cytellin and Reperfusion-Injury

This research is the first to use β-sitosterol on myocardial and renal tissues in renal ischemia/reperfusion (IR) damage. Female Wistar rats were randomly divided into three groups: control (sham), renal IR (50 min ischemia - 3 h reperfusion), and renal IR + 150 mg/kg/p.o. β-sitosterol (the rats were treated with β-sitosterol orally once 1 h before the IR procedure). β-Sitosterol pretreatment caused an increase in superoxide dismutase and glutathione activities and a decrease in malondialdehyde levels in the kidney and heart. Moreover, it alleviated histopathological changes and downregulated the levels of tumor necrosis factor-alpha and interleukin-6 and upregulated the levels of endothelial nitric oxide synthase. As conclusion, the potential of β-sitosterol for renal and cardiac necrosis and apoptosis appears to act by limiting inflammatory response and oxidative stress. Thus, the potential of this compound is noteworthy and may serve as a potential therapeutic in the treatment of acute organ damages due to renal IR.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Female; Glutathione; Hypolipidemic Agents; Interleukin-6; Ischemia; Kidney; Kidney Diseases; Malondialdehyde; Myocardium; Nitric Oxide Synthase Type III; Protective Agents; Rats, Wistar; Reperfusion Injury; Sitosterols; Superoxide Dismutase; Tumor Necrosis Factor-alpha

Traditional Chinese medicine has growing importance in the treatment of ischemia stroke due to its abundance and low drug resistance. In this study, we aim to investigate the therapeutic potential of daucosterol palmitate against ischemia stroke, as well as its neuro-protective mechanism. The dose-response effects of daucosterol palmitate in the protection from brain damage were evaluated in a cerebral ischemia/reperfusion (I/R) rat model. The correlation of neuro-protective effects of daucosterol palmitate with apoptosis inhibition was examined and the possible signaling targets were identified. Our findings revealed that daucosterol palmitate treatment after 2 h' ischemia significantly lowered brain damage, and neuronal cell apoptosis caused by I/R injury in a dose-response mode (20, 40 and 80 mg/kg). Western blot analysis indicated that daucosterol palmitate could reverse the effects of I/R injury on protein expression of PI3K and mTOR, and phosphorylation of Akt. Contrarily, inactivation of PI3K using wortmannin dramatically antagonized the effect of daucosterol palmitate for I/R injury. With these findings, it supports the application potential of daucosterol palmitate in the treatment of ischemia stroke. Besides, the PI3K/Akt/mTOR pathway might be potential cellular targets for daucosterol palmitate.

Topics: Animals; Apoptosis; Brain Ischemia; Dose-Response Relationship, Drug; Male; Neurons; Palmitates; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Plant Extracts; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Sitosterols; TOR Serine-Threonine Kinases

We previously reported that daucosterol (a sterolin) up-regulates the expression of insulin-like growth factor I (IGF1)(1) protein in neural stem cells. In this study, we investigated the effects of daucosterol on the survival of cultured cortical neurons after neurons were subjected to oxygen and glucose deprivation and simulated reperfusion (OGD/R)(2), and determined the corresponding molecular mechanism. The results showed that post-treatment of daucosterol significantly reduced neuronal loss, as well as apoptotic rate and caspase-3 activity, displaying the neuroprotective activity. We also found that daucosterol increased the expression level of IGF1 protein, diminished the down-regulation of p-AKT(3) and p-GSK-3β(4), thus activating the AKT(5) signal pathway. Additionally, it diminished the down-regulation of the anti-apoptotic proteins Mcl-1(6) and Bcl-2(7), and decreased the expression level of the pro-apoptotic protein Bax(8), thus raising the ratio of Bcl-2/Bax. The neuroprotective effect of daucosterol was inhibited in the presence of picropodophyllin (PPP)(9), the inhibitor of insulin-like growth factor I receptors (IGF1R)(10). Our study provided information about daucosterol as an efficient and inexpensive neuroprotectants, to which the IGF1-like activity of daucosterol contributes. Daucosterol could be potentially developed as a medicine for ischemic stroke treatment.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Brain; Caspase 3; Cell Survival; Cells, Cultured; Glucose; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Insulin-Like Growth Factor I; Myeloid Cell Leukemia Sequence 1 Protein; Neuroprotective Agents; Oxygen; Podophyllotoxin; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Receptors, Somatomedin; Reperfusion Injury; Signal Transduction; Sitosterols

Aloe vera continues to be used for wound healing as a folk medicine. We previously reported that A. vera gel has angiogenic activity. In this study, we report upon the isolation of an angiogenic component beta-sitosterol from A. vera and examination of its effect upon damaged blood vessels of the Mongolian gerbil. In a chick embryo chorioallantoic membrane assay, beta-sitosterol was found to have an angiogenic effect. It enhanced new vessel formation in gerbil brains damaged by ischaemia/reperfusion, especially in the cingulated cortex and septal regions, in a dose-dependent fashion (up to 500 microg/kg, p < 0.05, n = 34 - 40). beta-Sitosterol also enhanced the expressions of proteins related to angiogenesis, namely von Willebrand factors, vascular endothelial growth factor (VEGF), VEGF receptor Flk-1, and blood vessel matrix laminin (p < 0.05, n = 6). In addition, the intraperitoneal administration of beta-sitosterol at 500 microg/kg/day for a period of 19 days significantly improved the motion recovery of ischaemia/reperfusion-damaged gerbils as assessed by rota-rod testing (p < 0.001, n = 10). Our results suggest that beta-sitosterol has therapeutic angiogenic effects on damaged blood vessels.

Topics: Aloe; Angiogenesis Inducing Agents; Animals; Behavior, Animal; Blood Vessels; Blotting, Western; Brain; Chick Embryo; Dose-Response Relationship, Drug; Endothelial Growth Factors; Gerbillinae; Immunohistochemistry; Laminin; Lymphokines; Plant Extracts; Plant Leaves; Receptor Protein-Tyrosine Kinases; Receptors, Growth Factor; Receptors, Vascular Endothelial Growth Factor; Reperfusion Injury; Sitosterols; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; von Willebrand Factor