Recent Advances in the Mechanisms and Applications of Astragalus Polysaccharides in Liver Cancer Treatment: An Overview

Abstract

Astragalus polysaccharides (APS), bioactive compounds derived from Astragalus membranaceus, have emerged as promising natural agents in the treatment of hepatocellular carcinoma, a leading cause of cancer-related mortality. Preclinical studies indicate that APS exerts significant anti-liver cancer effects through multiple biological actions, including the promotion of apoptosis, inhibition of proliferation, suppression of epithelial-mesenchymal transition, regulation of autophagy, and modulation of immune responses. These therapeutic effects are closely associated with the regulation of critical signalling pathways, such as PI3K/AKT/mTOR, Wnt/β-catenin, JAK/STAT, and TGF-β/Smad. APS also reshapes the tumour microenvironment by enhancing macrophage activity, reducing the regulatory T cell function, and improving host immune response. In addition, APS exhibits synergistic effects when combined with conventional chemotherapeutics and interventional treatments such as transarterial chemoembolisation, improving efficacy and reducing toxicity. Despite the robust experimental evidence, limitations such as low bioavailability and a lack of large-scale clinical trials remain challenges for clinical translation. This review summarises the recent advances in understanding the anti-hepatocellular carcinoma activities of APS, their molecular targets and potential applications, aiming to provide a scientific basis for future studies and the development of APS-based therapeutic strategies.

Keywords: Astragalus polysaccharides; PI3K/AKT/mTOR; anti-liver cancer mechanisms; apoptosis; applications of Astragalus polysaccharides; immunomodulation; liver cancer; signalling pathways; traditional Chinese medicine.

Figure 1

Major bioactive components of Astragali radix (Huangqi) and their associated pharmacological functions.

Figure 2

Astragalus polysaccharides (APS) inhibit liver cancer cell proliferation by regulating cell cycle arrest through GSK-3β inhibition; the ┐ line means the inhibition of cell proliferation.

Figure 3

Inhibitory effect of Astragalus polysaccharides (APS) on Wnt/β-catenin signalling and induction of apoptosis and ferroptosis in liver cancer cells. The ┬ line means inhibition.

Figure 4

Astragalus polysaccharides (APS) regulate autophagy and inhibit liver cancer cell proliferation through the PI3K/AKT/mTOR signalling pathway.

Figure 5

Inhibition of liver cancer cell invasion and metastasis by Astragalus polysaccharides (APS).

Figure 6

Immunomodulatory mechanisms of Astragalus polysaccharides (APS) in liver cancer.

Figure 7

Multifaceted antitumour mechanisms of Astragalus polysaccharides (APS) in liver cancer. This figure illustrates the diverse mechanisms through which APS exert antitumour effects in hepatocellular carcinoma (HCC). APS inhibit tumour proliferation by downregulating cyclin D1 and p53 and upregulating p21, leading to cell cycle arrest. They promote apoptosis via mitochondrial pathways, characterised by increased Bax, cytochrome c, and caspase-3 levels and reduced Bcl-2 expression. APS also suppress the epithelial–mesenchymal transition (EMT) and metastasis by upregulating E-cadherin and downregulating mesenchymal markers such as N-cadherin, vimentin, and TGF-β. Immunomodulatory effects include activation of CD8⁺ T cells and natural killer (NK) cells, increased secretion of IL-2 and IFN-γ, and reduced Treg activity. Furthermore, APS remodel the tumour microenvironment (TME) by repolarising TAMs from the protumour M2 phenotype to the antitumour M1 phenotype and downregulating angiogenic factors such as VEGF and HIF-1α. Together, these mechanisms position APS as promising multifunctional agents for integrative liver cancer therapy.

Figure 8

Inhibition of liver cancer cell invasion and metastasis by Astragalus polysaccharides (APS). This figure illustrates the inhibitory effects of APS on the invasion and metastasis of liver cancer cells, specifically HepG2 and SMMC-7721 cell lines. APS modulate the JAK/STAT signalling pathway, leading to upregulation of the epithelial marker E-cadherin and downregulation of the mesenchymal markers vimentin and CXCR4. These changes inhibit the EMT, suppress cell migration and invasion, and reduce the metastatic potential. The data support the potential of APS as natural agents targeting metastasis in hepatocellular carcinoma.

Figure 9

Schematic illustration of the synthesis and mechanism of action of Astragalus polysaccharide-modified selenium nanoparticles (AASP–SeNPs) in liver cancer therapy. This figure shows that AASP–SeNPs are synthesised by reducing sodium selenite (Na₂SeO₃) with ascorbic acid in an Astragalus polysaccharide solution, producing spherical, monodisperse nanoparticles of approximately 50 nm in diameter. After being internalised by human liver cancer (HepG2) cells, AASP–SeNPs induce the accumulation of reactive oxygen species and a loss of the mitochondrial membrane potential (ΔΨm). This loss of ΔΨm triggers the release of cytochrome c from mitochondria. These events are accompanied by an increase in the proapoptotic protein Bax and a decrease in the antiapoptotic protein Bcl-2, shifting the balance toward apoptosis.

Figure 10

Synergistic effects of Astragalus polysaccharides (APS) with chemotherapeutic agents in liver cancer. This figure illustrates the synergistic actions of APS when used in combination with chemotherapeutic agents or interventional therapies in hepatocellular carcinoma (HCC). In the top left panel, APS enhance doxorubicin (Dox)-induced apoptosis through activation of endoplasmic reticulum (ER) stress pathways, including PERK, eIF2α, and CHOP, and increase expression of proapoptotic proteins Bax and Bim. The top right panel shows that APS combined with apatinib promote apoptosis and inhibit tumour migration and invasion, alongside reduced levels of tumour markers CA189 and CA724. In the bottom left panel, APS co-administered with cisplatin result in G1 cell cycle arrest, increased Sub-G1 cell population, and augmented apoptotic activity. The bottom right panel demonstrates that APS improve the therapeutic efficacy of transarterial chemoembolisation (TACE) by lowering serum alpha-fetoprotein (AFP) and total bilirubin levels, while also offering hepatic protection. Collectively, these data indicate that APS act as a multifunctional adjuvant capable of enhancing chemotherapeutic efficacy, reducing adverse effects, and modulating tumour-associated pathways in liver cancer treatment.

Figure 11

Mechanism of the compound Astragalus and Salvia extract (CASE) in inhibiting liver cancer progression via the MAPK–TGF-β/Smad pathway modulation.