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The combination of Panax ginseng and Angelica sinensis alleviates ischemia brain injury by suppressing NLRP3 inflammasome activation and microglial pyroptosis.
Phytomedicine. 2020 May 29; 76:153251.P

Abstract

BACKGROUND

The combination of Panax ginseng and Angelica sinensis (CPA) has been used to treat stroke for one thousand years and demonstrated clinically to have satisfied effects. However, the underlying mechanism remains unknown.

PURPOSE

We investigate whether CPA has neuroprotective effects via suppressing Nod-like receptor protein 3 (NLRP3) inflammasome and microglial pyroptosis against ischemic injury in transient middle cerebral artery occlusion (MCAO) rats.

METHODS

Male rats were divided randomly into sham operated, MCAO, MCC950 (NLRP3-specific inhibitor) and CPA groups. Neurological deficits, glucose uptake, infarct size, activation of NLRP3 inflammasomes, microglial pyroptosis and related signaling pathways were detected. BV-2 microglial cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) were used in in vitro experiments.

RESULTS

Compared with sham rats, elevated level of proinflammatory interleukin-1β (IL-1β) in plasma, neurological function deficit, reduced glucose uptake in ipsilateral hemisphere, obvious infarct size, the activation of NLRP3 inflammasomes and enhanced microglial pyroptosis were presented in MCAO rats. The administrations of MCC950 and CPA respectively reversed the results. In vitro OGD/R induced the release of lactate dehydrogenase, promoted NLRP3 inflammasomes activation and pyroptosis in BV-2 cells, which was significantly suppressed by treatment with ginsenoside Rd (Rd) and Z-ligustilide (LIG). Mechanistically, OGD/R induced high expression of dynamin-related protein 1 (Drp1) and mitochondrial fission, as well as NLRP3 inflammasomes activation and pyroptosis in BV-2 cells, which was attenuated by treatment with Rd and LIG. Moreover, the increased expression of Drp1 was validated in MCAO rats, and also abolished by MCC950 or CPA treatments.

CONCLUSION

CPA treatment attenuates cerebral injury via inhibition of NLRP3 inflammasomes activation and microglial pyroptosis after stroke, which at least partially involved in the amelioration of Drp1-mediated mitochondrial fission.

Authors+Show Affiliations

Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.Department of Pharmacology, Guangxi Institute of Chinese Medicine and Pharmaceutical Science, Nanning, Guangxi 530022, China.Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China. Electronic address: yonghuazhao@um.edu.mo.Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. Electronic address: tanhm@mail.sysu.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32531700

Citation

Hu, Jia, et al. "The Combination of Panax Ginseng and Angelica Sinensis Alleviates Ischemia Brain Injury By Suppressing NLRP3 Inflammasome Activation and Microglial Pyroptosis." Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, vol. 76, 2020, p. 153251.
Hu J, Zeng C, Wei J, et al. The combination of Panax ginseng and Angelica sinensis alleviates ischemia brain injury by suppressing NLRP3 inflammasome activation and microglial pyroptosis. Phytomedicine. 2020;76:153251.
Hu, J., Zeng, C., Wei, J., Duan, F., Liu, S., Zhao, Y., & Tan, H. (2020). The combination of Panax ginseng and Angelica sinensis alleviates ischemia brain injury by suppressing NLRP3 inflammasome activation and microglial pyroptosis. Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, 76, 153251. https://doi.org/10.1016/j.phymed.2020.153251
Hu J, et al. The Combination of Panax Ginseng and Angelica Sinensis Alleviates Ischemia Brain Injury By Suppressing NLRP3 Inflammasome Activation and Microglial Pyroptosis. Phytomedicine. 2020 May 29;76:153251. PubMed PMID: 32531700.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The combination of Panax ginseng and Angelica sinensis alleviates ischemia brain injury by suppressing NLRP3 inflammasome activation and microglial pyroptosis. AU - Hu,Jia, AU - Zeng,Cheng, AU - Wei,Jie, AU - Duan,Fengqi, AU - Liu,Sijun, AU - Zhao,Yonghua, AU - Tan,Hongmei, Y1 - 2020/05/29/ PY - 2020/02/27/received PY - 2020/05/02/revised PY - 2020/05/23/accepted PY - 2020/6/13/pubmed PY - 2020/6/13/medline PY - 2020/6/13/entrez KW - CPA KW - Ischemic stroke KW - NLRP3 inflammasomes KW - Pyroptosis SP - 153251 EP - 153251 JF - Phytomedicine : international journal of phytotherapy and phytopharmacology JO - Phytomedicine VL - 76 N2 - BACKGROUND: The combination of Panax ginseng and Angelica sinensis (CPA) has been used to treat stroke for one thousand years and demonstrated clinically to have satisfied effects. However, the underlying mechanism remains unknown. PURPOSE: We investigate whether CPA has neuroprotective effects via suppressing Nod-like receptor protein 3 (NLRP3) inflammasome and microglial pyroptosis against ischemic injury in transient middle cerebral artery occlusion (MCAO) rats. METHODS: Male rats were divided randomly into sham operated, MCAO, MCC950 (NLRP3-specific inhibitor) and CPA groups. Neurological deficits, glucose uptake, infarct size, activation of NLRP3 inflammasomes, microglial pyroptosis and related signaling pathways were detected. BV-2 microglial cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) were used in in vitro experiments. RESULTS: Compared with sham rats, elevated level of proinflammatory interleukin-1β (IL-1β) in plasma, neurological function deficit, reduced glucose uptake in ipsilateral hemisphere, obvious infarct size, the activation of NLRP3 inflammasomes and enhanced microglial pyroptosis were presented in MCAO rats. The administrations of MCC950 and CPA respectively reversed the results. In vitro OGD/R induced the release of lactate dehydrogenase, promoted NLRP3 inflammasomes activation and pyroptosis in BV-2 cells, which was significantly suppressed by treatment with ginsenoside Rd (Rd) and Z-ligustilide (LIG). Mechanistically, OGD/R induced high expression of dynamin-related protein 1 (Drp1) and mitochondrial fission, as well as NLRP3 inflammasomes activation and pyroptosis in BV-2 cells, which was attenuated by treatment with Rd and LIG. Moreover, the increased expression of Drp1 was validated in MCAO rats, and also abolished by MCC950 or CPA treatments. CONCLUSION: CPA treatment attenuates cerebral injury via inhibition of NLRP3 inflammasomes activation and microglial pyroptosis after stroke, which at least partially involved in the amelioration of Drp1-mediated mitochondrial fission. SN - 1618-095X UR - https://www.unboundmedicine.com/medline/citation/32531700/The_combination_of_Panax_ginseng_and_Angelica_sinensis_alleviates_ischemia_brain_injury_by_suppressing_NLRP3_inflammasome_activation_and_microglial_pyroptosis. L2 - https://linkinghub.elsevier.com/retrieve/pii/S0944-7113(20)30082-9 DB - PRIME DP - Unbound Medicine ER -
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