Systematic Transcriptome and Regulatory Network Analyses Reveal the Hypoglycemic Mechanism of Dendrobium fimbriatum

Qiong Zhang,Jing Li,Mei Luo,Gui-Yan Xie,Weiwei Zeng,Yuxin Wu,Yanhong Zhu,Xiangliang Yang,An-Yuan Guo

doi:10.1016/j.omtn.2019.10.033

Abstract

Type 2 diabetes (T2D) is a long-term metabolic disorder disease characterized by high blood sugar and relative lack of insulin. Previous studies have demonstrated that Dendrobium has potent glucose-lowing effects and may serve as add-ons or alternatives to classic medications for T2D prevention and treatment, but the underlying molecular mechanisms were still unclear. We performed biochemical and transcriptional profiling (RNA sequencing [RNA-seq] and microRNA sequencing [miRNA-seq]) analyses on the pancreas and liver of Dendrobium fimbriatum extract (DFE)-fed diabetic rats and control animals. Our sequencing and experimental data indicated that DFE significantly alleviated diabetes symptoms through inhibiting inflammation and preventing islet cell apoptosis in diabetic pancreas. Transcription factors in Stat/nuclear factor κB (NF-κB)/Irf families combined with miR-148a/375/9a served as key regulators in the inflammation and apoptosis pathways under DFE administration. Meanwhile, DFE improved the energy metabolism, lipid transport, and oxidoreductase activity in the liver, and thus decreased lipid accumulation and lipotoxicity-induced hepatocyte apoptosis. Our findings revealed that DFE may serve as a potential therapeutic agent to prevent T2D, and also showed the combination of transcriptome profiling and regulatory network analysis could act as an effective approach for investigating potential molecular mechanisms of traditional Chinese medicine on diseases.

Highlights

Diabetes mellitus (DM) is a worldwide metabolic disorder disease caused by pancreatic b cell dysfunction and insulin dysbiosis,[1] and mainly characterized by hyperglycemia and dyslipidemia.[2]
Diabetes mellitus is a metabolic disorder disease usually originating from the dysfunction of pancreatic b cells,[24] which could impair insulin target organs.[25]
Our data demonstrated: (1) Dendrobium fimbriatum extract (DFE) could reduce the severe inflammation in the diabetic pancreas and prevent the islet cell apoptosis, which could contribute to the protection or recovery of b cell function and mass; and (2) DFE could improve energy metabolism and strengthen the oxidoreductase activity and lipid transport in the diabetic liver, which may thereby decrease lipid accumulation and lipotoxicity-induced hepatocyte apoptosis

Summary

Introduction

Diabetes mellitus (DM) is a worldwide metabolic disorder disease caused by pancreatic b cell dysfunction and insulin dysbiosis,[1] and mainly characterized by hyperglycemia and dyslipidemia.[2] Most hypoglycemic agents used for diabetes treatment, including synthetic insulin and western medicine, may bring about side effects, such as hypoglycemia and myocardial infarction.[3] Traditional Chinese medicines (TCMs) as health food resources could serve as an effective supplement for diabetes therapy.[4]. TCM has more than 2,000 years of history and has been widely used in clinical studies for diabetes therapy. Rare research had systematically investigated the potential molecular mechanisms underlying the anti-hyperglycemia effects of D. fimbriatum on diabetes

Methods

Results

Conclusion