scholarly journals Fucoxanthinol from the Diatom Nitzschia Laevis Ameliorates Neuroinflammatory Responses in Lipopolysaccharide-Stimulated BV-2 Microglia

Marine Drugs ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 116 ◽  
Author(s):  
Yuelian Li ◽  
Lu Liu ◽  
Peipei Sun ◽  
Yifeng Zhang ◽  
Tao Wu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nuclear Translocation ◽  
Mitogen Activated Protein Kinase ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Quinone Oxidoreductase ◽  
Necrosis Factor Alpha ◽  
Food Ingredients ◽  
Nitzschia Laevis ◽  
Pre Treatment

In recent years, microalgae have drawn increasing attention as a valuable source of functional food ingredients. Intriguingly, Nitzschia laevis is rich in fucoxanthinol that is seldom found in natural sources. Fucoxanthinol, a marine xanthophyll carotenoid, possesses various beneficial bioactivities. Nevertheless, it’s not clear whether fucoxanthinol could exert anti-neuroinflammatory function. In light of these premises, the aim of the present study was to investigate the anti-inflammatory role of fucoxanthinol purified from Nitzschia laevis in Lipopolysaccharide (LPS)-stimulated microglia. The results showed that pre-treatment of fucoxanthinol remarkably attenuated the expression of LPS-induced nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and the production of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), prostaglandin E2 (PGE-2), nitric oxide (NO) and reactive oxygen species (ROS) induction. Modulation mechanism studies revealed that fucoxanthinol hampered nuclear factor-kappa B (NF-κB), Akt, and mitogen-activated protein kinase (MAPK) pathways. Meanwhile, fucoxanthinol led to the enhancement of nuclear translocation of NF-E2-related factor 2 (Nrf2), and the upregulation of heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO-1). Taken together, the results indicated that fucoxanthinol obtained from Nitzschia laevis had great potential as a neuroprotective agent in neuroinflammation and neurodegenerative disorders.

scholarly journals Anti-Inflammatory and Antioxidant Effects of Soroseris hirsuta Extract by regulating iNOS/NF-κB and NRF2/HO-1 Pathways in Murine Macrophage RAW 264.7 Cells

2021 ◽  
Vol 11 (10) ◽  
pp. 4711
Author(s):  
Woo Jin Lee ◽  
Wan Yi Li ◽  
Sang Woo Lee ◽  
Sung Keun Jung
Keyword(s):  
Nitric Oxide ◽  
Nuclear Translocation ◽  
Antioxidant Properties ◽  
Raw 264.7 Cells ◽  
Heme Oxygenase 1 ◽  
Raw 264.7 ◽  
Related Factor ◽  
Iκb Kinase ◽  
Anti Inflammatory ◽  
Antioxidant Effects

Until now, the physiological effects of Soroseris hirsuta were primarily unknown. Here we have evaluated the anti-inflammatory and antioxidant effects of Soroseris hirsuta extract (SHE) on lipopolysaccharide (LPS)-activated murine macrophages RAW 264.7 cells. SHE inhibited nitric oxide expression and inducible nitric oxide synthase expression in RAW 264.7 cells treated with LPS. Moreover, SHE suppressed LPS-induced phosphorylation of IκB kinase, inhibitor of kappa B, p65, p38, and c-JUN N-terminal kinase. Western blot and immunofluorescence analyses showed that SHE suppressed p65 nuclear translocation induced by LPS. Furthermore, SHE inhibited the reactive oxygen species in LPS-treated RAW 264.7 cells. SHE significantly increased heme oxygenase-1 expression and the nuclear translocation of nuclear factor erythroid 2-related factor 2. SHE suppressed LPS-induced interleukin-1β mRNA expression in RAW 264.7 cells. Thus, SHE is a promising nutraceutical as it displays anti-inflammatory and antioxidant properties.

scholarly journals Cinnamaldehyde Ameliorates Vascular Dysfunction in Diabetic Mice by Activating Nrf2

