Astragaloside IV protects blood-brain barrier integrity from LPS-induced disruption via activating Nrf2 antioxidant signaling pathway in mice

Liu, Hongli; Wang, Ping; Huang, Fei; Jin, Jinmei; Wu, Hui; Zhang, Beibei; Wang, Zhifei; Shi, Hailian; Wu, Xiaojun

doi:10.1016/j.taap.2017.12.019

Cited by 92 publications

(57 citation statements)

References 46 publications

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“…Accordingly, BBB is regarded as a therapeutic target for many cerebral diseases. LPS has been widely used as a potent inducer of BBB disruption under inflammatory condition (Li et al, ). Although we recently demonstrated that PNS could protect against OGD/R‐induced oxidative stress injury of BBB in vitro (Hu et al, ), whether PNS could also protect against LPS‐induced BBB dysfunction under inflammatory condition has not been known.…”

Section: Discussionmentioning

confidence: 99%

“…Trans-Endothelial Electrical Resistance (TEER) value is an indicator for the integrity evaluation of the bEnd.3 monolayer, which was monitored with a Millipore Millicell ERS system equipped with chopstick electrodes (Millipore, Billerica, MA, USA) as previously described with modification (Li et al, 2018). In brief, bEnd.3 cells in 0.5-ml DMEM normal culture medium were seeded into the upper "apical" chamber of the transwell inserts (3460; Corning, NY, USA) with the density of 4 × 10 5 cells per millilitre, whereas 1.5 ml of the same medium was added to the lower chamber.…”

Section: Trans-endothelial Electrical Resistance Measurementmentioning

confidence: 99%

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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

Liu

et al. 2019

Phytotherapy Research

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Trans-endothelial Electrical Resistance Measurementmentioning

confidence: 99%

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

Liu

et al. 2019

Phytotherapy Research

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“…Our study obtained the insignificant increase in SOD activity, however, obviously increased levels of T‐AOC, GSH‐PX, and CAT demonstrated that AMSL had a positive effect on improving antioxidant status of quails. These results may be caused by flavonoids (Shirataki, Takao, Yoshida, & Toda, ) that synergistically work with saponin substances, such as astragaloside IV in AMSL, which has been demonstrated to exert significant protective effects by decreasing the apoptotic ratio and attenuating reactive oxygen species (ROS) overproduction in H 2 O 2 ‐exposed human neuronal SH‐SY5Y cells (Liu, Zhang, Wang, Qiu, & Yu, ), and by reducing ROS levels and activating the Nrf2 antioxidant pathway in the brain endothelial cell line bEnd.3 (Li et al, ). Perhaps, the expression of antioxidant enzymes in quails in the present study was partly regulated by such components in AMSL through the Nrf2 pathway, so that the three enzymes cooperated with each other to maintain the health of the quails.…”

Section: Discussionmentioning

confidence: 99%

Effects of the stems and leaves of Astragalus membranaceus on growth performance, immunological parameters, antioxidant status, and intestinal bacteria of quail

Guo

Jin

Luan

et al. 2019

Animal Science Journal

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This study was designed to evaluate the potential application of the stems and leaves of Astragalus membranaceus (AMSL) in the poultry industry. Quails were divided into four groups and fed daily with an AMSL‐free diet (control) or with 1%, 3%, or 5% (w/w) AMSL‐incorporated diets for 35 days. The results showed that supplementing AMSL in the diet, especially at a concentration of 3%, increased daily gain and feed intake during the entire experiment (p < 0.05). The immune organ development of the thymus and bursa of Fabricius was promoted, and the immune system was enhanced by increasing the quantities of IgA and complements C3 and C4 (p < 0.05). The total antioxidant capacity and the activities of glutathione peroxidase and catalase were increased (p < 0.05). Moreover, the 3%–5% AMSL groups regulated the intestinal flora by promoting the proliferation of lactic acid bacteria and inhibiting the growth of coliform bacteria (p < 0.05). In conclusion, feeding incorporated diets with appropriate AMSL levels significantly increased growth performance, strengthened the immune system, improved antioxidative status, and regulated the intestinal microflora of quails, suggesting that AMSL has the potential to serve as a feed additive in the poultry industry.

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“…AS-IV has been reported to have protective effects on cerebral ischaemia-reperfusion injury as well as the integrity of the bloodbrain barrier. [45][46][47][48][49][50] With the low toxicity, AS-IV may be expected to be applied to the clinic for the treatment of central nervous system injury in the future. Previous studies have also shown that rapamycin, a classical mTORC1 inhibitor, could exert neuroprotective effects in SCI.…”

Section: Discussionmentioning

confidence: 99%

Dual regulation of microglia and neurons by Astragaloside IV‐mediated mTORC1 suppression promotes functional recovery after acute spinal cord injury

Lin

Pan

Huang

et al. 2019

J Cellular Molecular Medi

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Inflammation and neuronal apoptosis contribute to the progression of secondary injury after spinal cord injury (SCI) and are targets for SCI therapy; autophagy is reported to suppress apoptosis in neuronal cells and M2 polarization may attenuate inflammatory response in microglia, while both are negatively regulated by mTORC1 signalling. We hypothesize that mTORC1 suppression may have dual effects on inflammation and neuronal apoptosis and may be a feasible approach for SCI therapy. In this study, we evaluate a novel inhibitor of mTORC1 signalling, Astragaloside IV (AS‐IV), in vitro and in vivo. Our results showed that AS‐IV may suppress mTORC1 signalling both in neuronal cells and microglial cells in vitro and in vivo. AS‐IV treatment may stimulate autophagy in neuronal cells and protect them against apoptosis through autophagy regulation; it may also promote M2 polarization in microglial cells and attenuate neuroinflammation. In vivo, rats were intraperitoneally injected with AS‐IV (10 mg/kg/d) after SCI, behavioural and histological evaluations showed that AS‐IV may promote functional recovery in rats after SCI. We propose that mTORC1 suppression may attenuate both microglial inflammatory response and neuronal apoptosis and promote functional recovery after SCI, while AS‐IV may become a novel therapeutic medicine for SCI.

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Astragaloside IV protects blood-brain barrier integrity from LPS-induced disruption via activating Nrf2 antioxidant signaling pathway in mice

Cited by 92 publications

References 46 publications

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

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

Effects of the stems and leaves of Astragalus membranaceus on growth performance, immunological parameters, antioxidant status, and intestinal bacteria of quail

Dual regulation of microglia and neurons by Astragaloside IV‐mediated mTORC1 suppression promotes functional recovery after acute spinal cord injury

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