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Protective effects of Astragaloside IV on various liver diseases: From chemistry to herbal medicines (Review)

  • Authors:
    • Jialu Shi
    • Xiaoyu Zhou
    • Jiabin Wu
    • Liru Zeng
    • Xia Wang
    • Wei Li
    • Xiao Huang
    • Xiaoyu Deng
    • Wenhong Wang
  • View Affiliations / Copyright

    Affiliations: School of Physical Education and Health, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China, Key Laboratory of Bone Biomaterials and Dong Medicine-Regulated Organoid Regeneration of Hunan Provincial Universities, Biomedical Research Institute, Hunan University of Medicine, Huaihua, Hunan 418000, P.R. China, Shanghai Key Laboratory of Human Performance (Shanghai University of Sport), Shanghai University of Sport, Shanghai 200438, P.R. China, Key Laboratory of Bone Biomaterials and Dong Medicine-Regulated Organoid Regeneration of Hunan Provincial Universities, Biomedical Research Institute, Hunan University of Medicine, Huaihua, Hunan 418000, P.R. China
    Copyright: © Shi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 249
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    Published online on: July 7, 2026
       https://doi.org/10.3892/ijmm.2026.5920
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Abstract

Numerous liver diseases are characterized by late diagnosis, rapid progression and high incidence, seriously threatening public health. Though widely used, traditional treatments such as drug therapy, resection and transplantation have substantial limitations. Therefore, developing novel preventive strategies and specialized therapies is crucial. As Chinese medicine continues to modernize, increasing evidence suggests that certain Chinese medicine ingredients can protect the liver. Astragaloside IV (AS‑IV) is a natural saponin extracted from the root of the traditional herb Astragalus membranaceous. It exhibits diverse pharmacological activities, including anti‑inflammatory, antioxidant, antiapoptotic and anticancer properties, and is recognized for treating neurological, cardiovascular and metabolic disorders, and cancer. These discoveries indicate its substantial promise for the treatment of liver diseases. Therapeutic trials revealed its hepatoprotective effects for the treatment of various liver diseases, such as non‑alcoholic fatty liver disease, liver fibrosis, hepatocellular carcinoma and liver injury induced by heavy metals, drugs, or alcohol and involve various signaling pathways such as nuclear factor erythroid 2‑related factor 2, toll‑like receptor 4, acetyl‑CoA carboxylase, protein kinase B, nuclear factor κB and adenosine monophosphate‑activated protein kinase. The present study presents a narrative review that comprehensively summarizes existing evidence regarding the therapeutic influence of AS‑IV on diverse liver disorders and deeply analyzes the molecular mechanisms underlying its action in liver disease. The objective is to comprehensively offer insights and references for relevant scientific research and clinical drug development to improve nutritional supplements for liver health.
View Figures

Figure 1

Chemical formula of Astragaloside
IV.

Figure 2

Mechanisms by which AS-Ⅳ ameliorates
non-alcoholic fatty liver disease and liver fibrosis. BSH, bile
salt hydrolase; IL-1β, interleukin-1β; TNF-α, tumor necrosis
factor-α; IL-6, interleukin-6; TLR4, toll-like receptor 4; FXR,
farnesoid x receptor; GLP-1, glucagon-like peptide-1; ACC,
acetyl-CoA carboxylase; AMPK, adenosine monophosphate-activated
protein kinase; GSH-Px, glutathione peroxidase; Akt, protein kinase
B; mTOR, mammalian target of rapamycin; MDA, malondialdehyde; Bax,
b-cell lymphoma/leukemia-2-associated X protein; Bax, B cell
lymphoma 2; ROS, reactive oxygen species; ER, endoplasmic
reticulum; SREBP-1c, sterol regulatory element-binding protein-1c;
GRP78, glucose-regulated protein 78; CHOP, c/edp homologous
protein; PERK, phosphorylated protein kinase-like ER kinase; MAPK,
mitogen-activated protein kinase; AS-IV, Astragaloside IV; Nrf2,
nuclear factor erythroid 2-related factor 2; α-SMA, α-smooth muscle
actin; COLα1 (I), collagen type I alpha 1 chain; FN, fibronectin;
NF-κB, nuclear factor κB; GSK-3β, glycogen synthase kinase 3β; SOD,
superoxide dismutase; ECM, extracellular matrix.

