative diseases.

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PMID:  Pharmaceuticals (Basel). 2022 Nov 13 ;15(11). Epub 2022 Nov 13. PMID: 36422526 Abstract Title:  Asian Pigeonwing Plants () Synergized Mesenchymal Stem Cells by Modulating the Inflammatory Response in Rats with Cisplatin-Induced Acute Kidney Injury. Abstract:  Acute kidney injury is a heterogeneous set of disorders distinguished by a sudden decrease in the glomerular filtration rate, which is evidenced by an increase in the serum creatinine concentration or oliguria and categorized by stage and cause. It is an ever-growing health problem worldwide, with no reliable treatment. In the present study, we evaluated the role ofcombined with mesenchymal stem cells in treating cisplatin-induced acute kidney injury in rats. Animals were challenged with cisplatin, followed by 400 mg/kg of Asian pigeonwing extract and/or mesenchymal stem cells (106 cells/150 g body weight). Kidney functions and enzymes were recorded, and histopathological sectioning was also performed. The expression profile of IL-1, IL-6, and caspase-3 was assessed using the quantitative polymerase chain reaction. The obtained data indicated that mesenchymal stem cells combined with the botanical extract modulated the creatinine uric acid and urea levels. Cisplatin increased the level of malondialdehyde and decreased the levels of both superoxide dismutase and glutathione; however, the dual treatment was capable of restoring the normal levels. Furthermore, all treatments modulated the IL-6, IL-1, and caspase-3 gene expression profiles. The obtained data shed some light on adjuvant therapy usingand mesenchymal stem cells in treating acute kidney injury; however, further investigations are required to understand these agents' synergistic mechanisms fully. The total RNA was extracted from the control, the positive control, and all of the therapeutically treated animals. The expression profiles of the IL-6, IL-1, and caspase-3 genes were evaluated using the real-time polymerase chain reaction. Cisplatin treatment caused a significant upregulation in IL-6. All treatments could mitigate the IL-6-upregulating effect of cisplatin, with the mesenchymal stem cell treatment being the most effective. The same profile was observed in the IL-1and caspase-3 genes, except that the dual treatment (mesenchymal stem cells and the botanical extract) was the most effective in ameliorating the adverse effect of cisplatin; it downregulated caspase-3 expression better than the positive control.

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PMID:  Food Res Int. 2022 Dec ;162(Pt A):112008. Epub 2022 Oct 1. PMID: 36461234 Abstract Title:  Clitoria ternatea blue petal extract protects against obesity, oxidative stress, and inflammation induced by a high-fat, high-fructose diet in C57BL/6 mice. Abstract:  This study examined the chemical compounds and bioactivity of the aqueous extract of Clitoria ternatea blue petals and investigated its beneficial effects in vivo on a mouse model of obesity and metabolic syndrome. The extract mainly contained flavonoids, and nine compounds were tentatively identified. Male C57BL/6J mice were either fed a standard diet (SD) or a high-fat, high-fructose diet (HFFD) for 16 weeks, and HFFD-fed animals were treated with 0.25%, 0.5%, and 2% (w/w) of the aqueous extract in drinking water. The aqueous extract ameliorated oxidative stress and inflammation mediators. Furthermore, the aqueous extract reduced plasma leptin, free fatty acid, low-density lipoprotein cholesterol levels and hepatic malondialdehyde content. The aqueous extract significantly reduced total cholesterol and ameliorated insulin resistance. The results demonstrated that the aqueous extract of C. ternatea blue petals contains bioactive anthocyanins that exert substantial hypolipidemic and anti-inflammatory effects by promoting reverse cholesterol transport in HFFD-fed mice.

