Panax notoginseng saponins suppress lipopolysaccharide‐induced barrier disruption and monocyte adhesion on bEnd.3 cells via the opposite modulation of Nrf2 antioxidant and NF‐κB inflammatory pathways

Dysfunction of the blood‐brain barrier (BBB) is a prerequisite for the pathogenesis of many cerebral diseases. Oxidative stress and inflammation are well‐known factors accounting for BBB injury. Panax notoginseng saponins (PNS), a clinical commonly used drug against cerebrovascular disease, possess efficient antioxidant and anti‐inflammatory activity. In the present study, the protective effects of PNS on lipopolysaccharide (LPS)‐insulted cerebral microvascular endothelial cells (bEnd.3) were assessed and the underlying mechanisms were investigated. The results showed that PNS mitigated the decrease of Trans‐Endothelial Electrical Resistance, increase of paracellular permeability, and loss of tight junction proteins in bEnd.3 BBB model. Meanwhile, PNS suppressed the THP‐1 monocytes adhesion on bEnd.3 monolayer. Moreover, PNS prevented the pro‐inflammatory cytokines secretion and reactive oxygen species generation in bEnd.3 cells stimulated with LPS. Mechanism investigations suggested that PNS promoted the Akt phosphorylation, activated Nrf2 antioxidant signaling, and inhibited the NF‐κB activation. All the effects of PNS could be abolished by PI3K inhibition at different levels. Taken together, these observations suggest that PNS may act as an extrinsic regulator that activates Nrf2 antioxidant defense system depending on PI3K/Akt and inhibits NF‐κB inflammatory signaling to attenuate LPS‐induced BBB disruption and monocytes adhesion on cerebral endothelial cells in vitro.

• Publication year

  2019

• Venue

  Phytotherapy Research

• Publication date

  2019-12-01

• Fields of study

  Biology, Medicine, Chemistry, Environmental Science

• Identifiers
  DOI 10.1002/ptr.6488PMID 31468630
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Pro-Resolving Effect of Ginsenosides as an Anti-Inflammatory Mechanism of Panax ginseng

  2020cited by this paper
• Protective effects of panax notoginseng saponin on dextran sulfate sodium-induced colitis in rats through phosphoinositide-3-kinase protein kinase B signaling pathway inhibition

  2020cited by this paper
• Role of the Blood-Brain Barrier in Central Nervous System Insulin Resistance

  2019influential reference
• Blood-Brain Barrier: From Physiology to Disease and Back.

  2019influential reference
• Ginsenoside Rg1 attenuates protein aggregation and inflammatory response following cerebral ischemia and reperfusion injury

  2019influential reference
• Antioxidant and Anti-inflammatory Mechanisms of Neuroprotection by Ursolic Acid: Addressing Brain Injury, Cerebral Ischemia, Cognition Deficit, Anxiety, and Depression

  2019cited by this paper
• Anti-neuroinflammatory Potential of Natural Products in Attenuation of Alzheimer's Disease

  2018cited by this paper
• Panax notoginseng Saponins Protect Cerebral Microvascular Endothelial Cells against Oxygen-Glucose Deprivation/Reperfusion-Induced Barrier Dysfunction via Activation of PI3K/Akt/Nrf2 Antioxidant Signaling Pathway

  2018cited by this paper
• Recombinant FGF21 Protects Against Blood-Brain Barrier Leakage Through Nrf2 Upregulation in Type 2 Diabetes Mice

  2018cited by this paper
• Astragaloside IV protects blood‐brain barrier integrity from LPS‐induced disruption via activating Nrf2 antioxidant signaling pathway in mice

  2018influential reference
• Nrf2—a Promising Therapeutic Target for Defensing Against Oxidative Stress in Stroke

  2017cited by this paper
• 5-(3′,4′-Dihydroxyphenyl-γ-valerolactone), a Major Microbial Metabolite of Proanthocyanidin, Attenuates THP-1 Monocyte-Endothelial Adhesion

  2017cited by this paper
• Oxidative Stress and the Central Nervous System

  2017cited by this paper
• Dihydrocapsaicin Attenuates Blood Brain Barrier and Cerebral Damage in Focal Cerebral Ischemia/Reperfusion via Oxidative Stress and Inflammatory

  2017cited by this paper
• Nrf2 signaling pathway: Pivotal roles in inflammation.

