Banxia-Houpu decoction diminishes iron toxicity damage in heart induced by chronic intermittent hypoxia

• Published in: Pharmaceutical biology Vol. 60; no. 1; pp. 609 - 620
• Main Authors: Song, Ji-Xian, Zhao, Ya-Shuo, Zhen, Ya-Qin, Yang, Xin-Yue, Chen, Qi, An, Ji-Ren, Ji, En-Sheng
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 31.12.2022; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Animals; Apnea; Apoptosis; Apoptosis - drug effects; BAX protein; Bcl-2 protein; Biological Sciences; cardiac damage; Caspase-3; Cinnamates - pharmacology; CYBB protein; Depsides - pharmacology; Disease Models, Animal; Dose-Response Relationship, Drug; Drugs, Chinese Herbal - administration & dosage; Drugs, Chinese Herbal - pharmacology; heart; Heart Injuries - etiology; Heart Injuries - prevention & control; Hypoxia; Hypoxia - complications; Hypoxia - drug therapy; Iron; Iron - metabolism; iron absorption; leaves; Male; Mice; Mice, Inbred C57BL; Mitochondria; Mitochondria - drug effects; Mitochondria - pathology; mitochondrial disfunction; mitophagy; Obstructive sleep apnoea; Oxidative Stress - drug effects; Patients; Perilla; Protein folding; PTEN-induced putative kinase; Reactive oxygen species; Reactive Oxygen Species - metabolism; Rosmarinic Acid; sleep; Sleep apnea; Sleep Apnea, Obstructive - complications; Sleep disorders; TOR protein; Toxicity; rosmarinic acid; Obstructive sleep apnoea; mitochondrial disfunction; cardiac damage
• ISSN: 1388-0209; 1744-5116; 1744-5116
• DOI: 10.1080/13880209.2022.2043392

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. C57BL/6N mice were randomly divided into control, CIH and BHD groups. Mice were exposed to CIH (21 − 5% O 2 , 20 times/h, 8 h/d) and administered BHD (3.51, 7.01 and 14.02 g/kg, intragastrically) for 21 d. Cardiac and mitochondrial function, iron levels, apoptosis and mitophagy were determined. 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 2+ and Fe 3+ in vitro. These findings encourage the use of BHD to resist cardiovascular injury and provide the theoretical basis for clinical treatment in OSA patients.