MAGNOLİA BARK EKSTRAKTI UYGULAMASININ YAŞLI FARE KALP FONKSİYON YETERSİZLİĞİNDEKİ İYİLEŞTİRİCİ ETKİLERİ

Yıl 2024, Cilt: 25 Sayı: 2, 227 – 234, 29.04.2024

Simge Ünay , Irem Aktay , Belma Turan

https://doi.org/10.18229/kocatepetip.1302307

Öz

AMAÇ: Manolya ağacı (Magnolia) ekstraktının ek besin olarak kullanılmasının memelilerde çeşitli organlar ve dokular üzerinde anti-oksidan etkiler gösterdiği çeşitli çalışmalarla gösterilmiş olmasına karşın, fizyolojik yaşlanma ile ilişkili olarak gözlenen kalp yetersizliklerinde koruyucu etkisi ile ilişkili bir çalışma mevcut değildir. Bu nedenle bu çalışmada, magnolol ve honokiol bileşenleri içeren manolya ağacı ekstratı kompleksinin (MAHO-C) yaşlı farelerin (24 aylık) yetersiz kalp fonksiyonu üzerinde pozitif etkileri olup olmadığının incelenmesi hedeflenmiştir.
GEREÇ VE YÖNTEM: Bir grup yaşlı farelere (erkek BALB/c) standart fare yeminin yanı sıra MAHO-C (400 mg/kg/gün, 12 hafta boyunca oral olarak) takviyesi yapılırken, ikinci grup yaşlı fareler sadece standart yem ile beslenmiştir. Beslenme süresi bitiminde, farelerden in situ elektrokardiyogram (EKG) ölçümleri ve izole edilen kalp dokularında oksidatif stres ve antioksidan sistem parametrelerini kapsayan biyokimyasal analizler yapılmıştır.
BULGULAR: MMAHO-C takviyesi alan yaşlı farelere ilişkin EKG’lerde yapılan analizlerde, takviye almamış yaşlı farelerle karşılaştırıldığında, P-dalgası süresi, QRS-kompleksi süresi ve QT-aralığı gibi önemli EKG parametrelerinde düşüşler ile kalp atım hızında artma gözlenmiş olup bu değişimlerin istatistiksel olarak anlamı düzeyde olduğu gözlenmiştir. Kalp dokusunda yapılan biyokimyasal analizler, MAHO-C takviyeli yaşlı fare kalp dokularında arilesteraz aktivitesinde ve toplam antioksidan seviyesinde istatistiksel olarak anlamlı seviyelerde artma gözlenmiştir. Ek olarak, ek takviye alan gruplarda almayanlarla karşılaştırıldığında, reaktif oksijen türlerinin (ROS) kaynağı olan mitokondriyal enzim süksinat dehidrogenazın aktivitesinde ve toplam oksidan seviyesinde oranında istatistiksel olarak azalmalar ile ATP/ADP oranında istatistiksel olarak artış gözlenmiştir.
SONUÇ: Verilerimiz, MAHO-C takviyesinin fizyolojik yaşlanma ile ilişki kalp yetersizliklerinde özellikle antioksidan savunma sistemini ve mitokondriyi etkileyerek kalbin hem elektriksel ve hem de biyokimyasal özellikleri üzerinde pozitif etkiler oluşturabildiğini göstermektedir.

