Punicalagin (PA) not only binds type II collagen, but also blocks its MMP‐13‐mediated degradation, and genipin (GNP) is a collagen cross‐linking agent. We hypothesized that these drugs could mitigate the loss of cartilage if administered in the early phase of osteoarthritis, and experiments were designed to provide proof‐of‐concept. Porcine cartilage was exposed to both drugs in a manner designed to simulate intra‐articular (IA) injection. Based on penetration of PA into cartilage, the rate of drug diffusion was conservatively estimated at 2 μm per minute. GNP caused a measurable degree of cross‐linking, increased compressive resistance and coefficient of friction, and substantially inhibited degradation by collagenase, but not by hyaluronidase. Pre‐incubation of GNP with collagenase had no effect on enzymatic activity. PA did not cross‐link collagen nor affect the mechanical properties of cartilage. It did, however, increase resistance to degradation by collagenase and hyaluronidase. Furthermore, it reacted with collagenase in solution and inhibited its subsequent enzymatic activity. Effects of PA and GNP were not additive. The chondroprotective effect of semi‐weekly IA injections was investigated in the monoiodoacetate‐induced model of OA in rats. Quantitative histology suggested that injection of PA decreased the amount of cartilage lost compared to saline‐injected controls, and the addition of GNP made no difference. This study supports the notion that IA delivery of PA could mitigate OA‐induced cartilage erosion.

中文翻译：

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安石榴苷和京尼平对软骨的短期治疗效果及其对治疗骨关节炎的意义

Punicalagin (PA) 不仅能结合 II 型胶原蛋白，还能阻断其 MMP-13 介导的降解，京尼平 (GNP) 是一种胶原蛋白交联剂。我们假设这些药物如果在骨关节炎的早期使用可以减轻软骨的损失，并且实验旨在提供概念验证。以模拟关节内 (IA) 注射的方式将猪软骨暴露于两种药物中。基于 PA 对软骨的渗透，药物扩散速率保守估计为每分钟 2 μm。GNP 引起可测量的交联程度，增加抗压性和摩擦系数，并显着抑制胶原酶的降解，但不抑制透明质酸酶的降解。GNP 与胶原酶的预孵育对酶活性没有影响。PA 不会交联胶原蛋白，也不会影响软骨的机械性能。然而，它确实增加了对胶原酶和透明质酸酶降解的抵抗力。此外，它与溶液中的胶原酶反应并抑制其随后的酶活性。PA 和 GNP 的影响不是累加的。在大鼠单碘乙酸盐诱导的 OA 模型中研究了半周 IA 注射的软骨保护作用。定量组织学表明，与注射盐水的对照组相比，注射 PA 减少了软骨损失的数量，而添加 GNP 没有任何差异。这项研究支持 IA 递送 PA 可以减轻 OA 引起的软骨侵蚀的观点。此外，它与溶液中的胶原酶反应并抑制其随后的酶活性。PA 和 GNP 的影响不是累加的。在大鼠单碘乙酸盐诱导的 OA 模型中研究了半周 IA 注射的软骨保护作用。定量组织学表明，与注射盐水的对照组相比，注射 PA 减少了软骨损失的数量，而添加 GNP 没有任何差异。这项研究支持 IA 递送 PA 可以减轻 OA 引起的软骨侵蚀的观点。此外，它与溶液中的胶原酶反应并抑制其随后的酶活性。PA 和 GNP 的影响不是累加的。在大鼠单碘乙酸盐诱导的 OA 模型中研究了半周 IA 注射的软骨保护作用。定量组织学表明，与注射盐水的对照组相比，注射 PA 减少了软骨损失的数量，而添加 GNP 没有任何差异。这项研究支持 IA 递送 PA 可以减轻 OA 引起的软骨侵蚀的观点。定量组织学表明，与注射盐水的对照组相比，注射 PA 减少了软骨损失的数量，而添加 GNP 没有任何差异。这项研究支持 IA 递送 PA 可以减轻 OA 引起的软骨侵蚀的观点。定量组织学表明，与注射盐水的对照组相比，注射 PA 减少了软骨损失的数量，而添加 GNP 没有任何差异。这项研究支持 IA 递送 PA 可以减轻 OA 引起的软骨侵蚀的观点。