Search JIM Advanced Search

Journal of Integrative Medicine ›› 2025, Vol. 23 ›› Issue (6): 694-705.

• Original Experimental Research • Previous Articles     Next Articles

Astragaloside IV delayed the epithelial–mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways

Ying Huang a b ,  Chen-ling Chu c b ,  Wen-hui Qiu d b ,  Jia-yi Chen c b ,  Lu-xi Cao b ,  Shui-yu Ji b , Bin Zhu b, Guo-kun Wang e * ,  Quan-quan Shen b f *   

  1. a School of Public Health, Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
    b Urology & Nephrology Center, Department of Nephrology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
    c Department of Clinical Medicine and Stomatology, Hangzhou Normal University, Hangzhou 310014, Zhejiang Province, China
    d Basic Medical Sciences, Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
    e Department of Cardiovascular Surgery, Changhai Hospital, Naval Medical University, Shanghai 200433, China
    f Department of Nephrology, Zhejiang Provincial People’s Hospital Bijie Hospital, Bijie 551700, Guizhou Province, China
  • Received:2024-09-13 Accepted:2025-05-12 Online:2025-11-15 Published:2025-09-04

Objective

Peritoneal fibrosis (PF) is an adverse event that occurs during long-term peritoneal dialysis, significantly impairing treatment efficiency and adversely affecting patient outcomes. Astragaloside IV (AS-IV), a principal active component derived from Astragalus membranaceus (Fisch.) Bunge, has exhibited anti-inflammatory and antifibrotic effects in various settings. This study aims to investigate the potential therapeutic efficacy and mechanism of AS-IV in the treatment of PF.


Methods

The PF mouse model was established by intraperitoneal injection of 4.25% peritoneal dialysis fluid (100 mL/kg). The epithelial-mesenchymal transition (EMT) of HMrSV5 cells was induced by the addition of 10 ng/mL transforming growth factor β (TGF-β). The differentially expressed genes in HMrSV5 cells treated with AS-IV were screened using transcriptome sequencing analysis. The potential targets of AS-IV were screened using network pharmacology and analyzed using molecular docking and molecular dynamics simulations.


Results

Administration of AS-IV at doses of 20, 40, or 80 mg/kg effectively mitigated the increase in peritoneal thickness and the development of fibrosis in mice with PF. The expression of the fibrosis marker α-smooth muscle actin in the peritoneum was significantly decreased in AS-IV-treated mice. The treatment of AS-IV (10, 20, and 40 μmol/L) significantly delayed the EMT of HMrSV5 cells induced by TGF-β, as demonstrated by the decreased number of 5-ethynyl-2'-deoxyuridine-positive cells, reduced migrated area, and decreased expression of fibrosis markers. A total of 460 differentially expressed genes were detected in AS-IV-treated HMrSV5 cells through transcriptome sequencing, with notable enrichment in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT serine/threonine kinase 1 (AKT) signaling pathway. The reduced levels of phosphorylated PI3K (p-PI3K) and p-AKT were detected in HMrSV5 cells with AS-IV treatment. Epidermal growth factor receptor (EGFR) was predicted as a direct target of AS-IV, exhibiting strong hydrogen bond interactions. The activation of the PI3K-AKT pathway by the compound 740Y-P, and the activation of the EGFR pathway by NSC 228155 each partially counteracted the inhibitory effect of AS-IV on the EMT of HMrSV5 cells.


Conclusion

AS-IV delayed the EMT process in peritoneal mesothelial cells and slowed the progression of PF, potentially serving as a therapeutic agent for the early prevention and treatment of PF. Please cite this article as: Huang Y, Chu CL, Qiu WH, Chen JY, Cao LX, Ji SY, Zhu B, Wang GK, Shen QQ. Astragaloside IV delayed the epithelial-mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways. J Integr Med. 2025; 23(6):694-705.


Key words: Astragaloside IV, EGFR, Epithelial–mesenchymal transition, PI3K-AKT pathway, Peritonealfibrosis

No related articles found!
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] Bang-jiang Fang, Shuang Zhou, Xin-jun Pei, Jin-yang Huang, Bao-jin Chen, Yun Geng , Li-kun Yang. Effects of Yanggan Lidan Granule on insulin resistance in guinea pigs with induced cholesterol gallstones. Journal of Chinese Integrative Medicine, 2009, 7(12): 1159-1163
[2] Chuan-yue Niu. On some issues concerning the translation and standardization of traditional Chinese medicine terminology. Journal of Chinese Integrative Medicine, 2006, 4(6): 657-660
[3] Shao Li. Framework and practice of network-based studies for Chinese herbal formula. Journal of Chinese Integrative Medicine, 2007, 5(5): 489-493
[4] Xiao-feng Zhai, Zhe Chen, Bai Li, Feng Shen, Jia Fan, Wei-ping Zhou, Yun-ke Yang, Jing Xu, Xiao Qin, Le-qun Li, Chang-quan Ling. Traditional herbal medicine in preventing recurrence after resection of small hepatocellular carcinoma: A multicenter randomized controlled trial. Journal of Chinese Integrative Medicine, 2013, 11(2): 90-100
[5] Arthur Yin Fan, Hui Ouyang, Xinru Qian, Hui Wei, David Dehui Wang, Deguang He, Haihe Tian, Changzhen Gong, Amy Matecki, Sarah Faggert Alemi. Discussions on real-world acupuncture treatments for chronic low-back pain in older adults. Journal of Integrative Medicine, 2019, 17(2): 71-76
[6] Jia Xu, Fu-qing Zhang, Jian Pei, Jun Ji . Acupuncture for migraine without aura: A systematic review and meta-analysis. Journal of Integrative Medicine, 2018, 16(5): 312-321
[7] Mostafa Araj-Khodaei, Javad Ghazi Sha'rbaf, Somaiyeh Taheri-Targhi, Reza Mohammadinasab. Letter to the editor regarding "Galen's place in Avicenna's The Canon of Medicine: Respect, confirmation and criticism". Journal of Integrative Medicine, 2020, 18(3): 274
[8] Baoyi Shao, Saiying Hou, Yuenyan Chan, Changchun Shao, Lixing Lao. Remission of new-onset type 2 diabetes mellitus in an adolescent using an integrative medicine approach: A case report. Journal of Integrative Medicine, 2021, 19(1): 85-88
[9] Fulvio A. Scorza, Antonio-Carlos G. de Almeida, Carla A. Scorza, Ana C. Fiorini, Josef Finsterer. Parkinson's disease, heart disease and propolis consumption. Journal of Integrative Medicine, 2021, 19(5): 467-468
[10] Chia-Wei Lin, Wei-Chen Hsu, Chien-Lu Lu, Su-Hsing Cheng, Cheng-Pin Chen, Yu-Chang Hou. Integrated therapeutic plasma exchange and traditional Chinese medicine treatment in a patient with severe COVID-19: A case report. Journal of Integrative Medicine, 2022, 20(6): 575-580