beta-escin and Reperfusion-Injury

Hyperactivity of HPA axis results in intestinal dysfunction, which may play a role in brain injury caused by ischemic stroke (IS). Escin shows a neuroprotective effect but it may not penetrate blood brain barrier (BBB). Previous work in our laboratory showed that escin ameliorated intestinal injury in animals. The aim of this study is to investigate whether escin attenuates brain injury by improving intestinal dysfunction in middle cerebral artery occlusion (MCAO) rats, to mimic IS. MCAO rats and lipopolysaccharides (LPS)-induced Caco-2 cells were used to evaluate the effects of escin in vivo and in vitro. The results showed that escin could not penetrate BBB but reduced brain infarct volume, improved neurological function, inhibited neuroinflammation, ameliorated intestinal dysfunction and tissue integrity by increasing the expression of the tight junction protein in vivo and in vitro. Escin reduced the increased corticosterone and endotoxin level in blood of MCAO rats, regulated GR/p38 MAPK/NF-κB signaling pathway in ileal tissue and LPS/TLR4/NF-κB signaling pathway in ischemic brain tissue. These findings suggest that escin could attenuate ischemic brain injury by improving intestinal dysfunction, and it may be a promising way to protect brain injury by protecting intestine, instead of targeting the brain directly after IS.

Topics: Animals; Brain Injuries; Brain Ischemia; Brain-Gut Axis; Caco-2 Cells; Escin; Gastrointestinal Diseases; Humans; Hypothalamo-Hypophyseal System; Infarction, Middle Cerebral Artery; Intestinal Diseases; Ischemic Stroke; Lipopolysaccharides; NF-kappa B; Pituitary-Adrenal System; Rats; Reperfusion Injury; Stroke

Topics: Animals; Cell Hypoxia; Cell Survival; Cells, Cultured; Escin; Female; Glucose; L-Lactate Dehydrogenase; Mice; Mice, Inbred C57BL; Neurons; Neuroprotective Agents; Phosphoproteins; Phosphorylation; Reperfusion Injury; RNA Interference; RNA, Small Interfering; Signal Transduction; Sirolimus; TOR Serine-Threonine Kinases

To investigate the relationship between apoptosis-related genes and lung injury induced by intestinal ischemia reperfusion and to explore the effects and its possible mechanism of sodium aescinate.. Rat model of intestinal I/R injury was established with clamping of the superior mesenteric artery for 60 min and then clamping was relieved for 60 min. Twenty-four SD rats were randomly divided into three groups with eight rats in each: sham group, intestinal ischemia/reperfusion group (I/R group) and sodium aescinate group (SA + I/R group). Lung wet/dry weight ratio, lung coefficient and Superoxide dismutase (SOD), malondialdehyde (MDA) in plasma and lung tissue were measured, as well as the expression levels of Bcl-2 and Bax proteins in lung tissue were examined using immunohistochemical method.. Compared with sham group, lung wet/dry weight ratio, lung coefficient and MDA in plasma and lung tissue were significantly increased, and while the activity of SOD in plasma and lung tissue were decreased significantly in I/R group. At the same time, the protein expression level of Bcl-2 and Bax were significantly increased. But Bax protein expression was much greater than that of Bcl-2, the ratio of Bcl-2 to Bax was decreased significantly in I/R group than that in sham group. Compared with I/R group, lung wet/dry weight ratio, lung coefficient and MDA in plasma and lung tissue were significantly decreased, and while the activity of SOD in serum and lung tissue were significantly increased in SA + I/R group. At the same time, Bax protein expression was significantly decreased, both Bcl-2 protein expression and the ratio of Bcl-2 to Bax were significantly increased in SA + I/R group than that in I/R group.. Lung injury induced by intestinal ischemia reperfusion is correlated with abnormal expression levels of Bcl-2 and Bax protein which is caused by oxidative injury. Sodium aescinate can protect the lung injury induced by intestinal ischemia/reperfusion (I/R), which may be mediated by inhibiting lipid peroxidation, upregulating Bcl-2 gene protein expression, improving the ratio of Bcl-2/ Bax to inhibit lung apoptosis.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Escin; Female; Intestines; Ischemia; Lung Injury; Male; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Saponins

Topics: Animals; Escin; Intestines; Lipid Peroxidation; Male; Rats; Rats, Sprague-Dawley; Reperfusion Injury

