Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Changsari, 781101, Assam, India.
Toxicology & Experimental Medicine, CSIR-Central Drug Research Institute (CDRI), Lucknow, 226031, India.
Eur J Pharmacol. 2024 Nov 5;982:176940. doi: 10.1016/j.ejphar.2024.176940. Epub 2024 Aug 27.
Rheumatoid arthritis is an inflammatory condition primarily affecting the joints. Nuciferine (NCF), a key bioactive aporphine alkaloid biosynthesized in lotus leaves, exhibits promising anti-inflammatory and antioxidant properties. In this study, we investigated whether NCF could alleviate inflammatory arthritis conditions in a complete Freund's adjuvant (CFA)-mediated arthritis model in rats. The arthritis model was established through intradermal injection of CFA (100 μL) in the sub-plantar region of the right hind paw. The arthritic animals were treated orally with NCF at 5 and 10 mg/kg and indomethacin (Indo) at 5 mg/kg body weight as reference control. NCF treatment remarkably alleviated inflammatory joint swelling and arthritic index. The radiological and histological analysis revealed evidence of the beneficial effects of NCF. NCF treatment decreased the content of pro-inflammatory cytokines (TNF-α and IL-1β) and myeloperoxidase (MPO) activity and restored the anti-inflammatory cytokine (IL-10) in the paw joints. The serum levels of pro-inflammatory cytokines were also markedly reduced in the NCF (10 mg/kg) treatment group. Moreover, the arthritis-induced inflammatory mediators, including cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) and the toll-like receptor (TLR)-4, mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB) signaling proteins were substantially decreased in the NCF treatment groups. NCF treatment also restored the antioxidant defense enzymes and abrogated lipid peroxidation in the paw tissue. Our findings strongly suggest that NCF is a promising therapeutic molecule for rheumatoid arthritis, inspiring further research, and development in this area.
类风湿性关节炎是一种主要影响关节的炎症性疾病。荷叶中合成的关键阿朴啡类生物活性碱——荷叶碱（NCF）具有显著的抗炎和抗氧化特性。在这项研究中，我们研究了 NCF 是否可以减轻完全弗氏佐剂（CFA）介导的关节炎模型大鼠的炎症性关节炎。关节炎模型是通过在右后爪足底区域皮内注射 CFA（100μL）建立的。关节炎动物以 5 和 10mg/kg 的剂量口服给予 NCF 治疗，并以吲哚美辛（Indo）5mg/kg 作为参考对照进行治疗。NCF 治疗显著减轻了炎症性关节肿胀和关节炎指数。放射学和组织学分析显示了 NCF 的有益效果。NCF 治疗降低了促炎细胞因子（TNF-α和 IL-1β）和髓过氧化物酶（MPO）活性的含量，并恢复了爪关节中的抗炎细胞因子（IL-10）。NCF（10mg/kg）治疗组的血清促炎细胞因子水平也明显降低。此外，关节炎诱导的炎症介质，包括环氧化酶（COX）-2、诱导型一氧化氮合酶（iNOS）和 Toll 样受体（TLR）-4、丝裂原激活蛋白激酶（MAPK）和核因子-κB（NF-κB）信号蛋白，在 NCF 治疗组中显著减少。NCF 治疗还恢复了抗氧化防御酶并阻断了爪组织中的脂质过氧化。我们的研究结果强烈表明，NCF 是治疗类风湿性关节炎的有前途的治疗分子，这为该领域的进一步研究和开发提供了启示。
