Laboratory of Cardiovascular Physiology and Tissue Injury, National Institutes of Health/NIAAA, Bethesda, MD, USA.
Laboratory of Physiologic Studies, National Institutes of Health/NIAAA, Bethesda, MD, USA.
Br J Pharmacol. 2018 Jan;175(2):320-334. doi: 10.1111/bph.13722. Epub 2017 Feb 22.
β-Caryophyllene (BCP) is a plant-derived FDA approved food additive with anti-inflammatory properties. Some of its beneficial effects in vivo are reported to involve activation of cannabinoid CB receptors that are predominantly expressed in immune cells. Here, we evaluated the translational potential of BCP using a well-established model of chronic and binge alcohol-induced liver injury.
In this study, we investigated the effects of BCP on liver injury induced by chronic plus binge alcohol feeding in mice in vivo by using biochemical assays, real-time PCR and histology analyses. Serum and hepatic BCP levels were also determined by GC/MS.
Chronic treatment with BCP alleviated the chronic and binge alcohol-induced liver injury and inflammation by attenuating the pro-inflammatory phenotypic M1 switch of Kupffer cells and by decreasing the expression of vascular adhesion molecules intercellular adhesion molecule 1, E-Selectin and P-Selectin, as well as the neutrophil infiltration. It also beneficially influenced hepatic metabolic dysregulation (steatosis, protein hyperacetylation and PPAR-α signalling). These protective effects of BCP against alcohol-induced liver injury were attenuated in CB receptor knockout mice, indicating that the beneficial effects of this natural product in liver injury involve activation of these receptors. Following acute or chronic administration, BCP was detectable both in the serum and liver tissue homogenates but not in the brain.
Given the safety of BCP in humans, this food additive has a high translational potential in treating or preventing hepatic injury associated with oxidative stress, inflammation and steatosis.
This article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc.
β-石竹烯（BCP）是一种已获得美国食品和药物管理局批准的植物源性食品添加剂，具有抗炎特性。据报道，其在体内的一些有益作用涉及激活主要在免疫细胞中表达的大麻素 CB 受体。在这里，我们使用慢性和 binge 酒精诱导的肝损伤的成熟模型来评估 BCP 的转化潜力。
在这项研究中，我们通过生化分析、实时 PCR 和组织学分析，在体内研究了 BCP 对慢性加 binge 酒精喂养诱导的小鼠肝损伤的影响。还通过 GC/MS 测定血清和肝 BCP 水平。
BCP 的慢性治疗通过减轻库普弗细胞的促炎表型“M1”转换以及降低血管细胞间黏附分子 1、E-选择素和 P-选择素的表达和中性粒细胞浸润，缓解了慢性和 binge 酒精引起的肝损伤和炎症。它还对肝脏代谢失调（脂肪变性、蛋白质过度乙酰化和 PPAR-α 信号）产生有益影响。在 CB 受体敲除小鼠中，BCP 对酒精性肝损伤的这些保护作用减弱，表明这种天然产物对肝损伤的有益作用涉及这些受体的激活。在急性或慢性给药后，BCP 均可在血清和肝组织匀浆中检测到，但在脑组织中检测不到。
鉴于 BCP 在人类中的安全性，这种食品添加剂在治疗或预防与氧化应激、炎症和脂肪变性相关的肝损伤方面具有很高的转化潜力。
本文是关于“发明新疗法而无需重新发明轮子：药物再利用的力量”主题部分的一部分。要查看本部分中的其他文章，请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc.