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PMID:  Nutrients. 2021 Sep 16 ;13(9). Epub 2021 Sep 16. PMID: 34579104 Abstract Title:  Possible Role of Butyrylcholinesterase in Fat Loss and Decreases in Inflammatory Levels in Patients with Multiple Sclerosis after Treatment with Epigallocatechin Gallate and Coconut Oil: A Pilot Study. Abstract:  (1) Background. Multiple sclerosis (MS) is characterised by the loss of muscle throughout the course of the disease, which in many cases is accompanied by obesity and related to inflammation. Nonetheless, consuming epigallocatechin gallate (EGCG) and ketone bodies (especially-hydroxybutyrate (HB)) produced after metabolising coconut oil, have exhibited anti-inflammatory effects and a decrease in body fat. In addition, butyrylcholinesterase (BuChE), seems to be related to the pathogenesis of the disease associated with inflammation, and serum concentrations have been related to lipid metabolism. Objective. The aim of the study was to determine the role of BuChE in the changes caused after treatment with EGCG and ketone bodies on the levels of body fat and inflammation state in MS patients. (2) Methods. A pilot study was conducted for 4 months with 51 MS patients who were randomly divided into an intervention group and a control group. The intervention group received 800 mg of EGCG and 60 mL of coconut oil, and the control group was prescribed a placebo. Fat percentage and concentrations of the butyrylcholinesterase enzyme (BuChE), paraoxonase 1 (PON1) activity, triglycerides, interleukin 6 (IL-6), albumin andHB in serum were measured. (3) Results. The intervention group exhibited significant decreases in IL-6 and fat percentage and significant increases in BuChE,HB, PON1, albumin and functional capacity (determined by the Expanded Disability Status Scale (EDSS)). On the other hand, the control group only exhibited a decrease in IL-6. After the intervention, BuChE was positively correlated with the activity of PON1, fat percentage and triglycerides in the intervention group, whereas these correlations were not observed in the control group (4). Conclusions. BuChE seems to have an important role in lipolytic activity and the inflammation state in MS patients, evidenced after administering EGCG and coconut oil as aHB source.

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PMID:  Food Funct. 2023 Jan 23 ;14(2):1062-1071. Epub 2023 Jan 23. PMID: 36594273 Abstract Title:  Improvements in gait and balance in patients with multiple sclerosis after treatment with coconut oil and epigallocatechin gallate. A pilot study. Abstract:  Multiple sclerosis (MS) is a neurodegenerative disease that progressively decreases the muscular and functional capacity. Thus, there is an alteration in the ability to walk that affects balance, speed and resistance. Since MS pathology involves neuroinflammation, cellular oxidation and mitochondrial alterations, the objective of the study was to assess the impact of a nutritional intervention with coconut oil and epigallocatechin gallate (EGCG) on gait and balance. In order to do this, 51 patients with MS were enrolled and randomly distributed into an intervention group and a control group, which received either a daily dose of 800 mg of EGCG and 60 ml of coconut oil, or a placebo, all during a period of 4 months and which followed a Mediterranean isocaloric diet. Initial and final assessments consisted of the evaluation of quantitative balance (Berg scale), perceived balance (ABC scale), gait speed (10MWT) and resistance (2MWT). Besides, muscle strength was measured using a dynamometer and levels of-hydroxybutyrate (BHB) were measured in serum samples. In the intervention group, there was a significant improvement in the gait speed, quantitative balance and muscle strength of the right quadriceps; an improvement in gait resistance was observed in both groups. There were also significant and positive correlations between balance and gait scales. In conclusion, the administration of EGCG and coconut oil seems to improve gait speed and balance in MS patients, although the latter was not perceived by them. Furthermore, these variables appear to be related and contribute to functionality.

