Roy Himadri Shekhar, Kulkarni Chirag, Neethu K M, Babu Anand, Arora Malika, Jayamurugan Govindasamy, Mandal Dipankar, Guha Rajdeep, Chattopadhyay Naibedya, Ghosh Deepa
Chemical Biology Unit, Institute of Nano Science and Technology, Knowledge City, Sector-81, Mohali, Punjab, 140306, India.
Division of Endocrinology and Centre for Research in ASTHI, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India.
Arch Pharm Res. 2025 Aug;48(7-8):765-781. doi: 10.1007/s12272-025-01558-w. Epub 2025 Jul 29.
Collagenases (MMP-1, MMP-8, and MMP-13) play significant roles in the pathophysiology of osteoarthritis. Among these proteins, MMP-13 and MMP-8 are known for their catabolic roles in the degradation of the articular cartilage matrix. Using computational studies, we had previously observed that a metabolite of curcumin, Curcumin monoglucuronide (CMG), binds to MMPs involved in cartilage matrix destruction. The purpose of this study was to confirm the ability of CMG to protect cartilage by blocking the activity of these enzymes. The ability of CMG to bind and block the activities of MMP-13 and MMP-8 was established using several physicochemical methods. First, the protective effect of CMG on MMP-mediated cartilage destruction was demonstrated using cartilage explants in vitro. Second, the in vivo efficacy of CMG was tested by comparison with BI-4394, a specific MMP-13 inhibitor, using a rat anterior cruciate ligament transection (ACLT) model. These studies demonstrated that CMG was more effective than BI-4394 at preventing cartilage degeneration. In separate in vitro studies, CMG did not affect chondrocyte proliferation or the expression of NF-κB-mediated proinflammatory genes. Together, these findings demonstrate the therapeutic potential of CMG and emphasize the importance of inhibiting both MMP-13 and MMP-8 to achieve improved clinical outcomes.
胶原酶（基质金属蛋白酶-1、基质金属蛋白酶-8和基质金属蛋白酶-13）在骨关节炎的病理生理学中发挥着重要作用。在这些蛋白质中，基质金属蛋白酶-13和基质金属蛋白酶-8因其在关节软骨基质降解中的分解代谢作用而闻名。通过计算机研究，我们之前观察到姜黄素的一种代谢产物，姜黄素单葡萄糖醛酸苷（CMG），与参与软骨基质破坏的基质金属蛋白酶结合。本研究的目的是通过阻断这些酶的活性来证实CMG保护软骨的能力。使用多种物理化学方法确定了CMG结合并阻断基质金属蛋白酶-13和基质金属蛋白酶-8活性的能力。首先，在体外使用软骨外植体证明了CMG对基质金属蛋白酶介导的软骨破坏的保护作用。其次，使用大鼠前交叉韧带横断（ACLT）模型，通过与特异性基质金属蛋白酶-13抑制剂BI-4394比较，测试了CMG的体内疗效。这些研究表明，在预防软骨退变方面，CMG比BI-4394更有效。在单独的体外研究中，CMG不影响软骨细胞增殖或NF-κB介导的促炎基因的表达。总之，这些发现证明了CMG的治疗潜力，并强调了抑制基质金属蛋白酶-13和基质金属蛋白酶-8以实现更好临床结果的重要性。
