Panax notoginseng Saponins Attenuate Cerebral Ischemia-Reperfusion Injury via Mitophagy-Induced Inhibition of NLRP3 Inflammasome in Rats

² 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

^*Correspondence: biaotang@hnucm.edu.cn (Biao Tang)
^†These authors contributed equally.
Academic Editor: Mateusz Maciejczyk

Front. Biosci. (Landmark Ed) 2022, 27(11), 300; https://doi.org/10.31083/j.fbl2711300

Submitted: 6 August 2022 | Revised: 16 September 2022 | Accepted: 26 September 2022 | Published: 3 November 2022

This is an open access article under the CC BY 4.0 license.

Abstract

Background: The mitophagy/NLRP3 inflammasome pathway is a promising therapeutic target for cerebral ischemia-reperfusion (I/R). Panax notoginseng (Burkill) F.H. Chen, one of the most valuable components of traditional Chinese medicine, and Panax notoginseng saponins (PNS), the main active ingredients of P. notoginseng, 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. Methods: 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. Results: 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. Conclusions: 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.

Keywords

Panax notoginseng saponins

NLRP3 inflammasome

mitophagy

cerebral ischemia-reperfusion

PINK1

Parkin

Funding

81503385/National Natural Science Foundation of China

2021JJ30505/Hunan Provincial Natural Science Foundation of China

B202303079716/Hunan Provincial Health and Family Planning Commission Project

202024/Scientific Research Foundation of the Hunan University of Chinese Medicine

Figures

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Fig. 1.

NLRP3 inflammasome was activated, and suppressing it reduced injury during cerebral I/R in rats. (a) WB bands of NLRP3 inflammasome-related proteins in different groups. (b–i) Comparisons of relative protein expression levels among groups (n = 5). (j) TTC-stained brain slices; pale areas are infarcted (n = 8). * p $<$ 0.05, ** p $<$ 0.01 vs. the sham group; ${}^{\#}$ p $<$ 0.05, ${}^{\#\#}$ p $<$ 0.01 vs. the 0-h reperfusion group. (k) Statistical bar chart of determined cerebral-infarct volumes, created using Image-Pro Plus software (n = 8). (l) Statistical bar chart of evaluated NDS (n = 11). ** p $<$ 0.01 vs. sham group; ${}^{\#\#}$ p $<$ 0.01 vs. model group.

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