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Astragaloside IV: A multipotent phytochemical for treating fibrotic diseases (Review)

  • Authors:
    • Mingyu Wu
    • Ke Li
    • Jiabin Wu
    • Qiuyu Zhang
    • Xiaotong Ma
    • Wei Dai
    • Haoyang Gao
    • Xianyi Ding
    • Wenhong Wang
    • Weihua Xiao
  • View Affiliations / Copyright

    Affiliations: Shanghai Laboratory of Human Performance (Shanghai University of Sport), Shanghai University of Sport, Shanghai 200438, P.R. China
    Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 50
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    Published online on: December 24, 2025
       https://doi.org/10.3892/ijmm.2025.5721
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Abstract

Fibrosis is a maladaptive response of tissues or organs to adverse stresses, such as chronic inflammation, infection and mechanical injury. It further promotes parenchymal cell loss, abnormal myofibroblast proliferation and excessive extracellular matrix buildup, eventually triggering scar tissue hyperplasia or organ injury. Although a moderate fibrotic response is beneficial for compensatory tissue repair induced by exogenous or endogenous injury, excessive fibrosis is the basis for the promotion of multiorgan pathologies, such as cardiac hypertrophy, idiopathic pulmonary fibrosis, or renal tubulointerstitial fibrosis. In industrialized countries alone, fibrotic diseases account for ~45% of all‑cause mortality. Consequently, the development of medications that regulate the activation of growth factors, proliferation of fibrotic effector cells and deposition and degradation of the extracellular matrix is essential. Botanical compounds derived from Chinese medicine are generally considered natural tonics. Among these compounds, astragaloside IV (AS‑IV) is a bioactive product isolated from the roots of Astragalus membranaceus Bunge. On the basis of the multitarget therapeutic mechanism of Chinese herbal medicine, AS‑IV may have considerable benefits in improving multiorgan fibrosis and complex fibrotic diseases with multisignal cascades. It can effectively alleviate the fibrosis‑induced dysfunction of major tissues or organs, including the heart, lungs, kidneys and liver, by regulating the signal transduction of reactive oxygen species/caspase‑1/gasdermin D, transforming growth factor‑β/Smads, Wnt/β‑catenin and sirtuin 1‑nuclear factor‑κ B. The present review mainly focused on phytomedicine and highlights the potential of AS‑IV as an antifibrotic medication. It aimed to provide a novel reference for the application of AS‑IV in the nutritional intervention of fibrotic diseases.
View Figures

Figure 1

A general overview of AS-IV
regulation of fibrotic diseases. AKT, protein kinase B; ARE,
antioxidant response element; AS-IV, astragaloside IV; BDL, bile
duct ligation; BLM, bleomycin; cAMP, cyclic adenosine
monophosphate; CCL2, C-C motif chemokine ligand 2; CKD, chronic
kidney disease; COPD, chronic obstructive pulmonary disease; CT-1,
cardiotrophin-1; CTGF, connective tissue growth factor; CVB3,
coxsackievirus B3; DKD, diabetic kidney disease; ECM, extracellular
matrix; FNDC5, fibronectin type III domain-containing protein 5;
FOXO, forkhead box O; GSDMD-N, gasdermin D N-terminal domain;
GSH-Px, glutathione peroxidase; GSK-3β, glycogen synthase
kinase-3β; HCC, hepatocellular carcinoma; HG, high glucose; HIF1α,
hypoxia-inducible factor 1α; HMGB1, high mobility group box-1;
HO-1, heme oxygenase-1; IL-6, interleukin-6; ISO, isoproterenol;
IκBα, inhibitor of NF-kappa B α; K. pneumoniae,
Klebsiella pneumoniae; LC3 II, light chain 3 II; LDH,
lactate dehydrogenase; LPS, lipopolysaccharide; MAPK,
mitogen-activated protein kinase; MI, myocardial infarction;
miR-21, microRNA-21; mTOR, mammalian target of rapamycin; NF-κB,
nuclear factor-kappa B; NLRP3, nucleotide-binding oligomerization
domain-like receptor thermal protein domain associated protein 3;
NOX4, NADPH oxidase 4; NQO1, NAD(P)H:quinone oxidoreductase 1;
Nrf2, nuclear factor erythroid 2-related factor 2; PAH, pulmonary
artery hypertension; PAI-1, plasminogen activator inhibitor-1;
PGC-1α, peroxisome proliferator-activated receptor γ coactivator 1
α; PHD2, prolyl-4-hydroxylase 2; PI3K,
phosphatidylinositol-3-kinase; PICP, procollagen type I
carboxy-terminal propeptide; PINP, procollagen type I N-terminal
propeptide; PKA, protein kinase A; PS, porcine-serum; pSmad3C,
COOH-terminal phosphorylation of Smad3; pSmad3L, phosphorylation of
the linker region of Smad3; PTEN, phosphatase and tensin homolog;
RAF, rapidly accelerated fibrosarcoma; RAS, rat sarcoma; ROS,
reactive oxygen species; SIRT1, sirtuin 1; SOD, superoxide
dismutase; T2DM, type 2 diabetes mellitus; T-AOC, total antioxidant
capacity; TGF-β1, transforming growth factor-β1; TLR4, toll-like
receptor 4; TM, trabecular meshwork; TNF-α, tumor necrosis
factor-α; TRPM7, transient receptor potential cation channel,
subfamily M, member 7; UIRI, unilateral ischemia-reperfusion
injury; UUO, unilateral ureteral obstruction.

