{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:42:34Z","timestamp":1790422954220,"version":"4.1.0"},"reference-count":40,"publisher":"IMR Press","issue":"11","license":[{"start":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T00:00:00Z","timestamp":1667433600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81503385"],"award-info":[{"award-number":["81503385"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004735","name":"Hunan Provincial Natural Science Foundation of China","doi-asserted-by":"crossref","award":["2021JJ30505"],"award-info":[{"award-number":["2021JJ30505"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Hunan Provincial Health and Family Planning Commission Project","award":["B202303079716"],"award-info":[{"award-number":["B202303079716"]}]},{"name":"Scientific Research Foundation of the Hunan University of Chinese Medicine","award":["202024"],"award-info":[{"award-number":["202024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Landmark Ed)"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.31083\/j.fbl2711300","type":"journal-article","created":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T01:29:42Z","timestamp":1667525382000},"source":"Crossref","is-referenced-by-count":15,"title":["Panax notoginseng Saponins Attenuate Cerebral Ischemia-Reperfusion Injury via Mitophagy-Induced Inhibition of NLRP3 Inflammasome in Rats"],"prefix":"10.31083","volume":"27","author":[{"given":"Qian","family":"Xiao","sequence":"first","affiliation":[{"name":"Medical School, Hunan University of Chinese Medicine, 410208 Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhineng","family":"Kang","sequence":"first","affiliation":[{"name":"Medical School, Hunan University of Chinese Medicine, 410208 Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Canwen","family":"Liu","sequence":"first","affiliation":[{"name":"Medical School, Hunan University of Chinese Medicine, 410208 Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Tang","sequence":"first","affiliation":[{"name":"Medical School, Hunan University of Chinese Medicine, 410208 Changsha, Hunan, China"},{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2022,11,3]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Kim J, Thayabaranathan T, Donnan GA, Howard G, Howard VJ, Rothwell PM, et al. Global Stroke Statistics 2019. International Journal of Stroke. 2020; 15: 819\u2013838.","DOI":"10.1177\/1747493020909545"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Wu M, Yiang G, Liao W, Tsai A, Cheng Y, Cheng P, et al. Current Mechanistic Concepts in Ischemia and Reperfusion Injury. Cellular Physiology and Biochemistry. 2018; 46: 1650\u20131667.","DOI":"10.1159\/000489241"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Prabhakaran S, Ruff I, Bernstein RA. Acute Stroke Intervention. JAMA. 2015; 313: 1451.","DOI":"10.1001\/jama.2015.3058"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Malone K, Amu S, Moore AC, Waeber C. The immune system and stroke: from current targets to future therapy. Immunology and Cell Biology. 2019; 97: 5\u201316.","DOI":"10.1111\/imcb.12191"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Wang P, Shao B, Deng Z, Chen S, Yue Z, Miao C. Autophagy in ischemic stroke. Progress in Neurobiology. 2018; 163-164: 98\u2013117.","DOI":"10.1016\/j.pneurobio.2018.01.001"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Jiang X, Andjelkovic AV, Zhu L, Yang T, Bennett MVL, Chen J, et al. Blood-brain barrier dysfunction and recovery after ischemic stroke. Progress in Neurobiology. 2018; 163-164: 144\u2013171.","DOI":"10.1016\/j.pneurobio.2017.10.001"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Mizuma A, Yenari MA. Anti-Inflammatory Targets for the Treatment of Reperfusion Injury in Stroke. Frontiers in Neurology. 