Schisantherin A attenuates ischemia/reperfusion-induced neuronal injury in rats via regulation of TLR4 and C5aR1 signaling pathways

Shi, Yun; Zhang, Xiao Chuan; Chen, Chen; Tang, Miao; Wang, Zhi Wei; Liang, Xin; Ding, Fei; Wang, Cai Ping

doi:10.1016/j.bbi.2017.07.004

Cited by 27 publications

(22 citation statements)

References 40 publications

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“…SinA (molecular formula, C30H32O9; formula weight, 536.57) is one of the native lignans of Schisandra chinensis that formed by the polymerization of two phenylpropanoid derivatives. Studies have reported that SinA could reduce the ROS level [ 44 ], inhibit the P-glycoprotein expression [ 34 ], multidrug resistance-associated protein 1 [ 25 ], TLR4/CD88 [ 39 ], mitogen-activate protein kinase [ 45 ], and NF-kB pathways [ 10 , 28 , 46 ], and possesses antioxidant effects, anti-carcinogenic effects, and anti-hepatotoxic effects; and have protective effects on the respiratory system, nervous system, and bone tissues [ 10 , 25 , 28 , 34 , 39 , 44 , 45 , 46 ]. In the present study, the effects of SinA on the alcohol-induced liver injury were investigated, the underlying mechanisms were also explored.…”

Section: Discussionmentioning

confidence: 99%

“…Schisantherin A is a dibenzocyclooctadiene lignan that considered to be the most abundant and key effective constituent in the fruit of Schisandra chinensis [ 42 ]. Studies have found that schisantherin A has beneficial effects on the brain, heart, and bone due to the anti-inflammatory, antioxidant, and detoxification pharmacological activities [ 8 , 10 , 18 , 28 , 35 , 39 , 44 ]. Moreover, Zheng et al [ 45 ], reported that administration with schisantherin A ameliorated ischemia-reperfusion-induced dysfunction, histological damage, the inflammatory state and oxidative stress in the liver.…”

Section: Introductionmentioning

confidence: 99%

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Schisantherin A alleviated alcohol-induced liver injury by the regulation of alcohol metabolism and NF-kB pathway

Wang

et al. 2018

Exp. Anim.

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Schisantherin A (SinA), one of the most abundant active ingredients of Schisandra chinensis, was reported to protect and benefit the liver, however, its effect on alcohol-induced liver injury (ALI) was still not clear. In the present study, an ALI mice model was induced by feeding mice an alcohol-containing liquid diet for four weeks. Then, 100 mg/kg or 200 mg/kg SinA was administered to mice every day by gavage for the last two weeks. Histopathological analysis showed that alcohol-induced liver lipid vacuoles were reduced by SinA. The activities of aspartate aminotransferase (AST, 61.90 ± 14.65 vs. 93.65 ± 20.50, 50.46 ± 13.21 vs. 93.65 ± 20.50) and alanine transaminase (ALT, 41.29 ± 9.20 vs. 64.04 ± 18.13, 36.52 ± 7.71 vs. 64.04 ± 18.13) in the serum of ALI mice were significantly reduced by 100 mg/kg or 200 mg/kg SinA when compared with control mice. Alcohol-induced oxidative stress and the inflammatory response in the liver were suppressed by SinA in a dose-dependent manner. Meanwhile, treatment with SinA decreased alcohol dehydrogenase (ADH) activity and increased acetaldehyde dehydrogenase (ALDH) activity in ALI mice. Alcohol-induced upregulation of CYP2E1 and CYP1A2 in the liver was inhibited by SinA. Further, SinA suppressed activation of the NF-kB pathway in ALI mice. In conclusion, our findings demonstrate that SinA is able to protect against ALI, and this may be, at least in part, caused by regulation of alcohol metabolism and the NF-kB pathway. Our data suggest a therapeutic potential of SinA in the treatment of ALI.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Schisantherin A alleviated alcohol-induced liver injury by the regulation of alcohol metabolism and NF-kB pathway

Wang

et al. 2018

Exp. Anim.

