Neuroprotective Effect of Taohong Siwu Decoction on Cerebral Ischemia/Reperfusion Injury via Mitophagy-NLRP3 Inflammasome Pathway

Abstract

Objective: Globally, cerebral ischemia has been shown to be the second leading cause of death. Our previous studies have shown that Taohong Siwu Decoction (THSWD) exhibits obvious neuroprotective effects on cerebral ischemia/reperfusion (I/R) injury (CIRI). In this study, we further explored the modulatory effect of THSWD on mitochondrial autophagy in CIRI and the relationship between modulatory effect and NLRP3 inflammatory vesicle activation, so as to further explain the mechanism of neuroprotective effect of THSWD.Methods: Middle cerebral artery occlusion reperfusion (MCAO/R) model in rats was built to simulate I/R. Adult male SD rats (220–270 g) were randomly divided into the following four groups: the sham group, the MCAO/R group, the MCAO/R + THSWD group, and the MCAO/R + THSWD + Mitochondrial division inhibitor 1 (Mdivi-1) group. Neurological defect scores were used to evaluate neurological function. 2,3,5-Triphenyltetrazolium chloride (TTC) staining was conducted to measure cerebral infarct volume. Nissl staining, H&E staining and TUNEL staining were executed to detect ischemic cortical neuronal cell viability and apoptosis. Electron microscopy was used to observe the ultrastructural changes of mitochondria. Total Reactive Oxygen Species (ROS) in tissue were measured by fluorescence spectrophotometry, and the activation status of microglia was evaluated by Iba-1/CD16 immunofluorescence staining. The levels of mitophagy-related proteins (LC3, Parkin, PINK1), NLRP3 inflammasome-related proteins (NLRP3, ASC, Pro-caspase-1, Cleaved-caspase-1), and inflammatory cytokines (Pro-IL-18, Pro-IL-1β, IL-18, IL-1β) were evaluated by western blotting.Results: The studies showed that THSWD treatment alleviated cerebral infarction and neurological deficiencies. THSWD upregulated the expressions of autophagy markers (LC3-II/LC3-I and Beclin1) mitochondrial autophagy markers (Parkin and PINK1) after CIRI. Furthermore, THSWD treatment attenuated microglia activation and damage to mitochondrial structures, thereby reducing ROS production and NLRP3 inflammasome activation. In contrast, the mitochondrial autophagy inhibitor Mdivi-1 inhibited the above beneficial effects of THSWD.Conclusions: THSWD exhibits neuroprotective effects against MCAO/R in rats by enhancing mitochondrial autophagy and reducing NLRP3 inflammasome activation.

Insight into the Neuroprotective Effect of Genistein-3′-Sodium Sulfonate Against Neonatal Hypoxic-Ischaemic Brain Injury in Rats by Bioinformatics

“…In this study, GSS was found to decrease the high expression of GFAP and GBP2 after HIE in neonatal rats, indicating depressive effects of activation and A1-type polarisation on astrocytes. CD16 is one of the markers of microglial polarisation into the M1 type after activation [ 49 , 50 ]. GSS also reduced the transcription of both CD11b and CD16 mRNA as well as the protein level of CD11b, showing an inhibitory effect on the activation and polarisation of microglia.…”

Plant Photocatalysts: Photoinduced Oxidation and Reduction Abilities of Plant Leaf Ashes under Solar Light

“…For instance, the dehydrogenase activity (DHA) provides important information on the biological activity in many systems. Thus, the reduction of 2,3,5-triphenyltetrazolium chloride (TTC) to triphenylformazan (TPF) has been commonly used to estimate the DHA in soil, and TTC has been widely used as a hydrogen receptor in the enzymatic activity test [34][35][36][37]. Artificial enzyme mimetics have been intensively studied, due to some considerable shortcomings, such as a relatively low stability, and the poor recovery of natural enzymes [30,38].…”

Traditional Chinese medicine in treating ischemic stroke by modulating mitochondria: A comprehensive overview of experimental studies

“…Taohong Siwu decoction treatment for seven consecutive days decreased damage to mitochondrial structures following cerebral I/R injury ( Ji et al, 2022 ). Treatment with Huang-Lian-Jie-Du decoction, Danhong injection, and Baoyuan capsule eliminated the inhibitory effect of cerebral I/R on mitochondrial metabolism in MCAO models ( Wang et al, 2014 ; Zeng et al, 2021b ; Du et al, 2021 ).…”

“…YiQiFuMai powder injection inhibited the expression, phosphorylation, and translocation of Drp1 in oxidative stress-induced primary neurons and cerebral ischemia-injured rats, resulting in a significant improvement in cerebral infarction and neurological scores ( Xu et al, 2017 ). Taohong Siwu decoction, Danhong injection, and ANNAO tablets upregulated the expression of autophagy markers (LC3-II/LC3-I and Beclin1) ( Ji et al, 2022 ) and mitochondrial autophagy markers (Parkin ( Orgah et al, 2019 ) and PINK1 ( Zhang et al, 2020 )) after cerebral I/R injury. Mu-Xiang-You-Fang inhibits autophagy after OGD/R-induced PC12 cell injury through the AMPK-mTOR pathway ( Ma et al, 2020 ).…”