Geniposide attenuates inflammatory response by suppressing P2Y₁₄ receptor and downstream ERK1/2 signaling pathway in oxygen and glucose deprivation-induced brain microvascular endothelial cells

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• 作者：Fanghe Li^a ; ¹ ; ^{fhjingjing@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Weihong Li^a ; ² ; ^{liweihong.403@163.com" class="auth_mail" title="E-mail the corresponding author} ; Xingguang Li^a ; ³ ; ^{lixingguang@hotmail.com" class="auth_mail" title="E-mail the corresponding author} ; Feng Li^a ; ⁴ ; ^{lifeng95@vip.sina.com" class="auth_mail" title="E-mail the corresponding author} ; Linpeng Zhang^b ; ⁵ ; ^{zhanglinpeng1608@126.com" class="auth_mail" title="E-mail the corresponding author} ; Bingce Wang^c ; ⁶ ; ^{wangbingce@stu.pkuschool.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Guangrui Huang^a ; ⁷ ; ^{Huangggr2011@126.com" class="auth_mail" title="E-mail the corresponding author} ; Xiaojin Guo^d ; ⁵ ; ^{597406909@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Liangqin Wan^a ; ⁵ ; ^{779264240@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Yongqiang Liu^e ; ⁷ ; ^{Yongqiang.liu@fccc.edu" class="auth_mail" title="E-mail the corresponding author} ; Sai Zhang^a ; ⁵ ; ^{735668409@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Soyeon Kang^a ; ⁵ ; ^{2741510112@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Jiabao Ma^a ; ⁵ ; ^{mjbbjm0715@126.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Geniposide (PubChem CID ; 107848)
• 刊名：Journal of Ethnopharmacology
• 出版年：2016
• 出版时间：5 June 2016
• 年：2016
• 卷：185
• 期：Complete
• 页码：77-86
• 全文大小：4572 K

文摘

Fructus gardenia is widely used for treatment of stroke and infectious diseases in Chinese medicine. Geniposide is the key bioactive compound related to the pharmacodynamic actions of gardenia on ischemic stroke. The molecular mechanism by which geniposide improves the ischemic brain injury was observed in the study.

Aim of the study

Recent studies showed that geniposide had protective activities against the inflammatory response in ischemic stroke. However, the molecular mechanism of geniposide anti-inflammatory role has not yet been fully elucidated. In this study, we investigated the effect of geniposide on the expression of P2Y₁₄ receptor and downstream signaling pathway in brain microvascular endothelial cells (BMECs).

Materials and methods

An in vitro model of cerebral ischemia in BMECs was established by oxygen-glucose-deprivation (OGD). To further confirm the specific effect of geniposide on P2Y₁₄ receptor and downstream signaling pathways, we set up a UDP-glucose (an agonist of the P2Y₁₄ receptor) stimulated model. After administration of geniposide, the expression of P2Y₁₄ receptor, phosphorylation of RAF-1, mitogen activated protein kinase kinase1/2 (MEK1/2), extracellular signal-regulated kinase 1/2 (ERK1/2), level of interleukin-8 (IL-8), interleukin-1β (IL-1β), monocyte chemotactic protein 1 (MCP-1) in BMECs were determined.

Results

The mRNA and protein expression of P2Y₁₄ in the rat BMECs were up-regulated in OGD-induced injury. After administration of Geniposide, the expression of P2Y₁₄ receptor was significantly down-regulated, the phosphorylation of RAF-1, MEK1/2, ERK1/2 were suppressed. Similar data were obtained in UDP-glc stimulated model. We also observed that geniposide markedly declined the production of IL-8, IL-1β and MCP-1 in OGD-induced BMECs.

Conclusion

Geniposide exerted anti-inflammatory effects by interfering with the expression of P2Y₁₄ receptor, which subsequently inhibits the downstream ERK1/2 signaling pathways and the release of the pro-inflammatory cytokines IL-8, MCP-1, IL-1β. Therefore, this study provides the evidence for gardenia's clinical application in cerebral ischemia.