Investigating the Metabolic Level of Endogenous and Exogenous Substances on the Intervention of Traditional Chinese Medicine Fuzheng Yiliu Decoction in a Rat Orthotopic Liver Cancer Model

BACKGROUND: Fuzheng Yiliu decoction (FZYLD), a Chinese formula consisting of four herbs, can be clinically used as an adjuvant therapy after surgery or palliative treatment for advanced liver cancer. METHODS: This study identified the endogenous and exogenous metabolites of FZYLD in rat serum to characterize the underlying mechanism of its antitumor activity, as well as relieving cancer-related weakness. An orthotopic transplantation rat model of HepG2 cells was established and administered with FZYLD by gastric perfusion for 14 days. Cardiopulmonary function and tail suspension test were used to evaluate the bodily weakness of hepatocellular carcinoma (HCC) rats. Tumor weight and size were measured to calculate inhibition ratios. Serum of different concentrations of FZYLD was used to culture the 2-[N-(7-nitrobenz-2-oxa-1, 3-diaxol-4-yl) amino]-2-deoxyglucose-labeled HepG2 cells. IC(50) value was measured using MTT assay. Endogenous and exogenous metabolites in rat serum were detected using nuclear magnetic resonance or LC-MS/MS spectroscopy. RESULTS: FZYLD improved cardiopulmonary function, decreased immobility time in tail suspension test, and yielded tumor inhibition ratios of up to 27%. Serum endogenous markers, such as lipoproteins (high- and low-density lipoproteins), glucose, and valine, and lactic acid metabolic disturbance were recovered, to some extent, in HCC rats. Exogenous metabolites, diosgenin, apigenin-7-O-acetyl-β-D-glucoside, calycosin-7-glucoside, calycosin, ganoderic-acid-A, formononetin, and methylnissolin, became detectable in the blood. FZYLD-containing serum substantially inhibited the proliferation of HepG2-cells. IC(50) value was found to be 24.31%. Further, we confirmed that FZYLD could revert energy and lipid metabolism disorders and that its constituents could be bioactive components that induce apoptosis in cancer cells. CONCLUSION: The present study explained the mechanism of the effect of FZYLD on body empty, fatigue, and low immunity in patients with cancer, offering an efficient way for research of natural compounds in traditional Chinese medicine.