2020 ◽  
Vol 33 (7) ◽  
pp. 610-619 ◽  
Author(s):  
Peijian Wang ◽  
Yi Yang ◽  
Dan Wang ◽  
Qiyuan Yang ◽  
Jindong Wan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Vascular Dysfunction ◽  
Mesenteric Arteries ◽  
Heme Oxygenase 1 ◽  
No Production ◽  
Related Factor ◽  
Diabetic Mice ◽  
Quinone Oxidoreductase ◽  
Nrf2 Signaling Pathway

Abstract BACKGROUND Oxidative stress is known to be associated with the development of diabetes. Cinnamaldehyde (CA) is a spice compound in cinnamon that enhances the antioxidant defense against reactive oxygen species (ROS) by activating nuclear factor erythroid-related factor 2 (Nrf2), which has been shown to have a cardioprotection effect. However, the relationship between CA and Nrf2 in diabetic vascular complications remains unclear. METHODS Leptin receptor-deficient (db/db) mice were fed normal chow or diet containing 0.02% CA for 12 weeks. The vascular tone, blood pressure, superoxide level, nitric oxide (NO) production, renal morphology, and function were measured in each group. RESULTS CA remarkably inhibited ROS generation, preserved NO production, increased phosphorylated endothelial nitric oxide synthase (p-eNOS), attenuated the upregulation of nitrotyrosine, P22 and P47 in aortas of db/db mice, and apparently ameliorated the elevation of type IV collagen, TGF-β1, P22, and P47 in kidney of db/db mice. Feeding with CA improved endothelium-dependent relaxation of aortas and mesenteric arteries, and alleviated the remodeling of mesenteric arteries in db/db mice. Additionally, dietary CA ameliorated glomerular fibrosis and renal dysfunction in diabetic mice. Nrf2 and its targeted genes heme oxygenase-1 (HO-1) and quinone oxidoreductase-1 (NQO-1) were slightly increased in db/db mice and further upregulated by CA. However, these protective effects of CA were reversed in Nrf2 downregulation mice. CONCLUSIONS A prolonged diet of CA protects against diabetic vascular dysfunction by inhibiting oxidative stress through activating of Nrf2 signaling pathway in db/db mice.

scholarly journals Synthetic Ruthenium Complex TQ-6 Potently Recovers Cerebral Ischemic Stroke: Attenuation of Microglia and Platelet Activation

2020 ◽  
Vol 9 (4) ◽  
pp. 996
Author(s):  
Chih-Hsuan Hsia ◽  
Thanasekaran Jayakumar ◽  
Joen-Rong Sheu ◽  
Chih-Wei Hsia ◽  
Wei-Chieh Huang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ischemic Stroke ◽  
Platelet Activation ◽  
Nuclear Translocation ◽  
Radical Scavenging ◽  
Microglia Activation ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Cox 2

Activated microglia are crucial in the regulation of neuronal homeostasis and neuroinflammation. They also contribute to neuropathological processes after ischemic stroke. Thus, finding new approaches for reducing neuroinflammation has gained considerable attention. The metal ruthenium has gained notable attention because of its ability to form new complexes that can be used in disease treatment. [Ru(η6-cymene)2-(1H-benzoimidazol-2-yl)-quinoline Cl]BF4 (TQ-6), a potent ruthenium (II)-derived compound, was used in this study to investigate its neuroprotective action against microglia activation, middle cerebral artery occlusion (MCAO)-induced embolic stroke, and platelet activation, respectively. TQ-6 (2 μM) potently diminished inflammatory mediators (nitric oxide/inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2)) expression, nuclear factor kappa B (NF-κB) p65 phosphorylation, nuclear translocation, and hydroxyl radical (OH•) formation in LPS-stimulated microglia. Conversely, TQ-6 increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Moreover, it significantly reduced brain infarct volume and edema in MCAO mice. Additionally, it drastically inhibited platelet aggregation and OH• production in mice platelets. This study confirmed that TQ-6 exerts an anti-neuroinflammatory effect on microglia activation through neuroprotection, antiplatelet activation, and free radical scavenging. The authors propose that TQ-6 might mitigate neurodegenerative pathology by inhibiting the NF-κB-mediated downstream pathway (iNOS and COX-2) and enhancing Nrf2/HO-1 signaling molecules in microglia.

