Background: Stress is a known causative factor in modulating cognitive health, which overall well-being and quality of life are dependent on. Long-term stress has been shown to disrupt the balance of the hypothalamic–pituitary–adrenal (HPA) axis. Adaptogens, such as Withania somnifera (ashwagandha), are commonly used in Ayurvedic medicine for stress relief and ameliorating HPA-axis dysfunction. The aim of this study was to support the role of a root and leaf water-extracted ashwagandha extract (WS) in stress reduction by confirming the lowest clinically validated dose for stress management (125 mg/day) in a dose-dependent clinical study in adults with self-reported high stress. Methods: An 8-week, randomized, double-blinded, placebo-controlled study to compare the effects of three different WS extract doses (125, 250 and 500 mg) was performed. A total of 131 adults were enrolled, and 98 were included in the final analysis. Attenuation of chronic stress was measured using the 14-item Perceived Stress Scale (PSS) and biochemical-related stress parameters. Results: We have shown that aqueous WS extract (roots and leaves) safely reduces mild to moderate chronic stress at doses of 125 mg, 250 mg, and 500 mg/day for 8 weeks. Conclusions: Our findings demonstrate the stress-reduction capabilities of this well-characterized aqueous extract of WS (root and leaf) at the low dose of 125 mg/day, in a dose-dependent manner, via the modulation of the HPA axis. Trial registration: This study was registered with the Clinical Trials Registry—India (CTRI) with the registration number: CTRI/2019/11/022100.

Background: Mangroves have the ability to grow where no other vascular plants survive. Rhizophora mucronata is a true mangrove and traditionally used to treat diabetes and its allied complications. Objectives: In the present study, we standardized the 80% methanolic standardized extract of R. mucronata leaves (RH) and found out its antiradical and antidiabetic activities. Materials and Methods: The methanolic extract of R. mucronata leaves (RH) was standardized and quantified for phenolics, flavonoinds, gallic acid, quercetin, and coumarin. The reducing abilities and antiradical activities of RH were performed in vitro methods like, 1,1-diphenyl-2-picrylhydrazyl, nitric oxides, superoxides, hydroxyl, and ABTS (2,2'-azino-bis-3-ethyl benzthiazoline-6-sulphonic acid). Thereafter, RH was evaluated for it antidiabetic potentialities on streptozotocin (STZ)-induced type-2 diabetes. STZ (90 mg/kg, intraperitoneal) was administered to 2 days old pups to induce diabetes. RH was fed at doses of 50 and 100 mg/kg and glibenclamide (positive control) at 5 mg/kg, when the rats were 6 weeks old and continued for 10 weeks. Fasting glucose was monitored before and after the treatment. Further, lipid peroxides and reduced glutathione level were estimated on rat liver. Results: The results obtained from this study revealed RH possesses flavonoinds and also gallic acid, quercetin, and coumarin. Further, it has antiradical activities. It has also reduced blood glucose level in type-2 diabetic rats and reduced the formation of lipid peroxidation in liver. RH enhanced the level of glutathione in liver tissue. Conclusion: RH exhibits source of natural antioxidants and great potentialities as an antidiabetic agent by improving the hyperglycemia through its antiradical action.

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Trikatu, Sitopaladi, Hingavastaka, Avipattikara, Sringyadi and Talisadya are very popular Ayurvedic (churna) medicines practiced in India; however, unfortunately, they possess several quality control issues. The aim of this study was to find out a simple, accurate and sensitive HPTLC method for the detection and quantification of marker molecule, piperine (alkaloid) on these Ayurvedic formulations for standardization. Methanolic extraction (reflux) was performed from the above six churnas as well as three single ingredients Piper longum (pipul), Piper nigrum (marich) and Piper chaba (chai). HPTLC was done using piperine as a standard. The mobile phase was a mixture of toluene-ethyl acetate (7:3, v/v) and detection at 342λ. The Rf was detected at 0.39. Piperine was quantified in all samples. P. nigrum showed higher piperine than P. longum and P. chaba. The maximum piperine was noted in Hingavastaka churna and followed by Sringyadi churna, Sitopaladi churna, Talisadya churna, Trikatu churna and Avipattikara churna. This method can be successfully employed for standardization and quantitative analysis of piperine in Ayurvedic formulations (churnas) and also be helpful to clinicians and pharmacists to draw significant role of piperine present in all these samples.

Osteoarthritis is a chronic degenerative joint disease causing pain and disability. Glucosamine sulphate is a well known oral supplement for its treatment. The present pioneering study provides an overview of the accentuated transdermal delivery of glucosamine sulphate through the optimized gel formulation with guar gum and sodium carboxymethyl cellulose (Na-CMC). Response surface methodology based on the three-level three-factor central composite design provided the optimum concentration of guar gum, Na-CMC and glycerol for a maximum flux. The transdermal characterization, ex vivo permeation study and in vivo study were performed with optimized gel formulation. The factorial design predicted the optimum values of guar gum, Na-CMC and glycerol which were 418.53 mg, 444.97 mg and 2322.4 mg respectively for 25 g of the gel. This optimized gel demonstrated the maximum flux, i.e., 1047.46 μg cm⁻² h⁻¹. The optimized gel showed satisfactory results with respect to drug uniformity, pH, stability, rheological properties, zeta potential, drug–excipient compatibility and skin irritation. The release of the drug from the optimized transdermal gel followed the controlled first order Fickian (non-steady) release pattern. The in vivo study was carried out in a rat model of osteoarthritis induced by monosodium iodoacetate damaging the tibial plateau. In this study the optimized formulation effectively reduced the symptoms like reduction in swelling of the knee joint, gross changes in digitized radio images and morphological and histopathological alterations. Additionally the changes in the release pattern of the proinflammatory cytokine tumor necrosis factor-α illustrated the efficacy of the transdermal gel for the treatment of experimental osteoarthritis. Thus the optimized gel was found to be a unique potential vehicle for transdermal application of glucosamine sulphate which effectively attenuates the experimental osteoarthritis.