Betulin Derivatives Effectively Suppress Inflammation in Vitro and in Vivo

详细信息    查看全文

• 作者：Mirka Laavola ; Raisa Haavikko ; Mari Hämäläinen ; Tiina Leppänen ; Riina Nieminen ; Sami Alakurtti ; Vânia M. Moreira ; Jari Yli-Kauhaluoma ; Eeva Moilanen
• 刊名：Journal of Natural Products
• 出版年：2016
• 出版时间：February 26, 2016
• 年：2016
• 卷：79
• 期：2
• 页码：274-280
• 全文大小：425K
• ISSN：1520-6025

文摘

Betulin is a pharmacologically active triterpenoid found in the bark of the birch tree (Betula sp. L.). Betulin and betulinic acid are structurally related to anti-inflammatory steroids, but little is known about their potential anti-inflammatory properties. In the present study, the inflammatory gene expression and the anti-inflammatory properties of betulin, betulinic acid, and 16 semisynthetic betulin derivatives were investigated. Betulin derivatives 3, 4, and 5 selectively inhibited the expression of the inducible nitric oxide synthase (iNOS) in a post-transcriptional manner. They also inhibited nitric oxide (NO) production but had no effect on the other inflammatory factors studied. More interestingly, a new anti-inflammatory betulin derivative 9 with a wide-spectrum anti-inflammatory activity was discovered. Compound 9 was found to suppress the expression of cytokines interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1), as well as that of prostaglandin synthase-2 (COX-2) in addition to iNOS. The in vivo anti-inflammatory effect of compound 9 was indicated via significant suppression of the carrageenan-induced paw inflammation in mice. The results show, for the first time, that the pyrazole-fused betulin derivative (9) and related compounds have anti-inflammatory properties that could be utilized in drug development.