scholarly journals Antineuroinflammatory and Neuroprotective Effects of Gyejibokryeong-Hwan in Lipopolysaccharide-Stimulated BV2 Microglia

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Bo-Kyung Park ◽  
Young Hwa Kim ◽  
Yu Ri Kim ◽  
Jeong June Choi ◽  
Changsop Yang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mitogen Activated Protein Kinase ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Neuroprotective Effects ◽  
Bv2 Cells ◽  
Bv2 Microglia ◽  
Anti Inflammatory

Microglia, the central nervous system’s innate immune cells, mediate neuroinflammation and are implicated in a variety of neuropathologies. The present study investigated the antineuroinflammatory and neuroprotective effects of Gyejibokryeong-hwan (GBH), a traditional Korean medicine, in lipopolysaccharide- (LPS-) stimulated murine BV2 microglia. BV2 cells were pretreated with GBH, fluoxetine (FXT), or amitriptyline (AMT) for 1 h and then stimulated with LPS (100 ng/mL). The expression levels of nitric oxide (NO), cytokines, and chemokines were determined by the Griess method, ELISA, or real-time PCR. Western blotting was used to measure various transcription factors and mitogen activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt activity. GBH significantly reduced the levels of NO, inducible nitric oxide synthase (iNOS), cyclooxygenase- (COX-) 2, tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, IL-6, macrophage inhibitory protein- (MIP-) 1α, macrophage chemoattractant protein- (MCP-) 1, and IFN-γ inducible protein- (IP-) 10, regulated upon activation normal T cell expressed sequence (RANTES) in a dose-dependent manner. Expression of nuclear factor- (NF-) κB p65 was significantly decreased and phosphorylation of extracellular signal-regulated kinase (Erk), c-Jun NH2-terminal kinase (JNK), and PI3K/Akt by GBH, but not p38 MAPK, was decreased. Furthermore, production of anti-inflammatory cytokine IL-10 was increased and Heme oxygenase-1 (HO-1) was upregulated via the nuclear factor-E2-related factor 2 (NRF2)/cAMP response element-binding protein (CREB) pathway, collectively indicating the neuroprotective effects of GBH. We concluded that GBH may suppress neuroinflammatory responses by inhibiting NF-κB activation and upregulating the neuroprotective factor, HO-1. These results suggest that GBH has potential as anti-inflammatory and neuroprotective agents against microglia-mediated neuroinflammatory disorders.

scholarly journals Thymoquinone Prevents Dopaminergic Neurodegeneration by Attenuating Oxidative Stress Via the Nrf2/ARE Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Jianjian Dong ◽  
Xiaoming Zhang ◽  
Shijing Wang ◽  
Chenchen Xu ◽  
Manli Gao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nuclear Translocation ◽  
Nigella Sativa ◽  
Drug Candidate ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Protective Effects ◽  
Quinone Oxidoreductase ◽  
Neuroprotective Effects ◽  
Antioxidant Genes

