One study vouches for the combination of L-citrulline and L-arginine in powering up collegiate soccer players’ cycling performance

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Cureus. 2019 Dec 25 ;11(12):e6466. Epub 2019 Dec 25. PMID: 32021735

Abstract Title: 

Adaptogenic and Anxiolytic Effects of Ashwagandha Root Extract in Healthy Adults: A Double-blind, Randomized, Placebo-controlled Clinical Study.

Abstract: 

Background Stress, anxiety and impeded sleep are a frequent feature of life in modern societies. Across socio-economic strata, stress, anxiety and ineffective sleep detract from healthful living and serve as precursors of various ailments. The use of herbs to offset these antecedents and outcomes has greatly increased in recent years. Ashwagandha, an adaptogenic Ayurvedic herb, has been often used to combat and reduce stress and thereby enhance general wellbeing. While there have been other studies documenting the use of Ashwagandha for stress resistance, this is the first study to use a high-concentration root extract while also varying the dosage substantially. Therefore, this is the first study to offer insight into dose-response of a high concentration root extract. Material and methods In this eight-week, prospective, randomized, double-blind, placebo-controlled study, the stress-relieving effect of Ashwagandha root extract was investigated in stressed healthy adults. Sixty male and female participants with a baseline perceived stress scale (PSS) score>20 were randomized to receive capsules of Ashwagandha extract 125 mg, Ashwagandha extract 300 mg or identical placebo twice daily for eight weeks in a 1:1:1 ratio. Stress was assessed using PSS at baseline, four weeks and eight weeks. Anxiety was assessed using the Hamilton-Anxiety (HAM-A) scale and serum cortisol was measured at baseline and at eight weeks. Sleep quality was assessed using a seven-point sleep scale. A repeat measures ANOVA (general linear model) was used for assessment of treatment effect at different time periods. Post-hoc Dunnett's test was used for comparison of two treatments with placebo. Results Two participants (one each in 250 mg/day Ashwagandha and placebo) were lost to follow-up and 58 participants completed the study. A significant reduction in PSS scores was observed with Ashwagandha 250 mg/day (P

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J Ethnopharmacol. 2020 Jun 12 ;255:112759. Epub 2020 Mar 12. PMID: 32173425

Abstract Title: 

Withania somnifera (L.) Dunal: A potential therapeutic adjuvant in cancer.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: Withania somnifera (L.) Dunal (WS) is one of the moststudied Rasayana botanicals used in Ayurveda practice for its immunomodulatory, anti-aging, adaptogenic, and rejuvenating effects. The botanical is being used for various clinical indications, including cancer. Several studies exploring molecular mechanisms of WS suggest its possible role in improving clinical outcomes in cancer management. Therefore, research on WS may offer new insights in rational development of therapeutic adjuvants for cancer.AIM OF THIS REVIEW: The review aims at providing a detailed analysis of in silico, in vitro, in vivo, and clinical studies related to WS and cancer. It suggests possible role of WS in regulating molecular mechanisms associated with carcinogenesis. The review discusses potential of WS in cancer management in terms of cancer prevention, anti-cancer activity, and enhancing efficacy of cancer therapeutics.MATERIAL AND METHODS: The present narrative review offers a critical analysis of published literature on WS studies in cancer. The reported studies were analysed in the context of pathophysiology of cancer, commonly referred as 'cancer hallmarks'. The review attempts to bridge Ayurveda knowledge with biological insights into molecular mechanisms of cancer.RESULTS: Critical analysisof the published literature suggests an anti-cancer potential of WS with a key role in cancer prevention. The possible mechanisms for these effects are associated with the modulation of apoptotic, proliferative, and metastatic markers in cancer. WS can attenuate inflammatory responses and enzymes involved in invasion and metastatic progression of cancer.The properties of WS are likely to be mediated through withanolides, which may activate tumor suppressor proteins to restrict proliferation of cancer cells. Withanolides also regulate the genomic instability, and energy metabolism of cancer cells. The reported studies indicate the need for deeper understanding of molecular mechanisms of WS in inhibiting angiogenesis and promoting immunosurveillance. Additionally, WS can augment efficacy and safety of cancer therapeutics.CONCLUSION: The experimentally-supported evidence of immunomodulatory, anti-cancer, adaptogenic, and regenerative attributes of WS suggest its therapeutic adjuvant potential in cancer management. The adjuvant properties of withanolides can modulate multidrug resistance and reverse chemotherapy-induced myelosuppression. These mechanisms need to be further explored in systematically designed translational and clinical studies that will pave the way for integration of WS as a therapeutic adjuvant in cancer management.