  2017cited by this paper
• Limiting inflammation—the negative regulation of NF-κB and the NLRP3 inflammasome

  2017cited by this paper
• Ginsenosides Rd and Re co-treatments improve rotenone-induced oxidative stress and mitochondrial impairment in SH-SY5Y neuroblastoma cells.

  2017cited by this paper
• Chrysin Attenuates VCAM-1 Expression and Monocyte Adhesion in Lipopolysaccharide-Stimulated Brain Endothelial Cells by Preventing NF-κB Signaling

  2017cited by this paper
• Rapid endothelial cytoskeletal reorganization enables early blood–brain barrier disruption and long-term ischaemic reperfusion brain injury

  2016influential reference
• Ameliorative effects of egg white hydrolysate on recognition memory impairments associated with chronic exposure to low mercury concentration.

  2016cited by this paper
• Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism

  2016cited by this paper
• Blockade of Apoptosis Signal-Regulating Kinase 1 Attenuates Matrix Metalloproteinase 9 Activity in Brain Endothelial Cells and the Subsequent Apoptosis in Neurons after Ischemic Injury

  2016influential reference
• Protective actions of des-acylated ghrelin on brain injury and blood-brain barrier disruption after stroke in mice.

  2016cited by this paper
• Traditional uses, botany, phytochemistry, pharmacology and toxicology of Panax notoginseng (Burk.) F.H. Chen: A review.

  2016cited by this paper
• Inhibiting adhesion events by Panax notoginseng saponins and Ginsenoside Rb1 protecting arteries via activation of Nrf2 and suppression of p38 - VCAM-1 signal pathway.

  2016cited by this paper
• Immortalized endothelial cell lines for in vitro blood-brain barrier models: A systematic review.

  2016cited by this paper
• Energy metabolism and inflammation in brain aging and Alzheimer's disease.

  2016cited by this paper
• Enhanced Therapeutic Potential of Nano-Curcumin Against Subarachnoid Hemorrhage-Induced Blood–Brain Barrier Disruption Through Inhibition of Inflammatory Response and Oxidative Stress

  2015cited by this paper
• Neuroprotective effects of vildagliptin in rat rotenone Parkinson's disease model: role of RAGE‐NFκB and Nrf2‐antioxidant signaling pathways

  2015cited by this paper
• Dissecting molecular cross-talk between Nrf2 and NF-κB response pathways

  2015cited by this paper
• Efficacy and Safety of Panax notoginseng Saponin Therapy for Acute Intracerebral Hemorrhage, Meta-Analysis, and Mini Review of Potential Mechanisms of Action

  2015cited by this paper
• Xuesaitong injection as one adjuvant treatment of acute cerebral infarction: a systematic review and meta-analysis

  2015cited by this paper
• Apigenin protects blood-brain barrier and ameliorates early brain injury by inhibiting TLR4-mediated inflammatory pathway in subarachnoid hemorrhage rats.

  2015cited by this paper
• Suppression of NADPH oxidase- and mitochondrion-derived superoxide by Notoginsenoside R1 protects against cerebral ischemia–reperfusion injury through estrogen receptor-dependent activation of Akt/Nrf2 pathways

  2014cited by this paper
• Panaxatriol Saponins Attenuated Oxygen-Glucose Deprivation Injury in PC12 Cells via Activation of PI3K/Akt and Nrf2 Signaling Pathway

  2014cited by this paper
• Interactions of Oxidative Stress and Neurovascular Inflammation in the Pathogenesis of Traumatic Brain Injury

  2014cited by this paper
• The impact of microglial activation on blood-brain barrier in brain diseases

  2014influential reference
• Antioxidative effects of Panax notoginseng saponins in brain cells.

  2014cited by this paper
• Notoginsenoside R1 attenuates cardiac dysfunction in endotoxemic mice: an insight into oestrogen receptor activation and PI3K/Akt signalling

  2013cited by this paper
• Ginsenoside Rd inhibits the expressions of iNOS and COX-2 by suppressing NF-κB in LPS-stimulated RAW264.7 cells and mouse liver

  2013cited by this paper
• Panax notoginseng saponins attenuate atherosclerosis via reciprocal regulation of lipid metabolism and inflammation by inducing liver X receptor alpha expression.

