A Standardized Withania somnifera (Linn.) Root Extract with Piperine Alleviates the Symptoms of Anxiety and Depression by Increasing Serotonin Levels: A Double-Blind, Randomized, Placebo-Controlled Study.

Background: Withania somnifera (Linn) or Ashwagandha is used in Ayurveda and other traditional medicine systems as an adaptogen and a neuroprotective supplement. Objective: The effect of Ashwagandha root extract (ARE) standardized for 2.5% full-spectrum withanolides as per The United States Pharmacopeia (USP) protocol with piperine (500 mg with 5 mg of 95% piperine) once a day (12.5 mg withanolides/day) was evaluated in individuals with mild to moderate depression and anxiety. Methods: In a randomized, double-blind placebo-controlled study, for 90 days, 70 participants were randomized to ARE (n = 34) or placebo (n = 36) once daily at night. Mean change in the Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS), Groningen Sleep Quality Scale (GSQS), and quality of life (QOL) from screening to days 30, 60, and 90 were evaluated. Safety was evaluated by monitoring any incidence of adverse events and laboratory parameters. Two-way analysis of variance (ANOVA) and repeated-measure ANOVA were used to compare ARE and placebo, and the changes within the group at different time points. Results: Seventy individuals were randomized and all of them completed the study. The HARS, HDRS, GSQS, and QOL scores improved significantly (p < 0.001) in all the participants taking ARE compared to placebo on days 30, 60, and 90. Anxiety and depression improved from baseline to end of the study in both groups, but the quantum of improvement was significantly higher in ARE. Serum levels of serotonin increased in ARE, but showed a decrease in placebo, the difference being statically significant (p < 0.001). Biochemical and hematological parameters remained in the normal range in all participants and ARE was well tolerated during the study. Conclusion: The results of the study suggest that 500 mg of ARE standardized for 2.5% withanolides with 5 mg piperine is beneficial in improving depression, and anxiety, by increasing serum serotonin levels. The trial was registered prospectively with the Clinical Trial Registry of India (CTRI) with the registration number CTRI/2022/05/042640, on May 18, 2022.

A Short-Term Safety Evaluation of Silbinol®- an Extract from Pterocarpus marsupium in Healthy Adults- a Randomized, Double-Blind, Placebo-Controlled Study.

Background: Pterostilbene is an active molecule from the bark of the Pterocarpus marsupium tree with antioxidant and anti-inflammatory properties. Objective: This study aimed to evaluate the clinical safety of a standardized P. marsupium extract (PME) containing 90% pterostilbene (200 mg per day) in healthy adults. Methods: In a randomized, double-blind, placebo-controlled study, 60 healthy adult participants (27 males and 33 females) were randomized to receive PME-100 mg or placebo capsule twice a day for two months. The primary objectives of the study were to assess any changes in laboratory parameters, vital signs, and the occurrence of adverse events from screening to the final visit. Serum antioxidant enzyme levels were evaluated as a secondary outcome. Results: The hematological, lipid, glycemic, thyroid profiles and liver and renal functions remained within the normal range in all participants, with no difference between PME and placebo. Vital signs, including blood pressure, pulse rate, body weight, body mass index and electrocardiogram, did not reveal any significant differences between the PME and placebo groups at the beginning and end of the study. No serious adverse events were observed in any participant throughout the study period. The serum antioxidant profile was not significantly different between the treatment groups, although the glutathione levels were relatively higher in the PME group. Conclusions: Scientific evaluation of clinical safety of standardized extract is mandatory for its use as a supplement for various health benefits. The results of this study convincingly establish the safety of PME (>90% Pterostilbene) at 200 mg/day (100 mg bid) for human use. The study was approved by the Institutional Ethics Committee of BGS Global Institute of Medical Sciences & Hospital, Bangalore with the registration number CTRI/2019/08/020736.

The effects of Bacillus coagulans MTCC 5856 on functional gas and bloating in adults: A randomized, double-blind, placebo-controlled study.