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PMID:  Surg Neurol Int. 2021 ;12:141. Epub 2021 Apr 8. PMID: 33948312 Abstract Title:  Spontaneous regression of herniated cervical disc: A case report and literature review. Abstract:  BACKGROUND: We have reviewed 75 cases plus our own single instance of spontaneous regression of herniated cervical discs.METHODS: We searched PubMed and EMBASE databases (until September 2020) utilizing the following keywords; "spontaneous regression," "herniated cervical disc," and "Magnetic Resonance Imaging (MRI) studies."RESULTS: In the literature, we found 75 cases of herniated cervical discs which spontaneously regressed; to this, we added our case. Patients averaged 40.95 years of age. Discs were paracentral or foraminal in 84% of the cases, with most occurring at the C5-C6 (51%) and C6-C7 (36%) levels. Symptoms included neck pain/radiculopathy (91%) or myelopathy (9%). The average interval between initial presentation and spontaneous regression of herniated discs on MRI was 9.15 months. Interestingly, on MRI, extruded/sequestrated discs were more likely to undergo spontaneous regression versus protruding discs.CONCLUSION: Successive MRI studies documented the spontaneous regression of herniated cervical discs over an average of 9.15 months. Although this may prompt greater consideration for conservative treatment in younger patients without neurologic deficits, those with deficits should be considered for surgery.

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PMID:  World Neurosurg. 2019 Jan 3. Epub 2019 Jan 3. PMID: 30610984 Abstract Title:  Spontaneous Resorption of Herniated Lumbar Disk: Observational Retrospective Study in 9 Patients. Abstract:  BACKGROUND: Spontaneous resorption of herniated lumbar disk was explained in the literature by different mechanisms, and multiple predictive factors for resorption were reported in numerous studies. The purpose of this study was to evaluate the phenomena of spontaneous resorption of herniated lumbar disk without surgery (mechanisms, predictive factors, expected time for resorption, and proper time for conservative treatment).METHODS: This retrospective clinical case series included 9 patients with herniated lumbar disk on initial magnetic resonance imaging (MRI). The mean age was 396.3 years, and the male to female ratio was 2:1. All patients presented with back pain and sciatica without motor deficit. All patients refused surgical intervention; therefore, they were treated conservatively. Patients were followed-up clinically and radiologically (MRI) in the outpatient clinic on regular visits (for 18 months).RESULTS: Spontaneous resorption of herniated disk was found in all patients in a mean time of 8.73.2 months. All patients recovered clinically in a mean time of 5.71.6 weeks by conservative treatment. Large and/or sequestrated disks were associated with rapid resorption. Early recovery patients showed early spontaneous resorption of the disk.CONCLUSIONS: Spontaneous resorption of herniated lumbar disk can occur by different mechanisms (retraction, dehydration, and inflammatory mediated mechanism). Large and/or sequestrated disks are essential predictive factors for rapid spontaneous resorption. Furthermore, early clinical recovery is usually associated with quick resorption of the herniated disk.

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PMID:  Appl Physiol Nutr Metab. 2015 Sep ;40(9):899-906. Epub 2015 May 4. PMID: 26288392 Abstract Title:  Potential ergogenic activity of grape juice in runners. Abstract:  Recent studies have indicated that certain food products have ergogenic potential similar to that of sports supplements. The present study aimed to investigate the potential ergogenic effect of integral purple grape juice on the performance of recreational runners. Twenty-eight volunteers of both sexes (age, 39.88.5 years; peak oxygen consumption, 43.28.5 mL/(kgmin)) were randomized into either a group that received grape juice (grape juice group (GJG), n = 15; 10 mL/(kgmin) for 28 days) or a group that received an isocaloric, isoglycemic, and isovolumetric control beverage (control group (CG), n = 13). A time-to-exhaustion exercise test, anaerobic threshold test, and aerobic capacity test were performed, together with assessments of markers of oxidative stress, inflammation, immune response, and muscle injury, performed at baseline and 48 h after the supplementation protocol. The GJG showed a significant increase (15.3%) in running time-to-exhaustion (p = 0.002) without significant improvements in either anaerobic threshold (3.6%; p = 0.511) or aerobic capacity (2.2%; p = 0.605). In addition, GJG exhibited significant increases in total antioxidant capacity (38.7%; p = 0.009), vitamin A (11.8%; p = 0.016), and uric acid (28.2%; p = 0.005), whereas-1-acid glycoprotein significantly decreased (20.2%; p = 0.006) and high-sensitivity C-reactive protein levels remained unchanged. In contrast, no significant changes occurred in any of these variables in the CG. In conclusion, supplementation with purple grape juice shows an ergogenic effect in recreational runners by promoting increased time-to-exhaustion, accompanied by increased antioxidant activity and a possible reduction in inflammatory markers.

