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The naturally inspired multitarget-directed ligands (PC01–PC10 and PD01–PD26) were synthesized from piperine for the management of Alzheimer’s disease (AD). The compound PD07 showed significant inhibitory activity on ChEs, BACE1, and Aβ1–42 aggregation in in vitro studies. Further, compound PD07 effectively displaced the propidium iodide at the AChE PAS site. The compound PD07 exhibited significant lipophilicity in PAMPA studies. Additionally, PD07 demonstrated neuroprotective properties in the Aβ1–42 induced SH-SY5Y cell line. Furthermore, DFT calculations were performed using B3LYP/6-311G­(d,p) basis sets to explore the PD07 physical and chemical properties. The compound PD07 showed a similar binding interaction profile at active sites of AChE, BuChE, and BACE1 proteins as compared to reference ligands (donepezil, tacrine, and BSD) in molecular docking and dynamic simulation studies. In acute oral toxicity studies, compound PD07 exhibited no toxicity symptoms up to 300 mg/kg, po. The compound PD07 (10 mg/kg, po) improved memory and cognition in scopolamine-induced amnesia rats. Further, PD07 increased ACh levels in the brain by inhibiting the AChE activity. The results from in vitro, in silico, and in vivo studies suggested that compound PD07 is a potent multitarget-directed lead from piperine to overcome Alzheimer’s disease.

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Background and objective Blumea lacera (Burm.f.) DC. (Family—Asteraceae) is widely used for treating hemorrhoids by several ethnomedicinal practitioners and tribes in India. Thus, the main objective of the present investigation was to evaluate the potential of B. lacera leaf extract in the treatment of hemorrhoids using a croton oil-induced hemorrhoid rat model. Materials and Methods Ethanol extract of B. lacera (EBL) leaves was prepared using Soxhlet extraction, optimized using Box–Behnken design (BBD), and quantified using high-pressure liquid chromatography (HPLC). Furthermore, the vasoactive ions were estimated using ion-exchange chromatography. Hemorrhoids were induced in the recto-anal portion of experimental rats, followed by treatment with EBL (100, 200, and 400 mg/kg; par oral (p.o.)) and Pilex granules as a standard anti-hemorrhoid drug for 7 days. The anti-hemorrhoid potential was evaluated on the eighth day by assessing the severity of hemorrhoids, biochemical parameters, and histology of recto-anal tissue. Results Upon treatment with EBL and Pilex, there was a significant ( p < 0.05) reduction in the inflammatory severity index, concentration of Evans blue dye, recto-anal coefficient (RAC), elevated cytokines level, and restoration of altered antioxidant status. Furthermore, the histopathological results revealed a marked reduction in the inflammatory zones along with minimally dilated blood vessels. Conclusion The present study confirmed the traditional claims of the plant B. lacera in the treatment of hemorrhoids, which may be attributed to its anti-inflammatory and antioxidant potential in EBL, where quercetin could be considered the main contributor.