Background: Osteoarthritis (OA) is a disorder of joints involving degeneration and destruction of cartilages. Inflammation has been found to play an important role in the development of OA. Hidrosmin (HDS) is a flavone useful in venous insufficiency disorders and cancer. However, its role in OA remains unexplored. Here we reported the anti-inflammatory effect of Hidrosmin in OA utilizing both in vivo and in vitro studies. Methods: The primary chondrocytes were used for in vitro studies. Chondrocytes were submitted to immunofluorescence and toluidine blue staining. C57BL/6 male mice were used for In vivo experiment for creating an osteoarthritis model by surgical destabilization of the medial meniscus. CCK-8 assay was done for cell viability studies, Levels of nitric oxide were studied by Griess reaction, western blot analysis and qRT-PCR analysis was done for analyzing the levels of PGE-2, TNF-α, IL-6, collagen II, COX-2, iNOS, MMP-13, ADAMTS, Nrf2, HO-1, p65 and IκBα. Immunohistochemical assay and histopathological analysis were done for tissue studies. In silico analysis was done by performing molecular docking studies with MGL tools. Results: The in vitro results suggested HDS inhibited the levels of cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), prostaglandin E2 (PGE2), nitric oxide (NO) and IL-1β mediated levels of iNOS. Hidrosmin also suppressed the levels of ADAMTS-5 and IL-1β-induced MMP-13, whereas the levels of aggrecan and collagen II were up-regulated. Mechanistic study suggested HDS suppressed the nuclear factor kappa B (NF-κB) via targeting the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in chondrocytes. The outcomes of molecular docking studies confirmed that Nrf2 had a potential binding affinity with Hidrosmin as seen by lower binding energies. Conclusion: The findings of the study suggested HDS could be a potential molecule for halting the progression and development of osteoarthritis. conclusion: The findings of the study suggested HDS could be a potential molecule for halting the progression and development of osteoarthritis.

中文翻译：

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Hidrosmin 通过抑制人骨关节炎软骨细胞中涉及 Nrf2/HO1 通路的 NF-κB 的激活来减弱 IL1β 诱导的炎症反应

背景：骨关节炎 (OA) 是一种涉及软骨退化和破坏的关节疾病。已发现炎症在 OA 的发展中起重要作用。Hidrosmin (HDS) 是一种黄酮，可用于治疗静脉功能不全和癌症。然而，它在 OA 中的作用仍未得到探索。在这里，我们利用体内和体外研究报告了 Hidrosmin 在 OA 中的抗炎作用。方法：原代软骨细胞用于体外研究。对软骨细胞进行免疫荧光和甲苯胺蓝染色。C57BL/6 雄性小鼠用于通过内侧半月板手术不稳定创建骨关节炎模型的体内实验。CCK-8 测定用于细胞活力研究，通过 Griess 反应研究一氧化氮水平，进行蛋白质印迹分析和 qRT-PCR 分析以分析 PGE-2、TNF-α、IL-6、胶原蛋白 II、COX-2、iNOS、MMP-13、ADAMTS、Nrf2、HO-1、p65 和IκBα。对组织研究进行了免疫组织化学分析和组织病理学分析。计算机分析是通过使用 MGL 工具进行分子对接研究来完成的。结果：体外结果表明，HDS 抑制环氧合酶 2 (COX-2)、肿瘤坏死因子 α (TNF-α)、白细胞介素 6 (IL-6)、前列腺素 E2 (PGE2)、一氧化氮 (NO ) 和 IL-1β 介导的 iNOS 水平。Hidrosmin 还抑制 ADAMTS-5 和 IL-1β 诱导的 MMP-13 的水平，而聚集蛋白聚糖和胶原蛋白 II 的水平上调。机制研究表明，HDS 通过靶向软骨细胞中的核因子（红细胞衍生 2）样 2 (Nrf2) 来抑制核因子 kappa B (NF-κB)。分子对接研究的结果证实，Nrf2 与 Hidrosmin 具有潜在的结合亲和力，如较低的结合能所示。结论：研究结果表明，HDS 可能是阻止骨关节炎进展和发展的潜在分子。结论：研究结果表明，HDS 可能是阻止骨关节炎进展和发展的潜在分子。该研究的结果表明，HDS 可能是阻止骨关节炎进展和发展的潜在分子。结论：研究结果表明，HDS 可能是阻止骨关节炎进展和发展的潜在分子。该研究的结果表明，HDS 可能是阻止骨关节炎进展和发展的潜在分子。结论：研究结果表明，HDS 可能是阻止骨关节炎进展和发展的潜在分子。