cytochrome-c-t and rhodioloside

Dexamethasone (Dex) and other glucocorticoids are widely used to treat serious infections and immunological diseases, however they may cause steroid‑induced avascular necrosis of the femoral head (SANFH). Salidroside (Sal) has demonstrated an anti‑apoptotic effect on neurocytes by activating the phosphoinositide 3‑kinase (PI3K)/protein kinase B (Akt) signaling pathway. In the present study, primary osteoblasts were used in vitro and in rats in vivo to determine the anti-apoptotic effect of Sal on SANFH. The result of the present study demonstrated that pretreatment with Sal increased the cell survival rate while decreasing the cell apoptosis and lactate dehydrogenase release rate. Additionally, Sal also caused the reduction of TUNEL positive cells in TUNEL staining assay. Sal decreased the expression of cleaved caspase-3, cleaved caspase‑9, apoptosis regulator BAX and cytochrome C, while it increased the expression of B cell lymphoma‑2 and phosphorylated‑Akt in Dex‑induced osteoblasts. In vivo Sal protected against SANFH in rats by decreasing the percentage of empty lacunae. The present study demonstrated that Sal alleviated Dex‑induced osteoblast apoptosis by activating the PI3K/Akt signaling pathway and downregulating caspase‑3 expression in osteoblasts. Sal also protected against SANFH in a rat model of SANFH by decreasing the percentage of empty lacunae. The inhibition of the mitochondrial apoptosis pathway was also involved. Further research is required to determine the full underlying mechanisms by which Sal has an effect.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Caspase 9; Cell Survival; Cytochromes c; Dexamethasone; Femur Head Necrosis; Glucosides; Male; Mice; Mitochondria; Osteoblasts; Phenols; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Signal Transduction

Salidroside (Sal) is a natural antioxidant that elicits cardioprotective and neuroprotective effects in vivo and in vitro; however, its impact on hepatic ischemia/reperfusion (I/R) injury remains unclear. The purpose of this study was to investigate the hepatoprotective effects of salidroside against segmental (70%) warm hepatic I/R injury in rats. Animals were randomized into Sham, Sham+salidroside pretreatment (Sal), Sham+Sal+carboxyatractyloside (CATR), Sham+CATR, I/R, I/R+Sal, I/R+Sal+CATR and I/R+CATR groups. The hepatic artery, left portal vein and median liver lobes were occluded for 60min and then unclamped to allow reperfusion. Pretreatment with salidroside (20mg/kg/day for 7 days, intraperitoneally) significantly decreased serum alanine aminotransferase (sALT) and serum aspartate aminotransferase (sAST) levels after 6h and 24h of reperfusion and protected the liver against I/R-induced injury. However, this protective effect could be reversed by CATR, a mitochondrial permeability transition pore (MPTP) opener (5mg/kg 30min before I/R insult, intraperitoneally). Mechanistic studies have revealed that salidroside inhibits glycogen synthase kinase-3 beta (GSK-3β) activity and enhances the NF-E2-related factor (Nrf2)-dependent antioxidant response by activating the Akt signaling pathway, thereby reducing mitochondrial reactive oxygen species generation, increasing MPTP resistance and preventing apoptosis by suppressing cytochrome c release and caspase activation during reperfusion. Therefore, salidroside ameliorates hepatocyte death and apoptosis through activation of the GSK-3β/Nrf2-dependent antioxidant response and subsequent MPTP inhibition. These results provide experimental evidence supporting the clinical use of salidroside for hepatoprotection in surgical settings.

Topics: Animals; Antioxidants; Caspases; Cytochromes c; Cytoprotection; Enzyme Activation; Glucosides; Glycogen Synthase Kinase 3 beta; Liver; Male; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; NF-E2-Related Factor 2; Phenols; Rats; Rats, Sprague-Dawley; Reperfusion Injury

Heart disease is the leading cause of death worldwide. Ischemia-reperfusion injury can lead to apoptotic death of heart cells and subsequently heart failure. Rhodiola is an herbal medicine with two main bioactive compounds--salidroside (SAL) and tyrosol (TYR). This study aimed to investigate whether these two compounds can prevent ischemia/reperfusion-induced apoptosis in H9c2 cells.. Assays for total phenolics assay and Oxygen Radical Absorbance Capacity showed high antioxidant capacity of SAL and TYR. H9c2 cells were subjected to simulated ischemia/reperfusion (IR) in the presence and absence of SAL and/or TYR, and nuclei condensation, caspase-3 activity, cytochrome c release and JNK phosphorylation were determined.. In H9c2 cells, IR can lead to a 5-fold increase in p-JNK level. Apoptotic nuclei condensation, caspase-3 activity and cytochrome c release were markedly elevated, indicating the occurrence of apoptosis. SAL and TYR caused a dose-dependent inhibition of nuclear condensation. Furthermore, SAL and TYR, separately and in combination, significantly reduced caspase-3 activity, cytochrome c release and JNK activation. The anti-apoptotic effect of the combination was markedly higher than that of SAL or TYR alone.. The inhibition of the JNK signaling pathway is the key mechanism for the cytoprotective effect of SAL and TYR in IR-induced apoptosis.

Topics: Animals; Antioxidants; Apoptosis; Caspase 3; Cell Line; Cytochromes c; Dose-Response Relationship, Drug; Drug Therapy, Combination; Glucosides; JNK Mitogen-Activated Protein Kinases; MAP Kinase Signaling System; Myocardial Reperfusion Injury; Myocytes, Cardiac; Phenols; Phenylethyl Alcohol; Phosphorylation; Rats; Rhodiola

We used a rat pheochromocytoma (PC12) cell line to study the effects of salidroside on hydrogen peroxide (H(2)O(2))-induced apoptosis. In PC12 cells, H(2)O(2)-induced apoptosis was accompanied by the down-regulation of Bcl-2, the up-regulation of Bax, the release of mitochondrial cytochrome c to cytosol, and the activation of caspase-3, -8 and -9. However, salidroside suppressed the down-regulation of Bcl-2, the up-regulation of Bax and the release of mitochondrial cytochrome c to cytosol. Moreover, salidroside attenuated caspase-3, -8 and -9 activation, and eventually protected cells against H(2)O(2)-induced apoptosis. Taken together, these results suggest that treatment of PC12 cells with salidroside can block H(2)O(2)-induced apoptosis by regulating Bcl-2 family members and by suppressing cytochrome c release and caspase cascade activation.

Topics: Animals; Apoptosis; Bisbenzimidazole; Caspases; Cell Survival; Cytochromes c; DNA Fragmentation; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Enzyme Activation; Fluorescent Dyes; Formazans; Glucosides; Hydrogen Peroxide; L-Lactate Dehydrogenase; PC12 Cells; Phenols; Protective Agents; Rats; RNA, Messenger; Tetrazolium Salts