beta-escin and Brain-Ischemia

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

To perform a differential analysis of the efficacy of combination therapy by the drugs with different modalities (mexidol, aescusan, halidorum) in outpatients with chronic cerebral ischemia (CCI), stages I- III.. A study included 50 patients with CCI of atherosclerotic, hypertensive and mixed genesis (stage I - 20 patients, stage II - 20, stage III - 10 patients). In addition to somatic therapy, patients received three courses of mexidol, halidorum and aescusan combination therapy during 6 weeks with a 3 month interval between the courses. The changes in subjective complaints and objective clinical manifestations were evaluated after each course.. The therapeutic efficacy after durable complex therapy by repeated courses of antioxidants is supported by the results of clinical and neurological examinations. Mexidol in the combination with aescusan and halidorum contributed to the improvement of cognitive, adaptive, motor functions of the patients with CCI, stages I and II. To increase treatment efficacy in patients with CCI, stage III, we recommend to use the drugs that improve cognitive functions of the patients.. Цель исследования - проведение дифференцированного анализа эффективности комбинированного лечения препаратами различной модальности (мексидол, эскузан, галидор) у пациентов с хронической ишемией мозга (ХИМ) I, II и III стадий в амбулаторных условиях. Материал и методы. В исследование включены 50 пациентов с диагнозом хроническая ишемия головного мозга I-III стадии атеросклеротического, гипертонического и смешанного генеза (I стадия - 20 больных, II стадия - 20 больных, III стадия - 10 больных). На фоне базисной терапии пациенты получали три курса комбинированной терапии препаратами мексидол, галидор, эскузан в течение 6 нед с интервалом между курсами 3 мес. После каждого курса оценивались динамика субъективных жалоб пациентов и объективных клинических проявлений. Результаты и заключение. На основании данных клинико-неврологического обследования показана терапевтическая эффективность длительного комплексного лечения неоднократными курсами антиоксидантов. Применение мексидола в сочетании с эскузаном и галидором способствовало улучшению когнитивных, адаптационных, двигательных функций пациентов при ХИМ I и II стадий. С целью повышения эффективности лечения у пациентов с ХИМ III стадии нейропротективное действие используемых лекарственных средств целесообразно дополнить препаратами, улучшающими когнитивные функции.

Topics: Aged; Antioxidants; Bencyclane; Brain Ischemia; Chronic Disease; Drug Therapy, Combination; Escin; Female; Humans; Male; Middle Aged; Neuroprotective Agents; Picolines; Treatment Outcome

Considerable evidence has been accumulated demonstrating an important role for inflammation in ischemic brain injury and its contribution to greater cerebral damage after ischemia. Blocking the inflammatory reaction promotes neuroprotection and shows therapeutic potential for clinical treatment of ischemic brain injury. Escin, a natural mixture of triterpenoid saponin isolated from the seed of the horse chestnut, demonstrates antiedematous and anti-inflammatory effects. Here we assessed neuroprotective effects of escin with a transient global cerebral ischemia model. Global cerebral ischemia was induced by occluding both common carotid arteries and withdrawing 0.3ml of blood from the tail vein in mice. Treatment with escin was initiated 0.5h after ischemia induction and given once a day for three consecutive days. Then animals were assessed using the Morris water-maze test and step-down passive avoidance test. Acetylcholinesterase (AChE) activity, histological pathology, and expression of inflammatory genes in the hippocampus were determined. The results showed escin significantly improved learning and memory recovery and reduced hippocampal damage in the cerebral ischemic mice. However, donepezil merely improved learning and memory recovery but did not ameliorate hippocampal damage in the cerebral ischemic mice. Furthermore, we found escin significantly downregulated certain inflammatory gene expression and upregulated expression of granulocyte-macrophage colony-stimulating factor (GM-CSF), which was recently reported as a neuroprotective protein in the brain. Our results indicate that inhibition of inflammation and protection of hippocampal neurons by escin may be a potentially useful therapy for ischemic brain injury.

Topics: Animals; Brain Ischemia; Cognition Disorders; Escin; Hippocampus; Male; Mice

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