Anahtar Kelimeler

Antioksidant, Beslenme destekleri, Bifenolik bileşikleri, Kalp, Oksidatif stres

Destekleyen Kurum

Lokman Hekim Üniversitesi Bilimsel Araştırma Projeleri

Proje Numarası

202AP404-2022

Kaynakça

• 1. Prasad S, Sung B, Aggarwal BB. Age-associated chronic diseases require age-old medicine: role of chronic inflammation. Prev Med. 2012;54: 29-37.
• 2. Lakatta EG, Sollott SJ, Pepe S, The old heart: operating on the edge. Novartis Found Symp. 2001;235: 172-96.
• 3. Dillin A, Gottschling DE, Nyström T. The good and the bad of being connected: the integrons of aging. Curr Opin Cell Biol. 2014;(26):107-12.
• 4. Rodgers JL, Jones J, Bolleddu SI, et al. Cardiovascular Risks Associated with Gender and Aging. J Cardiovasc Dev Dis. 2019;6(2):1-19.
• 5. Lazzarini E Lodrini AM, Arici M, et al. Stress-induced premature senescence is associated with a prolonged QT interval and recapitulates features of cardiac aging. Theranostics. 2022;12(11):5237-57.
• 6. Lesnefsky EJ, Chen Q, Hoppel CL, Mitochondrial metabolism in aging heart. Circulation Research. 2016;118(10):1593-611.
• 7. Chason KD, Jaspers I, Parker J, et al. Age-Associated Changes in the Respiratory Epithelial Response to Influenza Infection. Journals of Gerontology. Series A: Biological Sciences and Medical Sciences. 2018;73(12):1643-50.
• 8. Ormazabal V, Nair S, Elfeky O, et al. Association between insulin resistance and the development of cardiovascular disease. Cardiovascular Diabetology. 2018;17(1):1-14.
• 9. Boudina S. Cardiac aging and insulin resistance: could insulin/insulin-like growth factor (IGF) signaling be used as a therapeutic target? Current Pharmaceutical Design. 2013;19(32):5684-94.
• 10. Olgar Y, Billur D, Tuncay E, Turan B. MitoTEMPO provides an antiarrhythmic effect in aged-rats through attenuation of mitochondrial reactive oxygen species. Exp Gerontol. 2020;136:110961.
• 11. Izzo NJ, Yuede CM, LaBarbera KM, et al. Preclinical and clinical biomarker studies of CT1812: A novel approach to Alzheimer's disease modification. Alzheimers Dement. 2021;17(8):1365-82.
• 12. Conti V, Izzo V, Corbi G, et al. Antioxidant supplementation in the treatment of aging-associated diseases. Frontiers in pharmacology. 2016;7:24.
• 13. Howlett SE. Age-associated changes in excitation-contraction coupling are more prominent in ventricular myocytes from male rats than in myocytes from female rats. Am J Physiol Heart Circ Physiol. 2010;298(2):659-70.
• 14. Thomàs-Moyà E, Gianotti M, Proenza AM, Lladó I. The age-related paraoxonase 1 response is altered by long-term caloric restriction in male and female rats. J Lipid Res. 2006;47(9):2042-8.
• 15. Goszcz K, Deakin SJ, Duthie GG, et al. Antioxidants in cardiovascular therapy: panacea or false hope?. Front Cardiovasc Med. 2015;2:29-50.
• 16. Duan J, Xiao J, Chen Y, et al. Inhibition of magnolol and honokiol on cytochrome P450 enzymes in rat and human liver microsomes. Chinese Herbal Medicines. 2015;7(2):167-72.
• 17. Jiang Y, Zhao Q, Li L, et al. Effect of Traditional Chinese Medicine on the Cardiovascular Diseases. Front Pharmacol. 2022;13:806300.
• 18. Xie Z, Zhao J, Wang H, et al. Magnolol alleviates Alzheimer's disease-like pathology in transgenic C. elegans by promoting microglia phagocytosis and the degradation of beta-amyloid through activation of PPAR-γ. Biomedicine & Pharmacotherapy. 2020; 124:109886.
• 19. Zhang GS, Wang RJ, Zhang HN, et al. Effects of chronic treatment with honokiol in spontaneously hypertensive rats. Biol Pharm Bull. 2010;33(3): 427-31.
• 20. Zhao C, Liu ZQ. Comparison of antioxidant abilities of magnolol and honokiol to scavenge radicals and to protect DNA. Biochimie. 2011;93(10):1755-60.
• 21. Oh S, Gadde UD, Bravo D, et al. Growth-promoting and antioxidant effects of magnolia bark extract in chickens uninfected or co-infected with Clostridium perfringens and Eimeria maxima as an experimental model of necrotic enteritis. Current Developments in Nutrition. 2018;2(4):9.
• 22. Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem. 2004;37(2):112-9.
• 23. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005;38(12):1103-11.
