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Icariin has shown the potential to treat osteoarthritis (OA), but the specific mechanism still needs further exploration. Therefore, this study attempted to reveal the effect and mechanism of icariin on OA based on in vitro and in vivo experiments. In vivo, a mouse model of OA was established by cutting the anterior cruciate ligament, and 10 mg/kg icariin was given to mice orally. Then, the OA injury and pathological changes of cartilage tissue in mice were identified by OA index and hematoxylin and eosin staining. In vitro, the viability of C28/I2 cells incubated with different concentrations of icariin was detected by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide assay. Subsequently, C28/I2 cells induced by IL-1β were used as the cell model of OA, the expression of Sirtuin (SIRT)-1 in cells was knocked down, and icariin was added for intervention. Next, western blot was used to observe the expression level of sirtuin 1 (SIRT-1)-Nrf2-heme oxygenase 1 (HO-1) signaling pathway-related proteins in cells of each group. Besides, cell viability and apoptosis were detected by MTT and apoptosis assay, and DNA damage was observed by comet assay. In vivo experiments, intragastric administration of icariin could effectively reduce the OA index of mice, improve the pathological changes of cartilage tissue, and obviously activated the SIRT-1-Nrf2-HO-1 signaling pathway. In vitro experiments, icariin did not exhibit toxic effect on C28/I2 cells, but could activate the SIRT-1-Nrf2-HO-1 signaling pathway, improve the viability, reduce the level of apoptosis and relieve the DNA damage in OA cells; however, these effects were inhibited by si- SIRT-1. Icariin can improve the symptoms of OA by activating the SIRT-1-Nrf2-HO-1 signaling pathway.

Titel:	Icariin alleviates the apoptosis of chondrocytes in osteoarthritis through regulating SIRT-1-Nrf2-HO-1 signaling.
Autor/in / Beteiligte Person:	Liu, YS ; Zhong, HB ; Liu, WL ; He, XH ; Zhan, XR ; Sun, CH
Link:	Zum Volltext
Zeitschrift:	Chemical biology & drug design, Jg. 103 (2024-04-01), Heft 4, S. e14518
Veröffentlichung:	Oxford : Wiley-Blackwell, 2006-, 2024
Medientyp:	academicJournal
ISSN:	1747-0285 (electronic)
DOI:	10.1111/cbdd.14518
Schlagwort:	Mice Animals NF-E2-Related Factor 2 metabolism Sirtuin 1 metabolism Heme Oxygenase-1 metabolism Signal Transduction Apoptosis Chondrocytes metabolism Osteoarthritis drug therapy Osteoarthritis metabolism Flavonoids
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Chem Biol Drug Des] 2024 Apr; Vol. 103 (4), pp. e14518. MeSH Terms: Chondrocytes* / metabolism ; Osteoarthritis* / drug therapy ; Osteoarthritis* / metabolism ; Flavonoids* ; Mice ; Animals ; NF-E2-Related Factor 2 / metabolism ; Sirtuin 1 / metabolism ; Heme Oxygenase-1 / metabolism ; Signal Transduction ; Apoptosis References: Abramoff, B., & Caldera, F. E. (2020). Osteoarthritis: Pathology, diagnosis, and treatment options. The Medical Clinics of North America, 104(2), 293–311. https://doi.org/10.1016/j.mcna.2019.10.007. ; Alam, F., Syed, H., Amjad, S., Baig, M., Khan, T. A., & Rehman, R. (2021). Interplay between oxidative stress, SIRT1, reproductive and metabolic functions. Current Research in Physiology, 4, 119–124. https://doi.org/10.1016/j.crphys.2021.03.002. ; Chen, W. F., Wu, L., Du, Z. R., Chen, L., Xu, A. L., Chen, X. H., Teng, J.‐J., & Wong, M. S. (2017). 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Grant Information: A2023244 Guangdong Provincial Medical Science and Technology Research Fund Contributed Indexing: Keywords: SIRT‐1‐Nrf2‐HO‐1 signaling pathway; chondrocyte; icariin; osteoarthritis Substance Nomenclature: 0 (NF-E2-Related Factor 2) ; VNM47R2QSQ (icariin) ; EC 3.5.1.- (Sirtuin 1) ; EC 1.14.14.18 (Heme Oxygenase-1) ; 0 (Flavonoids) Entry Date(s): Date Created: 20240403 Date Completed: 20240405 Latest Revision: 20240405 Update Code: 20240405

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Icariin alleviates the apoptosis of chondrocytes in osteoarthritis through regulating SIRT-1-Nrf2-HO-1 signaling.