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

Hongcheng Zhang; Qiwen Dai; Maogui Zeng; Yingying Liu; Jian Du; Wensheng Pang; Juan Hu; Liwu Chen

doi:10.2147/CMAR.S377621

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

Cancer Manag Res. 2022 Sep 17:14:2785-2801. doi: 10.2147/CMAR.S377621. eCollection 2022.

Authors

Hongcheng Zhang^#^{1

2}, Qiwen Dai^#^{1

2}, Maogui Zeng¹, Yingying Liu¹, Jian Du², Wensheng Pang², Juan Hu^{1

2}, Liwu Chen¹

Affiliations

¹ The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, 350003, People's Republic of China.
² The School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, People's Republic of China.

^# Contributed equally.

Abstract

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. IC₅₀ 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. IC₅₀ 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.

Keywords: Fuzheng Yiliu decoction; HCC rat model; ameliorating cancer-related weakness; anti-liver tumor; regulation of metabolic balance.

Grants and funding

The authors give thanks to Project 82174462, supported by the National Natural Science Foundation of China and Fujian Natural Science Foundation (2020J01249); supported by Central Committee to Guide Local Science and Technology Development (Grants No. 2020L3012), the authors acknowledge Bethune Medical Science Research Foundation Project (B19003CS), and the Professional technical service platform of research & development of traditional Chinese medicine & health products (14C26243501795).