Zhao Zijian, Xiao Jing, Wang Jiancheng, Dong Wanrong, Peng Zhihong, An Delie
College of Chemistry and Chemical Engineering, Hunan University, Changsha, Hunan 410082, PR China; Key Laboratory of Research and Utilization of Ethnomedicinal Plant Resources of Hunan Province, Huaihua University, Huaihua, Hunan 418008, PR China.
College of Chemistry and Chemical Engineering, Hunan University, Changsha, Hunan 410082, PR China.
Int Immunopharmacol. 2015 Dec;29(2):354-360. doi: 10.1016/j.intimp.2015.10.030. Epub 2015 Oct 31.
Sinomenine is an isoquinoline-type alkaloid found in Sinomenium acutum (Thunb.) Rehd. et Wils and S. acutum (Thunb.) Rehd. et Wils var. cinereum Rehd. et Wils. When used as a medicine, this compound exhibits anti-inflammatory properties; however, sinomenine's use as a medication is limited by side effects, a short half-life, and low efficacy. Owing to these limits, attempts have been made to synthesize sinomenine derivatives with enhanced efficacy. In this study, the anti-inflammatory effects of novel sinomenine derivatives (S1a-S1f) were examined on the basis of lipopolysaccharide-induced inflammatory factor expression in Raw264.7 cells, dimethylbenzene-induced ear oedema, and Evan's blue leakage in mice, and carrageenan-induced paw oedema in rats. Compared with sinomenine, the derivatives significantly inhibited the expression of the inflammatory factors IL-1β and IL-6 at the transcriptional and translational levels. Topical application of 3.250mg/kg of the derivatives also alleviated ear oedema. Compared with the vehicle, the derivatives significantly inhibited carrageenan-induced rat paw oedema after 6h. Among the derivatives, S1a exhibited the most potent anti-inflammatory activity. S1a also significantly increased the sinomenine-induced inhibition of Evan's blue leakage. Thus, S1a may elicit the strongest anti-inflammatory effects of the tested compounds. Based on these results, further development of this compound may be warranted.
青藤碱是一种异喹啉类生物碱，存在于青风藤（Sinomenium acutum (Thunb.) Rehd. et Wils）和灰背青藤（S. acutum (Thunb.) Rehd. et Wils var. cinereum Rehd. et Wils）中。作为一种药物，该化合物具有抗炎特性；然而，青藤碱作为药物的使用受到副作用、半衰期短和疗效低的限制。由于这些限制，人们已尝试合成具有更高疗效的青藤碱衍生物。在本研究中，基于脂多糖诱导的Raw264.7细胞炎症因子表达、二甲苯诱导的小鼠耳部水肿、伊文思蓝渗漏以及角叉菜胶诱导的大鼠爪部水肿，检测了新型青藤碱衍生物（S1a - S1f）的抗炎作用。与青藤碱相比，这些衍生物在转录和翻译水平上显著抑制了炎症因子IL - 1β和IL - 6的表达。局部应用3.250mg/kg的衍生物也减轻了耳部水肿。与赋形剂相比，衍生物在6小时后显著抑制了角叉菜胶诱导的大鼠爪部水肿。在这些衍生物中，S1a表现出最有效的抗炎活性。S1a还显著增强了青藤碱诱导的对伊文思蓝渗漏的抑制作用。因此，S1a可能在所测试的化合物中引发最强的抗炎作用。基于这些结果，该化合物可能值得进一步开发。
