Research Papers:
Notoginsenoside R1 ameliorates diabetic encephalopathy by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation
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Abstract
Yadong Zhai1,2,3,*, Xiangbao Meng1,2,3,*, Yun Luo1,2,3, Yongmei Wu4, Tianyuan Ye1,2,3, Ping Zhou1,2,3, Shilan Ding1,2,3, Min Wang5, Senbao Lu6, Lili Zhu7, Guibo Sun1,2,3 and Xiaobo Sun1,2,3
1Beijing 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, China
2Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, China
3Key Laboratory of Efficacy Evaluation of Chinese Medicine Against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing, China
4Department of Pharmacology, Changchun University of Traditional Chinese Medicine, Changchun, China
5College of Pharmacy, Harbin University of Commerce, Harbin, China
6Department of Bioengineering, Santa Clara University, Santa Clara, California, USA
7Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
*These authors have contributed equally to this work
Correspondence to:
Guibo Sun, email: [email protected]
Xiaobo Sun, email: [email protected]
Keywords: Notoginsenoside R1; diabetic encephalopathy; oxidative stress; Nrf2 pathway; NLRP3 inflammasome
Received: September 19, 2017 Accepted: December 04, 2017 Published: January 16, 2018
ABSTRACT
Numerous researches supported that oxidative stress and inflammation play important roles in the development of diabetic encephalopathy (DEP). Notoginsenoside R1 (NGR1), one major component of Panax notoginseng, is believed to have anti-oxidative, anti-inflammatory and neuroprotective properties. However, its neuroprotective effects against DEP and underlying mechanisms are still unknown. In this study, db/db mice as well as high-glucose (HG)-treated HT22 hippocampal neurons were used as in vivo and in vitro models to estimate NGR1 neuroprotection. NGR1 administration for 10 weeks could ameliorate cognitive dysfunction, depression-like behaviors, insulin resistance, hyperinsulinemia, dyslipidemia, and inflammation in db/db mice. NGR1 markedly decreased the oxidative stress induced by hyperglycemia in hippocampal neurons. NGR1 significantly activated the protein kinase B (Akt)/nuclear factor-erythroid 2-related factor2 (Nrf2) pathway, and inhibited NLRP3 inflammasome activation in hippocampal neurons, which might be essential for the neuroprotective effects of NGR1. Further supporting these results, we observed that pretreatment with the phosphatidylinositol 3-kinase inhibitor LY294002 abolished NGR1-mediated neuroprotective effects against oxidative stress and NLRP3 inflammasome activation in HG-treated HT22 hippocampal neurons. In conclusion, the present study demonstrates the neuroprotective effects of NGR1 on DEP by activating the Akt/Nrf2 pathway and inhibiting NLRP3 inflammasome activation. This study also provides a novel strategy for the application of NGR1 as a therapeutic agent for patients with DEP.
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