Notoginsenoside R1 ameliorates diabetic encephalopathy by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation

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.

Quercetin protects against diabetic encephalopathy via SIRT1/NLRP3 pathway in db/db mice

“…The activation of NLRP3 inflammatory bodies is closely related to the pathogenesis of DM . In a previous study, NLRP3 inflammasome is activated in the neurons of hippocampus in db/db mice . NLRP3 catalyzes the activation of caspase‐1, thereby promoting the maturation and secretion of IL‐1β and IL‐18 .…”

“…NLRP3 catalyzes the activation of caspase‐1, thereby promoting the maturation and secretion of IL‐1β and IL‐18 . Studies have found that inhibiting NLRP3 inflammasome activation can reduce IL‐1β levels in hippocampus of DM rats, and the expression level of hippocampal IL‐1β is related to cognitive function in DM mice . Quercetin has been shown to increase microglial activation and potently inhibit pro‐inflammatory factors .…”

“…53,54 In a previous study, NLRP3 inflammasome is activated in the neurons of hippocampus in db/db mice. 55 NLRP3 catalyzes the activation of caspase-1, thereby promoting the maturation and secretion of IL-1β and IL-18. 7,56 Studies have found that inhibiting NLRP3 inflammasome activation can reduce IL-1β levels in hippocampus of DM rats, 57 and the expression level of hippocampal IL-1β is related to cognitive function in DM mice.…”

“…7,56 Studies have found that inhibiting NLRP3 inflammasome activation can reduce IL-1β levels in hippocampus of DM rats, 57 and the expression level of hippocampal IL-1β is related to cognitive function in DM mice. 55 Quercetin has been shown to increase microglial activation and potently inhibit pro-inflammatory factors. 58 In addition, quercetin attenuates NLRP3 inflammatory activation and lipid accumulation in diabetic rats.…”

RETRACTED ARTICLE: Notoginsenoside R1 alleviates TNF-α-induced pancreatic β-cell Min6 apoptosis and dysfunction through up-regulation of miR-29a

“…For example, NGR1 ameliorated podocyte injury in rats with diabetic nephropathy through actuating phosphatidylinositol 3'-kinase (PI3K)/protein kinase B (AKT) signal ways [9]. Recent studies showed that NGR1 provided a novel treatment for diabetic kidney disease [10], and NGR1 could ameliorate diabetic encephalopathy [11]. However, seldom studies about the effects of NGR1 on DM were performed till now.…”