{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:19:21Z","timestamp":1790090361184,"version":"4.0.1"},"reference-count":59,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,9,20]],"date-time":"2019-09-20T00:00:00Z","timestamp":1568937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Ischemic stroke is a clinically common cerebrovascular disease whose main risks include necrosis, apoptosis and cerebral infarction, all caused by cerebral ischemia and reperfusion (I\/R) injury. This process has particular significance for the treatment of stroke patients. Notoginseng leaf triterpenes (PNGL), as a valuable medicine, have been discovered to have neuroprotective effects. However, it was not confirmed that whether PNGL may possess neuroprotective effects against cerebral I\/R injury. To explore the neuroprotective effects of PNGL and their underlying mechanisms, a middle cerebral artery occlusion\/reperfusion (MCAO\/R) model was established. In vivo results suggested that in MCAO\/R model rats, PNGL pretreatment (73.0, 146, 292 mg\/kg) remarkably decreased infarct volume, reduced brain water content, and improved neurological functions; moreover, PNGL (73.0, 146, 292 mg\/kg) significantly alleviated blood-brain barrier (BBB) disruption and inhibited neuronal apoptosis and neuronal loss caused by cerebral I\/R injury, while PNGL with a different concertation (146, 292 mg\/kg) significantly reduced the concentrations of IL-6, TNF-\u03b1, IL-1 \u03b2, and HMGB1 in serums in a dose-dependent way, which indicated that inflammation inhibition could be involved in the neuroprotective effects of PNGL. The immunofluorescence and western blot analysis showed PNGL decreased HMGB1 expression, suppressed the HMGB1-triggered inflammation, and inhibited microglia activation (IBA1) in hippocampus and cortex, thus dose-dependently downregulating inflammatory cytokines including VCAM-1, MMP-9, MMP-2, and ICAM-1 concentrations in ischemic brains. Interestingly, PNGL administration (146 mg\/kg) significantly downregulated the levels of p-P44\/42, p-JNK1\/2 and p-P38 MAPK, and also inhibited expressions of the total NF-\u03baB and phosphorylated NF-\u03baB in ischemic brains, which was the downstream pathway triggered by HMGB1. All of these results indicated that the protective effects of PNGL against cerebral I\/R injury could be associated with inhibiting HMGB1-triggered inflammation, suppressing the activation of MAPKs and NF-\u03baB, and thus improved cerebral I\/R-induced neuropathological changes. This study may offer insight into discovering new active compounds for the treatment of ischemic stroke.<\/jats:p>","DOI":"10.3390\/biom9100512","type":"journal-article","created":{"date-parts":[[2019,9,20]],"date-time":"2019-09-20T10:48:14Z","timestamp":1568976494000},"page":"512","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":127,"title":["HMGB1-triggered inflammation inhibition of notoginseng leaf triterpenes against cerebral ischemia and reperfusion injury via MAPK and NF-\u03baB signaling pathways"],"prefix":"10.3390","volume":"9","author":[{"given":"Weijie","family":"Xie","sequence":"first","affiliation":[{"name":"Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China"},{"name":"Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100193, China"},{"name":"Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China"},{"name":"Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100193, China"},{"name":"Key Laboratory of new drug discovery based on Classic Chinese medicine prescription, Chinese Academy of Medical Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5062-7843","authenticated-orcid":false,"given":"Ting","family":"Zhu","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China"},{"name":"Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100193, China"},{"name":"Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China"},{"name":"Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100193, China"},{"name":"Key Laboratory of new drug discovery based on Classic Chinese medicine prescription, Chinese Academy of Medical Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Dong","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China"},{"name":"Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100193, China"},{"name":"Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China"},{"name":"Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100193, China"},{"name":"Key Laboratory of new drug discovery based on Classic Chinese medicine prescription, Chinese Academy of Medical Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengwei","family":"Nan","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China"},{"name":"Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100193, China"},{"name":"Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China"},{"name":"Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100193, China"},{"name":"Key Laboratory of new drug discovery based on Classic Chinese medicine prescription, Chinese Academy of Medical Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangbao","family":"Meng","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China"},{"name":"Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100193, China"},{"name":"Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China"},{"name":"Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100193, China"},{"name":"Key Laboratory of new drug discovery based on Classic Chinese medicine prescription, Chinese Academy of Medical Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Zhou","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China"},{"name":"Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100193, China"},{"name":"Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China"},{"name":"Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100193, China"},{"name":"Key Laboratory of new drug discovery based on Classic Chinese medicine prescription, Chinese Academy of Medical Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guibo","family":"Sun","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China"},{"name":"Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100193, China"},{"name":"Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China"},{"name":"Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100193, China"},{"name":"Key Laboratory of new drug discovery based on Classic Chinese medicine prescription, Chinese Academy of Medical Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobo","family":"Sun","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China"},{"name":"Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100193, China"},{"name":"Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China"},{"name":"Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100193, China"},{"name":"Key Laboratory of new drug discovery based on Classic Chinese medicine prescription, Chinese Academy of Medical Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,20]]},"reference":[{"key":"ref_1","unstructured":"Jamison, J.T. 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