Studies have indicated that oxidative stress plays a crucial role in the development of Parkinson’s disease (PD) and other neurodegenerative conditions. Research has also revealed that nuclear factor erythroid 2-related factor 2 (Nrf2) triggers the expression of antioxidant genes via a series of antioxidant response elements (AREs), thus preventing oxidative stress. Thymoquinone (TQ) is the bioactive component of Nigella sativa, a medicinal plant that exhibits antioxidant and neuroprotective effects. In the present study we examined whether TQ alleviates in vivo and in vitro neurodegeneration induced by 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by acting as an activator of the Nrf2/ARE cascade. We showed that TQ significantly reduced MPP+-mediated cell death and apoptosis. Moreover, TQ significantly elevated the nuclear translocation of Nrf2 and significantly increased the subsequent expression of antioxidative genes such as Heme oxygenase 1 (HO-1), quinone oxidoreductase (NQO1) and Glutathione-S-Transferase (GST). The application of siRNA to silence Nrf2 led to an abolishment in the protective effects of TQ. We also found that the intraperitoneal injection of TQ into a rodent model of PD ameliorated oxidative stress and effectively mitigated nigrostriatal dopaminergic degeneration by activating the Nrf2-ARE pathway. However, these effects were inhibited by the injection of a lentivirus wrapped Nrf2 siRNA (siNrf2). Collectively, these findings suggest that TQ alleviates progressive dopaminergic neuropathology by activating the Nrf2/ARE signaling cascade and by attenuating oxidative stress, thus demonstrating that TQ is a potential novel drug candidate for the treatment of PD.

scholarly journals 5-Hydroxymaltol Derived from Beetroot Juice through Lactobacillus Fermentation Suppresses Inflammatory Effect and Oxidant Stress via Regulating NF-kB, MAPKs Pathway and NRF2/HO-1 Expression

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1324
Author(s):  
Su-Lim Kim ◽  
Hack Sun Choi ◽  
Yu-Chan Ko ◽  
Bong-Sik Yun ◽  
Dong-Sun Lee
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Mitogen Activated Protein Kinase ◽  
Raw 264.7 Cells ◽  
Heme Oxygenase 1 ◽  
Raw 264.7 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Mitogen Activated Protein

Inflammation is the first response of the immune system against bacterial pathogens. This study isolated and examined an antioxidant derived from Lactobacillus fermentation products using cultured media with 1% beet powder. The antioxidant activity of the beet culture media was significantly high. Antioxidant activity-guided purification and repeated sample isolation yielded an isolated compound, which was identified as 5-hydoxymaltol using nuclear magnetic resonance spectrometry. We examined the mechanism of its protective effect on lipopolysaccharide (LPS)-induced inflammation of macrophages. 5-Hydroxymaltol suppressed nitric oxide (NO) production in LPS-stimulated RAW 264.7 cells. It also suppressed tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and inducible nitric oxide synthase (iNOS) in the messenger RNA and protein levels in LPS-treated RAW 264.7 cells. Moreover, it suppressed LPS-induced nuclear translocation of NF-κB (p65) and mitogen-activated protein kinase activation. Furthermore, 5-hydroxymaltol reduced LPS-induced reactive oxygen species (ROS) production as well as increased nuclear factor erythroid 2–related factor 2 and heme oxygenase 1 expression. Overall, this study found that 5-hydroxymaltol has anti-inflammatory activities in LPS-stimulated RAW 264.7 macrophage cells based on its inhibition of pro-inflammatory cytokine production depending on the nuclear factor κB signaling pathway, inhibition of LPS-induced reactive oxygen species production, inhibition of LPS-induced mitogen-activated protein kinase induction, and induction of the nuclear factor erythroid 2–related factor 2/heme oxygenase 1 signaling pathway. Our data showed that 5-hydroxymaltol may be an effective compound for treating inflammation-mediated diseases.

Pistacia chinensisInhibits NO Production and Upregulates HO-1 Induction via PI-3K/Akt Pathway in LPS Stimulated Macrophage Cells

2012 ◽  
Vol 40 (05) ◽  
pp. 1085-1097 ◽  
Author(s):  
Taddesse Yayeh ◽  
Mei Hong ◽  
Qi Jia ◽  
Young-Chul Lee ◽  
Hyun-Jin Kim ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Protein Expression ◽  
Raw264.7 Cells ◽  
Akt Pathway ◽  
Heme Oxygenase 1 ◽  
No Production ◽  
Related Factor ◽  
Phenolic Lipids ◽  
Cox 2 ◽  
Pre Treatment

