Direct protection of neurons and astrocytes by matrine via inhibition of the NF-κB signaling pathway contributes to neuroprotection against focal cerebral ischemia

Xu, Min; Yang, Lei; Hong, Lizhi; Zhao, Xiaoyuan; Zhang, Huiling

doi:10.1016/j.brainres.2012.03.020

Cited by 54 publications

(34 citation statements)

References 66 publications

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“…It has been reported that oxymatrine protected animals against ischemia and reperfusion-induced liver, heart, and intestinal injuries involving extracellular signal regulated kinase, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinases signaling pathways [19]–[21]. In addition, the inhibitory effect of oxymatrine on NF-κB signaling pathway has been reported in pancreatic cancer [22] and cerebral ischemia in animals [23]. However, the effect of oxymatrine on NF-κB signaling pathway and the association with intestinal epithelial barrier dysfunction is unclear.…”

Section: Introductionmentioning

confidence: 99%

Oxymatrine Improves Intestinal Epithelial Barrier Function Involving NF-κB-Mediated Signaling Pathway in CCl4-Induced Cirrhotic Rats

et al. 2014

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Accumulating evidence suggests that intestinal epithelial barrier dysfunction plays an important role in the pathogenesis of hepatic cirrhosis and its complications such as gastrointestinal injury and hepatic encephalopathy. To date, there is no cure for cirrhosis-associated intestinal mucosal lesion and ulcer. This study aimed to investigate the effect of oxymatrine on intestinal epithelial barrier function and the underlying mechanism in carbon tetrachloride (CCl4)-induced cirrhotic rats. Thirty CCl4-induced cirrhotic rats were randomly divided into treatment group, which received oxymatrine treatment (63 mg/kg), and non-treatment group, which received the same dose of 5% glucose solution (vehicle). The blank group (n = 10 healthy rats) received no treatment. Terminal ileal samples were collected for histopathological examination. The expression level of nuclear factor-κB (NF-κB) p65 in ileal tissue was evaluated by immunohistochemistry. The gene and protein expression levels of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) in ileal tissues were analyzed by reverse-transcriptase polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Additionally, plasma endotoxin level was determined. In comparison to the blank group, a significant alteration in the morphology of intestinal mucosal villi in the non-treatment group was observed. The intestinal mucosal villi were atrophic, shorter, and fractured, and inflammatory cells were infiltrated into the lamina propria and muscular layer. Besides, serious swell of villi and loose structure of mucous membrane were observed. Oxymatrine reversed the CCl4-induced histological changes and restored intestinal barrier integrity. Moreover, oxymatrine reduced the protein expression level of NF-κB p65, TNF-α, and IL-6, which were elevated in the vehicle-treated group. In addition, the serum endotoxin level was significantly decreased after oxymatrine treatment in CCl4-induced cirrhotic rats. The results indicate that oxymatrine improves intestinal barrier function via NF-κB-mediated signaling pathway and may be used as a new protecting agent for cirrhosis-associated intestinal mucosal damage.

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Section: Introductionmentioning

confidence: 99%

Oxymatrine Improves Intestinal Epithelial Barrier Function Involving NF-κB-Mediated Signaling Pathway in CCl4-Induced Cirrhotic Rats

et al. 2014

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“…Matrine may also be used as an antioxidant that acts by promoting cell metabolism and regulating immune activities (7–10). It has been demonstrated that matrine has therapeutic effects on a variety of solid tumors, including breast, lung, stomach, esophageal, colorectal, cervical and ovarian cancer, as well as malignant lymphoma (11–13).…”

Section: Introductionmentioning

confidence: 99%

Matrine effectively inhibits the proliferation of breast cancer cells through a mechanism related to the NF-κB signaling pathway