BACKGROUND: Gut microbiome dysbiosis is a major cause of abdominal gas, bloating, and distension. Bacillus coagulans MTCC 5856 (LactoSpore) is a spore-forming, thermostable, lactic acid-producing probiotic that has numerous health benefits. We evaluated the effect of Lacto Spore on improving the clinical symptoms of functional gas and bloating in healthy adults. METHODS: Multicenter, randomized, double-blind, placebo-controlled study at hospitals in southern India. Seventy adults with functional gas and bloating with a gastrointestinal symptom rating scale (GSRS) indigestion score ≥ 5 were randomized to receive B coagulans MTCC 5856 (2 billion spores/day, N = 35) or placebo (N = 35) for 4 weeks. Changes in the GSRS-Indigestion subscale score for gas and bloating and global evaluation of patient's scores from screening to the final visit were the primary outcomes. The secondary outcomes were Bristol stool analysis, brain fog questionnaire, changes in other GSRS subscales, and safety. RESULTS: Two participants from each group withdrew from the study and 66 participants (n = 33 in each group) completed the study. The GSRS indigestion scores changed significantly (P < .001) in the probiotic group (8.91-3.06; P < .001) compared to the placebo (9.42-8.43; P = .11). The median global evaluation of patient's scores was significantly better (P < .001) in the probiotic group (3.0-9.0) than in the placebo group (3.0-4.0) at the end of the study. The cumulative GSRS score, excluding the indigestion subscale, decreased from 27.82 to 4.42% (P < .001) in the probiotic group and 29.12 to 19.33% (P < .001) in the placebo group. The Bristol stool type improved to normal in both the groups. No adverse events or significant changes were observed in clinical parameters throughout the trial period. CONCLUSIONS: Bacillus coagulans MTCC 5856 may be a potential supplement to reduce gastrointestinal symptoms in adults with abdominal gas and distension.

Probiotic Weizmannia coagulans MTCC 5856 as adjunct therapy in children's acute diarrhea-a randomized, double-blind, placebo-controlled study.

Objectives: Acute diarrhea in children is generally managed by replacing the lost fluid with oral rehydration solution (ORS). Probiotic supplementation has been reported to reduce the severity of diarrhea. In the present study, we investigated the effect of Weizmannia coagulans (Bacillus coagulans) MTCC 5856, along with ORS on acute diarrhea of all causes in non-hospitalized children. Methods: A total of 110 children of ages between 1 and 10 were enrolled in a double-blind placebo-controlled study and were randomly allocated to receive W. coagulans MTCC 5856 (4 × 108 spores, N = 54) + ORS and zinc (Zn) or a placebo (N = 56) + ORS and (Zn) for 5 days. The consistency of the stool, mean duration of diarrhea in hours, mean diarrhea frequency per day, and the dehydration status were collected as efficacy endpoints. Safety was evaluated by the occurrence of adverse events. Results: The mean age of the children was 5.55 ± 2.57 years (61 boys and 49 girls). The mean duration of diarrhea was 51.31 ± 20.99 h in the W. coagulans MTCC 5856 group and 62.74 ± 24.51 h in the placebo (p = 0.011) group. The frequency of diarrhea was lower in children supplemented with the probiotic, but the difference was not statistically significant. The perceived efficacy score and dehydration status improved significantly in the W. coagulans MTCC 5856 group compared with the placebo group. No adverse events were recorded. Conclusion: The results of the study suggest that W. coagulans MTCC 5856 could be supplemented along with ORS and zinc to reduce the duration of diarrhea in non-hospitalized children. Clinical Trial Registration: ClinicalTrials.gov, identifier CTRI/2022/06/043239.

Novel Emblica officinalis extract containing ß-glucogallin vs. metformin: a randomized, open-label, comparative efficacy study in newly diagnosed type 2 diabetes mellitus patients with dyslipidemia.

