Objectives: Cholinesterase inhibition is a common strategy to treat Alzheimer’s disease. In this study, we have investigated the cholinesterase inhibitory effects of a first-of-its-kind turmeric extract (REVERC3) having enriched content of bisdemethoxycurcumin as major active curcuminoid. Methods: The inhibition studies were performed using Ellman’s colorimetric assay. The kinetics of acetylcholinesterase and butyrylcholinesterase was determined in the presence of REVERC3 using the Lineweaver–Burk double reciprocal plots. Furthermore, we used AutoDock tools to predict the binding of bisdemethoxycurcumin with the active sites of cholinesterases. Results: REVERC3 showed 4.8- and 5.39-fold higher inhibitory potential of acetylcholinesterase and butyrylcholinesterase with IC50 values of 29.08 and 33.59 µg/mL, respectively, compared to the regular turmeric extract. The mode of binding of REVERC3 was competitive in the case of acetylcholinesterase while it was uncompetitive for the inhibition of butyrylcholinesterase. Docking analysis revealed that bisdemethoxycurcumin, the major constituent of REVERC3, has different preferences of binding in the active sites of acetylcholinesterase and butyrylcholinesterase. However, the best binding pose predictions are in line with the experimental binding mode of the cholinesterases. Conclusion: These results indicate that bisdemethoxycurcumin-enriched turmeric extract could improve the cholinergic functions via dual inhibition of cholinesterases. However, the predominant role of bisdemethoxycurcumin in REVERC3 must be further validated using preclinical studies and clinical trials.

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Objective: Withania somnifera, commonly known as Ashwagandha, Indian ginseng, has been used in Ayurvedic and indigenous medicinal preparations for various disease conditions since long time. In the present study, we investigated the protective effects of Viwithan, a standardized proprietary extract from Ashwagandha roots, against airway-inflammation and oxidative stress modulation in an ovalbumin (OVA)-induced murine model of inflammation. Methods: Allergic asthma was initiated in BALB/c mice by sensitizing with OVA on days 1 and 14, followed by intranasal challenge with OVA on days 27, 28, and 29. Mice were administered Viwithan (200 and 400 mg/kg) by oral gavage before challenge. Then, mice were evaluated for the presence of airway inflammation, production of allergen-specific cytokine response, lung pathology, and oxidative stress modulation. Results: The results showed that treatment with Viwithan attenuated OVA-induced lung inflammation in mice. Viwithan significantly attenuated inflammatory cell infiltration into the bronchoalveolar lavage fluid and markedly reduced the levels of pro-inflammatory cytokines, interleukin-10, and transforming growth factor-β1 in lung tissues. Viwithan treatment considerably reduced the lung weight in OVA-sensitized mice. Viwithan markedly attenuated the OVA-induced generation of reactive oxygen species in lung tissues. Conclusion: Together, these results suggested that Viwithan alleviates OVA-induced airway-inflammation and oxidative stress, highlighting the potential of standardized Ashwagandha extract as a useful therapeutic agent for pulmonary fibrosis management.