Department of Anatomy, Cell biology & Physiological Sciences; Faculty of Medicine; American University of Beirut, Beirut, Lebanon.
Department of anatomy, Cell biology & Physiological Sciences; Faculty of Medicine; American University of Beirut, Beirut, Lebanon.
Antiinflamm Antiallergy Agents Med Chem. 2021;20(3):239-249. doi: 10.2174/1871523019999201111191754.
Oleanolic acid (OA) is a naturally occurring pentacyclic triterpenoid with multifarious actions. The anti-inflammatory effect it exerts when taken orally is the most important; however, the underpinning mechanisms of such effects have not yet been fully explored.
In the present study, we evaluated the anti-inflammatory and anti-nociceptive effect of OA by injecting it directly into the knee joint using an animal model of osteoarthritis. Behavioral and electrophysiological studies were conducted to determine whether OA exerts a direct modulatory effect on primary sensory afferents that can lead to a decrease in pain-related behaviors and inflammatory responses. Rats were divided into two main groups: a pre- and a post-treatment group. Knee joint inflammation was induced by injecting a mixture of 3% kaolin and carrageenan (K/C). In the pre-treatment group, two different doses of OA [5 mg/ml (n=5) and 30 mg/ml (n=4); 0.1 ml per injection] were administered into the synovial cavity of the knee joint before induction of inflammation. In the post-treatment group, rats received only one dose [5 mg/ml (n=5)] of OA after induction of inflammation.
Results indicate that intra-articular injection of OA improves motor coordination and attenuates nociceptive behavior and inflammatory reactions. More importantly, we observed a direct depolarizing action of OA on articular sensory fibers, a crucial mechanism that activates descending inhibitory pathways and controls incoming nociceptive signals to the spinal cord.
Overall, our findings suggest that OA can be used as a preventive and therapeutic approach for the management of osteoarthritis.
齐墩果酸（OA）是一种具有多种作用的天然五环三萜。其口服时发挥的抗炎作用最为重要；然而，这种作用的潜在机制尚未得到充分探索。
在本研究中，我们通过在骨关节炎动物模型中直接向膝关节注射 OA 来评估其抗炎和镇痛作用。进行行为和电生理研究，以确定 OA 是否对初级感觉传入具有直接调节作用，从而导致与疼痛相关的行为和炎症反应减少。大鼠分为两个主要组：预处理组和后处理组。通过注射 3%高岭土和角叉菜胶（K/C）混合物诱导膝关节炎症。在预处理组中，OA 以两种不同剂量[5 mg/ml（n=5）和 30 mg/ml（n=4）；每次注射 0.1 ml]注入膝关节滑膜腔，然后诱导炎症。在后处理组中，大鼠在诱导炎症后仅接受一次 OA 治疗[5 mg/ml（n=5）]。
结果表明，关节内注射 OA 可改善运动协调能力，并减轻痛觉行为和炎症反应。更重要的是，我们观察到 OA 对关节感觉纤维具有直接去极化作用，这是一种激活下行抑制途径并控制传入脊髓的伤害性信号的关键机制。
总体而言，我们的研究结果表明，OA 可作为管理骨关节炎的预防和治疗方法。