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PMID:  Eur J Nutr. 2020 Oct ;59(7):2997-3007. Epub 2019 Nov 15. PMID: 31732851 Abstract Title:  A single dose of purple grape juice improves physical performance and antioxidant activity in runners: a randomized, crossover, double-blind, placebo study. Abstract:  PURPOSE: To investigate the effects of a single dose of juice on physical performance, oxidative stress, inflammation and muscle damage in runners.METHODS: Fourteen recreational male runners (399 years, VO=55.96.5 ml/kg/min) performed two running tests to exhaustion at 80% of VOafter ingesting grape juice or a placebo drink (10 ml/kg/day) randomly. Blood samples were taken before and 2 h after supplementation and immediately after running to analyze total antioxidant capacity (TAC), malondialdehyde (MDA), alpha-1 acid glycoprotein (A1GPA), high-sensitivity C-reactive protein (hs-CRP), creatine kinase (CK) and lactate dehydrogenase (LDH).RESULTS: The participants ran for an average of 59.227.8 min until exhaustion in the placebo group and for 68.429.7 min until exhaustion in the grape juice intake group, which was a significantly longer time (p=0.008). This improvement in physical performance was accompanied by a 43.6% increase in TAC (p=0.000) at the post-exercise timepoint compared to the level at baseline. MDA, A1GPA, hs-CRP, CK, and LDH did not exhibit changes. In contrast, no significant change in any variable was observed after consuming the placebo drink.CONCLUSION: The single-dose intake of purple grape juice demonstrated an ergogenic effect in recreational runners by increasing run time to exhaustion and increasing antioxidant activity.

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PMID:  Complement Ther Med. 2020 Nov ;54:102570. Epub 2020 Sep 15. PMID: 33183673 Abstract Title:  Effects of grape juice consumption on oxidative stress and inflammation in male volleyball players: A randomized, double-blind, placebo-controlled clinical trial. Abstract:  INTRODUCTION: Some foods are also demonstrated benefits, such as anti-inflammatory, antioxidant, and ergogenic activity, similar to that of sports supplements. Grape juice has been considered an important source of polyphenols and these compounds could promote positive effects to the sports players. In this sense, the objective was to evaluate the effects of purple grape juice consumption on indicators of oxidative stress, inflammation, muscle damage, global histone H4 acetylation levels, and muscle strength and muscle power in volleyball athletes.METHODS: This is a randomized double-blind clinical trial in which 12 male volleyball players (160.6 years old) participated in three different moments with match simulation: control (without beverage) (WB), grape juice (GJ) and placebo (PLA) (400 mL/day of grape juice or placebo (maltodextrin) for 14 days in a cross-over model). Before and immediately after each match, blood collection for analysis of indicators of systemic redox status, systemic concentrations of Interferon-(IFN-) and Interleukin-4 (IL-4), muscle damage, by Creatine Kinase (CK-NAC) and levels of global histone H4 acetylation were performed, as well as handgrip strength (HG) and lower limb power tests.RESULTS: Consumption of grape juice significantly reduced lipid peroxidation (p = 0.04) and Deoxyribonucleic Acid (DNA) damage (p = 0.01) after the match. IFN-levels, IL-4, CK-NAC, and histone H4 acetylation post-match did not alter with the grape juice consumption. Lower limb power improved after acute exercise in WB and GJ conditions (p

