Screening of a natural compound library identifies emodin, a natural compound from Rheum palmatum Linn that inhibits DPP4

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 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.

Antidiabetic potential of anthraquinones: A review

“…The authors further revealed that emodin binds to DPP‐4 protein with relatively low affinity at Glu205 and Glu206 positions. To confirm the in vitro data, oral administration of emodin (3–30 mg/kg/4 hr) reduced blood glucose level and plasma DPP‐4 activity and elevated glucagon‐like peptide‐1 activity in Balb/C and ob/ob (−/−) mice (Wang et al, ). Jang et al () have reported that emodin from S. tora L. inhibited aldose reductase activity and advanced glycation end products formation with IC 50 values of 15.9 and 118 μM, respectively.…”

“…Emodin isolated from R. palmatum L. inhibited the activity of DPP‐4 with an IC 50 values of 5.76 μM (Wang et al, ). The authors further revealed that emodin binds to DPP‐4 protein with relatively low affinity at Glu205 and Glu206 positions.…”

“…In addition, the upregulation of peroxisome proliferator activated receptor‐γ by emodin administration may have a crucial role in improving insulin sensitivity via increased glucose transporter 2 expression (Bing et al, ; Chen et al, ). Meanwhile, the high DPP‐4 inhibition and downregulation of glycogen synthase kinase‐3β expression by emodin showed the potential to improve insulin secretion and modulation of hepatic and muscle glycogen contents in vivo (Song et al, ;Wang et al, ; Wu, Chen, et al, ). The amelioration of diabetes‐associated complications and pancreatic β‐cell failure by emodin and catenarin administration are linked to the downregulation of the mitogen‐activated protein kinase p38, c‐Jun N‐terminal Kinases, NF‐kB, integrin‐linked kinase and desmin expression, and the restoration of nephrin expression in diabetic rats model (Bae et al, ; Chen et al, ; Shen et al, ; Heo, Yun, Noh, & Park, ; Wang et al, ).…”

“…In addition, the upregulation of peroxisome proliferator activated receptor-γ by emodin administration may have a crucial role in improving insulin sensitivity via increased glucose transporter 2 expression (Bing et al, 2018;Chen et al, 2012). Meanwhile, the high DPP-4 inhibition and downregulation of glycogen synthase kinase-3β expression by emodin showed the potential to improve insulin secretion and modulation of hepatic and muscle glycogen contents in vivo (Song et al, 2017;Wang et al, 2017;Wu, Chen, et al, 2014). Choi, Byoung, Seong, Jin, and Sunmin (2006) have reported that rhein (50 μM) isolated from Rheum rhizoma enhanced insulin-stimulated glucose uptake in Min6 cells and 3T3-L1 adipocytes.…”

Polyalthia Clerodane Diterpene Potentiates Hypoglycemia via Inhibition of Dipeptidyl Peptidase 4

“…Screening DPP-4 inhibitors for treating diabetes is a recently developing field (since 2006), when a study reported that DPP-4 might regulate insulin sensitivity via degradation of GLP-1 [22]. Up to now, few natural DPP-4 inhibitors have been reported [23] From plant origin, DPP-4 inhibitory activities of kaempferol and derivatives, linustatins, chrysin, stigmasterol, emodin, lupeol, mangiferin, vitisins, and soybean hydrolysates were all validated via direct enzymatic assay and in vivo hypoglycemic analysis [24,25,26,27,28,29,30,31]. Moreover, the methanolic extracts of Ficus benghalensis , Syzigium cumini , Ocimum sanctum , and Eucalyptus sp.…”