Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India.
Department of Pharmacy, Birla Institute of Science and Technology, Hyderabad, Telangana, India.
Mini Rev Med Chem. 2023;23(9):992-1032. doi: 10.2174/1389557522666220511140527.
Osteoarthritis (OA), a chronic degenerative musculoskeletal disorder, progressively increases with age. It is characterized by progressive loss of hyaline cartilage followed by subchondral bone remodeling and inflammaging. To counteract the inflammation, synovium releases various inflammatory and immune mediators along with metabolic intermediates, which further worsens the condition. However, even after recognizing the key molecular and cellular factors involved in the progression of OA, only disease-modifying therapies are available such as oral and topical NSAIDs, opioids, SNRIs, , providing symptomatic treatment and functional improvement instead of suppressing OA progression. Long-term use of these therapies leads to various life-threatening complications. Interestingly, mother nature has numerous medicinal plants containing active phytochemicals that can act on various targets involved in the development and progression of OA. Phytochemicals have been used for millennia in traditional medicine and are promising alternatives to conventional drugs with a lower rate of adverse events and efficiency frequently comparable to synthetic molecules. Nevertheless, their mechanism of action in many cases is elusive and uncertain. Even though many in vitro and in vivo studies show promising results, clinical evidence is scarce. Studies suggest that the presence of carbonyl group in the 2 position, chloro in the 6 and an electron- withdrawing group at the 7 position exhibit enhanced COX-2 inhibition activity in OA. On the other hand, the presence of a double bond at the C-C position of C ring in flavonoids plays an important role in Nrf activation. Moreover, with the advancements in the understanding of OA progression, SARs (structure-activity relationships) of phytochemicals and integration with nanotechnology have provided great opportunities for developing phytopharmaceuticals. Therefore, in the present review, we have discussed various promising phytomolecules, SAR as well as their nano-based delivery systems for the treatment of OA to motivate the future investigation of phytochemical-based drug therapy.
骨关节炎（OA）是一种慢性退行性肌肉骨骼疾病，随年龄增长而逐渐加重。其特征是透明软骨进行性丧失，随后出现软骨下骨重塑和炎症老化。为了对抗炎症，滑膜会释放各种炎症和免疫介质以及代谢中间产物，这进一步加重了病情。然而，即使已经认识到 OA 进展中涉及的关键分子和细胞因素，也只有疾病修饰疗法可用，例如口服和局部 NSAIDs、阿片类药物、SNRIs 等，只能提供对症治疗和功能改善，而不能抑制 OA 的进展。这些疗法的长期使用会导致各种危及生命的并发症。有趣的是，大自然拥有许多药用植物，其中含有可以作用于 OA 发展和进展中各种靶标的活性植物化学物质。植物化学物质在传统医学中已经使用了数千年，是传统药物的有前途的替代品，具有不良反应发生率低和效率高的特点，且通常与合成分子相当。然而，它们在许多情况下的作用机制仍然难以捉摸和不确定。尽管许多体外和体内研究显示出有希望的结果，但临床证据仍然缺乏。研究表明，在 2 位存在羰基、6 位存在氯和 7 位存在吸电子基团的情况下，黄酮类化合物中环的 C-C 位置存在双键，可增强对 OA 中 COX-2 的抑制活性。另一方面，在 C 环的 C-C 位置存在双键的黄酮类化合物在 Nrf 激活中起着重要作用。此外，随着对 OA 进展的理解的进步，植物化学物质的 SAR（构效关系）以及与纳米技术的结合为开发植物药提供了巨大的机会。因此，在本综述中，我们讨论了各种有前途的植物分子、SAR 以及它们用于治疗 OA 的基于纳米的递药系统，以激励未来对基于植物化学物质的药物治疗的研究。
