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Original Article
- Basic Research
- Alantolactone Attenuates Renal Fibrosis via Inhibition of Transforming Growth Factor β/Smad3 Signaling Pathway
- Kyeong-Min Lee, Yeo Jin Hwang, Gwon-Soo Jung
- Diabetes Metab J. 2024;48(1):72-82. Published online January 3, 2024
- DOI: https://doi.org/10.4093/dmj.2022.0231
- 8,510 View
- 280 Download
- 12 Web of Science
- 12 Crossref
-
Abstract
PDF
Supplementary Material
PubReader 
ePub - Background
Renal fibrosis is characterized by the accumulation of extracellular matrix proteins and interstitial fibrosis. Alantolactone is known to exert anticancer, anti-inflammatory, antimicrobial and antifungal effects; however, its effects on renal fibrosis remains unknown. Here, we investigated whether alantolactone attenuates renal fibrosis in mice unilateral ureteral obstruction (UUO) and evaluated the effect of alantolactone on transforming growth factor (TGF) signaling pathway in renal cells.
Methods
To evaluate the therapeutic effect of alantolactone, cell counting kit-8 (CCK-8) assay, histological staining, Western blot analysis, and real-time quantitative polymerase chain reaction were performed in UUO kidneys in vivo and in TGF-β-treated renal cells in vitro.
Results
Alantolactone (0.25 to 4 µM) did not affect the viability of renal cells. Mice orally administered 5 mg/kg of alantolactone daily for 15 days did not show mortality or liver toxicity. Alantolactone decreased UUO-induced blood urea nitrogen and serum creatinine levels. In addition, it significantly alleviated renal tubulointerstitial damage and fibrosis and decreased collagen type I, fibronectin, and α-smooth muscle actin (α-SMA) expression in UUO kidneys. In NRK-49F cells, alantolactone inhibited TGF-βstimulated expression of fibronectin, collagen type I, plasminogen activator inhibitor-1 (PAI-1), and α-SMA. In HK-2 cells, alantolactone inhibited TGF-β-stimulated expression of collagen type I and PAI-1. Alantolactone inhibited UUO-induced phosphorylation of Smad3 in UUO kidneys. In addition, it not only decreased TGF-β secretion but also Smad3 phosphorylation and translocation to nucleus in both kidney cell lines.
Conclusion
Alantolactone improves renal fibrosis by inhibiting the TGF-β/Smad3 signaling pathway in obstructive nephropathy. Thus, alantolactone is a potential therapeutic agent for chronic kidney disease. -
Citations
Citations to this article as recorded by
- Metixene hydrochloride hydrate mitigates kidney tubulointerstitial fibrosis by inhibiting Smad3 phosphorylation
Kyeong-Min Lee, Yeo Jin Hwang
Experimental and Molecular Pathology.2026; 145: 105025. CrossRef - Macrophage erythropoietin receptor signaling drives macrophage-myofibroblast transition via JAK2/STAT3 and TGF-β1/Smad3 pathways to exacerbate pulmonary fibrosis in mice
Pengfei Wu, Jialin Jia, Tianrong Jin, Xiaofeng Sun, Bangwei Luo, Guansong Wang, Zhiren Zhang
Biochemical and Biophysical Research Communications.2026; 808: 153453. CrossRef - Artemisinin and Its Derivatives: Promising Therapeutic Agents for Age-Related Macular Degeneration
Chun Liu, Xiaoqin Liu, Junguo Duan
Pharmaceuticals.2025; 18(4): 535. CrossRef - Alantolactone protects against doxorubicin-induced nephrotoxicity by modulating Nrf2/HO-1, NF-κB, and Bax/Bcl-2 activity: molecular and in silico insights
Mohammed F. Abuzinadah, Rasheed A. Shaik, Aftab Ahmad, Mohammed Nazrul Islam, Basma G. Eid
Molecular Biology Reports.2025;[Epub] CrossRef - Alantolactone mitigates thioacetamide-induced liver fibrosis in mice by inhibiting TLR4/MyD88/NF-κB axis
Haifa Almukadi, Nabih N. Alotaibi, Rasheed A. Shaik, Ashraf B. Abdel-Naim, Ahmed Esmat, Basma G. Eid
Asian Pacific Journal of Tropical Biomedicine.2025; 15(8): 333. CrossRef - Combined effects of nanoplastics and 3-BHA at environmentally relevant concentrations significantly aggravated kidney injury via TGF-β/SMAD signaling pathway in mice
Guanghua Xiong, Huangqi Shi, Yaxuan Jiang, Min Lu, Jinghong Liu, Shangrong Zhang, Xiaoqing Wu, Hongcheng Wang, Hongbo Liu, Yihong Yang, Yong Liu
Ecotoxicology and Environmental Safety.2025; 303: 119014. CrossRef - Artesunate alleviates kidney fibrosis by restoring klotho protein and suppressing Wnt/β-catenin signalling pathway
Goran H. Mohammad, Julius Kieswich, Abhishek Kumar, Kieran McCafferty, Ramyangshu Chakraborty, Christoph Thiemermann, Magdi M. Yaqoob
Frontiers in Cell and Developmental Biology.2025;[Epub] CrossRef - Natural products targeting TGF-β/Smad signaling in renal fibrosis: Multiomics-based novel molecular mechanisms and therapeutic strategies
Chen-Hui Jiang, Shui-Juan Zhang, Ping Li, Hua Miao, Ying-Yong Zhao
Phytomedicine.2025; 148: 157496. CrossRef - Alantolactone as a Bioactive Sesquiterpene Lactone: Molecular Mechanisms and Anticancer Potential for Pharmaceutical Development
Alice Njolke Mafe, Lipana Dorcas Bappa, Javad Sharifi‐Rad, William N. Setzer, Daniela Calina
Archiv der Pharmazie.2025;[Epub] CrossRef - TGF-β-Based Therapies for Treating Ocular Surface Disorders
Fernando T. Ogata, Sudhir Verma, Vivien J. Coulson-Thomas, Tarsis F. Gesteira
Cells.2024; 13(13): 1105. CrossRef - Alantolactone alleviates epithelial-mesenchymal transition by regulating the TGF-β/STAT3 signaling pathway in renal fibrosis
Yeo Jin Hwang, Gwon-Soo Jung, Kyeong-Min Lee
Heliyon.2024; 10(16): e36253. CrossRef - Sodium Phenylbutyrate Attenuates Cisplatin-Induced Acute Kidney Injury Through Inhibition of Pyruvate Dehydrogenase Kinase 4
Chang Joo Oh, Wooyoung Choi, Ha Young Lee, In-Kyu Lee, Min-Ji Kim, Jae-Han Jeon
Biomedicines.2024; 12(12): 2815. CrossRef
- Metixene hydrochloride hydrate mitigates kidney tubulointerstitial fibrosis by inhibiting Smad3 phosphorylation
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