Effects of Shu Gan Jian Pi formula on rats with carbon tetrachloride-induced liver fibrosis using serum metabonomics based on gas chromatography-time of flight mass spectrometry

Abstract

Liver fibrosis is a common stage in the majority of chronic liver diseases, regardless of the etiology, and its progression may lead to hepatic cirrhosis or hepatocellular carcinoma. Metabolomics, a powerful approach in systems biology, is a discipline used to qualitatively and quantitatively analyze the small molecule metabolites of cells at specific times and under certain conditions. The present study aimed to investigate serum metabolic changes following Shu Gan Jian Pi formula (SGJPF) treatment of carbon tetrachloride (CCl4)‑induced liver fibrosis in rats using gas chromatography‑time of flight mass spectrometry (GC‑TOFMS). In addition, the potential mechanisms were explored. Rat liver fibrosis was induced by twice‑weekly subcutaneous CCl4 injection for 12 continuous weeks. During the same period, the SGJPF group received 16.2 g/kg body weight SGJPF, diluted in water, once a day for 12 weeks. Rats in the control and model groups received oral administration of the same volume of saline solution. Serum samples from the control, model and SGJPF groups were collected after 12 weeks of treatment, and metabolic profile alterations were analyzed by GC‑TOF/MS. Metabolic profile analysis indicated that clustering differed between the three groups and the following 12 metabolites were detected in the serum of all three groups: Isoleucine; L‑malic acid; D‑erythro‑sphingosine; putrescine; malonic acid; 3,6‑anhydro‑D‑galactose, α‑ketoglutaric acid; ornithine; glucose; hippuric acid; tetrahydrocorticosterone; and fucose. The results demonstrated that SGJPF treatment mitigated the effects of CCl4‑induced liver fibrosis on biomarker levels, thus indicating that SGJPF may have a therapeutic effect on CCl4‑induced liver fibrosis in rats. The mechanism may involve the regulation of energy, amino acid, sphingolipid, cytochrome P450, glucose and water‑electrolyte metabolism.