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Article

HMGB1-triggered inflammation inhibition of notoginseng leaf triterpenes against cerebral ischemia and reperfusion injury via MAPK and NF-κB signaling pathways

by 1,2,3,4,5, 1,2,3,4,5, 1,2,3,4,5, 1,2,3,4,5, 1,2,3,4,5, 1,2,3,4,5, 1,2,3,4,5,* and 1,2,3,4,5,*
1
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
2
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 & Peking Union Medical College, Beijing 100193, China
3
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
4
Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China
5
Key Laboratory of new drug discovery based on Classic Chinese medicine prescription, Chinese Academy of Medical Sciences, Beijing 100193, China
*
Authors to whom correspondence should be addressed.
Biomolecules 2019, 9(10), 512; https://doi.org/10.3390/biom9100512
Received: 2 September 2019 / Revised: 18 September 2019 / Accepted: 18 September 2019 / Published: 20 September 2019
(This article belongs to the Special Issue Advances in Ginsenosides)
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-α, IL-1 β, 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-κB and phosphorylated NF-κB 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-κB, 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. View Full-Text
Keywords: notoginseng leaf triterpenes; HMGB1; cerebral ischemia and reperfusion injury; inflammation; MAPK; NF-κB notoginseng leaf triterpenes; HMGB1; cerebral ischemia and reperfusion injury; inflammation; MAPK; NF-κB
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MDPI and ACS Style

Xie, W.; Zhu, T.; Dong, X.; Nan, F.; Meng, X.; Zhou, P.; Sun, G.; Sun, X. HMGB1-triggered inflammation inhibition of notoginseng leaf triterpenes against cerebral ischemia and reperfusion injury via MAPK and NF-κB signaling pathways. Biomolecules 2019, 9, 512. https://doi.org/10.3390/biom9100512

AMA Style

Xie W, Zhu T, Dong X, Nan F, Meng X, Zhou P, Sun G, Sun X. HMGB1-triggered inflammation inhibition of notoginseng leaf triterpenes against cerebral ischemia and reperfusion injury via MAPK and NF-κB signaling pathways. Biomolecules. 2019; 9(10):512. https://doi.org/10.3390/biom9100512

Chicago/Turabian Style

Xie, Weijie, Ting Zhu, Xi Dong, Fengwei Nan, Xiangbao Meng, Ping Zhou, Guibo Sun, and Xiaobo Sun. 2019. "HMGB1-triggered inflammation inhibition of notoginseng leaf triterpenes against cerebral ischemia and reperfusion injury via MAPK and NF-κB signaling pathways" Biomolecules 9, no. 10: 512. https://doi.org/10.3390/biom9100512

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