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

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Ethnopharmacological relevanceIn 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. AimsWe 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 methodsJST 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. ResultsAdministration 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. ConclusionsJST is a valuable prescription for treatment of patients with DM in traditional clinics through inhibition of obesity, inflammatory condition and metabolism.