Historically, Chinese herbal medicines have been widely used in the treatment of hyperglycemia, but the mechanisms underlying their effectiveness remain largely unknown. Here, we screened a compound library primarily comprised of natural compounds extracted from herbs and marine organisms. The results showed that emodin, a natural compound from Rheum palmatum Linn, inhibited DPP4 activity with an in vitro IC 50 of 5.76 µM without inhibiting either DPP8 or DPP9. A docking model revealed that emodin binds to DPP4 protein through Glu205 and Glu206, although with low affinity. Moreover, emodin treatment (3, 10 and 30 mg/kg, P.O.) in mice decreased plasma DPP4 activity in a dose-dependent manner. Our study suggests that emodin inhibits DPP4 activity and may represent a novel therapeutic for the treatment of type 2 diabetes.
Wang, Z., Yang, L., Fan, H., Wu, P., Zhang, F., Zhang, C., … Li, M. (2017). Screening of a natural compound library identifies emodin, a natural compound from Rheum palmatum Linn that inhibits DPP4 . PeerJ, 5, e3283. https://doi.org/10.7717/peerj.3283