The root of Pueraria lobata has been utilized as a food source for thousands of years in China. Puerarin is the major bioactive and the most abundant secondary metabolite obtained from the root of P. lobata. The potential therapeutic effect of puerarin against Alzheimer's disease was screened by in silico methods and confirmed by the amyloid β-peptide-induced Alzheimer's disease (AD) rat model. The in silico study displayed that puerarin had the potential to penetrate across the blood–brain barrier and had high stability in molecular docking and dynamics simulation with acetylcholinesterase (AChE), cyclooxygenase-2 (COX-2) and caspase-3 (C3), which play a central role in the development of AD. The in vivo results showed that puerarin could restrain the AChE activity, restore the activities of antioxidant defense substances toward normal levels, and decrease the expression of inflammatory factors and apoptosis genes in the brain, especially down-regulating the expressions of COX-2 and C3. The histopathological examination of brain sections and behavioral testing also verified the biochemical observations, which further validates the in silico study. These results not only suggest that puerarin, as a potential compound, could relieve AD, but also broaden the applications of puerarin.

Pueraria lobata is utilized as a food source in China. The aim of this study is to combine virtual screening and molecular dynamics predictive model to screen out the potential synaptic plasticity-maintaining components from the root of P. lobate and to verify it by employing the amyloid β-injected rats’ model. Eighteen compounds were identified by HPLC-MS/MS; puerarin manifested the most potential to form a stable complex with calcium/calmodulin kinase IIα (CaMK IIα), which is the key protein in synaptic plasticity by the in silico study. The further in vivo assay showed that puerarin could elevate the synaptic thickness, density, and length, relieve calcium overload, regulate the expression of CaMK IIα, and other p38MAPK-CREB signaling pathway-related biochemical criteria. The behavioral test also verified the results. Results have confirmed that the root of P. lobate can work anti-AD by maintaining the synaptic plasticity and proved the reliability of using the in silico predictive model to determine active ingredients from the natural product.

Herb–drug interactions strongly challenge the clinical combined application of herbs and drugs. Herbal products consist of complex pharmacological-active ingredients and perturb the activity of drug-metabolizing enzymes. Panax notoginseng saponins (PNS)-based drugs are often combined with aspirin in vascular disease treatment in China. PNS was found to exhibit inhibitory effects on aspirin hydrolysis using Caco-2 cell monolayers. In the present study, a total of 22 components of PNS were separated and identified by UPLC-MS/MS. Using highly selective probe substrate analysis, PNS exerted robust inhibitory potency on human carboxylesterase 2 (hCE2), while had a minor influence on hCE1, butyrylcholinesterase (BChE) and paraoxonase (PON). These effects were also verified through molecular docking analysis. PNS showed a concentration-dependent inhibitory effect on hydrolytic activity of aspirin in HepaRG cells. The protein level of hCE2 in HepaRG cells was suppressed after PNS treatment, while the level of BChE or PON1 in the extracellular matrix were elevated after PNS treatment. Insignificant effect was observed on the mRNA expression of the esterases. These findings are important to understand the underlying efficacy and safety of co-administration of PNS and aspirin in clinical practice.