2017; 8: 467.","DOI":"10.3389\/fneur.2017.00467"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Mangan MSJ, Olhava EJ, Roush WR, Seidel HM, Glick GD, Latz E. Targeting the NLRP3 inflammasome in inflammatory diseases. Nature Reviews Drug Discovery. 2018; 17: 588\u2013606.","DOI":"10.1038\/nrd.2018.97"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Spel L, Martinon F. Inflammasomes contributing to inflammation in arthritis. Immunological Reviews. 2020; 294: 48\u201362.","DOI":"10.1111\/imr.12839"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Shao N, Yu X, Ma X, Lin W, Hao M, Kuang H. Exenatide Delays the Progression of Nonalcoholic Fatty Liver Disease in C57BL\/6 Mice, which may Involve Inhibition of the NLRP3 Inflammasome through the Mitophagy Pathway. Gastroenterology Research and Practice. 2018; 2018: 1\u20139.","DOI":"10.1155\/2018\/1864307"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Mai C, Wu M, Wang C, Su Z, Cheng Y, Zhang X. Palmatine attenuated dextran sulfate sodium (DSS)-induced colitis via promoting mitophagy-mediated NLRP3 inflammasome inactivation. Molecular Immunology. 2019; 105: 76\u201385.","DOI":"10.1016\/j.molimm.2018.10.015"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Xu Y, Wang J, Xu W, Ding F, Ding W. Prohibitin 2-mediated mitophagy attenuates renal tubular epithelial cells injury by regulating mitochondrial dysfunction and NLRP3 inflammasome activation. American Journal of Physiology-Renal Physiology. 2019; 316: F396\u2013F407.","DOI":"10.1152\/ajprenal.00420.2018"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Ren J, Pei Z, Chen X, Berg MJ, Matrougui K, Zhang Q, et al. Inhibition of CYP2E1 attenuates myocardial dysfunction in a murine model of insulin resistance through NLRP3-mediated regulation of mitophagy. Biochimica Et Biophysica Acta (BBA) - Molecular Basis of Disease. 2019; 1865: 206\u2013217.","DOI":"10.1016\/j.bbadis.2018.08.017"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"Liu H, You L, Wu J, Zhao M, Guo R, Zhang H, et al. Berberine suppresses influenza virus\u2010triggered NLRP3 inflammasome activation in macrophages by inducing mitophagy and decreasing mitochondrial ROS. Journal of Leukocyte Biology. 2020; 108: 253\u2013266.","DOI":"10.1002\/JLB.3MA0320-358RR"},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"Tong Q, Zhu PC, Zhuang Z, Deng LH, Wang ZH, Zeng H, et al. Notoginsenoside R1 for Organs Ischemia\/Reperfusion Injury: A Preclinical Systematic Review. Frontiers in Pharmacology. 2019; 10: 1204.","DOI":"10.3389\/fphar.2019.01204"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"Peiran L, Ying L, Mingzhuo Z, Ye Y, Xiuming C. The development of a Panax notoginseng medicinal liquor processing technology using the response surface method and a study of its antioxidant activity and its effects on mouse melanoma B16 cells. Food & Function. 2017; 8: 4251\u20134264.","DOI":"10.1039\/C7FO00880E"},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"Zhang X, Wu J, Zhang B. Xuesaitong injection as one adjuvant treatment of acute cerebral infarction: a systematic review and meta-analysis. BMC Complementary and Alternative Medicine. 2015; 15: 36.","DOI":"10.1186\/s12906-015-0560-4"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Hu S, Wu Y, Zhao B, Hu H, Zhu B, Sun Z, et al. Panax notoginseng Saponins Protect Cerebral Microvascular Endothelial Cells against Oxygen-Glucose Deprivation\/Reperfusion-Induced Barrier Dysfunction via Activation of PI3K\/Akt\/Nrf2 Antioxidant Signaling Pathway. Molecules. 2018; 23: 2781.","DOI":"10.3390\/molecules23112781"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Shi X, Yu W, Liu L, Liu W, Zhang X, Yang T, et al. Panax notoginseng saponins administration modulates pro- \/anti-inflammatory factor expression and improves neurologic outcome following permanent MCAO in rats. Metabolic Brain Disease. 