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

Abstract

Context 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. Objective To investigate whether BHD could reduce CIH-induced heart damage by regulating iron metabolism and mitochondrial function. Materials and methods 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. Results 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 . Discussion and conclusions These findings encourage the use of BHD to resist cardiovascular injury and provide the theoretical basis for clinical treatment in OSA patients.

Huperzine A-Liposomes Efficiently Improve Neural Injury in the Hippocampus of Mice with Chronic Intermittent Hypoxia

“… 53 Intrahippocampal iron causes toxic effects and cognitive dysfunction manifested by the damage of dendritic structure and downregulation of synapse-related proteins, including BDNF, SYP, PSD95, and tenascin C. 54 At the same time, excess iron could accelerate mitochondrial oxidative damage caused by CIH. 16 , 34 …”

“…Analysis of interaction with iron ions was carried out as previously described. 34 HuA, dissolved in methanol, reacted with Fe 2+ and Fe 3+ solutions in acetic acid-sodium acetate (HAc-NAc) buffer. Then HuA and mixture were simultaneously detected via full wavelength scanning.…”

A review of frequently used Kampo prescriptions: Part 2—Hangekobokuto

“…HKT improved CIH‐induced cardiac dysfunction and histological changes, attenuated mitochondrial damage and apoptosis, and activated mitophagy to resist cardiac injury. In addition, HKT suppressed ROS generation in cardiac tissue and reduced CIH‐induced iron deposits in the mitochondria [61].…”

Construction of a mitochondrial dysfunction related signature of diagnosed model to obstructive sleep apnea

“…Chronic intermittent hypoxia (CIH) is the most deleterious feature of OSA, as it can lead to oxidative damage in every organ ( Shan et al, 2007 ). CIH can suppress mitochondrial function and lead to the generation of reactive oxygen species (ROS) ( Wang et al, 2010 ; Huang et al, 2014 ; Zhao et al, 2019 ; Lin et al, 2021 ; Song et al, 2022 ). As mitochondrial status is important for the metabolic function of all organs, mitochondrial dysfunction at the cellular level that can affect systemic metabolic balance can significantly contribute to many diseases and have been defined as classical a hallmark of many diseases ( Srinivasan et al, 2017 ; Chapman et al, 2019 ).…”

“…Second, mitochondrial DNA (mtDNA) copy number is significantly reduced in patients with OSA, and it is a reliable biomarker for predicting cardiovascular risk in patients with OSA ( Kim et al, 2014 ). Third, Banxia-Houpu decoction reduced CIH-induced heart damage by regulating mitochondrial function ( Song et al, 2022 ). Fourth, attenuating mitochondria-dependent apoptosis has been suggested as a novel adjunct strategy for ameliorating OSA-induced neurocognitive impairment ( Xu et al, 2021 ).…”