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Curr Clin Pharmacol. 2020 Apr 13. Epub 2020 Apr 13. PMID: 32282308

Abstract Title: 

Assessment of Withania somnifera root extract efficacy in patients with generalized anxiety disorder: A randomized double-blind placebo-controlled trial.

Abstract: 

BACKGROUND: Anxiety disorders are the most universal psychiatric problems in the general population. Due to their chronic nature, these diseases are managed with a multi-drug regimen lasting for a long period of time. Medication discontinuation leads to 25% and 80% recurrence in the first month and the first year, respectively. Despite several treatment approaches, there is no specific and optimal method for patient management. Therefore, it is necessary to find some new theraputic approaches with fewer side effects. Withania somnifera is a plant with GABAergic property responsible for its anxiolytic effect. The aim of this study was to investigate the effect of W. somnifera root extract as an alternative therapy to reduce standard generalized anxiety disorder (GAD) symptoms.METHODS: Forty patients who met the inclusion criteria (with a confirmed diagnosis of GAD as stated in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) took part in this randomized double-blind placebo-controlled trial and were randomly selected for participation in the treatment group (W. somnifera extract, 1g/day; n = 22) or the placebo group (n = 18). All patients were under treatment with Selective Serotonin Reuptake Inhibitors (SSRIs) and were prescribed one capsule of the extract or placebo per day for six weeks. The Hamilton anxiety rating scale (HAM-A) was used to assess the severity of GAD symptoms at baseline as well as the second and sixth weeks of the trial.RESULTS: Comparison of the HAM-A scores during the course of the trial revealed a significant amelioration ofHAM-A score in the treatment group versus placebo (14 and 8 units reduction, respectively (P

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Nutrients. 2020 Apr 17 ;12(4). Epub 2020 Apr 17. PMID: 32316411

Abstract Title: 

Effects of Ashwagandha () on VO: A Systematic Review and Meta-Analysis.

Abstract: 

The purpose of this study was to systematically review the scientific literature about the effects of supplementation with Ashwagandha () on maximum oxygen consumption (VO), as well as to provide directions for clinical practice. A systematic search was conducted in three electronic databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines (PRISMA). The inclusion criteria were: (a) VOdata, with means± standard deviation before and after the supplement intervention, (b) the study was randomized controlled trial (RCT), (c) the article was written in English. The quality of evidence was evaluated according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.A meta-analysis was performed to determine effect sizes. Five studies were selected in the systematic review (162 participants) and four were included in the meta-analysis (142 participants). Results showed a significant enhancement in VOin healthy adults and athletes (= 0.04). The mean difference was 3.00 (95% CI from 0.18 to 5.82) with high heterogeneity. In conclusion, Ashwagandha supplementation might improve the VOin athlete and non-athlete people. However, further research is need to confirm this hypothesis since the number of studies is limited and the heterogeneity was high.

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Int J Physiol Pathophysiol Pharmacol. 2018 ;10(2):70-82. Epub 2018 Apr 20. PMID: 29755640

Abstract Title: 

Melatonin and tumeric ameliorate aging-induced changes: implication of immunoglobulins, cytokines, DJ-1/NRF2 and apoptosis regulation.