Pistacia chinensis has been used for various purposes in China including as an understock for grafting Pistacia vera. However, little attention was given to its health promoting effects. Therefore, in this study, we investigated the effect of Pistacia chinensis methanolic extract (PCME) containing resorcinol class of phenolic lipids on pro-inflammatory mediators and heme oxygenase-1(HO-1) in lipopolysaccharide stimulated RAW264.7 cells. While PCME (2.5–10 μg/ml) inhibited mRNA expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and interleukin (IL)-6, it up-regulated HO-1 expression. Likewise, PCME inhibited iNOS protein expression, but not COX-2, and reduced nitric oxide (NO) release. Moreover, Phosphorylated c-Jun N-terminal Kinase (JNK) was attenuated dose-dependently in PCME pre-treated RAW264.7 cells. In addition, PCME up-regulated HO-1 protein expression was diminished by pre-treatment of PI-3K inhibitor. Furthermore, nuclear factor erythroid 2 related factor 2 (Nrf2) repressor was attenuated time-dependently during PCME treatment. Taken together, our study showed (for the first time) that PCME inhibited NO production and up-regulated HO-1 induction via PI-3K/Akt pathway, suggesting the role of Pistacia chinensis as potential sources of anti-inflammatory and antioxidant natural compounds.

scholarly journals Farrerol Directly Targets GSK-3β to Activate Nrf2-ARE Pathway and Protect EA.hy926 Cells against Oxidative Stress-Induced Injuries

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Chaoqun Yan ◽  
Xiaoyan Zhang ◽  
Junqiu Miao ◽  
Hongxia Yuan ◽  
Enli Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Glycogen Synthase ◽  
Specific Inhibitor ◽  
Negative Regulator ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Quinone Oxidoreductase ◽  
Ea.Hy926 Cells

Oxidative stress-mediated endothelial injury is considered to be involved in the pathogenesis of various cardiovascular diseases. Farrerol, a typical natural flavanone from the medicinal plant Rhododendron dauricum L., has been reported to show protective effects against oxidative stress-induced endothelial injuries in our previous study. However, its action molecular mechanisms and targets are still unclear. In the present study, we determined whether farrerol can interact with glycogen synthase kinase 3β- (GSK-3β-) nuclear factor erythroid 2-related factor 2- (Nrf2-) antioxidant response element (ARE) signaling, which is critical in defense against oxidative stress. Our results demonstrated that farrerol could specifically target Nrf2 negative regulator GSK-3β and inhibit its kinase activity. Mechanistic studies proved that farrerol could induce an inhibitory phosphorylation of GSK-3β at Ser9 without affecting the expression level of total GSK-3β protein and promote the nuclear translocation of Nrf2 as well as the mRNA and protein expression of its downstream target genes heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) in EA.hy926 cells. Further studies performed with GSK-3β siRNA and specific inhibitor lithium chloride (LiCl) confirmed that GSK-3β inhibition was involved in farrerol-mediated endothelial protection and Nrf2 signaling activation. Moreover, molecular docking and molecular dynamics studies revealed that farrerol could bind to the ATP pocket of GSK-3β, which is consistent with the ATP-competitive kinetic behavior. Collectively, our results firstly demonstrate that farrerol could attenuate endothelial oxidative stress by specifically targeting GSK-3β and further activating the Nrf2-ARE signaling pathway.

scholarly journals Sanghuangporus sanghuang Mycelium Prevents Paracetamol-Induced Hepatotoxicity through Regulating the MAPK/NF-κB, Keap1/Nrf2/HO-1, TLR4/PI3K/Akt and CaMKKβ/LKB1/AMPK Pathways and Suppressing Oxidative Stress and Inflammation