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“…STA is one of the main active components of Schisandra chinensis lignans and has a good effect in the treatment of Parkinson disease, protecting against ischemia-reperfusion injury, anti-inflammation, and Alzheimer's disease, [13][14][15][16][17][18][19] but there is no explicit animal behavior experiment to confirm its sedative and hypnotic effects. This study showed that STA has sedative and hypnotic effects, and these effects may be related to its regulating the function of the GABAergic nervous system.…”

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confidence: 99%

Schisantherin A Exerts Sedative and Hypnotic Effects Through Regulating GABA and its Receptor in Mice and Rats

Wang

Liu

Sun

et al. 2019

Natural Product Communications

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Schisandra has been used to treat insomnia for hundreds of years in China. This study was aimed at proving the contribution of Schisantherin A (STA), the most abundant component in Schisandra, on sleeping, and uncover its mechanisms. Mouse autonomic activity and sleep tests were conducted for the behavioral examinations. The γ-aminobutyric acid (GABA), glutamic acid (Glu), and glutamic acid decarboxylase (GAD) in the blood and/or brain tissues of mice and rats were measured by enzyme-linked immunosorbent assay kits, and GABA A Rα1 and GABA A Rγ2 expressions in the brain tissues of rats were detected by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot. STA decreased the autonomic activities and sleep latency, increased the number of sleeping periods, sleep time, and duration in mice, showing a sedative and hypnotic effect. STA significantly elevated GABA, reduced Glu in the blood and brain, and increased GAD in the brain. STA upregulated the expressions of GABA A Rα1 and GABA A Rγ2 mRNA in the brain of rats. Thus, STA is an active component for sedative and hypnotic effects in Schisandra and these effects may be through its regulation of the GABA/Glu ratio, GAD, and GABA A expression in mice and rats.

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“…The activation of NF‐κB can induce the excessive generation of inflammatory mediators, such as tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β) and interleukin‐6 (IL‐6) (Shi et al . ), while the inhibition of TLR4/NF‐κB inflammatory pathway can exert strong protective effects on middle cerebral artery occlusion (MCAO) rats (Belinga et al . ).…”

mentioning

confidence: 99%

“…Among TLRs, TLR4 can exert strong regulatory effects on post-ischemic inflammatory responses by activating the transcriptional factors NF-jB (Garc ıa-Culebras et al 2017). The activation of NF-jB can induce the excessive generation of inflammatory mediators, such as tumor necrosis factor-a (TNF-a), interleukin-1b (IL-1b) and interleukin-6 (IL-6) (Shi et al 2017), while the inhibition of TLR4/NF-jB inflammatory pathway can exert strong protective effects on middle cerebral artery occlusion (MCAO) rats (Belinga et al 2016). Therefore, the regulation of astrocytes activation and associated TLR4/NF-jB inflammatory pathway may be essential in pathological processes in the CNS and could serve as a potential therapeutic target for ischemic stroke (Wu et al 2012).…”

mentioning

confidence: 99%

Z‐Guggulsterone attenuates astrocytes‐mediated neuroinflammation after ischemia by inhibiting toll‐like receptor 4 pathway

Liu

Zhang

et al. 2018

Journal of Neurochemistry

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Inflammatory damage plays a pivotal role in ischemic stroke pathogenesis and may represent one of the therapeutic targets. Z-Guggulsterone (Z-GS), an active component derived from myrrh, has been used to treat various diseases. The traditional uses suggest that myrrh is a good candidate for anti-inflammatory damage. This study was to investigate the anti-inflammatory and neuroprotective effects of Z-GS following cerebral ischemic injury, as well as the exact mechanisms behind them. Rat middle cerebral artery occlusion (MCAO) model and in vitro astrocytes oxygen-glucose deprivation (OGD) model were adopted to simulate ischemic stroke. Z-GS (30 or 60 mg/kg) was administered intraperitoneally immediately after reperfusion, while astrocytes were maintained in 30 or 60 μM Z-GS before OGD treatment. The results indicated that Z-GS significantly alleviated neurological deficits, infarct volume and histopathological damage in vivo, and increased the astrocytes viability in vitro. Moreover, the treatment of Z-GS inhibited the astrocytes activation and down-regulated the mRNA levels of pro-inflammatory cytokines. Furthermore, the activated TLR4-NF-κB signaling pathways induced by MCAO or OGD were significantly suppressed by Z-GS treatment, which was achieved via inhibiting the phosphorylation of JNK. Our results demonstrated that Z-GS exerted neuroprotective and anti-inflammatory properties through preventing activation of TLR4-mediated pathway in the activated astrocytes after ischemia injury. Therefore, Z-GS could be considered as a promising candidate for the treatment of ischemic stroke.

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Schisantherin A attenuates ischemia/reperfusion-induced neuronal injury in rats via regulation of TLR4 and C5aR1 signaling pathways

Cited by 27 publications

References 40 publications

Schisantherin A alleviated alcohol-induced liver injury by the regulation of alcohol metabolism and NF-kB pathway

Schisantherin A alleviated alcohol-induced liver injury by the regulation of alcohol metabolism and NF-kB pathway

Schisantherin A Exerts Sedative and Hypnotic Effects Through Regulating GABA and its Receptor in Mice and Rats

Z‐Guggulsterone attenuates astrocytes‐mediated neuroinflammation after ischemia by inhibiting toll‐like receptor 4 pathway

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