Abstract: 

Aging is associated with several biological, physiological, cellular and histological changes. In the present study, we investigated the effect of aging on different signaling pathways, including antioxidant system, apoptosis and immune status. Several natural products were used to ameliorate and block aging-related changes. Melatonin and turmeric have been known to ameliorate and decrease aging-related changes. However, the exact mechanism(s) of their action is not fully understood. In the present study, we tried to uncover the regulatory mechanism(s) by which melatonin and turmeric work against aging. We found that aging differentially regulated blood serum immunoglobulins; increased IgA and decreased IgE. Furthermore, all the serum cytokines investigated (TNF-α, IFN-γ, IL-6 and IL-8) were highly increased by aging. In addition, the antioxidant upstream regulators; DJ-1 and NRF2 were markedly repressed with aging in thymus tissues. We also found that aging induced apoptosis promoting genes p53 and Bax mRNA in thymus tissues. Finally, we found clear histological changes in thymus and spleen tissues. Administration of either melatonin or tumeric clearly ameliorated and blocked to some extinct the effect of aging. Altogether, aging was associated with downregulation of antioxidant regulators; DJ-1 and NRF2, promoted apoptosis and induced changes in the immune status. Furthermore, melatonin and tumeric markedly reversed the action of aging through activating DJ-1/NRF2 signaling pathway and inhibiting p53/Bax apoptotic pathway.

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PMID: 

Food Nutr Res. 2020 ;64. Epub 2020 Feb 4. PMID: 32110174

Abstract Title: 

Purple sweet potato color protects against hepatocyte apoptosis through Sirt1 activation in high-fat-diet-treated mice.

Abstract: 

Background: Recent evidence indicates that the inhibition of hepatocyte apoptosis is possible to develop a potential therapeutic strategy for nonalcoholic fatty liver disease (NAFLD). Our previous work suggested that purple sweet potato color (PSPC), a class of naturally occurring anthocyanins, effectively improved many features of high-fat diet (HFD)-induced NAFLD. However, whether PSPC ameliorates HFD-induced hepatocyte apoptosis has never been investigated.Objective: Here we investigated the effects of PSPC on HFD-induced hepatic apoptosis and the mechanisms underlying these effects.Design: Mice were divided into four groups: Control group, HFD group, HFD + PSPC group and PSPC group. PSPC was administered by daily oral gavage at doses of 700 mg/kg/day for 20 weeks. EX-527 (a SirT1-selective inhibitor) andsiRNA were used to demonstrate the Sirt1 dependence of PSPC-mediated effects on apoptotic and survival signaling pathwaysand.Results: Our results showed that PSPC reduced body weights, hepatic triglyceride contents, histopathological lesions and serum ALT levels in a mouse model of NAFLD induced by HFD. Furthermore, PSPC attenuated HFD-induced hepatocyte apoptosis ratio from 7.27± 0.92% to 1.79 ± 0.27% in mouse livers, which is insignificant compared with that of controls. Moreover, PSPC activated Sirt1 by boosting NADlevel in HFD-treated mouse livers. Furthermore, PSPC promoted Sirt1-dependent suppression of P53-mediated apoptotic signaling and activation of Akt survival signaling pathway in HFD-treated mouse livers, which was confirmed by EX527 treatment. Moreover,knockdown abolished these ameliorative effects of PSPC on apoptosis and P53 acetylation and protein expression in PA-treated L02 cells. Ultimately, PSPC reduced Caspase-3 activation and Bax level, and elevated the Bcl-2 level in HFD-treated mouse livers.Conclusion: PSPC protected against HFD-induced hepatic apoptosis by promoting Sirt1- dependent inhibition of p53-apoptotic pathway and facilitation of Akt survival pathway. This study indicates that PSPC is a candidate for nutritional intervention of NAFLD.

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PMID: 

Integr Med Res. 2018 Jun ;7(2):168-175. Epub 2018 Feb 20. PMID: 29989030

Abstract Title: 

Immunomodulatory activity of curcumin-entrapped poly d,l-lactic–glycolic acid nanoparticles in mice.