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PMID:  An Acad Bras Cienc. 2020 ;92(4):e20191551. Epub 2020 Nov 20. PMID: 33237140 Abstract Title:  Effects of grape juice consumption on muscle fatigue and oxidative stress in judo athletes: a randomized clinical trial. Abstract:  Physiological levels of reactive oxygen species (ROS) are important for intracellular and extracellular redox regulation in signaling and defense processes. Strenuous exercise can also contribute to this imbalance, and the muscle fatigue, evidenced by impaired strength or power generation, can be caused by various reasons, including oxidative stress. Antioxidants can prevent the formation of ROS by intercepting free radicals. Twenty judo athletes were included in this randomized, double-blind clinical trial into grape juice and placebo groups, and they consumed grape juice or placebo daily for 14 days in a crossover model. The outcomes were analyzed before and after combat simulations. The upper limb strength was higher in the grape juice group than in the placebo (p [group] = 0.003). The lipid damage levels were 10% higher in the placebo group (p [interaction] = 0.048). During the pre-exercise, the placebo group showed 19% more DNA damage than the grape juice group. The superoxide dismutase activity was 80% lower in the grape juice group (p [interaction]

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PMID:  Breast Cancer Res Treat. 2014 Jun ;145(2):371-9. Epub 2014 Apr 10. PMID: 24718774 Abstract Title:  Ultra-low-dose estriol and Lactobacillus acidophilus vaginal tablets (Gynoflor()) for vaginal atrophy in postmenopausal breast cancer patients on aromatase inhibitors: pharmacokinetic, safety, and efficacy phase I clinical study. Abstract:  Phase I pharmacokinetic (PK) study assessed circulating estrogens in breast cancer (BC) patients on a non-steroidal aromatase inhibitor (NSAI) with vaginal atrophy using vaginal ultra-low-dose 0.03 mg estriol (E3) and Lactobacillus combination vaginal tablets (Gynoflor()). 16 women on NSAI with severe vaginal atrophy applied a daily vaginal tablet of Gynoflor() for 28 days followed by a maintenance therapy of 3 tablets weekly for 8 weeks. Primary outcomes were serum concentrations and PK of E3, estradiol (E2), and estrone (E1) using highly sensitive gas chromatography-mass spectrometry. Secondary outcomes were clinical measures for efficacy and side effects; microscopic changes in vaginal epithelium and microflora; and changes in serum FSH, LH, and sex hormone-binding globulin. Compared with baseline, serum E1 and E2 did not increase in any of the women at any time following vaginal application. Serum E3 transiently increased after the first application in 15 of 16 women, with a maximum of 168 pg/ml 2-3 h post-insertion. After 4 weeks, serum E3 was slightly increased in 8 women with a maximum of 44 pg/ml. The vaginal atrophy resolved or improved in all women. The product was well tolerated, and discontinuation of therapy was not observed. The low-dose 0.03 mg E3 and Lactobacillus acidophilus vaginal tablets application in postmenopausal BC patients during AI treatment suffering from vaginal atrophy lead to small and transient increases in serum E3, but not E1 or E2, and therefore can be considered as safe and efficacious for treatment of atrophic vaginitis in BC patients taking NSAIs.

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PMID:  Int J Clin Pharmacol Ther. 2022 Sep ;60(9):384-391. PMID: 35713160 Abstract Title:  Effect of vitamin C on immune reconstitution after bone marrow transplantation. Abstract:  BACKGROUND: Vitamin C is an essential nutrient for the adequate function and maturation of the immune system. In vitro studies show that the development, proliferation, and functioning of T cells requires vitamin C, especially for natural killer (NK) cells. Their deficiency during the acute phase post-transplantation could cause greater morbidity and mortality in these patients. A prospective clinical trial using high-dose vitamin C was performed to determine if vitamin C supplementation improves reconstitution of NK lymphocytes after hematopoietic stem cell transplantation (HSCT).MATERIALS AND METHODS: We enrolled 24 patients who underwent autologous HSCT for multiple myeloma and lymphoma. Patients were randomized to receive standard treatment or standard treatment plus 20 g vitamin C once daily (1 - 10 days) and 500 mg twice daily (11 - 100 days) after transplantation.RESULTS: NK and CD3lymphocytes showed an increase from days +30 to +100 only in the vitamin C-treated group. Patients in the vitamin C group had a lower frequency of infections. No severe adverse events were reported.CONCLUSION: Our results suggest that high-dose vitamin C supplementation is an effective and safe therapeutic option to decrease the frequency of infections and enhance immune reconstitution after HSCT.

