Objective  To investigate the effect of astragalus polysaccharides on doxorubicin-induced cardiomyocyte injury based on transforming growth factor-β1 (TGF-β1)/SMAD family member 3 (Smad3) signaling pathway.

Methods  AC16 cardiomyocytes were randomly divided into a blank group, a model group, an astragalus polysaccharide group, and a positive control group. Except for the blank group, other groups were stimulated with doxorubicin (1 μmol/L) to construct a cardiomyocyte injury model. Cells in the astragalus polysaccharide group (50 μmol/L astragalus polysaccharide) and the positive control group (10 μmol/L irbesartan) were treated for 24 h. Cell viability was detected by the CCK-8 assay. Western blot was used to detect the expression of TGF-β receptor 1 (TGF-βR1), Smad3, p-Smad3, α-smooth muscle actin (α-SMA), and collagen-Ⅰ proteins in AC16 cells in each group. Flow cytometry was used to detect the apoptosis of AC16 cardiomyocytes.

Results  Compared with the blank group, the proliferation ability of the model group decreased, while the expression levels of TGF-βR1, p-Smad3, α-SMA, collagen-Ⅰ protein, and the levels of apoptosis increased significantly (P<0.01). Compared with the model group, the proliferation ability of the astragalus polysaccharide group and positive control group was increased, while the expression levels of TGF-βR1, p-Smad3 α-SMAm collagen-Ⅰ proteinm, and the levels of apoptosis decreased (P<0.01). There were no statistically significant differences in the expression levels of Smad3 among the groups (P>0.05).

Conclusion  Astragalus polysaccharides can reduce the expression levels of TGF-βR1 and p-Smad3 proteins, reduce apoptosis, improve myocardial injury caused by doxorubicin, and reduce cardiotoxicity.

1.Di Palo KE, Barone NJ. Hypertension and heart failure: prevention, targets, and treatment[J]. Cardiol Clin, 2022, 40(2): 237-244. DOI: 10.1016/j.ccl.2021.12.011.

2.Hanna A, Frangogiannis NG. Inflammatory cytokines and chemokines as therapeutic targets in heart failure[J]. Cardiovasc Drugs Ther, 2020, 34(6): 849-863. DOI: 10.1007/s10557-020-07071-0.

3.Su C, Wang Q, Luo H, et al. Si-Miao-Yong-An decoction attenuates cardiac fibrosis via suppressing TGF-β1 pathway and interfering with MMP-TIMPs expression[J]. Biomed Pharmacother, 2020, 127: 110132. DOI: 10.1016/j.biopha.2020.110132.

4.Zeng Z, Wang Q, Yang X, et al. Qishen granule attenuates cardiac fibrosis by regulating TGF-β/Smad3 and GSK-3β pathway[J]. Phytomedicine, 2019, 62: 152949. DOI: 10.1016/j.phymed.2019.152949.

5.Kaňuchová M, Urban L, Melegová N, et al. Genistein does not inhibit TGF-β1-induced conversion of human dermal fibroblasts to myofibroblasts[J]. Physiol Res, 2021, 70(5): 815-820. DOI: 10.33549/physiolres.934666.

6.Kim S, Han JH, Kim S, et al. p90RSK inhibition ameliorates TGF-β1 signaling and pulmonary fibrosis by inhibiting smad3 transcriptional activity[J]. Cell Physiol Biochem, 2020, 54(2): 195-210. DOI: 10.33594/000000214.

7.Yin L, Liu MX, Li W, et al. Over-expression of inhibitor of differentiation 2 attenuates post-infarct cardiac fibrosis through inhibition of TGF-β1/SMAD3/HIF-1α/IL-11 signaling pathway[J]. Front Pharmacol, 2019, 10: 1349. DOI: 10.3389/fphar.2019.01349.

8.Zeng Z, Wang Q, Yang X, et al. Qishen granule attenuates cardiac fibrosis by regulating TGF-β/Smad3 and GSK-3β pathway[J]. Phytomedicine, 2019, 62: 152949. DOI: 10.1016/j.phymed.2019.152949.

9.Han A, Lu Y, Zheng Q, et al. Qiliqiangxin attenuates cardiac remodeling via inhibition of TGF-β1/Smad3 and NF-κB signaling pathways in a rat model of myocardial infarction[J]. Cell Physiol Biochem, 2018, 45(5): 1797-1806. DOI: 10.1159/000487871.

