Osteoarthritis (OA), a progressive joint disorder, is principally characterized by the degeneration and destruction of articular cartilage. Previous research studies demonstrated that inflammation and ECM degradation play a major role in OA development. Hesperetin, the aglycone of neohesperidin found in the peel of Citrus aurantium L. (Rutaceae), demonstrated in several studies potential anti-inflammatory activity in a variety of diseases. However, the mechanisms by which hesperetin plays a protective role in osteoarthritis (OA) are not completely understood. In this study, we found the anti-inflammatory effects of hesperetin in the progression of OA in both in vitro and in vivo experiments. In vitro, IL-1β-induced expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nitric oxide (NO), tumor necrosis factor alpha (TNF-α), prostaglandin E2 (PGE2), and interleukin-6 (IL-6) were inhibited by hesperetin. Moreover, hesperetin down-regulated the IL-1β-stimulated matrix metalloproteinase-13 (MMP-13) and thrombospondin motifs 5 (ADAMTS-5) while up-regulating collagen type II and aggrecan. Mechanistically, we revealed that hesperetin suppressed nuclear factor kappa B (NF-κB) signaling by activating the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in IL-1β-induced chondrocytes. Hesperetin-induced repression of OA development is shown using a DMM model. Taken together, our findings suggest that hesperetin may be a novel potential therapeutic agent for repressing the development of OA.

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橙皮素对骨关节炎的保护作用：体内和体外研究

骨关节炎（OA）是一种进行性关节疾病，其主要特征是关节软骨的变性和破坏。先前的研究表明，炎症和ECM降解在OA的发展中起主要作用。橙皮素，在的剥离发现新橙皮苷糖苷配基枳壳L.（芸香科），证实在几项研究中潜在的抗炎活性在多种疾病。然而，橙皮素在骨关节炎（OA）中起保护作用的机制尚不完全清楚。在这项研究中，我们在体外和体内实验中均发现了橙皮素对OA进展的抗炎作用。体外，IL-1β诱导的诱导型一氧化氮合酶（iNOS），环氧化酶2（COX-2），一氧化氮（NO），肿瘤坏死因子α（TNF-α），前列腺素E2（PGE2）和白介素- 6种（IL-6）被橙皮素抑制。此外，橙皮素下调IL-1β刺激的基质金属蛋白酶13（MMP-13）和血小板反应蛋白基序5（ADAMTS-5），同时上调II型胶原蛋白和聚集蛋白聚糖。从机理上讲，我们发现橙皮素通过激活IL-1β诱导的软骨细胞中的核因子（类胡萝卜素衍生的2）样2（Nrf2）来抑制核因子κB（NF-κB）信号传导。用DMM模型显示橙皮素诱导的OA发育抑制。综上所述，我们的发现表明橙皮素可能是抑制OA发生的新型潜在治疗剂。