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Zhongfeng Capsules protects against cerebral ischemia-reperfusion injury via mediating the phosphoinositide 3-kinase/Akt and toll-like receptor 4/nuclear factor kappa B signaling pathways by regulating neuronal apoptosis and inflammation.
- Source :
-
Apoptosis : an international journal on programmed cell death [Apoptosis] 2022 Aug; Vol. 27 (7-8), pp. 561-576. Date of Electronic Publication: 2022 Jun 08. - Publication Year :
- 2022
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Abstract
- Inflammatory reaction and neuronal apoptosis are the major pathophysiological mechanisms involved in cerebral ischemia-reperfusion injury (CI/RI). It has been reported that Zhongfeng Capsules (ZFCs), which contain Panax notoginseng, Hirudo, Red ginseng, Eupolyphaga sinensis, Pangolin scales, Rhubarb, and Radix Salvia miltiorrhizae, have a definite therapeutic effect on CI/RI. However, the specific molecular mechanisms of ZFCs are unclear. In this study, the effects of ZFCs on middle cerebral artery occlusion were investigated in rats. Our results showed that neurological impairment and neuronal apoptosis were alleviated in ZFC-treated rats. Additionally, infarct volume and cerebral edema decreased and there was an improvement in histopathological features. Furthermore, the expression levels of IL-1β, IL-6, and TNF-α were downregulated in ZFC-treated rats. TLR 4, NF-κB, Bax, and Caspase-3 expression also tended to decrease, whereas the expression of Bcl-2, p-PI3K, p-Akt, and I-κBα increased. The results indicate that the ZFCs effectively protected the rats against CI/RI possibly via the TLR4/NF-κB signaling pathway. Additionally, the formulation regulated the transcriptional activity of NF-κB, secretion of downstream inflammatory factors, and the expression of Bcl-2-Bax proteins in the PI3K/Akt pathway. Our findings suggest that ZFCs suppress neuronal apoptosis and inflammatory reaction via the PI3K/Akt and TLR4/NF-κB signaling pathways, respectively. Moreover, activation of the PI3K/Akt pathway may result in the inhibition of proinflammatory cytokine secretion, which may be another mechanism by which ZFCs alleviate CI/RI.<br /> (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Subjects :
- Animals
Apoptosis
Capsules pharmacology
Capsules therapeutic use
Inflammation pathology
NF-kappa B genetics
NF-kappa B metabolism
Phosphatidylinositol 3-Kinase metabolism
Phosphatidylinositol 3-Kinases genetics
Phosphatidylinositol 3-Kinases metabolism
Proto-Oncogene Proteins c-akt genetics
Proto-Oncogene Proteins c-akt metabolism
Rats
Signal Transduction
Toll-Like Receptor 4 genetics
Toll-Like Receptor 4 metabolism
Toll-Like Receptor 4 therapeutic use
bcl-2-Associated X Protein metabolism
Brain Ischemia drug therapy
Brain Ischemia genetics
Brain Ischemia metabolism
Reperfusion Injury drug therapy
Reperfusion Injury genetics
Reperfusion Injury metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1573-675X
- Volume :
- 27
- Issue :
- 7-8
- Database :
- MEDLINE
- Journal :
- Apoptosis : an international journal on programmed cell death
- Publication Type :
- Academic Journal
- Accession number :
- 35674851
- Full Text :
- https://doi.org/10.1007/s10495-022-01739-8