10.Zhang Y, Chen B. Silencing circ_0062389 alleviates cardiomyocyte apoptosis in heart failure rats via modulating TGF-β1/Smad3 signaling pathway[J]. Gene, 2021, 766: 145154. DOI: 10.1016/j.gene.2020.145154.

11.Lai Q, Liu FM, Rao WL, et al. Aminoacylase-1 plays a key role in myocardial fibrosis and the therapeutic effects of 20(S)-ginsenoside Rg3 in mouse heart failure[J]. Acta Pharmacol Sin, 2022, 43(8): 2003-2015. DOI: 10.1038/s41401-021-00830-1.

12.武思晴, 苗明三, 苗晋鑫. 中药多糖改善心肌缺血再灌注损伤的作用机制[J]. 中国实验方剂学杂志, 2025, 31(9): 277-288. [Wu SQ, Miao MS, Miao JX. Mechanism of traditional Chinese medicine polysaccharide in ameliorating myocardial ischemia-reperfusion injury[J]. Chinese Journal of Experimental Materia Medica, 2025, 31(9): 277-288.] DOI: 10.13422/J. CNKI. Syfjx.20241921.

13.张慧, 罗进辉, 杨柳, 等. 黄芪多糖调节TGF-β1/Smad/AP-1信号通路对慢性肾衰竭大鼠肾纤维化的影响[J]. 中国老年学杂志, 2024, 44(16): 4040-4044. [Zhang H, Luo JH, Yang L, et al. Effects of astragalus polysaccharides on renal fibrosis in chronic kidney disease rats by regulating TGF-Β1SMADAP-1 signaling pathway[J]. Chinese Journal of Gerontology, 2024, 44(16): 4040-4044.] DOI: CNKI:SUN:ZLXZ.0.2024-16-046.

14.Boccellino M, Di Domenico M, Donniacuo M, et al. AT1-receptor blockade: Protective effects of irbesartan in cardiomyocytes under hypoxic stress[J]. PLoS One, 2018, 13(10): e0202297. DOI: 10.1371/journal.pone.0202297.

15.Qi P, Zhai Q, Zhang X. RUNX1 facilitates heart failure progression through regulating TGF-β-induced cardiac remodeling[J]. PeerJ, 2023, 11: e16202. DOI: 10.7717/peerj.16202.

16.González A, Schelbert EB, Díez J, et al. Myocardial interstitial fibrosis in heart failure: biological and translational perspectives[J]. J Am Coll Cardiol, 2018, 71(15): 1696-1706. DOI: 10.1016/j.jacc.2018.02.021.

17.Jia Q, Wang L, Zhang X, et al. Prevention and treatment of chronic heart failure through traditional Chinese medicine: role of the gut microbiota[J]. Pharmacol Res, 2020, 151(4): 104-115. DOI: 10.1016/j.phrs.2019.104552.

18.Wintrich J, Kindermann I, Ukena C, et al. Therapeutic approaches in heart failure with preserved ejection fraction: past, present, and future[J]. Clin Res Cardiol, 2020, 109(9): 1079-1098. DOI: 10.1007/s00392-020-01633-w.

19.Zhang L, Li Y, Fan CD, et al. Chinese medicinal formula Fu Xin decoction against chronic heart failure by inhibiting the NLRP3/caspase-1/GSDMD pyroptotic pathway[J]. Biomed Pharmacother, 2024, 174: 116548. DOI: 10.1016/j.biopha.2024.116548.

20.VH, Titus AS, Cowling RT, et al. Collagen receptor cross-talk determines α-smooth muscle actin-dependent collagen gene expression in angiotensin II-stimulated cardiac fibroblasts[J]. J Biol Chem, 2019, 294(51): 19723-19739. DOI: 10.1074/jbc.RA119.009744.

21.Feng F, Li N, Cheng P, et al. Tanshinone IIA attenuates silica-induced pulmonary fibrosis via inhibition of TGF-β1-Smad signaling pathway[J]. Biomed Pharmacother, 2020, 121: 109586. DOI: 10.1016/j.biopha.2019.109586.

22.Chen K, Chen W, Liu SL, et al. Epigallocatechingallate attenuates myocardial injury in a mouse model of heart failure through TGFβ1/Smad3 signaling pathway[J]. Mol Med Rep, 2018, 17(6): 7652-7660. DOI: 10.3892/mmr.2018.8825.

