Exploring the mechanism of Huangqi’s anti liver cancer effect based on network pharmacology and molecular docking
Huangqi is the dried root of the leguminous plants Astragalus membranaceus and Astragalus membranaceus. It is produced in Northeast, North, and Northwest China and has the effects of replenishing qi, promoting yang, nourishing the body, stabilizing the surface, promoting diuresis, reducing swelling, disinfecting and eliminating pus. Research has shown that through various cancer models and cell lines, Huangqi has been found to have direct anti proliferative or pro apoptotic effects on tumor cells to shrink or stabilize tumors. Huangqi injection has a certain degree of inhibitory effect on cell proliferation activity in liver tumors at different stages. The specific mechanism is that Huangqi injection inhibits cell proliferation activity and induces apoptosis through G1/S phase blockade and caspase-9/3 pathway activation, thereby inhibiting the development of liver cancer. Flavonoids, saponins, anthraquinones, aromatic hydrocarbons and other compounds were isolated from Huangqi injection. This article summarizes the recent advances in the anti-tumor mechanism and pharmacodynamics of flavonoids. However, the targets and mechanisms of their anti liver cancer effects are not yet fully understood. This article uses network pharmacology methods to collect potential effective substances in Huangqi and studies its anti liver cancer targets and pharmacological effects, providing a theoretical basis for experimental research on the molecular mechanism of Huangqi’s anti liver cancer effects in the later stage.

Liver cancer is one of the most common malignant tumors in the world, ranking second globally. In the early stages of liver cancer, surgical resection, liver transplantation, local ablation, and other treatment methods can improve the survival rate of patients. Liver cancer is a multi gene disease with complex pathogenesis and signal transduction pathways, and a single treatment method is difficult to achieve successful therapeutic effects. Therefore, using targeted drugs to regulate multiple signaling pathways has become a new paradigm for the treatment of liver cancer.

Huangqi is a commonly used qi tonic, and studies have shown that Huangqi extract may be a potential anti-tumor drug. The polysaccharide components of authentic medicinal herb Hengshan Huangqi have the activity of inhibiting the proliferation, adhesion, spreading, and migration of human cervical cancer cells Si Ha. Quercetin is a natural plant flavonoid. Its biological activity has been widely studied. It has obvious inhibitory effect on the growth of malignant cells in leukemia, breast cancer, liver cancer, ovarian cancer, colorectal cancer, stomach cancer and endometrial cancer. According to research reports, quercetin enhances the anti liver cancer effect mediated by amphotericin B through p53/Bcl xl. Shannaphthol inhibits the proliferation, migration, and invasion of HepG2 cells by downregulating miR-21, upregulating PTEN, and inactivating the PI3K/AKT/mTOR signaling pathway. The combination of genistein and isoferulic acid inhibits HepG2 cell proliferation through cell cycle regulation mediated by cyclin D1, CDK6, and p21.

This study screened 20 active ingredients of Astragalus membranaceus through TCMSP, and identified 88 common targets that intersect with disease targets. Six key proteins and their corresponding six monomeric compounds were screened through PPI network and topological analysis, and the molecular docking scores mentioned above indicate that. The MAPK8/Fox O signaling pathway is crucial for the development of cancer and fatty liver, as the components and targets have a certain degree of binding affinity. Research has confirmed that tamoxifen plays a role in breast cancer cells (MCF-7, T47D, ZR-75 and MDA-MB-231) and liver cells (LO2) through MAPK8/Fox O signaling pathway. Inducing fatty liver by interfering with the MAPK8/Fox O signaling pathway. Studies by He et al. have shown that inducing mastitis in mice with lipopolysaccharides results in increased phosphorylation levels of p38MAPK, ERK, and JNK in the MAPK signaling pathway, which are involved in the inflammatory response. Huangqi protein induces programmed necrosis in HepG2 cells by affecting the p53 signaling pathway, thereby inhibiting the growth of liver cancer cells.

Target enrichment analysis suggests that Astragalus membranaceus may exert anti liver cancer effects through negative regulation of apoptosis, ATP binding, protein complexes, and other biological functions such as PI3K Akt signaling pathway, Hepatitis B signaling pathway, HIF-1 signaling pathway, and tumor necrosis factor signaling pathway. The MTT results showed that all six compounds had a certain inhibitory effect on liver cancer HepG2 cells. RT qPCR results showed that different concentrations of curcumin could upregulate six genes, which were consistent with the genes involved in the PI3K Akt signaling pathway, Hepatitis B signaling pathway, HIF-1 signaling pathway, and tumor necrosis factor signaling pathway. It has been determined that the PI3K Akt signaling pathway is differentially expressed in many human cancers. For example, PIK3R1 has anti-cancer effects in hepatocellular carcinoma and renal cancer. Wu et al. found that TNF – α monomer intervention in NF – κ B activation in liver cancer cells can increase cell apoptosis. siRNA can specifically inhibit the mRNA encoded by NF – κ B/p65, downregulate P-gp levels, and promote liver cancer cell apoptosis. Chen et al. found that the HBp/FOXO3/miRNA-30b-5p/MINPP1 axis promotes the development of HBV positive HCC cells through glycolysis pathways. MiRNA-30b-5p/MINPP1 has also been proposed as a novel biomarker for early diagnosis of HBV positive HCC and a potential drug target for anti-tumor therapy.

Based on network pharmacology and molecular docking, this study elucidated the effective active ingredients, potential targets, and biological pathways of traditional Chinese medicine Huangqi in treating liver cancer. Experimental verification lays the foundation for subsequent research on the pharmacological mechanism of action.