Anti-inflammatory actions of the natural plant product, Honokiol

描述(申请人提供)：和厚朴酚(HNK)是一种从厚朴属植物的叶和根茎中提取的天然提取物，长期以来一直被亚洲传统医学用于治疗血栓和胃肠道疾病。为了确定HNK是否具有抗炎特性，我们在炎症性类风湿性关节炎(RA)的小鼠模型上测试了它的效果。我们的初步研究表明，体内炎症和疾病进展以及体外促炎细胞因子的产生和细胞激活都明显受到抑制，而没有增加细胞死亡或体内毒性。这些初步发现表明，HNK在治疗慢性炎症性疾病方面有希望，如RA，这种疾病影响了大量的人。HNK还抑制了通过CD40以及EBV编码的CD40模拟物LMP1的信号传递，CD40是一种免疫受体，被认为在RA中发挥作用，EBV编码的CD40模拟物与加剧自身免疫性疾病有关。由于HNK具有多种抗炎作用，它可能会被证明比针对单一分子的治疗更有效。它在传统医学中的长期使用也表明，它可以是有效的，没有危险的副作用。这一探索性项目将检验HNK在RA小鼠模型中具有有效抗炎特性的假设，以及它的作用将通过与GABA受体相互作用来减少促炎细胞因子的产生。第一个具体目标将集中在优化小鼠RA疾病模型的抗炎作用，第二个目标将研究HNK的作用机制。 公共卫生相关性：该项目研究一种名为和厚朴酚(HNK)的天然植物产品，它是从厚朴属植物中提取的，多年来一直作为亚洲传统药物使用，没有显著的毒副作用。在人类类风湿性关节炎(RA)的小鼠模型上进行的对照研究，我们的初步工作表明，HNK可以抑制炎症和疾病的进展。有趣的是，初步数据表明，HNK通过神经系统的一种受体向细胞传递信号。目前的项目试图在这些研究的基础上，确定使用HNK作为慢性炎症性疾病治疗的最佳方式，并更好地了解HNK如何发挥其抗炎作用。

DESCRIPTION (provided by applicant): Honokiol (HNK) is a natural extract of the leaves and root stems of the Magnolia plant that has long been used in traditional Asian medicine to treat thrombotic and gastrointestinal disorders. To determine if HNK has anti-inflammatory properties, we tested its effects in a mouse model of inflammatory rheumatoid arthritis (RA). Our initial studies show that both in vivo inflammation and disease progression and in vitro pro-inflammatory cytokine production and cellular activation were markedly inhibited, without increased cell death or in vivo toxicity. These preliminary findings suggest that HNK has promise in the treatment of chronic inflammatory diseases such as RA, which affects a large number of people. HNK also inhibited signaling via CD40, an immune receptor that has been implicated as playing a role in RA, as well as an EBV-encoded CD40 mimic called LMP1, that has been implicated in exacerbating autoimmune disease. Because HNK has multiple anti-inflammatory actions, it could prove more effective than treatments targeting a single molecule. Its long prior use in traditional medicine also suggests that it can be effective without dangerous side effects. This exploratory project will test the hypothesis that HNK will have effective anti-inflammatory properties in a mouse model of RA, and that its action will be exerted via interaction with GABA receptors to decrease production of pro-inflammatory cytokines. The first specific Aim will focus on optimizing anti-inflammatory effects in the mouse RA disease model, and the second Aim will examine the mechanism of action of HNK. PUBLIC HEALTH RELEVANCE: This project studies a natural plant product called Honokiol (HNK), which is extracted from plants of the species Magnolia, and has been used for many years as a traditional Asian medicine, without notable toxic side effects. Using controlled studies in a mouse model of human rheumatoid arthritis (RA), our initial work has shown that HNK can inhibit inflammation and progression of the disease. Interestingly, preliminary data indicate that HNK delivers signals to cells through a type of receptor of the nervous system. The current project seeks to build upon these studies to determine the optimal way to use HNK as a treatment for chronic inflammatory disease, and to better understand how HNK exerts its anti- inflammatory effects.