Laraib Iqra, Qasim Sumera, Uttra Ambreen Malik, Ahmed Shaimaa R
Department of Pharmacology, College of Pharmacy, University of Sargodha, Sargodha, 40100, Pakistan.
Department of Pharmacology, College of Pharmacy, Jouf University, 72341, Sakakah, Aljouf, Saudi Arabia.
Inflammopharmacology. 2025 Apr 23. doi: 10.1007/s10787-025-01756-4.
The monocyclic monoterpenoid ocimene (OC) has undergone pharmacological testing as a possible inhibitor of pyroptosis triggered by TLR4/NLRP3 pathway, involved in progression of several diseases, such as rheumatoid arthritis (RA), inflammation, and chronic pain. Arthritis was evaluated using formaldehyde-induced arthritis rat model. Potential targets of OC against adjuvant-induced arthritis (AIA) in rats were examined using pharmacological testing and an integrative research strategy. CFA (o.1 ml) was used to assess the anti-arthritic effects of OC during a 28-day study period. To ascertain the therapeutic effects and identify pharmacological mechanisms, a variety of techniques were used, including macroscopic examination, gene expression profiling using PCR, an estimate of PGE-2, anti-CCP, 5-LOX besides markers of oxidative stress via ELISA, as well as radiographic examination. Oral administration of OC (50, 100, and 200 mg/kg) significantly (p < 0.001) decreased paw edema in the formaldehyde-induced arthritis. Inhibition of the NLRP3 inflammasome led to a significant downregulation of NFκB, caspase-1, and ASC, a decrease in the release of IL-1β and IL-18, and a modulation of GSDMD-mediated pyroptosis, hence reducing bone erosion and joint inflammation by blocking TLR4/NLRP3/GSDMD signaling. Levels of IL-4 and IL-10 were elevated in comparison to the disease control group. In addition, ELISA revealed that levels of the primary mediators of inflammation PGE-2 and 5-LOX, as well as malondialdehyde (MDA), a marker of oxidative stress, were significantly lower in the treated rats. In contrast, other antioxidant markers, such as glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD), were upregulated following the treatment. In addition, OC altered the actions of the COX enzyme, which reduced inflammation and eased RA-related discomfort. Therefore, it can be concluded that OC exhibited anti-arthritic attributes via modulation of TLR4/NLRP3/GSDMD signaling-mediated pyroptosis.
单环单萜罗勒烯（OC）已作为一种可能的焦亡抑制剂进行了药理学测试，焦亡由TLR4/NLRP3途径触发，该途径与多种疾病的进展有关，如类风湿性关节炎（RA）、炎症和慢性疼痛。使用甲醛诱导的关节炎大鼠模型评估关节炎。采用药理学测试和综合研究策略，研究了OC对大鼠佐剂性关节炎（AIA）的潜在靶点。在为期28天的研究期间，使用弗氏完全佐剂（0.1 ml）评估OC的抗关节炎作用。为了确定治疗效果并识别药理机制，使用了多种技术，包括宏观检查、使用PCR进行基因表达谱分析、通过ELISA估计PGE-2、抗CCP、5-LOX以及氧化应激标志物，以及影像学检查。口服OC（50、100和200 mg/kg）显著（p < 0.001）减轻了甲醛诱导的关节炎中的爪部水肿。抑制NLRP3炎性小体导致NFκB、半胱天冬酶-1和ASC显著下调，IL-1β和IL-18的释放减少，以及GSDMD介导的焦亡受到调节，从而通过阻断TLR4/NLRP3/GSDMD信号传导减少骨侵蚀和关节炎症。与疾病对照组相比，IL-4和IL-10水平升高。此外，ELISA显示，治疗组大鼠中炎症的主要介质PGE-2和5-LOX以及氧化应激标志物丙二醛（MDA）的水平显著降低。相反，其他抗氧化标志物，如谷胱甘肽（GSH）、过氧化氢酶（CAT）和超氧化物歧化酶（SOD）在治疗后上调。此外，OC改变了COX酶的作用，从而减轻了炎症并缓解了与RA相关的不适。因此，可以得出结论，OC通过调节TLR4/NLRP3/GSDMD信号传导介导的焦亡表现出抗关节炎特性。