Figure 2

Molecular structure of astragaloside
IV.

Figure 3

The mechanisms of AS-IV against
cardiac fibrosis. AS-IV, astragaloside IV; CCL2, C-C motif
chemokine ligand 2; collagen I, type I collagen; CT-1,
cardiotrophin-1; FFA, free fatty acid; FNDC5, fibronectin type III
domain-containing protein 5; GSDMD, gasdermin D; IL-17,
interleukin-17; MAPK, mitogen-activated protein kinase; NF-κB,
nuclear factor-kappa B; NLRP3, nucleotide-binding oligomerization
domain-like receptor thermal protein domain associated protein 3;
PGC-1α, peroxisome proliferator-activated receptor γ coactivator 1
α; PICP, procollagen type I carboxy-terminal propeptide; PINP,
procollagen type I N-terminal propeptide; ROS, reactive oxygen
species; SIRT1, sirtuin 1; TGF-β, transforming growth factor-β;
TNF-α, tumor necrosis factor-α; TRPM7, transient receptor potential
cation channel, subfamily M, member 7.

Figure 4

The mechanisms of AS-IV against
pulmonary fibrosis. AGE, advanced glycation end-product; AKT,
protein kinase B; AS-IV, astragaloside IV; ECM, extracellular
matrix; EMT, epithelial-mesenchymal transition; FOXO, forkhead box
O; GSH-Px, glutathione peroxidase; HIF1α, hypoxia-inducible factor
1α; HMGB1, high mobility group box-1; IL-1β, interleukin-1β; LDH,
lactate dehydrogenase; lncRNA-ATB, long non-coding RNA activated by
transforming growth factor β; MAPK, mitogen-activated protein
kinase; miR-21, microRNA-21; MMP, matrix metalloproteinase; mTOR,
mammalian target of rapamycin; NF-κB, nuclear factor-kappa B;
NLRP3, nucleotide-binding oligomerization domain-like receptor
thermal protein domain associated protein 3; NOX4, NADPH oxidase 4;
PAH, pulmonary artery hypertension; PHD2, prolyl-4-hydroxylase 2;
PI3K, phosphatidylinositol-3-kinase; PTEN, phosphatase and tensin
homolog; RAF, rapidly accelerated fibrosarcoma; RAGE, receptor for
AGE; RAS, rat sarcoma; ROS, reactive oxygen species; RUNX1,
runt-related transcription factor 1; SOD, superoxide dismutase;
T-AOC, total antioxidant capacity; TGF-β1, transforming growth
factor-β1; TIMP4, tissue inhibitor of metalloprotease 4; TNF-α,
tumor necrosis factor-α; ZEB1, zinc finger E-box binding homeobox
1.

Figure 5

The mechanisms of AS-IV against renal
fibrosis. AKT, protein kinase B; ALDH2, acetaldehyde dehydrogenase
2; AS-IV, astragaloside IV; cAMP, cyclic adenosine monophosphate;
CD36, cluster of differentiation 36; CTGF, connective tissue growth
factor; CX3CL1, C-X3-C motif ligand 1; Cx43, connexin43; DKD,
diabetic kidney disease; ECM, extracellular matrix; EMT,
epithelial-mesenchymal transition; ERK, extracellular
signal-regulated kinase; FN, fibronectin; GSDMD-N, gasdermin D
N-terminal domain; GSK-3β, glycogen synthase kinase-3β; HG, high
glucose; IκBα, inhibitor of NF-kappa B α; JNK, c-Jun N-terminal
kinase; LC3 II, light chain 3 II; LEF1, lymphoid enhancer binding
factor-1; LPS, lipopolysaccharide; MAPK, mitogen-activated protein
kinase; MEK, mitogen-activated protein kinase kinase; miR-192,
microRNA-192; mTOR, mammalian target of rapamycin; mTORC1, mTOR
complex 1; NF-κB, nuclear factor-kappa B; NLR, nucleotide-binding
oligomerization domain-like receptor; NLRP3, nucleotide-binding
oligomerization domain-like receptor thermal protein domain
associated protein 3; NOX4, NADPH oxidase 4; Nrf2, nuclear factor
erythroid 2-related factor 2; p70S6K, ribosomal protein S6 kinase
β-1; PA, palmitic acid; PAI-1, plasminogen activator inhibitor-1;
p-H3, phosphorylated histone H3; PI3K,
phosphatidylinositol-3-kinase; PKA, protein kinase A; pSmad3C,
COOH-terminal phosphorylation of Smad3; pSmad3L, phosphorylation of
the linker region of Smad3; RAF, rapidly accelerated fibrosarcoma;
ROS, reactive oxygen species; RTEC, renal tubular epithelial cell;
SIRT1, sirtuin 1; TGF-β1, transforming growth factor-β1; TLR4,
toll-like receptor 4; UII, Urotensin II; UUO, unilateral ureteral
obstruction; ZEB2, zinc finger E-box binding homeobox 2; α-SMA,
α-smooth muscle actin.

