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中药调节缺血性心脑血管疾病 NLRP3 炎性小体的药理作用及机制

Pharmacological Effects and Mechanisms of Chinese Medicines Modulating NLRP3 Inflammasomes in Ischemic Cardio/Cerebral Vascular Disease.

机构信息

* The Second Clinical School of Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, P. R. China.

† State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macao 999078, Macao SAR of P. R. China.

出版信息

Am J Chin Med. 2018;46(8):1727-1741. doi: 10.1142/S0192415X18500878. Epub 2018 Dec 10.

Abstract

Cardio/cerebral-vascular diseases seriously threaten human health and are the leading cause of death. As such, there is great interest in identifying a potential mechanism that controls the development process of cardio/cerebral vascular diseases. Present studies demonstrate that inflammasomes play an important role in the process of ischemic cardio/cerebral vascular diseases (ICCVDs). Among the pathological process of ICCVDs, inflammasomes activated the sterile inflammatory response that accelerated the development of diseases and aggravated the acute lesion of tissue. As the most thoroughly studied inflammasome, the NLRP3 inflammasome has been proven to be a potential therapeutic target for ICCVDs. In this review, we summarized the mechanisms of Chinese herbal medicine which can affect ICCVDs via the regulation of the NLRP3 inflammasome. Our study discovers that active compounds of Chinese medicines have a negative effect on NLRP3 in different ICCVDs models. Astragaloside IV may influence the receptor of the cell membrane to inhibit NLRP3 activation. Resveratrol, colchicinesis, salvianolic acid B, chrysophanol and sulforaphane may directly damage the formation of NLRP3 by inhibiting ASC or Caspase-1. Most of the active natural compounds can negatively regulate the downstream products of NLRP3 inflammasome such as IL-18 and IL1 . In addition, Chinese medicines such as sinomenine, ruscogenin, resveratrol, arctigenin and cepharanthineas may downregulate NLRP3 inflammasome by inducing autophagy activation. Due to the advantages of multi-target effects, Chinese herbal medicine can be treated as a splendid therapy for ICCVDs by inhibiting NLRP3 inflammasome.

摘要

心脑血管疾病严重威胁人类健康,是导致人类死亡的主要原因。因此,寻找一种潜在的机制来控制心脑血管疾病的发展过程具有重要意义。目前的研究表明,炎症小体在缺血性心脑血管疾病(ICCVDs)的病理过程中发挥着重要作用。在 ICCVDs 的病理过程中,炎症小体激活了无菌性炎症反应,加速了疾病的发展,并加重了组织的急性损伤。作为研究最透彻的炎症小体,NLRP3 炎症小体已被证明是 ICCVDs 的潜在治疗靶点。在这篇综述中,我们总结了通过调节 NLRP3 炎症小体来影响 ICCVDs 的中草药机制。我们的研究发现,中草药的活性化合物在不同的 ICCVDs 模型中对 NLRP3 有负面影响。黄芪甲苷 IV 可能通过影响细胞膜受体来抑制 NLRP3 的激活。白藜芦醇、秋水仙碱、丹酚酸 B、大黄素和萝卜硫素可能通过抑制 ASC 或 Caspase-1 直接损害 NLRP3 的形成。大多数活性天然化合物可以通过负调控 NLRP3 炎症小体的下游产物如 IL-18 和 IL-1β来发挥作用。此外,汉防己甲素、鲁斯可皂苷元、白藜芦醇、牛蒡子苷元和蝙蝠葛苏林碱等中草药可能通过诱导自噬激活来下调 NLRP3 炎症小体。由于具有多靶点作用的优势,中草药可以通过抑制 NLRP3 炎症小体来作为 ICCVDs 的一种出色治疗方法。

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