A standardized black pepper seed extract containing ß-caryophyllene improves cognitive function in scopolamine-induced amnesia model mice via regulation of brain-derived neurotrophic factor and MAPK proteins.

ß-caryophyllene (BCP), a natural sesquiterpene present in plants, is a selective agonist of cannabinoid receptor type-2 (CB2) of the endocannabinoid system. In this study, we have prepared an extract from Piper nigrum (black pepper) seeds using supercritical fluid extraction, standardized to contain 30% BCP (ViphyllinTM ). The beneficial effects of prophylactic treatment with Viphyllin on cognitive functions were demonstrated in Scopolamine-induced dementia model mice. Male Swiss albino mice (25-30 g) were administered with Viphyllin (50 mg and 100 mg/kg body weight p.o.) or donepezil (1.60 mg/kg) for 14 days. Subsequently, cognitive deficits were induced by treating the animals intraperitoneally with Scopolamine (0.75 mg/kg). The cognitive behavior of mice was evaluated using a novel object recognition test (NORT) and Morris water maze (MWM) test. The brain homogenates were studied for biochemical parameters including cholinesterase activities and antioxidant status. Western blot analysis was performed to investigate the mechanism of action. Viphyllin dose dependently improved the recognition and spatial memory and cholinergic functions in Scop-treated mice. The extract was found protective against Scop-induced oxidative damage and histopathologic changes in the brain. At 100 mg/kg Viphyllin markedly reduced the proBDNF/mBDNF ratio (p < .05) and augmented the TrkB expression (p < .01). Viphyllin (100 mg/kg) was found to be neuroprotective by reducing the Scop-induced upregulation of p-JNK and p-p38 MAPK proteins, Bax/Bcl-2 ratio, and caspase activation in the brain. Viphyllin also exerted anti-inflammatory effects by downregulating Cox-2, TNF-α, and NOS-2 in Scop-induced mice (p < .05). To summarize, our data encourage Viphyllin as a functional ingredient/dietary supplement for brain health and cognition. PRACTICAL APPLICATIONS: Black pepper is a culinary spice having several medicinal attributes. Essential oils in the seeds of the plant give aroma and flavor to it. Here we have prepared an extract from the seeds of black pepper using supercritical fluid extraction, characterized for the presence of ß-caryophyllene (not <30%). This research work further validates the neuroprotective mechanism of the extract in Scopolamine-induced cognitive impairment model mice. The findings from this study strongly suggest the beneficial neuroactive properties of black pepper seed extract having the presence of BCP, a CB2 receptor agonist. It can thus be used potentially as a functional food ingredient for cognition and brain function.

Molecular docking analysis of Withaferin A from Withania somnifera with the Glucose regulated protein 78 (GRP78) receptor and the SARS-CoV-2 main protease.

Design and development of an effective compound to combat COVID-19 is clearly critical in the current circumstances. Therefore, it is of interest to document the molecular docking analysis data of the cellular receptor Glucose regulated protein 78 (GRP78) with Withaferin A from Withania somnifera in the context of COVID-19 pandemic for further consideration. Here, we report the optimal interaction features of withaferin A, artemisinin, curcumin and andrographolide with the GRP78 receptor having low binding energies (-8.7, -7.89, -6.21 and -6.17 kcal/mol respectively) in this report. In order to gain additional insights, the interaction pattern of compounds with SARS-CoV-2 main protease (Mpro) was studied.

A double blind, placebo-controlled randomized comparative study on the efficacy of phytosterol-enriched and conventional saw palmetto oil in mitigating benign prostate hyperplasia and androgen deficiency.

BACKGROUND: The present clinical trial was conducted to evaluate the efficacy and tolerability of a standardized saw palmetto oil containing 3% ß-sitosterol in the treatment of benign prostate hyperplasia (BPH) and androgen deficiency. METHODS: Subjects aged 40-65 years with symptomatic BPH were randomized to 12-week double-blind treatment with 500 mg doses of ß-sitosterol enriched saw palmetto oil, conventional saw palmetto oil and placebo orally in the form of capsules (n = 33 in each group). BPH severity was determined using the International Prostate Symptom Score (IPSS), uroflowmetry, serum measurement of prostate specific antigen (PSA), testosterone and 5α-reductase. During the trial, the androgen deficiency was evaluated using Aging Male Symptoms (AMS) scale, the Androgen Deficiency in the Aging Male (ADAM) questionnaire, serum levels of free testosterone. RESULTS: Subjects treated with ß-sitosterol enriched saw palmetto oil showed significant decrease in IPSS, AMS and ADAM scores along with reduced postvoiding residual volume (p < 0.001), PSA (p < 0.01) and 5α-reductase from baseline to end of 12-week treatment as compared to placebo. There was also a significant increment in the maximum and average urine flow rate (p < 0.001), and serum free testosterone level of subjects treated with enriched saw palmetto oil as compared to placebo. CONCLUSION: This study demonstrates the efficacy of ß-sitosterol enriched saw palmetto oil superior to conventional oil thus extending the scope of effective BPH and androgen deficiency treatment with improved quality of life through the intake of functional ingredients. TRIAL REGISTRATION: CTRI/2018/12/016724 dated 19/12/2018 prospectively registered. URL: http://ctri.nic.in/Clinicaltrials/advsearch.php.

Informal rural healthcare providers in North and South India.

Rural households in India rely extensively on informal biomedical providers, who lack valid medical qualifications. Their numbers far exceed those of formal providers. Our study reports on the education, knowledge, practices and relationships of informal providers (IPs) in two very different districts: Tehri Garhwal in Uttarakhand (north) and Guntur in Andhra Pradesh (south). We mapped and interviewed IPs in all nine blocks of Tehri and in nine out of 57 blocks in Guntur, and then interviewed a smaller sample in depth (90 IPs in Tehri, 100 in Guntur) about market practices, relationships with the formal sector, and their knowledge of protocol-based management of fever, diarrhoea and respiratory conditions. We evaluated IPs' performance by observing their interactions with three patients per condition; nine patients per provider. IPs in the two districts had very different educational backgrounds-more years of schooling followed by various informal diplomas in Tehri and more apprenticeships in Guntur, yet their knowledge of management of the three conditions was similar and reasonably high (71% Tehri and 73% Guntur). IPs in Tehri were mostly clinic-based and dispensed a blend of allopathic and indigenous drugs. IPs in Guntur mostly provided door-to-door services and prescribed and dispensed mainly allopathic drugs. In Guntur, formal private doctors were important referral providers (with commissions) and source of new knowledge for IPs. At both sites, IPs prescribed inappropriate drugs, but the use of injections and antibiotics was higher in Guntur. Guntur IPs were well organized in state and block level associations that had successfully lobbied for a state government registration and training for themselves. We find that IPs are firmly established in rural India but their role has grown and evolved differently in different market settings. Interventions need to be tailored differently keeping in view these unique features.