| Jiaqi Ganxian Granule (JGG) is a famous Traditional Chinese Medicine (TCM), which has been long used in clinical practice for treating liver fibrosis. This TCM is focus on activating blood and eliminatingstasis, smoothing liver to recuperate qi, and strengthen spleen to regulate qi, which consist of three demolition parties (i.e, JianPi, Liqi and HuoXue), is a very complex mixture containing ten components,. But which separated prescription plays the most important roles in complex prescription is unknown. Therefore, to study the key point and synergistic effect of TCM, simplification of prescription was used.The first part of this study,112 Sprague-Dawley (SD) rats was divided into 7 groups (Control, CCl4 treated model group, Colchicine intervention group, FuFang intervention group, JianPi intervention group, LiQi intervention group and HuoXue intervention group). Hepatic fibrosis was induced with 1ml·kg-1 40% CCl4 i.p., diluted in olive oil, twice weekly for 8 weeks, drug intervention was started with the first dose of 40% CCl4 or olive oil at 1 ml·kg-1:Colchicine intervention group was treated by colchicine at 0.1 ml·kg-1; other traditional medicine intervention groups were treated respectively by FuFang decoction and the three demolition parties, all the concentration of the TCMs were 0.02 g·ml-1, and the dosage of administration were performed orally once a day by gavage at 10 ml·kg-1 for 8 weeks. The HE staining and Mallory staining showed that TCMs did inhibit hepatic fibrosis and lower hepatic collagen content (P<0.05); Serum markers tests results showed that the level of Collagen Type ? (C?), Procollagen ? (PC?), Hyaluronic acid (HA) and Laminin (LN) in serum were significantly increased in model group compared with the control group (P<0.01), while the contents of C?, PC?, HA and LN were all significantly decreased in the TCMs group compared with model group (P<0.01); The result of Hyp content change test showed that Hyp increased significantly in liver of model rats compared to the control, while TCMs group can reduced the collagen accumulation in liver significantly. This part indicated that JGG FuFang decotion and three demolition parties (i.e, JianPi, Liqi and HuoXue) have a good function to intervene the process of liver fibrosis, and JianPi demolition party plays the most important role.However, the mechanism underlying its anti-hepatic fibrosis is still not clear. So the second part of this study, an ultra-performance liquid chromatography-time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS)-based metabolomics strategy was used to profile the metabolic characteristic of serum obtained from carbon tetrachloride (CCl4)-induced hepatic fibrosis model in SD rats with TCMs treatment. Through principal component analysis (PCA) and partial least square discriminant analysis (PLS-DA) showed that metabolic perturbations induced by CC14 were inhibited after treatment of TCMs,17 different metabolites related to CCl4 in positive mode. Among these compounds, change tendency of 10 potential drug-targets were restored after intervention with FuFang and three demolition parties; 10 different metabolites related to CCl4 in negtive mode. Among these compounds, change tendency of 8 potential drug-targets were restored after intervention with FuFang and three demolition parties. The current study indicates that JGG has significant anti-fibrosis effect on CCl4-induced liver fibrosis in rats, which might be by regulating the dysfunction of sphingolipid metabolism, glycerophospholipid metabolism, N-acylethanolamine biosynthesis, fat digestion and absorption, Arachidonic acid metabolism and Fatty acid biosynthesisOur findings indicated that metabolomics approach may provide a useful tool for exploring potential biomarkers involved in hepatic fibrosis and elucidate the mechanisms underlying action of therapies used in traditional Chinese medicine. |
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