  2012cited by this paper
• Panax Notogingseng Saponins Suppress RAGE/ MAPK Signaling and NF-kappaB Activation in Apolipoprotein-E-deficient Atherosclerosis-prone mice

  2012cited by this paper
• Ginsenoside Re ameliorates inflammation by inhibiting the binding of lipopolysaccharide to TLR4 on macrophages.

  2012cited by this paper
• Pharmacodynamics of ginsenosides: antioxidant activities, activation of Nrf2, and potential synergistic effects of combinations.

  2012cited by this paper
• Anti-neuroinflammation effect of ginsenoside Rbl in a rat model of Alzheimer disease.

  2011cited by this paper
• RhoA and NF-κB are involved in lipopolysaccharide-induced brain microvascular cell line hyperpermeability.

  2011cited by this paper

• S1PR3 Inactivation Aggravates Cerebrovascular Endothelial Cell Permeability Mediated by cPLA2 and STAT3 Phosphorylation Under Oxidative Stress

  2026cites this paper
• Research progress on the mechanism of panax notoginseng saponin in the treatment of atherosclerosis.

  2026cites this paper
• Polyphenols Limit Cerebral Endothelial Cell Dysfunction Under Inflammatory Conditions Related to Oral and Gut Microbiota.

  2026cites this paper
• The biological functions of ginsenoside and its applications in animal husbandry

  2025cites this paper
• The potential therapeutic role of ginsenosides on fibrosis-associated diseases: a review on molecular mechanisms and call for further research.

  2025cites this paper
• Engineered Panax notoginseng polysaccharide micelles inhibit macrophage polarization and delay the progression of rheumatoid arthritis via JAK2-STAT3 signaling pathway

  2025cites this paper
• Ameliorative effects of Panax notoginseng water extract on polystyrene nanoplastics-induced inflammation and immunotoxicity in RAW 264.7 and Litopenaeus vannamei

  2025cites this paper
• Targeting Epac1 to protect the blood brain barrier from inflammation-induced dysfunction: Evidence from an in vitro model.

  2025cites this paper
• Endothelial Dysfunctions in Blood–Brain Barrier Breakdown in Alzheimer's Disease: From Mechanisms to Potential Therapies

  2024cites this paper
• Taraxacum coreanum (Korean Dandelion) Extract Protects Against Lipopolysaccharide-Induced Blood–Brain Barrier Destruction via Regulation of Tight Junctions and Inflammatory Responses in bEnd.3 Cells

  2024cites this paper
• Comparative efficacy of the five most common traditional Chinese medicine monomers in reducing intimal hyperproliferation in arterial balloon injury models: A network meta-analysis

  2024cites this paper
• GSK3β Substrate-competitive Inhibitors Regulate the gut Homeostasis and Barrier Function to Inhibit Neuroinflammation in Scopolamine-induced Alzheimer’s Disease Model Mice

  2024cites this paper
• Effects of Sodium Nitroprusside on Lipopolysaccharide-Induced Inflammation and Disruption of Blood–Brain Barrier

  2024cites this paper
• A novel co-culture model for investigation of the effects of LPS-induced macrophage-derived cytokines on brain endothelial cells

  2023cites this paper
• Clinical efficacy and safety of Panax notoginseng saponins in treating chronic obstructive pulmonary disease with blood hypercoagulability: A meta-analysis of randomized controlled trials.

  2023cites this paper
• 20(S)‐Protopanaxadiol saponins isolated from Panax notoginseng target caveolin‐1 against intestinal barrier dysfunction by alleviating inflammatory injury and oxidative stress in experimental murine colitis

  2023cites this paper
• The Potential Relevance of PnDREBs to Panax notoginseng Nitrogen Sensitiveness

  2023cites this paper
• Interfering TRIB3 protects the blood brain barrier through PI3K/Akt pathway to alleviate cerebral ischemia-reperfusion injury in diabetes mellitus mice.

  2023cites this paper
• Saponin protects against cyclophosphamide-induced kidney and liver damage via antioxidant and anti-inflammatory actions.