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PMID:  JAMA Netw Open. 2022 Oct 3 ;5(10):e2239380. Epub 2022 Oct 3. PMID: 36315143 Abstract Title:  Effect of High-Intensity Interval Training in Patients With Atrial Fibrillation: A Randomized Clinical Trial. Abstract:  IMPORTANCE: Patients with atrial fibrillation (AF) experience poor functional capacity and quality of life (QOL). High-intensity interval training (HIIT) has been shown to elicit greater improvements in functional capacity and QOL compared with moderate to vigorous intensity continuous training (MICT) in other cardiovascular populations, yet HIIT remains understudied in AF.OBJECTIVE: To compare the effects of 12 weeks of HIIT and MICT-based cardiovascular rehabilitation (CR) on functional capacity and general QOL in patients with persistent and permanent AF. Disease-specific QOL, resting heart rate (HR), time in AF, and physical activity (PA) levels were also assessed.DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial, conducted between November 17, 2015, and February 4, 2020, at a tertiary-care cardiovascular health center in Ottawa, Canada, recruited 94 patients with persistent and permanent AF.INTERVENTIONS: High-intensity interval training (23 minutes: two 8-minute interval training blocks of 30-second work periods at 80%-100% of peak power output interspersed with 30-second recovery) or CR (60 minutes: continuous aerobic conditioning within 67%-95% of peak HR and 12-16 of 20 ratings of perceived exertion) twice weekly for 12 weeks.MAIN OUTCOMES AND MEASURES: The primary outcomes were changes in functional capacity (6-minute walk test [6MWT] distance) and general QOL (Short Form 36) from baseline to 12 weeks' follow-up. Secondary outcomes included changes in disease-specific QOL (Atrial Fibrillation Severity Scale), resting HR, time in AF, and PA levels. An intention-to-treat analysis was used to compare changes between groups.RESULTS: Of the 94 patients who consented, 86 participated (mean [SD] age, 69 [7] years; 57 [66.3%] men). No significant differences in improvements in 6MWT distance (mean [SD], 21.3 [34.1] vs 13.2 [55.2] m; P=.42) and general QOL (Physical Component Summary, 0.5[6.1] vs 1.1 [4.9] points; P=.87) between HIIT and CR were observed. No significant differences in improvements in disease-specific QOL (AF symptoms: -1.7 [4.3] vs -1.5 [4] points, P=.59), resting HR (-3.6 [10.6] vs -2.9 [12.4] beats per minute, P=.63), and moderate to vigorous PA levels (37.3 [93.4] vs 14.4 [125.7] min/wk; P=.35) between HIIT and CR were detected. Participants attended a mean (SD) of 18.3 (6.1) (75.1%) HIIT sessions and 20.0 (4.5) (83.4%) CR sessions (P=.36).CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, twice-weekly 23-minute HIIT was as efficacious as twice-weekly 60-minute CR in improving functional capacity, general...

PMID:  Scand J Med Sci Sports. 2022 Nov 25. Epub 2022 Nov 25. PMID: 36427275 Abstract Title:  High-intensity interval training improves metabolic syndrome in women with breast cancer receiving Anthracyclines. Abstract:  INTRODUCTION: Anthracycline chemotherapy is a frequent treatment for breast cancer, whereas it can increase risk of physiologic side-effects, such as metabolic syndrome (MetS). Exercise has been used as a non-pharmacological strategy to decrease MetS. Specifically, high-intensity interval training (HIIT) has been shown to improve MetS in patients with diabetes or cardiac rehabilitation patients; however, the effects of HIIT on MetS and associated biomarkers in patients with breast cancer receiving anthracycline chemotherapy have not been previously explored. Therefore, we purposed to determine the effects of HIIT on MetS in breast cancer patients undergoing anthracycline chemotherapy.METHODS: In total, 30 patients with breast cancer were recruited prior to initiating treatment and randomized into HIIT (n = 15) or control (n = 15). The HIIT group attended supervised cycling sessions 3days/week for 8weeks. MetS was assessed by waist circumference, blood pressure, fasting levels of high-density lipoprotein cholesterol (HDL-C), triglycerides, and glucose. Circulating levels of MetS-related biomarkers were also measured (total cholesterol, insulin, HbA1c, leptin, adiponectin, and c-reactive protein).RESULTS: After 8weeks, MetS z-score was significantly improved in the HIIT group compared with controls (-7.60, 95% CI: -9.08 to -6.13, p

