1st School of Medicine, Guangzhou University of Chinese Medicine, 12 Jichang Road, Baiyun Area, Guangzhou 510405, PR China; The Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, PR China.
1st School of Medicine, Guangzhou University of Chinese Medicine, 12 Jichang Road, Baiyun Area, Guangzhou 510405, PR China; The Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, PR China; Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Biomed Pharmacother. 2023 Dec;168:115751. doi: 10.1016/j.biopha.2023.115751. Epub 2023 Oct 24.
Knee Osteoarthritis (KOA) is an age-related progressive degenerative joint disease, which is featured with pain, joint deformity, and disability. Accumulating evidence indicated oxidative stress plays a crucial role in the occurrence and development of KOA. Curcumin is a polyphenolic compound with significant antioxidant activity among various diseases while catalase (CAT) is an enzyme degrading hydrogen peroxide in treating oxidative diseases. We previously showed that the expression of CAT was low in cartilage. However, the combination of curcumin and CAT in KOA is still elusive. In this study, we demonstrated that the combination of curcumin and CAT has the potential to inhibit the IL1β-induced chondrocyte apoptosis without cytotoxicity in vitro. Mechanistically, we found that the synergistic application curcumin and CAT not only promotes curcumin's regulation of the NRF2/HO-1 signaling pathway to enhance antioxidant enzyme expression to remove superoxide radicals, but also CAT can further remove downstream hydrogen peroxide which enhances the ability to scavenge reactive oxygen species (ROS). In vivo, studies revealed that combination of curcumin and catalase could better inhibit oxidative stress-induced chondrocyte injury by promoting the expression of ROS scavenging enzymes. In sum, the combination of curcumin and catalase can be used to treat KOA. Thus, combination of curcumin and catalase may act as a novel therapeutic agent to manage KOA and our research gives a rationale for their combined use in the therapeutic of KOA.
膝骨关节炎(KOA)是一种与年龄相关的进行性退行性关节疾病,其特征为疼痛、关节畸形和功能障碍。越来越多的证据表明,氧化应激在 KOA 的发生和发展中起着关键作用。姜黄素是一种具有多种疾病显著抗氧化活性的多酚化合物,而过氧化氢酶(CAT)是一种在治疗氧化疾病时降解过氧化氢的酶。我们之前的研究表明,CAT 在软骨中的表达水平较低。然而,姜黄素和 CAT 在 KOA 中的联合应用仍不清楚。在这项研究中,我们证明了姜黄素和 CAT 的联合应用具有抑制 IL1β诱导的软骨细胞凋亡的潜力,同时在体外没有细胞毒性。从机制上讲,我们发现姜黄素和 CAT 的协同应用不仅促进了姜黄素对 NRF2/HO-1 信号通路的调节,以增强抗氧化酶的表达来清除超氧自由基,而且 CAT 还可以进一步清除下游的过氧化氢,从而增强清除活性氧(ROS)的能力。在体内研究中,结果表明姜黄素和 CAT 的联合应用可以通过促进 ROS 清除酶的表达,更好地抑制氧化应激诱导的软骨细胞损伤。总之,姜黄素和 CAT 的联合应用可以用于治疗 KOA。因此,姜黄素和 CAT 的联合应用可能成为治疗 KOA 的一种新的治疗剂,我们的研究为它们在 KOA 治疗中的联合应用提供了理论依据。
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