PMID: 

Pak J Biol Sci. 2018 Jan ;21(6):262-274. PMID: 30311477

Abstract Title: 

Possible Protective Role of Whey Protein on the Rat's Liver Tissues Treated with Nandrolone decanoate.

Abstract: 

BACKGROUND AND OBJECTIVE: Nandrolone and whey protein are used as supplementary food and athletic food. The aim of this study was to evaluate the possible histological and ultrastructural alterations in the liver of adult rats after treatment of the anabolic androgenic steroids (Nandrolone decanoate) and whey protein.MATERIALS AND METHODS: Twenty eight Wistar Albino male rats were used in the present study divided into 4 groups: Control group received 0.5 mL of saline solution by oral, Nandrolone group injected intramuscular (10 mg kg-1 b.wt./week for 3 months), whey protein group treated by oral (5 mg kg-1 b.wt./week for 3 months) and Nandrolone and whey protein group. At the end of the experimentation, all the rats were sacrificed and liver samples were processed for histological and ultrastructural examination. Haematoxylin and eosin stains for general histological examination and Mallory trichrome stain for collagen fibers.RESULTS: Light microscopy examination of the liver of the nandrolone group showed bleeding and widening of the blood sinusoids. Degeneration, vacuolation, coagulative necrosis and pyknotic nuclei were observed. In addition, increased collagen fibers were detected. Whey protein group showed more or less normal hepatocytes, blood sinusoids and collagen fibers. The nandrolone and whey protein group illustrated normal appearance of hepatocytes with vacuolation in some of the hepatocytes and normal blood sinusoids and collagen fibers were noticed. Electron microscopic examination of the nandrolone group showed depletion of the nuclear chromatin, damaged mitochondria, increased of lysosomes, some lipid droplets, damaged blood sinusoids and space of Disse and increased of Kupffer cells, whereas the whey protein group appeared normal. The nandrolone and whey protein group showed well developed hepatocytes, regular space of Disse and normal hepatic sinusoids.CONCLUSIONS: Whey protein may be ameliorate the hepatic architecture after treatment with nandrolone.

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PMID: 

Nutr Rev. 2018 07 1 ;76(7):539-551. PMID: 29688559

Abstract Title: 

Effect of whey protein supplementation on body composition changes in women: a systematic review and meta-analysis.

Abstract: 

Context: A preponderance of evidence supports the beneficial effects of whey protein (WP) supplementation on body composition in men; however, there is currently insufficient evidence to make an equivalent claim in women.Objective: This systematic review and meta-analysis assessed the effects of WP supplementation with or without energy restriction (ER) and resistance training (RT) on changes in body mass, lean mass, and fat mass in women.Data Sources: Pubmed, Scopus, Cochrane, and CINAHL were searched using the keywords"whey protein,""body composition,"and"lean mass."Data Extraction: Two researchers independently screened 1845 abstracts and extracted 276 articles. Thirteen randomized controlled trials with 28 groups met the inclusion criteria.Results: Globally, WP supplementation increased lean mass (WMD, 0.37 kg; 95% confidence interval [CI], 0.06 to 0.67) while not influencing changes in fat mass (-0.20 kg; 95%CI, -0.67 to 0.27) relative to non-WP control. The beneficial effect of WP on lean mass was lost when only studies with RT were included in the analysis (n = 7 comparisons; 0.23 kg; 95%CI, -0.17 to 0.63). The beneficial effect of WP on lean mass was more robust when only studies with an ER component were included (n = 6 comparisons; 0.90 kg; 95%CI, 0.31 to 1.49). There was no effect of WP on lean mass in studies without ER (n = 9 comparisons; 0.22 kg; 95%CI, -0.12 to 0.57).Conclusion: Whey protein supplementation improves body composition by modestly increasing lean mass without influencing changes in fat mass. Body composition improvements from WP are more robust when combined with ER .

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PMID: 

J Am Coll Nutr. 2018 01 ;37(1):60-70. Epub 2017 Oct 31. PMID: 29087242

Abstract Title: 

Whey Protein Supplementation Improves Body Composition and Cardiovascular Risk Factors in Overweight and Obese Patients: A Systematic Review and Meta-Analysis.

