Matrine attenuates focal cerebral ischemic injury by improving antioxidant activity and inhibiting apoptosis in mice

Abstract

Matrine, an active constituent of the Chinese herb, Sophora flavescens Ait., and it is known for its antioxidant, anti-inflammatory and antitumor activities. It has been demonstrated that matrine exerts protective effects against heart failure by decreasing the expression of caspase-3 and Bax, and increasing Bcl-2 levels. In this study, we aimed to determine whether these protective effects of matrine can be applied to cerebral ischemia. Following 7 successive days of treatment with matrine (7.5, 15 and 30 mg/kg) and nimodipine (1 mg/kg) by intraperitoneal injection, male Institute of Cancer Research (ICR) mice were subjected to middle cerebral artery occlusion (MCAO). Following reperfusion, the neurobehavioral score and brain infarct volume were estimated, and morphological changes were analyzed by hematoxylin and eosin (H&E) staining and electron microscopy. The percentage of apoptotic neurons was determined by flow cytometry. The levels of oxidative stress were assessed by measuring the levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), and the total antioxidant capacity (T-AOC). Western blot analysis and immunofluorescence staining were used to examine the expression of the apoptosis-related proteins, caspase-3, Bax and Bcl-2. Our results revealed that pre-treatment with matrine significantly decreased the infarct volume and improved the neurological scores. Matrine also reduced the percentage of apoptotic neurons and relieved neuronal morphological damage. Furthermore, matrine markedly decreased the MDA levels, and increased SOD, GSH-Px and CAT activity, and T-AOC. Western blot analysis and immunofluorescence staining revealed a marked decrease in caspase-3 expression and an increase in the Bcl-2/Bax ratio in the group pre-treated with matrine (30 mg/kg) as compared with the vehicle-treated group. The findings of the present study demonstrate that matrine exerts neuroprotective effects against cerebral ischemic injury and that these effects are associated with its antioxidant and anti-apoptotic properties.

Decrease in Oxidative Stress Parameters after Post‐Ischaemic Recombinant Human Erythropoietin Administration in the Hippocampus of Rats Exposed to Focal Cerebral Ischaemia

“…In our experimental conditions, 24 hr after the induction of cerebral ischaemia, a statistically significant increase in the hippocampal SOD and GSH‐Px activities was detected in MCAO/Veh animals in comparison with the control groups. Although different published studies reported decrease in SOD and GSH‐Px activities after focal cerebral ischaemia induced by MCAO , results similar to our findings were described by several authors. They showed that a rise in the SOD and/or GSH‐Px activities occur in various models of cerebral ischaemia and in different brain regions.…”

Neuroprotective effect of heat shock protein 60 on matrine-suppressed microglial activation

“…Matrine (MT), the major active component of members of the Sophora genus, is used to treat inflammatory diseases and cancer in traditional Chinese medicine (10,11). Kan et al (12) demonstrated that MT could attenuate the severity of experimental autoimmune encephalomyelitis through reducing levels of chemokine ligand 2 and C-X-C motif chemokine 10, and suggested that MT may be an effective immunomodulatory therapeutic approach for MS through inhibiting immune cell recruitment mechanisms.…”

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

“…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.…”

“…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].…”