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芳樟醇通过 Nrf2/HO-1 信号通路在体内外抑制骨关节炎的进展。

Linalool inhibits the progression of osteoarthritis via the Nrf2/HO-1 signal pathway both in vitro and in vivo.

机构信息

Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.

Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.

出版信息

Int Immunopharmacol. 2022 Dec;113(Pt A):109338. doi: 10.1016/j.intimp.2022.109338. Epub 2022 Oct 29.

DOI:10.1016/j.intimp.2022.109338
PMID:36330908
Abstract

Osteoarthritis (OA) is a chronic injury of joints, which is characterized by the destruction and degeneration of articular cartilage. Currently, there is a lack of effective treatments for OA. Linalool is a natural compound with anti-inflammatory effects in various diseases. However, the anti-inflammatory effect of linalool in the development of osteoarthritis remains unclear. This study aimed to investigate the anti-inflammatory effect of linalool on IL-1β-induced mouse chondrocytes, as well as its protective effect on joints in a mouse model of OA. Mouse chondrocytes were co-treated with 10 ng/mL IL-1β and different concentration gradients of linalool. These in vitro experiments demonstrated that linalool could inhibit the expression of Interleukin-1β (IL-1β)-induced inflammatory factors, such as nitric oxide synthase, cyclooxygenase-2 (COX-2), nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Furthermore, linalool reduced the catabolism of the extracellular matrix (ECM) by inhibiting the expression of matrix metalloproteinase-13 (MMP-13) and thrombospondin motif-5 (ADAMTS5) while upregulating the expression of type II collagen (COL II) and aggrecan. Regarding the mechanism of OA, it was observed that linalool inhibited the signal transduction of nuclear factor kappa B (NF-κB) by activating the nuclear factor-erythroid 2-related factor-2 (Nrf2) in chondrocytes. The inhibitory effect of linalool on the development of OA was demonstrated by the mouse DMM model experiment. The results suggested that linalool may be a potential drug for the treatment of OA.

摘要

骨关节炎(OA)是一种慢性关节损伤,其特征是关节软骨的破坏和退化。目前,OA 缺乏有效的治疗方法。芳樟醇是一种具有多种疾病抗炎作用的天然化合物。然而,芳樟醇在骨关节炎发展中的抗炎作用尚不清楚。本研究旨在探讨芳樟醇对 IL-1β诱导的小鼠软骨细胞的抗炎作用及其对 OA 小鼠模型关节的保护作用。用 10ng/mlIL-1β和不同浓度梯度的芳樟醇共同处理小鼠软骨细胞。这些体外实验表明,芳樟醇可以抑制白细胞介素-1β(IL-1β)诱导的炎症因子的表达,如一氧化氮合酶、环氧化酶-2(COX-2)、一氧化氮(NO)、前列腺素 E2(PGE2)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)。此外,芳樟醇通过抑制基质金属蛋白酶-13(MMP-13)和血小板反应蛋白基序 5(ADAMTS5)的表达,同时上调 II 型胶原(COL II)和聚集蛋白的表达,减少细胞外基质(ECM)的分解代谢。关于 OA 的发病机制,观察到芳樟醇通过激活核因子-红细胞 2 相关因子-2(Nrf2)抑制软骨细胞中核因子-κB(NF-κB)的信号转导。DMM 模型实验表明芳樟醇对 OA 的发展具有抑制作用。结果表明,芳樟醇可能是治疗 OA 的一种潜在药物。

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