Abstract: 

BACKGROUND: Previous literature shows possible benefits of whey protein supplementation in promoting weight loss. However, most studies do not have enough power to show beneficial effects on body composition and cardiovascular disease (CVD) risk factors. This meta-analysis evaluated effects of whey protein in individuals who are overweight and obese.METHODS: We comprehensively searched the databases of MEDLINE, Embase, and Cochrane databases. The inclusion criteria were published randomized control trials (RCTs) comparing whey protein supplementation to placebo or controls in individuals who are overweight or obese. The primary outcome was the differences in the change in body composition (body weight, waist circumference, total fat mass, body lean mass). We also examined the changes in CVD risk factors as secondary outcomes. We calculated pooled mean difference (MD) with 95% confidence intervals (CIs) using a random effects model.RESULTS: Nine RCTs were included in the meta-analysis. There was a significant reduction of body weight (MD = 0.56, 95% CI: 0.30-0.81), lean mass (MD = 0.77, 95% CI: 0.59-0.96), and fat mass (MD = 1.12, 95% CI: 0.77-1.47) favoring the whey protein group. There were improvements in multiple CVD risk factors including levels of systolic blood pressure, diastolic blood pressure, glucose, high-density lipoprotein, and total cholesterol (all p values

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PMID: 

Int J Dev Neurosci. 2019 May ;74:18-26. Epub 2019 Feb 26. PMID: 30822517

Abstract Title: 

Quercetin promotes learning and memory performance concomitantly with neural stem/progenitor cell proliferation and neurogenesis in the adult rat dentate gyrus.

Abstract: 

The decline in neurogenesis is a very critical problem in Alzheimer disease. Different biological activities have been reported for medicinal application of quercetin. Herein, we investigated the neurogenesis potential of quercetin in a rat model of Alzheimer's disease induced by amyloid-beta injection. Rats were randomly divided into Control, Alzheimer + Saline and Alzheimer + Quercetin groups. Following the administration of Amyloid-beta, rats in the Alzheimer + Quercetin group received 40 mg/kg/day quercetin orally for one month. Our data demonstrated amyloid-β injection could impair learning and memory processing in rats indicated by passive avoidance test evaluation. We noted that one-month quercetin treatment alleviated the detrimental effects of amyloid-β on spatial learning and memory parameters using Morris water maze analysis. Quercetin was found to increase the number of proliferating neural stem/progenitor cells.Notably, quercetin increased the number of DCX-expressing cells, indicating the active dynamic growth of neural progenitor cells in the dentate gyrus of the hippocampus. We further observed that the quercetin improved the number of BrdU/NeuN positive cells contributed to enhanced adult neurogenesis.Based on our results, quercetin had the potential to promote the expression of BDNF, NGF, CREB, and EGR-1 genes involved in regulating neurogenesis. These data suggest that quercetin can play a valuable role in alleviating Alzheimer's disease symptoms by enhancing adult neurogenesis mechanism.

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PMID: 

J Nutr Biochem. 2020 Mar ;77:108327. Epub 2019 Dec 19. PMID: 31926451

Abstract Title: 

Ferulic acid maintains the self-renewal capacity of embryo stem cells and adipose-derived mesenchymal stem cells in high fat diet-induced obese mice.

Abstract: 

Self-renewal is required for embryo stem cells (ESCs) and adipose-derived mesenchymal stem cells (ADMSCs). This study examined the ability of ferulic acid in mouse ESCs and ADMSCs, in a high fat diet-induced mouse model. Initially, five natural compounds of ferulic acid, xanthohumol, curcumin, ascorbic acid, and quercetin were screened in ESCs using an alkaline phosphate(AP) assay, as a self-renewal biomarker. A ferulic acid treatment was the highest APstaining in hop-hit screening compounds. Also a ferulic acid increased Nanog mRNA levels in ESCs. The in vivo effects of ferulic acid were next examined in an obese mouse model. C57BL/6 J male mice were fed either a high fat diet (HFD) or control diet with ferulic acid (5 g/kg diet) for 8 weeks. Ferulic acid exhibited weight loss and improved glucose homeostasis, lipid profiling, and hepatic steatosis in a HFD-induced mouse model. Next, ADMSCs (Sca-1CD45), a hallmark of fat stem cells, were then isolated and quantified from mouse abdominal adipose tissue. A HFD decreased the Sca-1CD45cell population of ADMSCs, but HFD-induced obese mice given ferulic acid showed an increased the Sca-1CD45cell population of ADMSCs. Moreover, ferulic acid enhanced NANOG mRNA levels in human ADMSCs and its related gene mRNA expression. Overall, this study suggests that ferulic acid preserves self-renewal in ESCs, and contributes to ADMSCs self-renewal and effective weight control in obesity.