Figure 3

Mechanisms by which Astragaloside Ⅳ
ameliorate hepatocellular carcinoma. MRP2, multidrug
resistance-associated protein 2; HO-1, heme oxygenase 1; NQO1,
DT-diaphorase; PAI-1, plasminogen activator inhibitor-1; Smad,
mothers against decapentaplegic homolog; STAT, signal transducer
and activator of transcription; p-gp, p-glycoproterin; IL-12,
interleukin-12; PD-L1, programmed death-ligand 1; Wnt,
wingless-type mmtv integration site family; TGF4, T cell factor-4;
TGF, transforming growth factor; EMT, epithelial-mesenchymal
transition; ZFP, zinc finger protein transcription; KAT2A, lysine
acetyltransferase 2A; CNDP1, carboxypeptidase n domain containing
protein 1; miR, microRNA.

Figure 4

Mechanism of AS-Ⅳ amelioration of
liver injury induced by various hepatotoxin substances. PPARα,
peroxisome proliferator-activated receptor α; FSP1, ferroptosis
suppressor protein 1; APAP, acetaminophen; SIRT1, sirtuin 1; ATO,
atorvastatin; LPS, lipopolysaccharide; 4-HNE, 4-hydroxy-2-nonena;
LBP, lipopolysaccharide-binding protein; DAO, diamine oxidase; NLRP
3, nod-like receptor protein 3; MPO, myeloperoxidase; IRI,
ischemia-reperfusion injury; GCR, glucocorticoid receptor; AS-IV,
Astragaloside IV; MDA, malondialdehyde; SOD, superoxide dismutase;
GSH-Px, glutathione peroxidase; ROS, reactive oxygen species.
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Spandidos Publications style
Shi J, Zhou X, Wu J, Zeng L, Wang X, Li W, Huang X, Deng X and Wang W: Protective effects of Astragaloside IV on various liver diseases: From chemistry to herbal medicines (Review). Int J Mol Med 58: 249, 2026.
APA
Shi, J., Zhou, X., Wu, J., Zeng, L., Wang, X., Li, W. ... Wang, W. (2026). Protective effects of Astragaloside IV on various liver diseases: From chemistry to herbal medicines (Review). International Journal of Molecular Medicine, 58, 249. https://doi.org/10.3892/ijmm.2026.5920
MLA
Shi, J., Zhou, X., Wu, J., Zeng, L., Wang, X., Li, W., Huang, X., Deng, X., Wang, W."Protective effects of Astragaloside IV on various liver diseases: From chemistry to herbal medicines (Review)". International Journal of Molecular Medicine 58.3 (2026): 249.
Chicago
Shi, J., Zhou, X., Wu, J., Zeng, L., Wang, X., Li, W., Huang, X., Deng, X., Wang, W."Protective effects of Astragaloside IV on various liver diseases: From chemistry to herbal medicines (Review)". International Journal of Molecular Medicine 58, no. 3 (2026): 249. https://doi.org/10.3892/ijmm.2026.5920
Copy and paste a formatted citation
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Spandidos Publications style
Shi J, Zhou X, Wu J, Zeng L, Wang X, Li W, Huang X, Deng X and Wang W: Protective effects of Astragaloside IV on various liver diseases: From chemistry to herbal medicines (Review). Int J Mol Med 58: 249, 2026.
APA
Shi, J., Zhou, X., Wu, J., Zeng, L., Wang, X., Li, W. ... Wang, W. (2026). Protective effects of Astragaloside IV on various liver diseases: From chemistry to herbal medicines (Review). International Journal of Molecular Medicine, 58, 249. https://doi.org/10.3892/ijmm.2026.5920
MLA
Shi, J., Zhou, X., Wu, J., Zeng, L., Wang, X., Li, W., Huang, X., Deng, X., Wang, W."Protective effects of Astragaloside IV on various liver diseases: From chemistry to herbal medicines (Review)". International Journal of Molecular Medicine 58.3 (2026): 249.
Chicago
Shi, J., Zhou, X., Wu, J., Zeng, L., Wang, X., Li, W., Huang, X., Deng, X., Wang, W."Protective effects of Astragaloside IV on various liver diseases: From chemistry to herbal medicines (Review)". International Journal of Molecular Medicine 58, no. 3 (2026): 249. https://doi.org/10.3892/ijmm.2026.5920
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