title: Anti-inflammatory effects of novel sinomenine derivatives.
abstract: 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.
authors.affiliation: 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.
authors.forename: Zijian
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan University, Changsha, Hunan 410082, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xiao
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan University, Changsha, Hunan 410082, PR China.
authors.forename: Jiancheng
authors.initials: J
authors.lastname: Wang
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan University, Changsha, Hunan 410082, PR China.
authors.forename: Wanrong
authors.initials: W
authors.lastname: Dong
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan University, Changsha, Hunan 410082, PR China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Peng
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan University, Changsha, Hunan 410082, PR China. Electronic address: deliean@hnu.edu.cn.
authors.forename: Delie
authors.initials: D
authors.lastname: An
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D002351:Carrageenan; D004396:Coloring Agents; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005070:Evans Blue; D005528:Foot / Q000473:pathology; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000633:toxicity; D008297:Male; D051379:Mice; D009019:Morphinans / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D032841:Sinomenium / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D014992:Xylenes
chemical_list: D000893:Anti-Inflammatory Agents; D004396:Coloring Agents; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009019:Morphinans; D014409:Tumor Necrosis Factor-alpha; D014992:Xylenes; C577686:interleukin-6, mouse; D005070:Evans Blue; C009271:sinomenine; D002351:Carrageenan
keywords: Anti-inflammation; Derivatives; IL-1β; IL-6; Sinomenine; TNF-α