chrysin and Hypoxia

Topics: Caspase 3; Cell Line, Tumor; Flavonoids; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Ki-67 Antigen; Male; PC-3 Cells; Poly(ADP-ribose) Polymerase Inhibitors; Prostatic Neoplasms; Proto-Oncogene Proteins c-bcl-2; Signal Transduction; Vascular Endothelial Growth Factor A

: To investigate the protective effect of 7-hydroxyethyl chrysin (7-HEC) on rats with exercise-induced fatigue in hypobaric hypoxic condition.Forty healthy male Wistar rats were randomly divided into four groups with 10 rats in each group: control group, model group, chrysin group and 7-HEC group. The rats in control group were raised at local altitude but other three groups were raised in a simulating altitude of for hypobaric hypoxia treatment. The chrysin group and 7-HEC group were given chrysin or 7-HEC by gavage for respectively; while the control group and model group were given the same amount of sterilized water. The weight-bearing swimming tests were performed 3 d later, and the weight-bearing swimming time was documented. After rats were sacrificed, the liver and skeletal muscle tissue samples were taken for pathological examination and determination of lactate, malondialdehyde (MDA), total superoxide dismutase (T-SOD) and glycogen levels. Blood urea nitrogen was also determined. Compared with the model group, weight-bearing swimming times were significantly prolonged in 7-HEC group [ vs. (4.04±1.30) min, <0.01]; pathological changes in liver and skeletal muscle tissue were attenuated; generation rate of blood urea nitrogen vs. 0.60) mmol·L·min, <0.05], lactate [liver: (0.14±0.05) vs. (0.10±0.03) mg·g·min, skeletal muscle: vs. (0.18±] and MDA [liver: (0.48) vs. (0.78±0.28) nmol·mg·min, skeletal muscle: (0.87±0.19) vs. (0.63±0.11) nmol·mg·min] were significantly reduced (all < 0.05); glycogen content [liver: (15.16±2.69) vs. skeletal muscle: (1.46±0.49) vs.0.48) mg/g] and T-SOD [liver: (1.87±0.01) vs. (2.68±0.12) U/mL, skeletal muscle: 0.42) vs. 0.96) U/mL] were significantly improved (all <0.05). 7-HEC has significant protective effect on the rats with exercise-induced fatigue in hypobaric hypoxia condition.

Topics: Altitude; Animals; Fatigue; Flavonoids; Hypoxia; Male; Rats; Rats, Wistar

Topics: Biomimetics; Bruch Membrane; Cell Line; Choroidal Neovascularization; Collagen; Drug Combinations; Endothelial Cells; Flavonoids; Humans; Hypoxia; Laminin; Nanofibers; Permeability; Proteoglycans; Retinal Pigment Epithelium

Chrysin (CH), the main ingredient of many medicinal plants, has been reported to be a very potent flavonoid possessing a large number of pharmacological activities. Recent studies have shown that CH significantly improves hemodynamic parameters such as right ventricular pressure, right ventricular hypertrophy, and pulmonary vascular remodeling in a rat model of chronic hypoxia-induced pulmonary hypertension (CHPH). These improvements are through the inhibition of NOX4 expression, reactive oxygen species and malondialdehyde production, pulmonary arterial smooth muscle cell (PASMC) proliferation, and collagen accumulation. In this study, we investigated another mechanism by which CH alleviates CHPH by regulating intracellular calcium concentrations ([Ca]i) in PASMCs, as well as the underlying signaling pathway. The results show that (1) in CHPH model rats, CH substantially attenuated elevated right ventricular pressure, right ventricular hypertrophy, and pulmonary vascular remodeling; (2) in cultured rat distal PASMCs, CH inhibited the hypoxia-triggered promotion of cell proliferation, store-operated Ca entry and [Ca]i; and (3) CH significantly suppressed the hypoxia-upregulated HIF-1α, BMP4, TRPC1, and TRPC6 expression in distal pulmonary arteries (PAs) and cultured rat distal PASMCs. These results indicate that CH likely exerts its CHPH protective activity by regulating [Ca]i, which may result from the downregulation of HIF-1α, BMP4, TRPC1, and TRPC in PASMCs.

Topics: Animals; Antihypertensive Agents; Bone Morphogenetic Protein 4; Calcium; Calcium Signaling; Cell Proliferation; Cells, Cultured; Flavonoids; Hypertension, Pulmonary; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Pulmonary Artery; Rats, Sprague-Dawley; TRPC Cation Channels; Vascular Remodeling; Ventricular Function, Right; Ventricular Pressure; Ventricular Remodeling

Baicalin and its aglycone baicalein are the major flavonoid components of the root of Scutellaria baicalensis. Recent studies have shown that they can attenuate oxidative stress in various in vitro models as they possess potent antioxidant activities. This study investigated alternative protective mechanisms of baicalein in a cardiomyocyte model.. Neonatal rat cardiomyocytes pretreated with the test compound were subjected to hypoxia/reoxygenation. The extent of cellular damage was accessed by the amount of released lactate dehydrogenase. Pretreatment with baicalein up to 10 microM reduced lactate dehydrogenase release significantly (P<0.001), while pretreatment with baicalin up to 100 microM was ineffective. The cardioprotective effect of baicalein is not due to its antioxidant effect, because an adverse effect rather than a protective effect was observed when baicalein was present during hypoxia. Cotreatment with N-acetylcysteine attenuated the protective effect of baicalein and concomitantly increased intracellular reactive oxygen species level and the cytotoxic effect of baicalein, but N-acetylcysteine alone did not have such effects. In addition, cotreatment with catalase, but not superoxide dismutase or mannitol, reversed the cardioprotective effect of baicalein, suggesting the involvement of hydrogen peroxide in the cardioprotective mechanism. The NAD(P)H:quinone oxidoreductase inhibitors dicoumarol and chrysin also abolished the cardioprotective effect of baicalein. While pretreatment with baicalein did not increase antioxidant enzyme activities, it alleviated calcium accumulation in cardiomyocytes undergoing simulated ischemia.. These results highlight the important role of hydrogen peroxide produced during the auto-oxidation of baicalein in the cardioprotective effect of baicalein.

Topics: Acetylcysteine; Animals; Antioxidants; Calcium; Catalase; Cells, Cultured; Dicumarol; Enzyme Inhibitors; Flavanones; Flavonoids; Hypoxia; L-Lactate Dehydrogenase; Myocytes, Cardiac; Rats