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 897
Author(s):  
Wen-Ping Jiang ◽  
Jeng-Shyan Deng ◽  
Shyh-Shyun Huang ◽  
Sheng-Hua Wu ◽  
Chin-Chu Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Kinase ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Mitogen Activated Protein Kinase ◽  
Heme Oxygenase 1 ◽  
Molecular Evidence ◽  
Related Factor ◽  
Serum Aminotransferase ◽  
Compound C

Liver damage induced by paracetamol overdose is the main cause of acute liver failure worldwide. In order to study the hepatoprotective effect of Sanghuangporus sanghuang mycelium (SS) on paracetamol-induced liver injury, SS was administered orally every day for 6 days in mice before paracetamol treatment. SS decreased serum aminotransferase activities and the lipid profiles, protecting against paracetamol hepatotoxicity in mice. Furthermore, SS inhibited the lipid peroxidation marker malondialdehyde (MDA), hepatic cytochrome P450 2E1 (CYP2E1), and the histopathological changes in the liver and decreased inflammatory activity by inhibiting the production of proinflammatory cytokines in paracetamol-induced acute liver failure. Moreover, SS improved the levels of glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase in the liver. Significantly, SS diminished mitogen-activated protein kinase (MAPK), Toll-like receptor 4 (TLR4), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and the nuclear factor-kappa B (NF-κB) axis, as well as upregulated the Kelch-like ECH-associated protein 1 (Keap1)/erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway, in paracetamol-induced mice. SS mainly inhibited the phosphorylation of the liver kinase B1 (LKB1), Ca2+/calmodulin-dependent kinase kinase β (CaMKKβ), and AMP-activated protein kinase (AMPK) protein expression. Furthermore, the protective effects of SS on paracetamol-induced hepatotoxicity were abolished by compound C, an AMPK inhibitor. In summary, we provide novel molecular evidence that SS protects liver cells from paracetamol-induced hepatotoxicity by inhibiting oxidative stress and inflammation.

scholarly journals Notoginsenoside R1 attenuates sevoflurane-induced neurotoxicity

2020 ◽  
Vol 11 (1) ◽  
pp. 215-226
Author(s):  
Yibing Zhang ◽  
Yong Zhao ◽  
Yongwang Ran ◽  
Jianyou Guo ◽  
Haifeng Cui ◽  
...  
Keyword(s):  
Neuronal Degeneration ◽  
Apoptotic Cell ◽  
Volatile Anesthetic ◽  
Adenosine Monophosphate ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Sprague Dawley ◽  
Quinone Oxidoreductase ◽  
Neuroprotective Effects ◽  
Cell Counts

AbstractBackgroundSevoflurane, a volatile anesthetic, is known to induce widespread neuronal degeneration and apoptosis. Recently, the stress-inducible protein sestrin 2 and adenosine monophosphate-activated protein kinase (AMPK) have been found to regulate the levels of intracellular reactive oxygen species (ROS) and suppress oxidative stress. Notoginsenoside R1 (NGR1), a saponin isolated from Panax notoginseng, has been shown to exert neuroprotective effects. The effects of NGR1 against neurotoxicity induced by sevoflurane were assessed.MethodsSprague-Dawley rat pups on postnatal day 7 (PD7) were exposed to sevoflurane (3%) anesthesia for 6 h. NGR1 at doses of 12.5, 25, or 50 mg/kg body weight was orally administered to pups from PD2 to PD7.ResultsPretreatment with NGR1 attenuated sevoflurane-induced generation of ROS and reduced apoptotic cell counts. Western blotting revealed decreased cleaved caspase 3 and Bad and Bax pro-apoptotic protein expression. NGR1 substantially upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression along with increased heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase-1 levels, suggesting Nrf2 signaling activation. Enhanced sestrin-2 and phosphorylated AMPK expression were noticed following NGR1 pretreatment.ConclusionThis study revealed the neuroprotective effects of NGR1 through effective suppression of apoptosis and ROS via regulation of apoptotic proteins and activation of Nrf2/HO-1 and sestrin 2/AMPK signaling cascades.

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