To investigate the effects of sodium beta-aescin on neutrophil migration and expression of adhesion molecules (ICAM-1 and E-selectin) after middle cerebral artery occlusion (MCAO) in rats.. Rats were pretreated with sodium beta-aescin for 7 d and then subjected to cerebral ischemia/reperfusion (I/R) injury induced by an MCAO. After a 2-h ischemia and a 24-h reperfusion, the infarct volume and neurological deficit were determined by the method of TTC staining and the Longa's score. The effect of sodium beta-aescin on the migration of neutrophils was evaluated by measuring the activity of myeloperoxidase (MPO) enzyme. The expressions of adhesion molecules were determined by immunohistochemistry and Western blot.. Sodium beta-aescin significantly reduced the cerebral infarct volume and ameliorated the neurological deficit (P<0.05 or P<0.01). The MPO activity and the expressions of ICAM-1 and E-selectin in the vehicle-treated rats were increased significantly (P<0.01) after cerebral I/R. After treatment with sodium beta-aescin, the enzymatic activity of MPO and the expressions of these adhesion molecules were significantly reduced compared with the vehicle-treated group (P<0.05 or P<0.01).. Sodium beta-aescin can attenuate brain injury, down-regulate the protein expressions of ICAM-1 and E-selectin, and reduce the migration of neutrophils after cerebral I/R.

Topics: Aesculus; Animals; Cell Movement; Cerebral Infarction; Down-Regulation; E-Selectin; Escin; Infarction, Middle Cerebral Artery; Intercellular Adhesion Molecule-1; Male; Neuroprotective Agents; Neutrophils; Peroxidase; Plants, Medicinal; Rats; Rats, Sprague-Dawley; Reperfusion Injury

To investigate the effects of beta-aescin on apoptosis induced by transient focal brain ischemia in rats.. Rats were pretreated with beta-aescin for 7 d and then subjected to brain ischemia/reperfusion (I/R) injury induced by a middle cerebral artery occlusion. After 2 h ischemia and 24 h reperfusion, Hematoxylin-Eosin (HE) staining, in situ end-labeling of nuclear DNA fragmentation (TUNEL) were employed to determine the level of apoptosis. The expressions of caspase-3 and Bcl-2 in the cortex were determined by immunohistochemistry and Western blot. The release of cytochrome c was analyzed by Western blot.. The increased numbers of HE- and TUNEL-positive staining cells were significantly observed at 24 h after reperfusion. The immunoreactivity was inhibited by beta-aescin (30, 60 mg/kg) (P<0.01 or P<0.05 vs vehicle-treated). After cerebral I/R, cytochrome c was released into the cytosol and caspase-3 was activated, whereas Bcl-2 expression was inhibited. beta-Aescin (30, 60 mg/kg) markedly inhibited the expression of caspase-3 and the release of cytochrome c, and up-regulated the expression of Bcl-2 (P<0.05, P<0.01 vs vehicle-treated).. beta-Aescin could potently inhibit caspase-3 activation and the release of cytochrome c, increasing the expression of Bcl-2 after cerebral I/R in rats. These findings on the inhibitory effects of beta-aescin on brain ischemic injury-induced apoptosis might have important theoretical basis for the treatment on ischemic cerebrovascular diseases.

Topics: Animals; Apoptosis; Brain Ischemia; Caspase 3; Caspases; Cerebral Cortex; Cytochromes c; Escin; Infarction, Middle Cerebral Artery; Male; Mitochondria; Neuroprotective Agents; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Reperfusion Injury

To investigate the protective effects of sodium beta-aescin on cerebral ischemia-reperfusion injury in rats.. Rats were pretreated with sodium beta-aesein for 7 d and then subjected to cerebral ischemia-reperfusion injury induced by a middle cerebral artery occlusion (MCAO). The neurological outcome was evaluated by the Longa's method; The infarct volume was assessed by hemmatoxylin-Eosin staining and the cerebral water content was measured by dry weight method. The activities of SOD, GSH-Px, CAT, Na+ -K+ -ATPase and the MDA content were measured in the cortex and hippocampus of ischemic and non-ischemic hemisphere.. Sodium beta-aescin significantly reduced the volume of cerebral infarct and water content, and ameliorated the neurological deficit (P < 0.05). In vehicle-treated rats, the activities of SOD, GSH-Px and Na+ -K+ -ATPase in the cortex and hippocampus of ischemic hemisphere were all decreased (P < 0.01) , while the CAT activity was slightly elevated and the MDA of content was significantly increased (P < 0.01) compared with the sham-operated group. After treated with sodium beta-aescin, the effects on recovery of SOD, GSH-Px, Na+ -K+ -ATPase activities were observed (P < 0.05), and the MDA content was reduced (P < 0.05).. These results showed that pretreatment with sodium beta-aescin can attenuate brain injury and its antioxidant activity on rats which encountered cerebral ischemia-reperfusion.

Topics: Animals; Brain; Brain Ischemia; Catalase; Escin; Glutathione Peroxidase; Male; Malondialdehyde; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Sodium-Potassium-Exchanging ATPase; Superoxide Dismutase