  2023cites this paper
• Semen Ziziphi Spinosae attenuates blood–brain barrier dysfunction induced by lipopolysaccharide by targeting the FAK-DOCK180-Rac1-WAVE2-Arp3 signaling pathway

  2022cites this paper
• Protective Effect of Panax Notoginseng Saponins on Apolipoprotein-E-deficient Atherosclerosis-prone mice.

  2022cites this paper
• Piceatannol Protects Brain Endothelial Cell Line (bEnd.3) against Lipopolysaccharide-Induced Inflammation and Oxidative Stress

  2022cites this paper
• Panax notoginseng saponins prevent colitis-associated colorectal cancer via inhibition IDO1 mediated immune regulation.

  2022cites this paper
• Protective Effect of PI3K/AKT Signaling Pathway in Ischemic Stroke

  2022cites this paper
• The mechanism of ferroptosis regulating oxidative stress in ischemic stroke and the regulation mechanism of natural pharmacological active components.

  2022cites this paper
• Weipiling decoction alleviates N-methyl-N-nitro-N′-nitrosoguanidine-induced gastric precancerous lesions via NF-κB signalling pathway inhibition

  2022cites this paper
• Antioxidant and anti-inflammation effects of dietary phytochemicals: The Nrf2/NF-κB signaling pathway and upstream factors of Nrf2.

  2022cites this paper
• MitoQ protects against high glucose-induced brain microvascular endothelial cells injury via the Nrf2/HO-1 pathway.

  2021cites this paper
• De novo and comparative transcriptomic analysis explain morphological differences in Panax notoginseng taproots

  2021cites this paper
• Phytotherapeutics Attenuation of Oxidative Stress, Inflammation and Lipid Peroxidation in Severe and Chronic Diseases

  2021cites this paper
• Qihu Preparation Ameliorates Diabetes by Activating the AMPK Signaling Pathway in db/db Mice

  2021cites this paper
• Baicalin protects LPS-induced blood-brain barrier damage and activates Nrf2-mediated antioxidant stress pathway.

  2021cites this paper
• Protective Effects of Complement Component 8 Gamma Against Blood-Brain Barrier Breakdown

  2021cites this paper
• Physiological and Pathological Factors Affecting Drug Delivery to the Brain by Nanoparticles

  2021cites this paper
• Comparative Analysis of Compatibility Influence on Invigorating Blood Circulation for Combined Use of Panax Notoginseng Saponins and Aspirin Using Metabolomics Approach

  2021cites this paper
• Multidirectional effects of saponin fraction isolated from the leaves of sea buckthorn Elaeagnus rhamnoides (L.) A. Nelson.

  2021cites this paper
• Effect of Panax notoginseng Saponins and Major Anti-Obesity Components on Weight Loss

  2021cites this paper
• XQ-1H promotes cerebral angiogenesis via activating PI3K/Akt/GSK3β/β-catenin/VEGF signal in mice exposed to cerebral ischemic injury.

  2021cites this paper
• Protective effects of panax notoginseng saponin on dextran sulfate sodium-induced colitis in rats through phosphoinositide-3-kinase protein kinase B signaling pathway inhibition

  2020cites this paper
• Panax Notoginseng Saponins Inhibits Ventricular Remodeling after Myocardial Infarction in Rats Through Regulating ATF3/MAP2K3/p38 MAPK and NF κ B Pathway

  2020cites this paper
• 25-OH-PPD inhibits hypertrophy on diabetic cardiomyopathy via the PI3k/Akt/GSK-3β signaling pathway

  2020cites this paper
• LC/MS Analysis of Saponin Fraction from the Leaves of Elaeagnus rhamnoides (L.) A. Nelson and Its Biological Properties in Different In Vitro Models

  2020cites this paper
• Neuroprotection Against Oxidative Stress: Phytochemicals Targeting TrkB Signaling and the Nrf2-ARE Antioxidant System

  2020cites this paper
• Research progress of mechanisms for tight junction damage on blood–brain barrier inflammation

  2020cites this paper
• Pananx notoginseng saponins attenuate CCL2-induced cognitive deficits in rats via anti-inflammation and anti-apoptosis effects that involve suppressing over-activation of NMDA receptors.

  2020cites this paper
• Pro-Resolving Effect of Ginsenosides as an Anti-Inflammatory Mechanism of Panax ginseng

  2020cites this paper