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麦芽酚通过核因子-红细胞 2 相关因子 2/血红素氧合酶-1 信号通路抑制骨关节炎的进展,。

Maltol inhibits the progression of osteoarthritis the nuclear factor-erythroid 2-related factor-2/heme oxygenase-1 signal pathway and .

机构信息

Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

出版信息

Food Funct. 2021 Feb 15;12(3):1327-1337. doi: 10.1039/d0fo02325f.

DOI:10.1039/d0fo02325f
PMID:33443518
Abstract

Osteoarthritis (OA) is a common degenerative joint disease characterized by articular cartilage degeneration and inflammation. Currently, there is hardly any effective treatment for OA due to its complicated pathology and the severe side effects of the treatment drugs used. It has been reported that maltol, a Maillard reaction product derived from ginseng, inhibits inflammation and oxidative stress in several animal models. However, the potential anti-inflammatory effects of maltol in OA treatment are unknown. This study aimed to evaluate the anti-inflammatory effects of maltol on interleukin (IL)-1β-induced mouse chondrocytes and protective effects of maltol on these chondrocytes in medial meniscus destabilization (DMM) OA mouse models. Mice, randomly divided into maltol (n = 15), vehicle (n = 15) and control (n = 15) groups were treated with the same dose of maltol or saline, respectively. The cartilage tissues were extracted for histological analysis 8 weeks postoperative. For the in vitro studies, chondrocytes were treated with 10 ng mL-1 IL-1β combined with maltol at different concentrations. In vitro assays showed that the maltol pre-treatment significantly inhibited the expressions of multiple inflammatory factors induced by IL-1β, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α). In addition, maltol alleviated the degradation of the extracellular matrix (ECM) by inhibiting the expressions of matrix metalloproteinase-13 (MMP13) and thrombospondin motif 5 (ADAMTS5), as well as reversing the degradation of aggrecan and collagen II. Moreover, maltol suppressed nuclear factor kappa B (NF-κB) signaling by activating the nuclear factor-erythroid 2-related factor-2 (Nrf2) in in vitro and in vivo studies. These findings indicate that maltol reduces the inflammation induced by IL-1β in chondrocytes. Therefore, the results of this study indicated that maltol may be a potential drug for the effective treatment of OA.

摘要

骨关节炎(OA)是一种常见的退行性关节疾病,其特征为关节软骨退化和炎症。目前,由于其复杂的病理学和治疗药物的严重副作用,几乎没有有效的 OA 治疗方法。据报道,来自人参的美拉德反应产物麦芽酚可抑制几种动物模型中的炎症和氧化应激。然而,麦芽酚在 OA 治疗中的抗炎作用尚不清楚。本研究旨在评估麦芽酚对白细胞介素(IL)-1β诱导的小鼠软骨细胞的抗炎作用,以及麦芽酚对内侧半月板不稳定(DMM)OA 小鼠模型中这些软骨细胞的保护作用。将小鼠随机分为麦芽酚(n=15)、载体(n=15)和对照组(n=15),分别给予相同剂量的麦芽酚或生理盐水。术后 8 周提取软骨组织进行组织学分析。在体外研究中,用 10ng mL-1 IL-1β联合不同浓度的麦芽酚处理软骨细胞。体外实验表明,麦芽酚预处理可显著抑制 IL-1β诱导的多种炎症因子的表达,如诱导型一氧化氮合酶(iNOS)、环氧化酶-2(COX-2)、前列腺素 E2(PGE2)、一氧化氮(NO)、白细胞介素-6(IL-6)和肿瘤坏死因子(TNF-α)。此外,麦芽酚通过抑制基质金属蛋白酶-13(MMP13)和血小板反应蛋白基序 5(ADAMTS5)的表达,以及逆转聚集蛋白聚糖和胶原 II 的降解,缓解细胞外基质(ECM)的降解。此外,麦芽酚通过在体外和体内研究中激活核因子-红细胞 2 相关因子-2(Nrf2)来抑制核因子-κB(NF-κB)信号通路。这些发现表明,麦芽酚可减少软骨细胞中 IL-1β诱导的炎症。因此,本研究结果表明,麦芽酚可能是治疗 OA 的一种潜在药物。

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