ABSTRACT
Objectives:
In this study, it is aimed to examine the protective effect of magnolia extract (ME), a herbal material obtained from Magnolia Officinalis, which is claimed to have an important role in anti-inflammation, antioxidative stress and antiapoptosis, with increased reactive oxygen species (ROS) production due to aging and depolarized mitochondrial membrane potential (MMP) in cardiomyocytes and its suppressive effect on apoptosis and endoplasmic reticulum (ER) stress at the molecular level.
Materials and Methods:
In the study, an in vitro aging model was created using rat left ventricular cell line H9c2. H9c2 cells treated with D-galactose (D-Gal; 50 mg/mL) for 48 hours were incubated with 5 µM ME for 24 hours and their effects on ROS production and MMP depolarization in aged cardiomyocytes were examined. ROS and MMP measurements were performed under confocal microscopy using fluorescent dyes dichlorofluorescin diacetate (DCFDA) and carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP). With the ER- stress markers Calregulin and glucose-regulated protein 78, qRT-PCR measurements of the change in expression of the apoptosis marker equilibrative nucleoside transporter 1 after ME treatment were analyzed.
Results:
Incubation of aging-modeled cardiomyocytes with ME provides significant suppression of aging-related ROS production and regulation of depolarized MMP. In addition, we observed that ER-stress and apoptosis developed by mitochondrial dysfunction were suppressed by ME treatment, by examining the expressions of stress and apoptosis marker genes.
Conclusion:
Our findings show that Magnolia officinalis extract, known for its cardioprotective effects, can be applied as a new treatment approach in aging-related heart failure by regulating mitochondrion dysfunction that develops uncontrollably with cardiac aging at the functional and molecular level.
Keywords:
Aging, Magnolia Officinalis, Cardiomyocytes, ROS, Mitochondria, ER Stress, Apoptosis
References
1Dutta D, Calvani R, Bernabei R, et al. Contribution of impaired mitochondrial autophagy to cardiac aging: mechanisms and therapeutic opportunities. Circ Res. 2012;110:1125-1138.
2Marzetti E, Wohlgemuth SE, Anton SD, et al. Cellular mechanisms of cardioprotection by calorie restriction: state of the science and future perspectives. Clin Geriatr Med. 2009;25:715-732.
3Balaban RS, Nemoto S, Finkel T. Mitochondria, oxidants, and aging. Cell. 2005;120:483-495.
4Judge S, Jang YM, Smith A, et al. Age-associated increases in oxidative stress and antioxidant enzyme activities in cardiac interfibrillar mitochondria: implications for the mitochondrial theory of aging. FASEB J. 2005;19:419-421.
5Wei YH, Lee HC. Oxidative stress, mitochondrial DNA mutation, and impairment of antioxidant enzymes in aging. Exp Biol Med (Maywood). 2002;227:671-682.
6Ly JD, Grubb DR, Lawen A. The mitochondrial membrane potential (deltapsi(m)) in apoptosis; an update. Apoptosis. 2003;8:115-128.
7Durak A, Bitirim CV, Turan B. Titin and CK2a are New Intracellular Targets in Acute Insulin Application-Associated Benefits on Electrophysiological Parameters of Left Ventricular Cardiomyocytes From Insulin-Resistant Metabolic Syndrome Rats. Cardiovasc Drugs Ther. 2020;34:487-501.
8Essick EE, Sam F. Oxidative stress and autophagy in cardiac disease, neurological disorders, aging and cancer. Oxid Med Cell Longev. 2010;3:168-177.
9Olgar Y, Tuncay E, Degirmenci S, et al. Ageing-associated increase in SGLT2 disrupts mitochondrial/sarcoplasmic reticulum Ca2+ homeostasis and promotes cardiac dysfunction. J Cell Mol Med. 2020;24:8567-8578.
10Olgar Y, Degirmenci S, Durak A, et al. Aging related functional and structural changes in the heart and aorta: MitoTEMPO improves aged-cardiovascular performance. Exp Gerontol. 2018;110:172-181.
11Poivre M, Duez P. Biological activity and toxicity of the Chinese herb Magnolia officinalis Rehder & E. Wilson (Houpo) and its constituents. J Zhejiang Univ Sci B. 2017;18:194-214.
12Ho JH, Hong CY. Cardiovascular protection of magnolol: cell-type specificity and dose-related effects. J Biomed Sci. 2012;19:70.
13Sun W, Zhang Z, Chen Q, et al. Magnolia extract (BL153) protection of heart from lipid accumulation caused cardiac oxidative damage, inflammation, and cell death in high-fat diet fed mice. Oxid Med Cell Longev. 2014;2014:205849.
14Hong CY, Huang SS, Tsai SK. Magnolol reduces infarct size and suppresses ventricular arrhythmia in rats subjected to coronary ligation. Clin Exp Pharmacol Physiol. 1996;23:660-664.
15Yuan Y, Zhou X, Wang Y, et al. Cardiovascular Modulating Effects of Magnolol and Honokiol, Two Polyphenolic Compounds from Traditional Chinese Medicine-Magnolia Officinalis. Curr Drug Targets. 2020;21:559-572.
16Zhang Z, Chen J, Zhou S, et al. Magnolia bioactive constituent 4-O-methylhonokiol prevents the impairment of cardiac insulin signaling and the cardiac pathogenesis in high-fat diet-induced obese mice. Int J Biol Sci. 2015;11:879-891.
17Zhang B, Zhai M, Li B, et al. Honokiol Ameliorates Myocardial Ischemia/Reperfusion Injury in Type 1 Diabetic Rats by Reducing Oxidative Stress and Apoptosis through Activating the SIRT1-Nrf2 Signaling Pathway. Oxid Med Cell Longev. 2018;2018:3159801.
18Zorov DB, Juhaszova M, Sollott SJ. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev. 2014;94:909-950.
19Li J, Zhang D, Brundel BJJM, et al. Imbalance of ER and Mitochondria Interactions: Prelude to Cardiac Ageing and Disease? Cells. 2019;8:1617.
20Lesnefsky EJ, Moghaddas S, Tandler B, et al. Mitochondrial dysfunction in cardiac disease: ischemia--reperfusion, aging, and heart failure. J Mol Cell Cardiol. 2001;33:1065-1089.
21Karbowski M, Kurono C, Wozniak M, et al. Free radical-induced megamitochondria formation and apoptosis. Free Radic Biol Med. 1999;26:396-409.
22Terman A, Kurz T, Navratil M, et al. Mitochondrial turnover and aging of long-lived postmitotic cells: the mitochondrial-lysosomal axis theory of aging. Antioxid Redox Signal. 2010;12:503-535.
