Department of Physiology, Pamukkale University, Faculty of Medicine, Denizli, Turkey.
Department of Analytical Chemistry, Ataturk University, Faculty of Pharmacy, Erzurum, Turkey.
Clin Rheumatol. 2020 Aug;39(8):2399-2408. doi: 10.1007/s10067-020-04958-z. Epub 2020 Feb 26.
Osteoarthritis (OA) is a degenerative chronic illness that most frequently occurs in the knee joint. Daidzein (DZ) an isoflavone has anti-inflammatory and antioxidant activity. The aim of this study was to evaluate the effectiveness of DZ as a treatment for experimental knee OA (KOA) in rats.
An experimental KOA model was induced by monosodium iodoacetate (MIA) in rats. Thereafter, 49 Wistar albino male rats (250-300 g, 12-16 weeks old) were randomly divided into 7 groups: C (healthy control); DC (KOA + saline); hyaluronic acid (HA); HA+ intraarticular (ia) DZ; oral (po) DZ; ia DZ; HA + po DZ groups. DZ and/or HA were administered intraarticularly to the rats as 50 μL on days 1, 7, 14, and 21. Alternatively, the DZ was administered orally as 0.5 mL twice daily for 21 days. After the treatment, rats were sacrificed by decapitation under general anesthesia. Serum samples were analyzed to determine the total oxidant status (TOS) and total antioxidant status (TAS) and the levels of TNF-α, IL-1β, MMP-13, and DZ. Knee joint samples underwent histopathological examination, and TNF-α, IL-1β, NOS2, and MMP-13 were analyzed with immunohistochemical methods.
HA, DZ, and DZ + HA effectively reduced the levels of TNF-α, IL-1β, and MMP-13 in the serum of the DC group (p < 0.001). In groups that received HA, DZ, or DZ + HA, the serum TAS increased compared with the DC group (p < 0.05). When the DZ + HA combination was used, a more pronounced reduction in the levels of TNFα, NOS2, IL-1β, and MMP-13 was observed in knee joints. In addition, the cracks on the cartilage surface and fibrillation were completely improved in the groups that received HA, DZ, or DZ + HA compared with the DC group.
DZ had anti-inflammatory and antioxidant effects in a rat OA model. Therefore, DZ, as monotherapy or especially in combination with HA, may be a promising and beneficial therapy for OA. Key Points •DZ has been shown to reduce TNF-α, IL-1β, and MMP-13 both in serum and in tissue samples taken from the knee-joints. •The cracks on the cartilage surface and fibrillation in KOA were completely improved by using DZ and DZ + HA combination. •DZ may be useful to eliminate/reduce/ameliorate inflammation and oxidative damage in the pathogenesis of KOA. •DZ, alone or in combination with HA, may be a promising natural compound with beneficial effects in the treatment of KOA.
骨关节炎（OA）是一种常见于膝关节的退行性慢性疾病。大豆苷元（DZ）是一种异黄酮，具有抗炎和抗氧化作用。本研究旨在评估 DZ 治疗实验性膝骨关节炎（KOA）大鼠的疗效。
通过向大鼠注射单碘乙酸（MIA）诱导实验性 KOA 模型。此后，将 49 只 Wistar 白化雄性大鼠（250-300g，12-16 周龄）随机分为 7 组：C（健康对照组）；DC（KOA+盐水）；透明质酸（HA）；HA+关节内（ia）DZ；口服（po）DZ；ia DZ；HA+po DZ 组。在第 1、7、14 和 21 天，DZ 和/或 HA 以 50μL 的量关节内给药。或者，DZ 以 0.5mL 的剂量每天口服 2 次，共 21 天。治疗后，大鼠在全麻下断头处死。分析血清样本以测定总氧化剂状态（TOS）和总抗氧化状态（TAS）以及 TNF-α、IL-1β、MMP-13 和 DZ 的水平。对膝关节样本进行组织病理学检查，并采用免疫组化方法分析 TNF-α、IL-1β、NOS2 和 MMP-13。
HA、DZ 和 DZ+HA 有效降低了 DC 组血清中 TNF-α、IL-1β 和 MMP-13 的水平（p<0.001）。与 DC 组相比，接受 HA、DZ 或 DZ+HA 的组的血清 TAS 增加（p<0.05）。当使用 DZ+HA 联合治疗时，在接受 HA、DZ 或 DZ+HA 的组中，关节中 TNFα、NOS2、IL-1β 和 MMP-13 的水平降低更为明显。此外，与 DC 组相比，接受 HA、DZ 或 DZ+HA 的组的软骨表面裂缝和纤维化得到完全改善。
DZ 在大鼠 OA 模型中具有抗炎和抗氧化作用。因此，DZ 作为单一疗法或特别是与 HA 联合使用，可能是一种有前途和有益的 OA 治疗方法。 关键点 • DZ 可降低血清和膝关节组织样本中 TNF-α、IL-1β 和 MMP-13 的水平。 • KOA 时软骨表面的裂缝和纤维化通过使用 DZ 和 DZ+HA 联合治疗得到完全改善。 • DZ 可能有助于消除/减少/改善 KOA 发病机制中的炎症和氧化损伤。 • DZ 单独或与 HA 联合使用可能是一种有前途的天然化合物，对 KOA 的治疗具有有益作用。