The efficacy of Emblica officinalis extract (EOE) containing 10% ß-glucogallin was compared against metformin in newly diagnosed subjects with diabetic dyslipidemia which is a significant factor in cardiovascular disease. Daily administration with EOE-1 g, EOE-2 g, or metformin 500 mg for 90 days significantly decreased fasting blood sugar and postprandial blood sugar (FBS and PPBS), hemoglobin A1c (HbA1c) and lipid levels in all three treatment groups. The FBS, PPBS and HbA1c were significantly lower in the EOE-2 g group compared with metformin and EOE-1 g groups. The reductions in LDL and TC in the EOE-2 g group were also significantly higher than in the EOE-1 g group and were comparable to the metformin group. No serious adverse effects were observed in any study participants. EOE-1 g and 2 g day-1 are safe and potent antidiabetic agents, with comparable efficacy to the pharmaceutical drug, metformin. Supplementation with EOE-2 g day-1 showed greater efficacy than metformin in reducing circulating glucose levels.

Pharmacology of α-spinasterol, a phytosterol with nutraceutical values: A review.

α-Spinasterol is a phytosterol found in various edible and non-edible plant sources. The edible plant materials containing α-spinasterol include spinach leaves, cucumber fruits, seeds of pumpkin and watermelon, argan seed oil, cactus pear seed oil and Amaranthus sp. It is a bioavailable nutraceutical, and it can cross the blood-brain barrier. It possesses several important pharmacological properties such as anti-diabetes mellitus, antiinflammation, hypolipidemic, antiulcer, neuroprotection, anti-pain and antitumour activities. For this review, literature search was made focusing on the pharmacological properties of α-spinasterol using PubMed and Google Scholar data bases. Recent studies show the promising antidiabetic properties of α-spinasterol. Its anti-diabetic mechanisms include enhancement of insulin secretion, reduction in insulin resistance, anti-diabetic nephropathy, increase in glucose uptake in muscle cells and inhibition of glucose absorption from intestine. Besides, it is a safe antiinflammatory agent, and its antiinflammatory mechanisms include inhibition of cyclooxygenases, antagonism of TRPV1 receptor and attenuation of proinflammatory cytokines and mediators. It is a promising and safe nutraceutical molecule for human health care. Food supplements, value-added products and nutraceutical formulations can be developed with α-spinasterol for the management of diabetes, chronic inflammatory diseases and improving general health. This review provides all scattered pharmacological studies on α-spinasterol in one place and highlights its immense value for human health care.

Can Selenium Reduce the Susceptibility and Severity of SARS-CoV-2?-A Comprehensive Review.

The SARS-CoV-2 infection is a highly contagious viral infection, which has claimed millions of lives in the last two years. The infection can cause acute respiratory distress, myocarditis, and systemic inflammatory response in severe cases. The interaction of the viral spike protein with the angiotensin-converting enzyme in various tissues causes damage to vital organs and tissues, leading to complications in the post-infection period. Vaccines and antiviral drugs have improved patient response to the infection, but the long-term effect on vital organs is still unknown. Investigations are now focused on supportive nutrient therapies, which can mitigate the susceptibility as well as the long-term complications of COVID-19. Selenium is one such micronutrient that plays a vital role in preventing oxidative stress induced by the virus. Further, selenium is important for effective immune response, controlling systemic inflammation, and maintain overall health of humans. We examine the role of selenium in various aspects of SARS-CoV-2 infection and address the importance of selenium supplementation in reducing the susceptibility and severity of infection in this review.