Figure 6

The mechanisms of AS-IV against liver
fibrosis. ARE, antioxidant response element; AS-IV, astragaloside
IV; GSH, glutathione; GSK-3β, glycogen synthase kinase-3β; HO-1,
heme oxygenase-1; HSC, hepatic stellate cell; MAPK,
mitogen-activated protein kinase; NQO1, NAD(P)H:quinone
oxidoreductase 1; PAI-1, plasminogen activator inhibitor-1; pERK,
phosphorylated extracellular signal-regulated kinase; pJNK,
phosphorylated c-Jun N-terminal kinase; pNrf2, phosphorylated
nuclear factor erythroid 2-related factor 2; pSmad3C, COOH-terminal
phosphorylation of Smad3; pSmad3L, phosphorylation of the linker
region of Smad3; ROS, reactive oxygen species; TGF-β1, transforming
growth factor-β1.
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Copy and paste a formatted citation
Spandidos Publications style
Wu M, Li K, Wu J, Zhang Q, Ma X, Dai W, Gao H, Ding X, Wang W, Xiao W, Xiao W, et al: Astragaloside IV: A multipotent phytochemical for treating fibrotic diseases (Review). Int J Mol Med 57: 50, 2026.
APA
Wu, M., Li, K., Wu, J., Zhang, Q., Ma, X., Dai, W. ... Xiao, W. (2026). Astragaloside IV: A multipotent phytochemical for treating fibrotic diseases (Review). International Journal of Molecular Medicine, 57, 50. https://doi.org/10.3892/ijmm.2025.5721
MLA
Wu, M., Li, K., Wu, J., Zhang, Q., Ma, X., Dai, W., Gao, H., Ding, X., Wang, W., Xiao, W."Astragaloside IV: A multipotent phytochemical for treating fibrotic diseases (Review)". International Journal of Molecular Medicine 57.2 (2026): 50.
Chicago
Wu, M., Li, K., Wu, J., Zhang, Q., Ma, X., Dai, W., Gao, H., Ding, X., Wang, W., Xiao, W."Astragaloside IV: A multipotent phytochemical for treating fibrotic diseases (Review)". International Journal of Molecular Medicine 57, no. 2 (2026): 50. https://doi.org/10.3892/ijmm.2025.5721
Copy and paste a formatted citation
x
Spandidos Publications style
Wu M, Li K, Wu J, Zhang Q, Ma X, Dai W, Gao H, Ding X, Wang W, Xiao W, Xiao W, et al: Astragaloside IV: A multipotent phytochemical for treating fibrotic diseases (Review). Int J Mol Med 57: 50, 2026.
APA
Wu, M., Li, K., Wu, J., Zhang, Q., Ma, X., Dai, W. ... Xiao, W. (2026). Astragaloside IV: A multipotent phytochemical for treating fibrotic diseases (Review). International Journal of Molecular Medicine, 57, 50. https://doi.org/10.3892/ijmm.2025.5721
MLA
Wu, M., Li, K., Wu, J., Zhang, Q., Ma, X., Dai, W., Gao, H., Ding, X., Wang, W., Xiao, W."Astragaloside IV: A multipotent phytochemical for treating fibrotic diseases (Review)". International Journal of Molecular Medicine 57.2 (2026): 50.
Chicago
Wu, M., Li, K., Wu, J., Zhang, Q., Ma, X., Dai, W., Gao, H., Ding, X., Wang, W., Xiao, W."Astragaloside IV: A multipotent phytochemical for treating fibrotic diseases (Review)". International Journal of Molecular Medicine 57, no. 2 (2026): 50. https://doi.org/10.3892/ijmm.2025.5721
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