Effects of Jowiseungki-tang on high fat diet-induced obesity in mice and functional analysis on network pharmacology and metabolomics analysis

Abstract

Ethnopharmacological relevance: In traditional Chinese and Korean medicine, Jowiseungki-tang (JST) is a prescription for diabetes mellitus (DM) treatment. However, little scientific evidence is known of its effect in diabetic condition.

Aims: We assessed the effects of JST on high-fat diet (HFD)-induced obesity with inflammatory condition in mice and to analyze the therapeutic function of JST on network pharmacology as well as targeted metabolomics.

Materials and methods: JST administration at 100 mg/kg and 500 mg/kg for a period of 4 weeks in HFD-induced obese mice, body weight gain, energy utility, calorie intake, and levels of glucose, insulin, total cholesterol, triglyceride, LDL-cholesterol as well as interleukin-6 were measured. Measurements of HDL-cholesterol (HDL-C) were performed and compared to those of the control group. Moreover, the therapeutic function of JST on obesity was analyzed furtherly based on network pharmacology and targeted metabolomics methods.

Results: Administration of JST at 100 mg/kg and 500 mg/kg for a period of 4 weeks in HFD-induced obesity mice significantly decreased the body weight gain, energy utility, calorie intake, and levels of insulin, total cholesterol, LDL-cholesterol, triglyceride, and interleukin-6. However, HDL-cholesterol (HDL-C) levels showed marked elevation relative to control groups. JST administration strongly inhibited expressions of inducible nitric oxide synthase, inflammatory proteins, and cyclooxygenase-2 in the pancreas, stomach, and liver tissues, and reduced hepatic steatosis and pancreatic hyperplasia. In network pharmacological analysis, the putative functional targets of JST are underlie on modulation of cofactor-, coenzyme-, and fatty acid-bonding, insulin resistance, and inflammatory response, fine-tuned the phosphatase binding and signal pathway activation, such as mitogen activated protein kinases, phosphatidylinositol 3-kinases/protein kinase B, protein kinase C, and receptor of glycation end products as well-advanced glycation end products. According to the metabolomics analysis, the contents and energy metabolites, and medium and long chain fatty acids was significantly changed in mice pancreases.

Conclusions: JST is a valuable prescription for treatment of patients with DM in traditional clinics through inhibition of obesity, inflammatory condition and metabolism.

Keywords: Diabetes mellitus; High fat diet; Jowiseungki-tang; Metabolomics; Network pharmacology.