Tian-Huang Formula, a Traditional Chinese Medicinal Prescription, Improves Hepatosteatosis and Glucose Intolerance Targeting AKT-SREBP Nexus in Diet-Induced Obese Rats.

The progressive increase of metabolic diseases underscores the necessity for developing effective therapies. Although we found Tian-Huang formula (THF) could alleviate metabolic disorders, the underlying mechanism remains to be fully understood. In the present study, firstly, male Sprague-Dawley rats were fed with high-fat diet plus high-fructose drink (HFF, the diet is about 60% of calories from fat and the drink is 12.5% fructose solution) for 14 weeks to induce hepatosteatosis and glucose intolerance and then treated with THF (200 mg/kg) for 4 weeks. Then, metabolomics analysis was performed with rat liver samples and following the clues illustrated by Ingenuity Pathway Analysis (IPA) with the metabolomics discoveries, RT-qPCR and Western blotting were carried out to validate the putative pathways. Our results showed that THF treatment reduced the body weight from 735.1 ± 81.29 to 616.3 ± 52.81 g and plasma triglyceride from 1.5 ± 0.42 to 0.88 ± 0.33 mmol/L; meanwhile, histological examinations of hepatic tissue and epididymis adipose tissue showed obvious alleviation. Compared with the HFF group, the fasting serum insulin and blood glucose level of the THF group were improved from 20.77 ± 6.58 to 9.65 ± 5.48 mIU/L and from 8.96 ± 0.56 to 7.66 ± 1.25 mmol/L, respectively, so did the serum aspartate aminotransferase, insulin resistance index, and oral glucose tolerance (