A randomized, double-blind clinical trial of a herbal formulation (GlycaCare-II) for the management of type 2 diabetes in comparison with metformin.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major public health concern with growing prevalence with multiple debilitating complications. GlycaCare-II is a proprietary herbal formulation supplement for T2DM containing extracts of Cinnamomum cassia, Momordica charantia, Pterocarpus marsupium, Gymnema sylvestre, Salacia reticulata, Eugenia jambolana, and a bioavailability enhancer piperine from Piper nigrum. OBJECTIVE: The antihyperglycemic potential of GlycaCare-II was compared against metformin in a double-blind study. DESIGN: It was a randomized, two-arm design on prediabetic (N = 29; 12 in metformin and 17 in GlycaCare-II arm, respectively) and newly diagnosed diabetic (N = 40; 16 in metformin and 24 in GlycaCare-II) patients for 120 days. OUTCOME MEASURES: Changes in diabetic panel glycosylated hemoglobin (HbA1c), fasting blood sugar (FBS), and postprandial blood sugar (PBS) were the primary endpoints. Lipid profile, liver profile, thyroid-stimulating hormone, bilirubin and creatinine were the secondary endpoints. RESULT: Twice a day treatment for 120 days with GlycaCare-II led to a statistically significant change in HbA1c (p < 0.001), FBS (p < 0.001), PBS (p < 0.001) on both prediabetic and newly diagnosed diabetic patients. GlycaCare-II showed a similar potential as metformin in the treatment of T2DM. In the prediabetic group, both GlycaCare-II and metformin were comparable for all the hyperglycemic index parameters. In the case of newly diagnosed diabetic patients, GlycaCare-II showed a significantly better reduction for PBS (p = 0.026) as compared to metformin, while all other parameters in the diabetic panel were comparable. No adverse events were reported throughout the trial period. CONCLUSION: These results suggest that GlycaCare-II is effective in managing T2DM in both newly diagnosed diabetic and prediabetic patients.

A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of a Nutritional Supplement (ImmuActiveTM) for COVID-19 Patients.

BACKGROUND: SARS-CoV-2 has emerged as a global threat due to its infectivity and rapid transmission. We evaluated the safety and efficacy of herbal and mineral formulation (ImmuActive) as an adjunct therapy in COVID-19 patients. METHODS: A randomized, double-blind, placebo-controlled study was conducted in 100 COVID-19 patients in three centers in Southern India, and 92 subjects completed the study. Subjects were followed up until they were discharged from the hospital or for a maximum of 28 days, whichever was earlier. The primary outcome parameters were the mean change and time required to change the ordinal scale of disease severity by one unit. The secondary outcomes were the time required to turn RT-PCR negative or get discharged from the hospital, change in modified Jackson's Symptom Severity score, and COVID-19 quality of life questionnaire. RESULTS: The ordinal scale at the end of the study was significantly lower in COVID-19 patients supplemented with ImmuActive (0.57) than placebo (1.0), with a p value of 0.0043. The ordinal scale decreased by one unit within 2.35 days in ImmuActive-supplemented patients, while it took 3.36 days in placebo-supplemented patients. Days of hospitalization and time required to turn RT-PCR negative were comparatively lower in the ImmuActive arm than the placebo arm. Change in modified Jackson's Symptom Severity Score and COVID-19 QOL were significant from screening to the end of the study in both ImmuActive and placebo arms. There were no adverse events observed during the study period. CONCLUSION: The study results suggest that ImmuActive could be a beneficial and safe adjunct treatment for effectively managing COVID-19 infection symptoms.

An exploratory study of selenium status in healthy individuals and in patients with COVID-19 in a south Indian population: The case for adequate selenium status.

The acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has affected millions of individuals, causing major health and economic disruptions worldwide. The pandemic is still raging, with a second and third wave in a few countries, while new infections steadily rise in India. Nutrition and immune status are two critical aspects of fighting the virus successfully. Recently, selenium status was reported to positively correlate with the survival of patients with COVID-19 compared with non-survivors. We analyzed the blood serum levels in 30 apparently healthy individuals and in 30 patients with confirmed COVID-19 infection in the southern part of India. The patients showed significantly lower selenium levels of 69.2 ± 8.7 ng/mL than controls 79.1 ± 10.9 ng/mL. The difference was statistically significant (P = 0.0003). Interestingly, the control group showed a borderline level of selenium, suggesting that the level of this micronutrient is not optimum in the population studied. The results of this exploratory study pave the way for further research in a larger population and suggest that selenium supplementation may be helpful in reducing the effects of the virus.

