A New Potent Inhibitor against α-Glucosidase Based on an In Vitro Enzymatic Synthesis Approach.

Inhibiting the activity of intestinal α-glucosidase is considered an effective approach for treating type II diabetes mellitus (T2DM). In this study, we employed an in vitro enzymatic synthesis approach to synthesize four derivatives of natural products (NPs) for the discovery of therapeutic drugs for T2DM. Network pharmacology analysis revealed that the betulinic acid derivative P3 exerted its effects in the treatment of T2DM through multiple targets. Neuroactive ligand-receptor interaction and the calcium signaling pathway were identified as key signaling pathways involved in the therapeutic action of compound P3 in T2DM. The results of molecular docking, molecular dynamics (MD) simulations, and binding free energy calculations indicate that compound P3 exhibits a more stable binding interaction and lower binding energy (-41.237 kcal/mol) with α-glucosidase compared to acarbose. In addition, compound P3 demonstrates excellent characteristics in various pharmacokinetic prediction models. Therefore, P3 holds promise as a lead compound for the development of drugs for T2DM and warrants further exploration. Finally, we performed site-directed mutagenesis to achieve targeted synthesis of betulinic acid derivative. This work demonstrates a practical strategy of discovering novel anti-hyperglycemic drugs from derivatives of NPs synthesized through in vitro enzymatic synthesis technology, providing potential insights into compound P3 as a lead compound for anti-hyperglycemic drug development.

Chemical composition, pharmacological activity and development strategies of Rubus chingii: A review.

Raspberries are used for both food and medicine, but it has not yet attracted widespread attention. In this paper, the chemical constituen of the original plant raspberry. R. chingii is one of the new "Zhe Bawei" medicinal materials selected in 2017. "Zhe Bawei" refers to eight kinds of genuine medicinal materials in Zhejiang Province. The chemical constituents, pharmacological effects, processing, and application of Rubus chingii Hu were reviewed to provide a reference for its further development. Relevant literature in recent years was collected in databases such as China Knowledge Network, Web of Science, Elsevier, PubMed, and X-Mol, using "raspberry", "Rubus chingii", "traditional use", "chemical composition", "pharmacology", etc. as keywords individually or in combination. The summary of pharmacological activities shows that the relationship between the pharmacological activities of raspberry is still not deep enough. More in-depth research should be carried out in this direction to explore the mechanism of action of its active ingredients and provide effective reference for the further development of the raspberry industry. In the future, with the participation of more researchers, it is expected to develop innovative drugs based on raspberry for the treatment of diseases.