2017; 32: 221\u2013233.","DOI":"10.1007\/s11011-016-9901-3"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Liu L, Zhu L, Zou Y, Liu W, Zhang X, Wei X, et al. Panax notoginseng saponins promotes stroke recovery by influencing expression of Nogo-A, NgR and p75NGF, in vitro and in vivo. Biological & Pharmaceutical Bulletin. 2014; 37: 560\u2013568.","DOI":"10.1248\/bpb.b13-00770"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Tang B, She X, Deng CQ. Effect of the combination of astragaloside IV and Panax notoginseng saponins on pyroptosis and necroptosis in rat models of cerebral ischemia-reperfusion. Experimental and Therapeutic Medicine. 2021; 22: 1123.","DOI":"10.3892\/etm.2021.10557"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"Li Q, Zhang T, Wang J, Zhang Z, Zhai Y, Yang G, et al. Rapamycin attenuates mitochondrial dysfunction via activation of mitophagy in experimental ischemic stroke. Biochemical and Biophysical Research Communications. 2014; 444: 182\u2013188.","DOI":"10.1016\/j.bbrc.2014.01.032"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"Yu J, Li X, Matei N, McBride D, Tang J, Yan M, et al. Ezetimibe, a NPC1L1 inhibitor, attenuates neuronal apoptosis through AMPK dependent autophagy activation after MCAO in rats. Experimental Neurology. 2018; 307: 12\u201323.","DOI":"10.1016\/j.expneurol.2018.05.022"},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"Zhang X, Yan H, Yuan Y, Gao J, Shen Z, Cheng Y, et al. Cerebral ischemia-reperfusion-induced autophagy protects against neuronal injury by mitochondrial clearance. Autophagy. 2013; 9: 1321\u20131333.","DOI":"10.4161\/auto.25132"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"Li JR, Xu HZ, Nie S, Peng YC, Fan LF, Wang ZJ, et al. Fluoxetine-enhanced autophagy ameliorates early brain injury via inhibition of NLRP3 inflammasome activation following subrachnoid hemorrhage in rats. Journal of Neuroinflammation. 2017; 14: 186.","DOI":"10.1186\/s12974-017-0959-6"},{"key":"ref26","unstructured":"Li JX, Yang XQ, Tang B, Liu XD, Tang YH, Deng CQ, et al. [Effect of astragaloside IV combined with Panax notoginseng saponins on cerebral ischemia-reperfusion injury and study of pharmacokinetics in rats]. Zhongguo Zhong Yao Za Zhi. 2017; 42: 3786\u20133794."},{"key":"ref27","doi-asserted-by":"crossref","unstructured":"Li H, Deng C, Chen B, Zhang S, Liang Y, Luo X. Total saponins of Panax Notoginseng modulate the expression of caspases and attenuate apoptosis in rats following focal cerebral ischemia-reperfusion. Journal of Ethnopharmacology. 2009; 121: 412\u2013418.","DOI":"10.1016\/j.jep.2008.10.042"},{"key":"ref28","doi-asserted-by":"crossref","unstructured":"Yuan Y, Zheng Y, Zhang X, Chen Y, Wu X, Wu J, et al. BNIP3L\/NIX-mediated mitophagy protects against ischemic brain injury independent of PARK2. Autophagy. 2017; 13: 1754\u20131766.","DOI":"10.1080\/15548627.2017.1357792"},{"key":"ref29","doi-asserted-by":"crossref","unstructured":"Li S, Chen L, Zhou X, Li J, Liu J. MiRNA-223-3p and let-7b-3p as potential blood biomarkers associated with the ischemic penumbra in rats. Acta Neurobiologiae Experimentalis. 2019; 79: 205\u2013216.","DOI":"10.21307\/ane-2019-018"},{"key":"ref30","doi-asserted-by":"crossref","unstructured":"Fann DY, Lim Y, Cheng Y, Lok K, Chunduri P, Baik S, et al. Evidence that NF-\u03baB and MAPK Signaling Promotes NLRP Inflammasome Activation in Neurons Following Ischemic Stroke. Molecular Neurobiology. 2018; 55: 1082\u20131096.","DOI":"10.1007\/s12035-017-0394-9"},{"key":"ref31","doi-asserted-by":"crossref","unstructured":"Chen A, Xu Y, Yuan J. Ginkgolide B ameliorates NLRP3 inflammasome activation after hypoxic\u2010ischemic brain injury in the neonatal male rat. International Journal of Developmental Neuroscience. 