Novel Combinatorial Regimen of Garcinol and Curcuminoids for Non-alcoholic Steatohepatitis (NASH) in Mice.

Non-alcoholic steatohepatitis (NASH) is a progressive form of Non-alcoholic fatty liver disease (NAFLD), a chronic liver disease with a significant unmet clinical need. In this study, we examined the protective effects of Garcinia indica extract standardized to contain 20% w/w of Garcinol (GIE) and 95% Curcuminoids w/w from Curcuma longa (Curcuminoids) in a Stelic animal model (STAM) of NASH. The STAM mice developed steatosis, hepatocyte ballooning, and inflammation, which were significantly reduced by the combination of GIE and Curcuminoids, resulting in a lower NAFLD activity score. The treatment reduced fibrosis as observed by Sirius red staining, liver hydroxyproline content and mRNA levels of TGF- ß and collagen in the liver. Immunostaining with alpha-smooth muscle actin (α SMA) revealed a significant reduction in hepatic stellate cells. Intriguingly, the combination regimen markedly decreased the mRNA levels of MCP1 and CRP and both mRNA and protein levels of TNF-α. NF-kB, reduced the hepatic and circulating FGF21 levels and altered the nonenzymatic (glutathione) and enzymatic antioxidant markers (Glutathione peroxidase, and superoxide dismutase). Our results suggest that the combination of GIE and Curcuminoids can reduce the severity of NASH by reducing steatosis, fibrosis, oxidative stress, and inflammation. The results suggest that the combinatorial regimen could be an effective supplement to prevent the progression of liver steatosis to inflammation and fibrosis in NASH.

Standardized Emblica officinalis fruit extract inhibited the activities of α-amylase, α-glucosidase, and dipeptidyl peptidase-4 and displayed antioxidant potential.

BACKGROUND: Emblica officinalis, known as amla in Ayurveda, has been used as a folk medicine to treat numerous pathological conditions, including diabetes. However, the novel extract of E. officinalis fruit extract (amla fruit extract, AFE, Saberry®) containing 100 g kg-1 ß-glucogallin along with hydrolyzable tannins has not yet been extensively studied for its antidiabetic potential. OBJECTIVE: The aim of this study was to investigate the antidiabetic and antioxidant activities of AFE and its stability during gastric stress as well as its thermostability. METHODS: The effect of AFE on the inhibition of pancreatic α-amylase and salivary α-amylase enzymes was studied using starch and yeast α-glucosidase enzyme using 4-nitrophenyl α-d-glucopyranoside as substrate. Further, 2,2-diphenyl-1-picrylhydrazyl radical scavenging and reactive oxygen species inhibition assay was performed against AFE. RESULTS: AFE potently inhibited the activities of α-amylase and α-glucosidase in a concentration-dependent manner with half maximal inhibitory concentration (IC50 ) values of 135.70 µg mL-1 and 106.70 µg mL-1 respectively. Furthermore, it also showed inhibition of α-glucosidase (IC50 562.9 µg mL-1 ) and dipeptidyl peptidase-4 (DPP-4; IC50 3770 µg mL-1 ) enzyme activities. AFE is a potent antioxidant showing a free radical scavenging activity (IC50 2.37 µg mL-1 ) and protecting against cellular reactive oxygen species (IC50 1.77 µg mL-1 ), and the effects elicited could be attributed to its phytoconstituents. CONCLUSION: AFE showed significant gastric acid resistance and was also found to be thermostable against wet heat. Excellent α-amylase, α-glucosidase, and DPP-4 inhibitory activities of AFE, as well as antioxidant activities, strongly recommend its use for the management of type 2 diabetes mellitus. © 2019 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.