Abstract
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 IC50 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.
Highlights
Type 2 diabetes mellitus (T2DM) is a metabolic disease associated with insulin resistance and pancreatic β-cell failure (Defronzo, 2009)
We discovered that emodin from the herb Rheum palmatum Linn inhibited Dipeptidyl peptidase 4 (DPP4) activity with an IC50 of 5.76 μM without inhibiting of either DPP8 or DPP9
The results suggested that emodin showed greater than 50% inhibition in the DPP4 activity assay at 10 μM
Summary
Type 2 diabetes mellitus (T2DM) is a metabolic disease associated with insulin resistance and pancreatic β-cell failure (Defronzo, 2009). Enhancing pancreatic insulin secretion while protecting pancreatic β-cells represents a promising therapeutic approach for the treatment of type 2 diabetes. Glucagon-like peptide 1 (GLP-1) is one of the incretin hormones released from cells in the gastrointestinal tract in response to nutrient absorption. Especially GLP-1, regulate post-prandial insulin secretion by inhibiting glucagon release and stimulating insulin biosynthesis and secretion (Baggio & Drucker, 2007). In T2DM patients, GLP-1 is critical for glucose homeostasis (Mulvihill & Drucker, 2014). Dipeptidyl peptidase 4 (DPP4), which was first identified by Hopsu-Havuand Glenner, rapidly degrades the active form of GLP-1 (GLP-17-36) to inactive GLP-19-36 within minutes in vivo (Hopsu-Havu & Glenner, 1966; Mulvihill & Drucker, 2014).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
