Upadhyay Prabhat, Kalra Diya, Nilakhe Aishwarya Shrikant, Aggrawal Vijay, Gupta Sarika
Molecular Science Lab, National Institute of Immunology (NII), New Delhi, India.
Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Front Nutr. 2023 Nov 16;10:1217051. doi: 10.3389/fnut.2023.1217051. eCollection 2023.
Osteoarthritis (OA) is a debilitating disease with significant personal and socioeconomic burdens worldwide.
To address this, we developed a multitargeted formulation called PL02, which includes standardized extracts of L, , and collagen peptide. We tested the pharmacological efficacy of PL02 in a rodent model of OA induced by Monosodium iodoacetate (MIA).
Our results demonstrate that oral administration of PL02 has antioxidant effects by down-regulating NOS, reduces pain-related behavior, and mitigates inflammation by inhibiting IL-1b and TNF-α production, as well as downregulating CGRP1 and COX-II. PL02 also exhibits anti-catabolic and chondroprotective activity by significantly downregulating MMP13 and upregulating BCL2. Additionally, PL02 demonstrates chondrogenic activity by significantly upregulating SOX-9 (a master regulator of chondrogenesis), Coll-I, and aggrecan, which are major components of articular cartilage. Furthermore, PL02 prevents microarchitectural deterioration of subchondral bone.
Overall, PL02 is an orally active, multi-targeted therapy that not only alleviates pain and inflammation but also effectively halts cartilage and subchondral bone deterioration. It represents a safe and promising candidate for the treatment and management of OA.
骨关节炎（OA）是一种使人衰弱的疾病，在全球范围内造成了重大的个人和社会经济负担。
为了解决这一问题，我们开发了一种名为PL02的多靶点制剂，其中包括L、 以及胶原肽的标准化提取物。我们在碘乙酸钠（MIA）诱导的骨关节炎啮齿动物模型中测试了PL02的药理功效。
我们的结果表明，口服PL02通过下调一氧化氮合酶（NOS）具有抗氧化作用，减轻疼痛相关行为，并通过抑制白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）的产生以及下调降钙素基因相关肽1（CGRP1）和环氧化酶-2（COX-II）来减轻炎症。PL02还通过显著下调基质金属蛋白酶13（MMP13）和上调B细胞淋巴瘤-2（BCL2）表现出抗分解代谢和软骨保护活性。此外，PL02通过显著上调性别决定区Y框蛋白9（SOX-9，软骨生成的主要调节因子）、I型胶原蛋白（Coll-I）和聚集蛋白聚糖（关节软骨的主要成分）表现出软骨生成活性。此外，PL02可防止软骨下骨的微结构退化。
总体而言，PL02是一种口服活性的多靶点疗法，不仅能减轻疼痛和炎症，还能有效阻止软骨和软骨下骨的退化。它是治疗和管理骨关节炎的一种安全且有前景的候选药物。
