Medical School, Hunan University of Chinese Medicine, 410208 Changsha, Hunan, China.
National Key Laboratory Cultivation Base of Chinese Medicinal Powder & Innovative Medicinal Jointly Established by Province and Ministry, Hunan University of Chinese Medicine, 410208 Changsha, Hunan, China.
Front Biosci (Landmark Ed). 2022 Nov 3;27(11):300. doi: 10.31083/j.fbl2711300.
The mitophagy/NLRP3 inflammasome pathway is a promising therapeutic target for cerebral ischemia-reperfusion (I/R). () F.H. Chen, one of the most valuable components of traditional Chinese medicine, and saponins (PNS), the main active ingredients of , are patent medicines commonly used to treat cardio- and cerebrovascular diseases. However, their effects on the mitophagy and the NLRP3 inflammasome activation in I/R remain unclear. Therefore, in this study, we investigated how PNS might affect the mitophagy/NLRP3 inflammasome pathway in I/R.
Cerebral I/R injury was induced by middle cerebral-artery occlusion, and expression levels of NLRP3 inflammasome signaling pathway-associated proteins were detected by western blot. We tested I/R injury using a neurological-deficit score, infarct volume, and hematoxylin and eosin staining, after which we detected both mitophagy- and NLRP3 inflammasome-related proteins in PNS-treated rats to determine whether PNS could attenuate I/R injury and the possible mechanisms involved.
Our results showed that cerebral I/R could induce activation of the NLRP3 inflammasome, aggravating brain injury, whereas PNS effectively alleviated cerebral I/R injury in rats by inhibiting the NLRP3 inflammasome and promoting mitophagy via the PINK1/Parkin pathway. Moreover, mitophagy inhibited the NLRP3 inflammasome and mediated the anti-injury effects of PNS.
In conclusion, PNS could promote mitophagy via the PINK1/Parkin pathway by inhibiting activation of the NLRP3 inflammasome, alleviating cerebral I/R injury in rats.
自噬/NLRP3 炎性小体途径是脑缺血再灌注（I/R）的有前途的治疗靶点。（）陈富华，是中药最有价值的成分之一，和 皂甙（PNS），是 的主要活性成分，是常用于治疗心脑血管疾病的专利药物。然而，它们对 I/R 中自噬和 NLRP3 炎性小体激活的影响尚不清楚。因此，在这项研究中，我们研究了 PNS 如何影响 I/R 中的自噬/NLRP3 炎性小体途径。
通过大脑中动脉闭塞诱导脑 I/R 损伤，通过 Western blot 检测 NLRP3 炎性小体信号通路相关蛋白的表达水平。我们使用神经缺陷评分、梗塞体积和苏木精和伊红染色测试 I/R 损伤，然后在 PNS 处理的大鼠中检测自噬和 NLRP3 炎性小体相关蛋白，以确定 PNS 是否可以减轻 I/R 损伤及其可能涉及的机制。
我们的结果表明，脑 I/R 可诱导 NLRP3 炎性小体的激活，加重脑损伤，而 PNS 通过抑制 NLRP3 炎性小体并通过 PINK1/Parkin 途径促进自噬，有效减轻大鼠脑 I/R 损伤。此外，自噬抑制 NLRP3 炎性小体并介导 PNS 的抗损伤作用。
总之，PNS 通过抑制 NLRP3 炎性小体的激活，通过 PINK1/Parkin 途径促进自噬，减轻大鼠脑 I/R 损伤。
