Protective Effects Of Matrine Research Articles

Matrine attenuates high-fat diet-induced in vivo and ox-LDL-induced in vitro vascular injury by regulating the PKCα/eNOS and PI3K/Akt/eNOS pathways.

Lipid metabolism disorders lead to vascular endothelial injury. Matrine is an alkaloid that has been used to improve obesity and diabetes and for the treatment of hepatitis B. However, its effect on lipid metabolism disorders and vascular injury is unclear. Here, we investigated the effect of matrine on high‐fat diet fed mice and oxidized low‐density lipoprotein (ox‐LDL)‐induced human umbilical vein endothelial cells (HUVECs). Computational virtual docking analyses, phosphoinositide 3‐kinase (PI3K) and protein kinase C‐α (PKCα) inhibitors were used to localize matrine in vascular injuries. The results showed that matrine‐treated mice were more resistant to abnormal lipid metabolism and inflammation than vehicle‐treated mice and exhibited significantly alleviated ox‐LDL‐stimulated dysfunction of HUVECs, restored diminished nitric oxide release, decreased reactive oxygen species generation and increased expression phosphorylation of AKT‐Ser473 and endothelial nitric oxide synthase (eNOS)‐Ser1177. Matrine not only up‐regulates eNOS‐Ser1177 but also down‐regulates eNOS‐Thr495, a PKCα‐controlled negative regulator of eNOS. Using computational virtual docking analyses and biochemical assays, matrine was also shown to influence eNOS/NO via PKCα inhibition. Moreover, the protective effects of matrine were significantly abolished by the simultaneous application of PKCα and the PI3K inhibitor. Matrine may thus be potentially employed as a novel therapeutic strategy against high‐fat diet‐induced vascular injury.

Protective effects of matrine on experimental autoimmune encephalomyelitis via regulation of ProNGF and NGF signaling

Inflammation, demyelination, oligodendrocyte (OLG) death, and axonal degeneration are primary characteristics of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). OLGs generate myelin sheaths that surround axons, while damage to OLGs leads to demyelination and neurological functional deficit. Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae Flave, has been recently found to effectively ameliorate clinical signs in EAE. Its therapeutic mechanism has, however, not been completely elucidated. In the present study, we found that MAT retarded the disease process, attenuated the clinical severity of EAE rats, ameliorated inflammation and demyelination, and suppressed the apoptosis of OLGs in the central nervous system (CNS) of EAE rats. In addition, MAT markedly blocked increased expression of the proNGF-p75NTR death signaling complex, which is known to mediate OLG death in EAE animals. At the same time, MAT also prevented a decrease in the levels of NGF and its receptor TrkA, which together mediate the cell survival pathway and differentiation of OLGs. ProNGF, NGF, and the downstream effector proteins play an important role in the growth, differentiation, and apoptosis of OLGs as well as the reparative response to neuronal damage. These findings thus indicate that MAT improves clinical severity of EAE in part by reducing OLG apoptosis via restoring the ratios of proNGF:NGF and the respective receptors p75NTR:TrkA in vivo. Taken together, these results suggest that MAT may be a promising agent for MS treatment based on its protective effect on OLGs.

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

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.

Protective effects of matrine against progression of high-fructose diet-induced steatohepatitis by enhancing antioxidant and anti-inflammatory defences involving Nrf2 translocation

The present study was aimed to investigate the hepatoprotective effects of matrine against nonalcoholic steatohepatitis induced by a high-fructose diet. After being fed a high-fructose diet (HFD) for 4weeks, male Wistar rats were orally administered matrine in three different doses (40, 80, or 160mg/kg) once daily. Serum and liver samples were collected after treatment with matrine for 4weeks. Lipid droplets within hepatocytes, infiltration of inflammatory cells, and necrotic foci in the liver were morphologically alleviated by matrine in a dose-dependent manner compared with the HFD group. ALT and AST in the blood and the triglyceride content in the liver also decreased. The increased malondialdehyde and depleted glutathione by HFD were ameliorated in a dose-related manner with matrine. Matrine promoted Nrf2 translocation to the nucleus with subsequently up-regulated antioxidative enzyme protein expression, and it enhanced antioxidant activities compared with the HFD group (p<0.05). The increased activity of nuclear factor-kappa B in the liver and the tumour necrosis factor-alpha levels in plasma induced by HFD were inhibited by matrine as well (p<0.05). In this study, we also found that matrine ameliorated HFD-induced hyperglycaemia and insulin resistance. Taken together, our findings demonstrate that matrine is effective in preventing conversion of high-fructose diet-induced hepatic steatosis into nonalcoholic steatohepatitis in rats.

Protective effects of matrine against hypothermic injury of gel entrapment hepatocytes

Protective effects of matrine against hypothermic injury of gel entrapment hepatocytes

Protective effect of matrine against ischemia and reperfusion injury in rat partial liver transplantation

Protective effect of matrine against ischemia and reperfusion injury in rat partial liver transplantation

Protective effect of matrine on sinusoidal endothelial cells of rat liver isograft

Protective effect of matrine on sinusoidal endothelial cells of rat liver isograft

Protective effects of matrine and oxymatrine on stress ulcer in relation to their effects on the central nervous system

Protective effects of matrine and oxymatrine on stress ulcer in relation to their effects on the central nervous system