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PMID:  Exp Gerontol. 2023 Jan ;171:112039. Epub 2022 Nov 25. PMID: 36442700 Abstract Title:  The effect of high intensity interval training with genistein supplementation on mitochondrial function in the heart tissue of elderly rats. Abstract:  INTRODUCTION: For the most part, heart disease increases with age; on the other hand, although the role of exercise and antioxidants in the health of the elderly has been reported, the simultaneous effect of these two interventions is a new research topic. Thus, the aim of this study was to evaluate the effect of eight weeks of high intensity interval training (HIIT) and genistein (G) supplementation on oxidative stress, apoptosis and mitochondrial biogenesis in the heart tissue of elderly rats.METHODS: In this experimental study, 40 elderly female Sprague-Dawley rats aged 20  2 months and weighing 250  30 g were randomly divided into five groups of eight animals, including: (1) control (C), (2) sham (Sh), (3) HIIT, (4) HIIT + G and (5) G. Also, to evaluate the effect of time passage on the variables, 8 healthy young rats were included in the healthy young control group. HIIT protocol was performed for eight weeks, three sessions with an intensity of 95-90 % VOat high intensity intervals and 45-45 % VOat low intensity intervals. Ge was received daily at a dose of 60 mg/kg peritoneally. Data analysis was performed using one-way ANOVA with Tukey's post hoc test (P  0.05).RESULTS: In the HIIT and HIIT + G groups, levels of Bax, Bax/Bcl-2 ratio, MDA, PAB, GSSG were lower and levels of PGC-1, TFAM, GSH, GSH/GSSG ratio and NDUFS7 were higher than the control and sham groups (P  0.05). In the HIIT + G group, levels of Bcl-2 were significantly higher than the control group (P  0.05). In the HIIT + G group, levels of Bax, GSSG, Bax/Bcl-2 ratio, and PAB were lower, and levels of GSH/GSSG ratio, Bcl-2, PGC-1, TFAM and NDUFS7 were higher than the G consumption group (P  0.05). In the HIIT + G group, levels of PGC-1and TFAM were significantly higher and levels of MDA and PAB were lower than the HIIT group (P  0.05).CONCLUSION: Both HIIT and G consumption seem to have beneficial effects on reducing oxidative stress; in addition, the interaction of these two variables on the improvement of apoptosis and mitochondrial biogenesis is more favorable than the effect of either one alone. However, more studies are needed on different pathways of apoptosis following G administration.

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PMID:  Front Cardiovasc Med. 2022 ;9:1046560. Epub 2022 Nov 17. PMID: 36465439 Abstract Title:  The impact of high-intensity interval training on vascular function in adults: A systematic review and meta-analysis. Abstract:  AIM: We performed a systematic review and meta-analysis to investigate the effects of high-intensity interval training (HIIT) compared with moderate-intensity continuous training (MICT) or with no exercise (CON) on vascular function in adults who were free of cardiometabolic diseases and those with cardiometabolic diseases.METHODS: A search across three electronic databases including Scopus, PubMed, and Web of Science was conducted through February 2022 to identify the randomized trials evaluating HIIT vs. MICT and/or CON on vascular function as measured using brachial artery flow-mediated dilation (FMD) in adults. Separate analyses were conducted for HIIT vs. MICT and/or CON to calculate weighted mean differences (WMD) and 95% confidence intervals (95% CIs) using random or fixed models.RESULTS: A total of 36 studies involving 1,437 participants who were either free of cardiometabolic diseases or had cardiometabolic diseases were included in the meta-analysis. HIIT effectively increased FMD when compared with MICT [1.59% (95% CI 0.87-2.31),= 0.001] or CON [3.80% (95% CI 2.58-5.01),= 0.001]. Subgroup analysis showed that HIIT increased FMD in participants with cardiovascular and metabolic diseases, but not in participants who were free of cardiometabolic diseases. In addition, HIIT effectively increased FMD regardless of age and body mass index.CONCLUSION: We confirm that HIIT is effective for improving vascular function in individuals with metabolic disorders and cardiovascular diseases and has a superior effect compared to MICT, demonstrating time efficiency.SYSTEMATIC REVIEW REGISTRATION: [https://www.crd.york.ac.uk/prospero], identifier [CRD42022320863].

