尾-Caryophyllene ameliorates cisplatin-induced nephrotoxicity in a cannabinoid 2 receptor-dependent manner

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• 作者：Bé ; la Horvá ; th^a ; Partha Mukhopadhyay^a ; Malek Kechrid^a ; Vivek Patel^a ; Galin Tanchian^a ; David A. Wink^b ; Jü ; rg Gertsch^c ; Pá ; l Pacher^a ; ^{pacher@mail.nih.gov}
• 关键词：Nephropathy ; Cisplatin ; (E)-尾-caryophyllene ; Cannabinoid 2 receptor ; Inflammation ; Oxidative stress ; Cell death ; Free radicals
• 刊名：Free Radical Biology and Medicine
• 出版年：2012
• 期刊代码：105_08915849
• 类别：med
• 出版时间：15 April, 2012
• 卷：52
• 期：8
• 页码：1325-1333
• 文件大小：1940 K

摘要

(E)-尾-caryophyllene (BCP) is a natural sesquiterpene found in many essential oils of spice (best known for contributing to the spiciness of black pepper) and food plants with recognized anti-inflammatory properties. Recently it was shown that BCP is a natural agonist of endogenous cannabinoid 2 (CB₂) receptors, which are expressed in immune cells and mediate anti-inflammatory effects. In this study we aimed to test the effects of BCP in a clinically relevant murine model of nephropathy (induced by the widely used antineoplastic drug cisplatin) in which the tubular injury is largely dependent on inflammation and oxidative/nitrative stress. 尾-caryophyllene dose-dependently ameliorated cisplatin-induced kidney dysfunction, morphological damage, and renal inflammatory response (chemokines MCP-1 and MIP-2, cytokines TNF-伪 and IL-1尾, adhesion molecule ICAM-1, and neutrophil and macrophage infiltration). It also markedly mitigated oxidative/nitrative stress (NOX-2 and NOX-4 expression, 4-HNE and 3-NT content) and cell death. The protective effects of BCP against biochemical and histological markers of nephropathy were absent in CB₂ knockout mice. Thus, BCP may be an excellent therapeutic agent to prevent cisplatin-induced nephrotoxicity through a CB₂ receptor-dependent pathway. Given the excellent safety profile of BCP in humans it has tremendous therapeutic potential in a multitude of diseases associated with inflammation and oxidative stress.