Shao

Yang

et al. 2013

Oncology Letters

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Matrine is an alkaloid isolated from Sophora flavescens. The present study aimed to determine whether matrine effectively inhibits the proliferation of breast cancer cells, and the underlying mechanism(s) of its antitumor function. The effects of matrine on the cell viability of ER-positive MCF7 cells, HER2-positive BT-474 cells and highly metastatic MDA-MB-231 cells were measured using MTT and apoptosis assays. Western blot analysis was performed to investigate the expression levels of the inhibitor of κB (IκB) kinase β (IKKβ) in cells treated with or without matrine. It was observed that the matrine treatment resulted in the death of the three types of cancer cells, but significantly less toxicity was observed in the control cancer cells. The experimental results also suggested that the antitumor effects of matrine on breast cancer cells may be associated with the downregulation of IKKβ expression by matrine, as indicated by the western blot analysis results. The present results suggested that matrine may be used as an effective drug candidate for treating breast cancers in the future, following further research.

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“…10). Further, given that the brain of MAT-treated EAE rats exhibited a high expression of BDNF [22] and that BDNF could be induced in a cAMP/PKA-dependent manner [23], we also examined if MAT could stimulate BDNF expression through the cAMP/PKA pathway in primary astrocyte culture. Results showed that MAT indeed increased mRNA expression of BDNF in a dose-dependent manner (Fig.…”

Section: Mat Induced Astrocyte Camp/pka Signaling Thereby Upregulatimentioning

confidence: 99%

“…For example, MAT has an antinociceptive effect and stimulates the ascending dynorphinergic neurons that project to the spinal cord [21]. MAT protects neurons and astrocytes against focal cerebral ischemia by inhibiting the expression of NF-κB [22] or through its anti-oxidant and anti-apoptotic properties [23]. Further, MAT treatment improves motor function and increases axonal density in mice with spinal cord injury, likely through inhibition of epidermal growth factor receptor signaling [24].…”

Section: Introductionmentioning

confidence: 99%

Matrine Treatment Blocks NogoA-Induced Neural Inhibitory Signaling Pathway in Ongoing Experimental Autoimmune Encephalomyelitis

Kan

Zhang

et al. 2016

Mol Neurobiol

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Myelin-associated inhibitors, such as NogoA, myelin-associated glycoprotein (MAG), and oligodendrocyte myelin glycoprotein (OMgp), play a pivotal role in the lack of neuroregeneration in multiple sclerosis, an inflammatory demyelinating disease of the central nervous system (CNS). Matrine (MAT), a monomer that is used in traditional Chinese medicine as an anti-inflammatory agent, has shown beneficial effects in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. However, the underlying mechanisms of MAT-induced EAE amelioration are not fully understood. In the present study, we show that MAT treatment suppressed ongoing EAE, and this effect correlated with an increased expression of growth-associated protein 43, an established marker for axonal regeneration. MAT treatment significantly reduced the levels of NogoA, its receptor complex NgR/p75NTR/LINGO-1, and their downstream RhoA/ROCK signaling pathway in the CNS. In contrast, intracellular cyclic AMP (cAMP) levels and its protein kinase (protein kinase A (PKA)), which can promote axonal regrowth by inactivating the RhoA, were upregulated. Importantly, adding MAT in primary astrocytes in vitro largely induced cAMP/PKA expression, and blockade of cAMP significantly diminished MAT-induced expression of PKA and production of BDNF, a potent neurotrophic factor for neuroregeneration. Taken together, our findings demonstrate that the beneficial effects of MAT on EAE can be attributed not only to its capacity for immunomodulation, but also to its directly promoting regeneration of the injured CNS.

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Direct protection of neurons and astrocytes by matrine via inhibition of the NF-κB signaling pathway contributes to neuroprotection against focal cerebral ischemia

Cited by 54 publications

References 66 publications

Oxymatrine Improves Intestinal Epithelial Barrier Function Involving NF-κB-Mediated Signaling Pathway in CCl4-Induced Cirrhotic Rats

Oxymatrine Improves Intestinal Epithelial Barrier Function Involving NF-κB-Mediated Signaling Pathway in CCl4-Induced Cirrhotic Rats

Matrine effectively inhibits the proliferation of breast cancer cells through a mechanism related to the NF-κB signaling pathway

Matrine Treatment Blocks NogoA-Induced Neural Inhibitory Signaling Pathway in Ongoing Experimental Autoimmune Encephalomyelitis

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