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PMID:  Curr Alzheimer Res. 2022 Dec 7. Epub 2022 Dec 7. PMID: 36503461 Abstract Title:  High-Intense Interval Training Prevents Cognitive Impairment And Increases The Expression Of Muscle Genes Fndc5 And Ppargc1a In A Rat Model Of Alzheimer's Disease. Abstract:  BACKGROUND: Alzheimer's disease is the most common neurodegenerative disease in the world, characterized by the progressive loss of neuronal structure and function, whose main histopathological landmark is the accumulation of-amyloid in the brain.OBJECTIVE: It is well known that exercise is a neuroprotective factor and that muscles produce and release myokines that exert endocrine effects in inflammation and metabolic dysfunction. Thus, this work intends to establish the relationship between the benefits of exercise through the chronic training of HIIT on cognitive damage induced by the Alzheimer's model by the injection ofamyloid 1-42.METHODS: For this purpose, forty-eight male Wistar rats were divided into four groups: Sedentary Sham (SS), Trained Sham (ST), Sedentary Alzheimer's (AS), and Trained Alzheimer's (AT). Animals were submitted to stereotactic surgery and received a hippocampal injection of A1-42 or a saline solution. Seven days after surgery, twelve days of treadmill adaptation followed by five maximal running tests (MRT) and fifty-five days of HIIT, rats underwent the Morris water maze test. The animals were then euthanized, and their gastrocnemius muscle tissue was extracted to analyze the Fibronectin type III domain containing 5 (FNDC5), PPARG Coactivator 1 Alpha (PPARGC1A), and Integrin subunit beta 5 (ITGB5-R) expression by qRT-PCR in addition to cross-sectional areas.RESULTS: The HIIT prevents the cognitive deficit induced by the infusion of amyloid1-42 (p

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PMID:  J Strength Cond Res. 2023 Mar 1 ;37(3):688-709. Epub 2022 Nov 15. PMID: 36508686 Abstract Title:  Effects of Concurrent Resistance and Endurance Training Using Continuous or Intermittent Protocols on Muscle Hypertrophy: Systematic Review With Meta-Analysis. Abstract:  Monserd-Vilar, A, Balsalobre-Fernndez, C, Hoffman, JR, Alix-Fages, C, and Jimnez, SL. Effects of concurrent resistance and endurance training using continuous or intermittent protocols on muscle hypertrophy: Systematic review with meta-analysis. J Strength Cond Res 37(3): 688-709, 2023-The purpose of this systematic review with meta-analysis was to explore the effects of concurrent resistance and endurance training (CT) incorporating continuous or intermittent endurance training (ET) on whole-muscle and type I and II muscle fiber hypertrophy compared with resistance training (RT) alone. Randomized and nonrandomized studies reporting changes in cross-sectional area at muscle fiber and whole-muscle levels after RT compared with CT were included. Searches for such studies were performed in Web of Science, PubMed, Scopus, SPORTDiscus, and CINAHL electronic databases. The data reported in the included studies were pooled in a random-effects meta-analysis of standardized mean differences (SMDs). Twenty-five studies were included. At the whole-muscle level, there were no significant differences for any comparison (SMD0.33) or combined with continuous ET (SMD>0.27), but not compared with CT incorporating only continuous ET (SMD

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