2018; 69: 106\u2013111.","DOI":"10.1016\/j.ijdevneu.2018.07.004"},{"key":"ref32","doi-asserted-by":"crossref","unstructured":"Zhang S, Jiang L, Che F, Lu Y, Xie Z, Wang H. Arctigenin attenuates ischemic stroke via SIRT1-dependent inhibition of NLRP3 inflammasome. Biochemical and Biophysical Research Communications. 2017; 493: 821\u2013826.","DOI":"10.1016\/j.bbrc.2017.08.062"},{"key":"ref33","doi-asserted-by":"crossref","unstructured":"Hou Y, Wang Y, He Q, Li L, Xie H, Zhao Y, et al. Nrf2 inhibits NLRP3 inflammasome activation through regulating Trx1\/TXNIP complex in cerebral ischemia reperfusion injury. Behavioural Brain Research. 2018; 336: 32\u201339.","DOI":"10.1016\/j.bbr.2017.06.027"},{"key":"ref34","doi-asserted-by":"crossref","unstructured":"Rabuffetti M, Sciorati C, Tarozzo G, Clementi E, Manfredi AA, Beltramo M. Inhibition of Caspase-1-Like Activity by Ac-Tyr-Val-Ala-Asp-Chloromethyl Ketone Induces Long-Lasting Neuroprotection in Cerebral Ischemia through Apoptosis Reduction and Decrease of Proinflammatory Cytokines. The Journal of Neuroscience. 2000; 20: 4398\u20134404.","DOI":"10.1523\/JNEUROSCI.20-12-04398.2000"},{"key":"ref35","doi-asserted-by":"crossref","unstructured":"Meng L, Lin J, Huang Q, Liang P, Huang J, Jian C, et al. Panax notoginseng Saponins Attenuate Oxygen-Glucose Deprivation\/Reoxygenation-Induced Injury in Human SH-SY5Y Cells by Regulating the Expression of Inflammatory Factors through miR-155. Biological & Pharmaceutical Bulletin. 2019; 42: 462\u2013467.","DOI":"10.1248\/bpb.b18-00799"},{"key":"ref36","doi-asserted-by":"crossref","unstructured":"Lan R, Zhang Y, Wu T, Ma Y, Wang B, Zheng H, et al. Xiao-Xu-Ming Decoction Reduced Mitophagy Activation and Improved Mitochondrial Function in Cerebral Ischemia and Reperfusion Injury. Behavioural Neurology. 2018; 2018: 1\u201312.","DOI":"10.1155\/2018\/4147502"},{"key":"ref37","doi-asserted-by":"crossref","unstructured":"Shen Z, Zheng Y, Wu J, Chen Y, Wu X, Zhou Y, et al. PARK2-dependent mitophagy induced by acidic postconditioning protects against focal cerebral ischemia and extends the reperfusion window. Autophagy. 2017; 13: 473\u2013485.","DOI":"10.1080\/15548627.2016.1274596"},{"key":"ref38","doi-asserted-by":"crossref","unstructured":"Liang X, Yang Y, Huang Z, Zhou J, Li Y, Zhong X. Panax notoginseng saponins mitigate cisplatin induced nephrotoxicity by inducing mitophagy via HIF-1\u03b1. Oncotarget. 2017; 8: 102989\u2013103003.","DOI":"10.18632\/oncotarget.19900"},{"key":"ref39","doi-asserted-by":"crossref","unstructured":"Eiyama A, Okamoto K. PINK1\/Parkin-mediated mitophagy in mammalian cells. Current Opinion in Cell Biology. 2015; 33: 95\u2013101.","DOI":"10.1016\/j.ceb.2015.01.002"},{"key":"ref40","doi-asserted-by":"crossref","unstructured":"Lan R, Wu J, Wu T, Ma Y, Wang B, Zheng H, et al. Mitophagy is activated in brain damage induced by cerebral ischemia and reperfusion via the PINK1\/Parkin\/p62 signalling pathway. Brain Research Bulletin. 2018; 142: 63\u201377.","DOI":"10.1016\/j.brainresbull.2018.06.018"}],"container-title":["Frontiers in Bioscience-Landmark"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/FBL\/27\/11\/10.31083\/j.fbl2711300","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T12:10:21Z","timestamp":1732709421000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/FBL\/27\/11\/10.31083\/j.fbl2711300"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,3]]},"references-count":40,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2022]]}},"alternative-id":["S2768-6701(22)00648-7"],"URL":"https:\/\/doi.org\/10.31083\/j.fbl2711300","relation":{},"ISSN":["2768-6701","2768-6698"],"issn-type":[{"value":"2768-6701","type":"print"},{"value":"2768-6698","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,3]]},"article-number":"300"}}