rosmarinic-acid and Hypoxia

Obstructive sleep apnoea (OSA) causes chronic intermittent hypoxia (CIH), which results in mitochondrial dysfunction and generates reactive oxygen species (ROS) in the heart. Excessive free iron could accelerate oxidative damage, which may be involved in this process. Banxia-Houpu decoction (BHD) was reported to improve the apnoea hypopnoea index in OSA patients, but the specific mechanism was still unclear.. To investigate whether BHD could reduce CIH-induced heart damage by regulating iron metabolism and mitochondrial function.. BHD (7.01 g/kg) significantly improved cardiac dysfunction, pathological change and mitochondrial structure induced by CIH. BHD increased the Bcl-2/Bax ratio (1.4-fold) and inhibited caspase 3 cleavage in CIH mice (0.45-fold). BHD activated mitophagy by upregulating Parkin (1.94-fold) and PINK1 (1.26-fold), inhibiting the PI3K-AKT-mTOR pathway. BHD suppressed ROS generation by decreasing NOX2 (0.59-fold) and 4-HNE (0.83-fold). BHD reduced the total iron in myocardial cells (0.72-fold) and mitochondrial iron by downregulating Mfrn2 (0.81-fold) and MtFt (0.78-fold) proteins, and upregulating ABCB8 protein (1.33-fold). Rosmarinic acid, the main component of Perilla Leaf in BHD, was able to react with Fe. These findings encourage the use of BHD to resist cardiovascular injury and provide the theoretical basis for clinical treatment in OSA patients.

Topics: Animals; Apoptosis; Cinnamates; Depsides; Disease Models, Animal; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Heart Injuries; Hypoxia; Iron; Male; Mice; Mice, Inbred C57BL; Mitochondria; Oxidative Stress; Reactive Oxygen Species; Rosmarinic Acid; Sleep Apnea, Obstructive

To study the protective effect of rosmarinic acid (Ros A) on the primary cardiomyocyte hypoxia/reoxygenation (H/R) injury.. Primary cardiomyocytes of rats were cultured in vitro to establish the H/R injury of cardiomyocytes and observe the changes in the cell viability and LDH leakage. The changes in ATP content and ROS in cardiomyocytes were measured by using chemiluminescence and fluorescent probe technique. The effects of rosmarinic acid on the apoptosis of cardiomyocytes, cleaved-caspase 3, Akt and p-Akt protein expression were further detected by flow cytometry and western blot analysis.. According to the experimental results, Ros A at doses of 25, 50, 100 mg x L(-1) could inhibit the decrease in H/R-induced cell viability, LDH leakage and excessive ROS generation, and maintain the ATP level in cells. Ros A at doses of 50, 100 mg x L(-1) could remarkably inhibit the H/R-induced cardiomyocyte apoptosis and down-regulate the expression of cleaved caspase-3. Moreover, Ros A at doses of 100 mg x L(-1) could significantly up-regulate the expression of p-Akt.. Ros A has the significant effect in resisting the cardiomyocyte H/R injury, improve cardiomyocyte energy metabolism and reduce cell apoptosis, which is related to the activation of Akt pathway.

Topics: Adenosine Triphosphate; Animals; Apoptosis; Caspase 3; Cell Hypoxia; Cell Survival; Cells, Cultured; Cinnamates; Depsides; Humans; Hypoxia; Male; Myocytes, Cardiac; Oxygen; Plant Extracts; Protective Agents; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Rosmarinic Acid; Rosmarinus

Topics: Animals; Cinnamates; Complement Activation; Depsides; Hemodynamics; Hypoxia; Kidney; Leukocyte Count; Lung; Organ Size; Platelet Count; Rabbits; Respiratory Distress Syndrome; Rosmarinic Acid; Zymosan