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PMID: 

Biomed Res Int. 2018 ;2018:4178021. Epub 2018 Mar 15. PMID: 29736392

Abstract Title: 

Quercetin Stimulates Bone Marrow Mesenchymal Stem Cell Differentiation through an Estrogen Receptor-Mediated Pathway.

Abstract: 

Objectives: The present study aimed to investigate the overall effect of quercetin on mouse bone marrow mesenchymal stem cell (BMSC) proliferation and osteogenic differentiation.Materials and Methods: BMSCs were treated with different concentrations of quercetin for 6 days. The effects of quercetin on cell proliferation were assessed at predetermined times using Cell Counting Kit-8 (CCK-8) assay. The cells were then treated with quercetin, estrogen, or an estrogen receptor (ER) antagonist (which was also administered in the presence of quercetin or estrogen) for 7 or 21 days. The effects of quercetin on BMSC osteogenic differentiation were analyzed by an alkaline phosphatase (ALP) assay kit, Alizarin Red S staining (ARS), quantitative real-time PCR (qPCR), and western blotting.Results: The CCK-8 and ALP assays and ARS staining showed that quercetin significantly enhanced BMSC proliferation, ALP activity, and extracellular matrix production and mineralization, respectively. The qPCR results indicated that quercetin promoted osterix, runt-related transcription factor 2, and osteopontintranscription in the presence of osteoinduction medium, and the western blotting results indicated that quercetin enhanced bone morphogenetic protein 2 (BMP2), Smad1, Smad4, RUNX2, OSX, and OPN expression and Smad1 phosphorylation. Treatment with the ER inhibitor ICI182780 blocked the effects of quercetin.Conclusions: Our data demonstrated that quercetin promotes BMSC proliferation and osteogenic differentiation. Quercetin enhances BMP signaling pathway activation and upregulates the expression of downstream genes, such as,, and, via the ER.

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PMID: 

Curr Drug Targets. 2019 ;20(3):347-353. PMID: 30062965

Abstract Title: 

Potential Non-neoplastic Applications for Polyphenols in Stem Cell Utilization.

Abstract: 

While polyphenols may have important effects on pluripotential stem cells that make them noteworthy as potential antineoplastic agents, their action on stem cells may portend other health benefits, such as treatments for cardiovascular and neurocognitive disorders. Resveratrol, the beststudied polyphenol, has been found to enable stem cells to differentiate into cardiomyocytes, neurons, osteocytes, and pancreatic beta cells, as well as facilitating augmentation of stem cell populations and protecting them from toxic injury. Curcumin protects mesenchymal stem cells from toxicity, and prevents them from facilitating chondrocytic hypertrophy. Quercetin enabled osteocytic and pancreatic beta cell differentiation, and protected neuronal stem cells from injury. Epigallocatechin gallate prevented damage to osteocyte precursors and averted differentiation into undesirable adipocytes. Genistein facilitated osteogenesis while preventing adipogenesis. Several other polyphenols, daidzein, caffeic and chlorogenic acid, kaempferol, and piceatannol, protect stems cells from reactive oxygen species and foster stem cells differentiation away from adipocytic and toward osteocytic lineages. Further research should better elucidate the pharmacokinetic profiles of each polyphenol, explore novel delivery systems, and expand investigation beyond rodent models to additional species.

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PMID: 

Protein Cell. 2019 06 ;10(6):417-435. Epub 2018 Aug 1. PMID: 30069858

Abstract Title: 

Chemical screen identifies a geroprotective role of quercetin in premature aging.