Abstract: 

Background: Studies have shown that curcumin fromhas a wide range of medicinal and immunomodulatory properties. These activities have, however, been hindered by its low bioavailability. Meanwhile, incorporation of nanoparticles has been shown to increase bioavailability of certain drugs. This study was, therefore, conducted to comparatively evaluate the immunomodulatory activity of free and nanoparticulate curcumin in mice.Methods: Healthy albino mice were sensitized with sheep red blood cells (SRBCs) and thereafter free and nanoparticulate curcumin were administered orally at doses of 5 mg/kg/day and 10 mg/kg/day for 10 days to the mice. The assessment of the immunomodulatory activity was carried out by determining the humoral and cell-mediated immune responses using hemagglutination and delayed-type hypersensitivity assays, respectively. Hematological components and some lymphoid organs of treated mice were further evaluated.Results: The study showed that nanoparticulate curcumin stimulated higher early cell-mediated immune response at 5 mg/kg and 10 mg/kg when compared to control. While nanoparticulate curcumin significantly stimulated primary humoral immune response with 9.00 ± 1.00 antibody titre ( 

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PMID: 

J Cell Physiol. 2020 Apr 23. Epub 2020 Apr 23. PMID: 32324260

Abstract Title: 

Melatonin inhibits Müller cell activation and pro-inflammatory cytokine production via upregulating the MEG3/miR-204/Sirt1 axis in experimental diabetic retinopathy.

Abstract: 

Diabetic retinopathy (DR) is the most common ocular complication caused by diabetes mellitus and is the main cause of visual impairment in working-age people. Reactive gliosis and pro-inflammatory cytokine production by Müller cells contribute to the progression of DR. Melatonin is a strong anti-inflammatory hormone, mediating the cytoprotective effect of a variety of retinal cells against hyperglycemia. In this study, melatonin inhibited the gliosis activation and inflammatory cytokine production of Müller cellsin both in vitro and in vivo models of DR. The melatonin membrane blocker, Luzindole, invalidated the melatonin-mediated protective effect on Müller cells. Furthermore, melatonin inhibited Müller cell activation and pro-inflammatory cytokine production by upregulating the long noncoding RNA maternally expressed gene 3/miR-204/sirtuin 1 axis. In conclusion, our study suggested that melatonin treatment could be a novel therapeutic strategy for DR.

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PMID: 

J Photochem Photobiol B. 2018 Sep ;186:69-80. Epub 2018 Jul 9. PMID: 30015062

Abstract Title: 

Immunosenescence-like state is accelerated by constant light exposure and counteracted by melatonin or turmeric administration through DJ-1/Nrf2 and P53/Bax pathways.

Abstract: 

The awareness of the interrelationship between immunosenescence and constant light exposure can provide new insights into the consequences of excessive exposure to light at night due to light pollution or shift work. Here, we investigated whether constant light exposure (LL) acts as an inducer of immunosenescence. We also determined the role of melatonin or turmeric in reversing the putative effects of constant light and explored for the first time the underlying molecular mechanisms. Young (3-4-month-old) rats were exposed daily to LL alone or in combination with each of melatonin and turmeric for 12 weeks. A group of aged rats (18-months old; n = 6) was used as a reference for natural immunosenescence. Constant light exposure resulted in remarkable pathophysiological alterations resembling those noticed in normal aged rats, manifested as apparent decreases in antioxidant activities as well as Nrf2 and DJ-1 expressions, striking augmentation in oxidative stress, proinflammatory cytokines and expression of TNFα, Bax, and p53 genes, and deleterious changes of lymphoid organs, Co-administration of melatonin or turmeric was able to reverse all alterations induced by LL through upregulation of Nrf2/DJ-1 and downregulation of p53/Bax pathways. These data suggest that LL accelerates immunosenescence via oxidative stress and apoptotic pathways. They also demonstrate for the first time that turmeric is comparable to melatonin in boosting the immune function and counteracting the LL-associated immunosenescence. These effects suggest that turmeric supplementation can be used as an inexpensive intervention to prevent circadian disruption-related immunosenescence. However, to validate the effects of turmeric on humans further studies are warranted.

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