23.Wang J, Xiang H, Lu Y, et al. Role and clinical significance of TGFβ1 and TGFβR1 in malignant tumors (review)[J]. Int J Mol Med, 2021, 47(4): 55. DOI: 10.3892/ijmm.2021.4888.

24.Zhang F, Dang Y, Li Y, et al. Cardiac contractility modulation attenuate myocardial fibrosis by Inhibiting TGF-β1/Smad3 signaling pathway in a rabbit model of chronic heart failure[J]. Cell Physiol Biochem, 2016, 39(1): 294-302. DOI: 10.1159/000445624.

25.Ren Y, Wu Y, He W, et al. SMOC2 plays a role in heart failure via regulating TGF-β1/Smad3 pathway-mediated autophagy[J]. Open Med (Wars), 2023, 18(1): 20230752. DOI: 10.1515/med-2023-0752.

26.Li N, Hang W, Shu H, et al. Pirfenidone alleviates cardiac fibrosis induced by pressure overload via inhibiting TGF-β1/Smad3 signalling pathway[J]. J Cell Mol Med, 2022, 26(16): 4548-4555. DOI: 10.1111/jcmm.17478.

27.Albadrani GM, BinMowyna MN, Bin-Jumah MN, et al. Quercetin prevents myocardial infarction adverse remodeling in rats by attenuating TGF-β1/Smad3 signaling: different mechanisms of action[J]. Saudi J Biol Sci, 2021, 28(5): 2772-2782. DOI: 10.1016/j.sjbs.2021.02.007.

28.施敏, 魏佳明, 袁惠, 等. 黄芪活性成分治疗心力衰竭作用机制的研究进展[J]. 中国实验方剂学杂志, 2024, 30(3): 208-217. [Shi M, Wei JM, Yuan H, et al. Mechanism of active ingredients of astragalus membranacus in treating heart failure: a review[J]. Chinese Journal of Experimental Materia Medica, 2024, 30(3): 208-217.] DOI: 10.13422/j.cnki.syfjx.20231102.

29.林姗姗. 慢性心力衰竭中医诊疗指南的制定研究[D]. 天津: 天津中医药大学, 2021: 115-122. DOI: 10.27368/d.cnki.gtzyy.2021.000338.

30.李江平. 黄芪联合丹参川芎嗪治疗慢性充血性心力衰竭疗效观察[J]. 中国医药科学, 2020, 10(18): 72-74, 78. [Li JP. Observation on the therapeutic efficacy of astragalus combined with salvia miltiorrhiza ligustrazine in patients with chronic congestive heart failure[J]. China Medicine and Pharmacy, 2020, 10(18): 72-74, 78.] DOI: 10.3969/j.issn.2095-0616.2020.18.017.

31.潘金萍, 杨小英, 伍燕宏, 等. 黄芪防治心血管疾病研究进展[J]. 河南中医, 2025, 45(10): 1612-1620. [Pan JP, Yang  XY, Wu  YH, et al. Research progress on the prevention and treatment of cardiovascular diseases with Huangqi[J]. Henan Chinese Medicine, 2025, 45(10): 1612-1620.] DOI: 10.16367/j.issn.1003-5028. 2025.10.0262.

32.李珍一, 杨关林, 闫承慧, 等. 黄芪多糖应用的相关研究进展 [J]. 辽宁中医杂志, 2016, 43(7): 1553-1555. [Li ZY, Yang  GL, Yan CH, et al. Research progress on application of astragalus polysaccharides[J]. Liaoning Journal of Traditional Chinese Medicine, 2016, 43(7): 1553-1555.] DOI: 10.13192/J. ISSN. 1000-1719.2016.07.068.

33.Cao Y, Shen T, Huang X, et al. Astragalus polysaccharide restores autophagic flux and improves cardiomyocyte function in doxorubicin-induced cardiotoxicity[J]. Oncotarget, 2017, 8(3): 4837-4848. DOI: 10.18632/oncotarget.13596.

34.朱晓雨. 黄芪多糖通过TGF-β1/Smads信号通路抑制异丙肾上腺素诱导大鼠心肌纤维化[D]. 辽宁锦州: 锦州医科大学, 2017. DOI: 10.14066/j.cnki.cn21-1349/r.2017.08.011.