Abstract: 

Aging increases the risk of various diseases. The main goal of aging research is to find therapies that attenuate aging and alleviate aging-related diseases. In this study, we screened a natural product library for geroprotective compounds using Werner syndrome (WS) human mesenchymal stem cells (hMSCs), a premature aging model that we recently established. Ten candidate compounds were identified and quercetin was investigated in detail due to its leading effects. Mechanistic studies revealed that quercetin alleviated senescence via the enhancement of cell proliferation and restoration of heterochromatin architecture in WS hMSCs. RNA-sequencing analysis revealed the transcriptional commonalities and differences in the geroprotective effects by quercetin and Vitamin C. Besides WS hMSCs, quercetin also attenuated cellular senescence in Hutchinson-Gilford progeria syndrome (HGPS) and physiological-aging hMSCs. Taken together, our study identifies quercetin as a geroprotective agent against accelerated and natural aging in hMSCs, providing a potential therapeutic intervention for treating age-associated disorders.

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PMID: 

Inflammopharmacology. 2018 Feb ;26(1):147-156. Epub 2018 Jan 15. PMID: 29335826

Abstract Title: 

High-salt- and cholesterol diet-associated cognitive impairment attenuated by tannins-enriched fraction of Emblica officinalis via inhibiting NF-kB pathway.

Abstract: 

Metabolic disorders are closely associated with dietary habits and seem to be related to neuroinflammation and neurodegenerative disease in humans. Emblica officinalis (EOT) fruits not only have good nutritional value but also have excellent therapeutic potential. We used a tannins-enriched fraction of EOT fruit with the expectation of controlling diet-induced neuroinflammation and cognitive impairment in rats. A high-salt and cholesterol diet (HSCD) was used to induce neuroinflammation and cognitive impairment in rats. The diet of the rats was then supplemented with EOT (100 and 200 mg/kg b.w.) for 7 weeks. In order to evaluate the neuroprotective effects of EOT; in silico study, neurobehavioral tests, biochemical analyses, and immunohistochemical studies were performed. In silico study of p50 (NF-κB1) receptors with emblicanin (the main constituent of EOT) suggests that EOT has binds to NF-κB. EOT treatment reversed the HSCD-induced behavioral and memory disturbances in a step-down-type passive avoidance test. EOT treatment also inhibited HSCD-induced NF-κB upstream signaling, including the release of Th1, such as TNF-α, and downstream signaling Th2, such as IL-10, by flow cytometer. In addition, EOT treatment attentuated the HSCD-induced increase in the level of cognitive impairment markers, such as amyloid β. Furthermore, immunohistochemical results demonstrated that EOT modulated neuronal cell death by inhibiting the overexpression of NF-kB in brain. This study confirms that EOT may be a promising therapy in ameliorating the neurotoxicity of HSCD; however further studies are warranted to elucidate the exact mechanism of action of EOT.

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PMID: 

Microvasc Res. 2019 01 ;121:14-23. Epub 2018 Sep 4. PMID: 30189210

Abstract Title: 

Chebulagic acid and Chebulinic acid inhibit TGF-β1 induced fibrotic changes in the chorio-retinal endothelial cells by inhibiting ERK phosphorylation.

Abstract: 

PURPOSE: Diabetic retinopathy (DR) is characterized by pro-inflammatory, pro-angiogenic and pro-fibrotic environment during the various stages of the disease progression. Basement membrane changes in the retina and formation of fibrovascular membrane are characteristically seen in DR. In the present study the effect of Alcoholic (AlE) extracts of Triphala an ayurvedic herbal formulation and its chief compounds, Chebulagic (CA), Chebulinic (CI) and Gallic acid (GA) were evaluated for TGFβ1-induced anti-fibrotic activity in choroid-retinal endothelial cells (RF/6A).METHOD: RF/6A cells were treated with TGFβ1 alone or co-treated with AlE, CA, CI or GA. The mRNA and protein expression of fibrotic markers (αSMA, CTGF) were assessed by qPCR and western blot/ELISA. Functional changes were assessed using proliferation assay and migration assay. To deduce the mechanism of action, downstream signaling wasassessed by western blot analysis along with in silico docking studies.RESULT: AlE (50 μg/ml) CA and CI at 10 μM reduced the expression of pro-fibrotic genes (αSMA and CTGF) induced by TGFβ1, by inhibiting ERK phosphorylation. GA did not inhibit TGFβ1 mediated changes in RF/6A cells. In silico experiments shows that CA and CI has favourable binding energy to bind with TGFβreceptor and inhibit the downstream signaling, while GA did not.CONCLUSION: Hence this study identifies Triphala and its chief compounds CA and CI as potential adjuvants in the management of DR.

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