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Icariin (ICA) is a bioactive flavonoid extracted from Epimedium brevicornum Maxim and exhibits a variety of pharmacological activities including antiinflammatory and antioxidant effects. Recently, icariin has shown renoprotective role by inhibiting pathological matrix. However, the underlying mechanisms of the efficacy remain unknown. This study aimed to determine the effects of icariin on renal fibrosis and explore its molecular mechanisms. Chronic kidney disease (CKD) was induced in rats with 5/6 ablation and infarction (A/I) operation. Four weeks later, rats were treated with vehicle or 20 mg/kg (low dose) or 40 mg/kg (high dose) of icariin by daily gavage. Furthermore, to further elucidate the effect mechanisms of icariin, in vitro, NRK-49F cells stimulated by 8 ng/ml IL-1β were treated with icariin in the presence or absence of SB431542 or the neutralizing antibody of transforming growth factor-β (TGF-β) for 24 h. We showed that icariin treatment for 8 weeks dose-dependently improved 5/6 (A/I)-induced kidney injury and fibrosis, and blocked the release of inflammatory cytokine IL-1β. In vitro, icariin inhibited IL-1β/TGF-β-mediated activation of renal fibroblasts. In summary, anti-fibrotic effects of icariin were interconnected with the inhibition of renal fibroblast activation caused by IL-1β/TGF-β signaling.

Titel:	Icariin attenuates renal fibrosis in chronic kidney disease by inhibiting interleukin-1β/transforming growth factor-β-mediated activation of renal fibroblasts.
Autor/in / Beteiligte Person:	Wang, M ; Wang, L ; Zhou, Y ; Feng, X ; Ye, C ; Wang, C
Link:	Zum Volltext
Zeitschrift:	Phytotherapy research : PTR, Jg. 35 (2021-11-01), Heft 11, S. 6204-6215
Veröffentlichung:	<June 1990-> : Chichester : Wiley ; <i>Original Publication</i>: London : Heyden & Son, c1987-, 2021
Medientyp:	academicJournal
ISSN:	1099-1573 (electronic)
DOI:	10.1002/ptr.7256
Schlagwort:	Animals Fibroblasts Fibrosis Flavonoids pharmacology Interleukin-1beta Rats Transforming Growth Factors Kidney pathology Renal Insufficiency, Chronic drug therapy
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Phytother Res] 2021 Nov; Vol. 35 (11), pp. 6204-6215. <i>Date of Electronic Publication: </i>2021 Aug 23. MeSH Terms: Kidney* / pathology ; Renal Insufficiency, Chronic* / drug therapy ; Animals ; Fibroblasts ; Fibrosis ; Flavonoids / pharmacology ; Interleukin-1beta ; Rats ; Transforming Growth Factors References: Anders, H. J. (2016). Of Inflammasomes and Alarmins: IL-1β and IL-1α in kidney disease. Journal of the American Society of Nephrology, 27(9), 2564-2575. ; Bohle, A., Mackensen-Haen, S., von Gise, H., Grund, K. E., Wehrmann, M., Batz, C., … Müller, C. (1990). The consequences of tubulo-interstitial changes for renal function in glomerulopathies. A morphometric and cytological analysis. Pathology, Research and Practice, 186(1), 135-144. ; Chen, D. Q., Feng, Y. L., Cao, G., & Zhao, Y. Y. (2018). Natural products as a source for antifibrosis therapy. 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Biomedicine & Pharmacotherapy, 109, 2309-2317. ; Zhou, Z., Ni, J., Li, J., Huo, C., Miao, N., Yin, F., … Lu, L. (2020). RIG-I aggravates interstitial fibrosis via c-Myc-mediated fibroblast activation in UUO mice. Journal of Molecular Medicine (Berlin, Germany), 98(4), 527-540. ; Zu, Y., Mu, Y., Li, Q., Zhang, S. T., & Yan, H. J. (2019). Icariin alleviates osteoarthritis by inhibiting NLRP3-mediated pyroptosis. Journal of Orthopaedic Surgery and Research, 14(1), 307. Contributed Indexing: Keywords: 5/6 (A/I) rats; TGF-β; icariin; inflammation; renal fibrosis Substance Nomenclature: 0 (Flavonoids) ; 0 (Interleukin-1beta) ; 76057-06-2 (Transforming Growth Factors) ; VNM47R2QSQ (icariin) Entry Date(s): Date Created: 20210824 Date Completed: 20211125 Latest Revision: 20211125 Update Code: 20240513

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Icariin attenuates renal fibrosis in chronic kidney disease by inhibiting interleukin-1β/transforming growth factor-β-mediated activation of renal fibroblasts.