Anti-Diabetic Indole-Terpenoids From Penicillium sp. HFF16 Isolated From the Rhizosphere Soil of Cynanchum bungei Decne.

Na Xiao,Ang Xiao,Xinru Zhang,Fandong Kong,Mingtian Yang,Mingyu Zhang,Shengnan Zhang,Yiru Xu,Guojun Pan,Guotong Chen,Gangping Hao,Haonan Li,Fujin Lv,Jinyi Yu,Liman Zhou

doi:10.3389/fchem.2021.792810

Abstract

Finding novel anti-diabetic compounds with effective suppression activities against hepatic glucagon response is urgently required for the development of new drugs against diabetes. Fungi are well known for their ability to produce new bioactive secondary metabolites. As part of our ongoing research, five new indole-terpenoids (1–5), named encindolenes D-H, were isolated from the fungus Penicillium sp. HFF16 from the rhizosphere soil of Cynanchum bungei Decne. The structures of the compounds were elucidated by spectroscopic data and ECD analysis. In the anti-diabetic activity assay, compounds 1–5 could inhibit the hepatic glucose production with EC50 values of 17.6, 30.1, 21.3, 9.6, and 9.9 μM, respectively, and decrease the cAMP contents in glucagon-induced HepG2 cells.

Highlights

Microorganism have been proven to be an important source of structurally novel and biologically active natural compounds, many of which have potential for drug development
Diabetes is a group of metabolic diseases characterized by hyperglycemia, which is caused by impaired peripheral glucose uptake and elevated hepatic glucose production (Unger and Cherrington, 2012; Jiang et al, 2021)
Enhanced glucagon response is proposed to be responsible for increased hepatic glucose production; it is proposed that suppression of hepatic glucagon response may provide therapeutic advantages in diabetes management (Ozcan et al, 2012; Xiao et al, 2017)

Summary

INTRODUCTION

Microorganism have been proven to be an important source of structurally novel and biologically active natural compounds, many of which have potential for drug development. More and more attention has been paid to the study of active metabolites from fungi, of which paxilline-type indolediterpenoids is well known for their diverse structures and bioactivities (Kong et al, 2019). Finding novel and effective suppression of hepatic glucagon response anti-diabetic compounds is urgently required. From Mount Tai, China, were investigated, which resulted in the isolation and identification of five new indole-terpenoids with weak anti-inflammatory activities (Pan GJ et al, 2021). All of the compounds exhibited moderate anti-diabetic effects on glucagon-stimulated cAMP accumulation and hepatic glucose production in HepG2 cells. The isolation, structural elucidation, and bioactivities of these compounds were described

MATERIALS AND METHODS

RESULTS AND DISCUSSION

CONCLUSION

DATA AVAILABILITY STATEMENT