• 24. Cakmak A, Zeyrek D, Atas A, Erel O. Paraoxonase activity in athletic adolescents. Pediatr Exerc Sci. 2010;22(1):93-104.
• 25. Degirmenci S, Olgar Y, Durak A, Tuncay E, Turan B. Cytosolic increased labile Zn2+ contributes to arrhythmogenic action potentials in left ventricular cardiomyocytes through protein thiol oxidation and cellular ATP depletion. J Trace Elem Med Biol. 2018; 48:202-12.
• 26. Merentie M, Lipponen JA, Hedman M, et al. Mouse ECG findings in aging, with conduction system affecting drugs and in cardiac pathologies: Development and validation of ECG analysis algorithm in mice. Physiol Rep. 2015;3(12):e12639.
• 27. Xing S, Tsaih SW, Yuan R, Svenson KL, Jorgenson LM, et al. Genetic influence on electrocardiogram time intervals and heart rate in aging mice. Am J Physiol Heart Circ Physiol. 2009;296(6):1907-13.
• 28. Herrmann S, Fabritz L, Layh B, Kirchhof P, Ludwig A. Insights into sick sinus syndrome from an inducible mouse model. Cardiovasc Res. 2011;90(1):38-48.
• 29. Liu Y, Jansen HJ, Krishnaswamy PS, Bogachev O, Rose RA. Impaired regulation of heart rate and sinoatrial node function by the parasympathetic nervous system in type 2 diabetic mice. Sci Rep. 2021;14;11(1):12465.
• 30. Billur D, Aktay I, Bayram P, Bitirim CV, Turan B, Morphological and functional analysis of cardiac ameliorations in elderly rats supplemented with a magnolol extract complex. Int. J. Morphol. 2023;41(3):915-25.
• 31. Bou-Teen D, Kaludercic N, Weissman D, et al. Mitochondrial ROS and mitochondria-targeted antioxidants in the aged heart. Free Radical Biology and Medicine. 2021;167: 109-24.
• 32. Huang L, Zhang K, Guo, Y, et al. Honokiol protects against doxorubicin cardiotoxicity via improving mitochondrial function in mouse hearts. Scientific Reports. 2017;7(1): 1-12.
• 33. Lo YC, Che-Ming T, Chieh-Fu C, et al. Magnolol and honokiol isolated from Magnolia officinalis protect rat heart mitochondria against lipid peroxidation. Biochemical Pharmacology. 1994;47(3):549-53.
• 34. Leopold JA, Antioxidants and coronary artery disease: from pathophysiology to preventive therapy. Coronary Artery Disease. 2015;26(2):176.
• 35. Magnani JW, Gorodeski EZ, Johnson VM, et al. P wave duration is associated with cardiovascular and all-cause mortality outcomes: the National Health and Nutrition Examination Survey. Heart Rhythm. 2011;8(1):93-100.
• 36. Luo X, Yu W, Liu Z, et al. Ageing Increases Cardiac Electrical Remodelling in Rats and Mice via NOX4/ROS/CaMKII-Mediated Calcium Signalling. Oxid Med Cell Longev. 2022;8538296.
• 37. Lee YM, Hsiao G, Chen HR, et al. Magnolol reduces myocardial ischemia/reperfusion injury via neutrophil inhibition in rats. European Journal of Pharmacology. 2011;422(1-3):159-67.
• 38. Pillai VB, Samant S, Sundaresan NR, et al. Honokiol blocks and reverses cardiac hypertrophy in mice by activating mitochondrial Sirt3. Nature Communications. 2015;6(1): 1-16.
• 39. Yan M, Sun S, Xu K, et al. Cardiac aging: from basic research to therapeutics. Oxidative Medicine and Cellular Longevity. 2021;1:1-13.
• 40. Tsai YC, Cheng PY, Kung CW, et al. Beneficial effects of magnolol in a rodent model of endotoxin shock. European Journal of Pharmacology. 2010;641(1):67-73.
• 41. Hong TD, Ellis RH, A protocol to determine seed storage behaviour (No. 1). Bioversity International. 1996;1-62.
• 42. Kim GD, Oh J, Park HJ, et al. Magnolol inhibits angiogenesis by regulating ROS-mediated apoptosis and the PI3K/AKT/mTOR signaling pathway in mES/EB-derived endothelial-like cells. International Journal of Oncology. 2013;43(2): 600-10.
• 43. Yuan Y, Zhou X, Wang Y, et al. Cardiovascular modulating effects of Magnolol and Honokiol, two polyphenolic compounds from traditional Chinese medicine-Magnolia officinalis. Current Drug Targets. 2020;21(6): 559-72.
• 44. Du K, Wang Y, Tang K, et al. A study on the relationship between succinate dehydrogenase and mitoKATPC in the mechanism of ischemic postconditioning protecting against MIRI under CPB in adult rats. Research Square. 2022;(8):1-21.

AMELIORATIVE EFFECTS OF MAGNOLIA BARK EXTRACT CONSUMPTION IN ELDERLY MICE CARDIAC DYSFUNCTION

Yıl 2024, Cilt: 25 Sayı: 2, 227 – 234, 29.04.2024

Simge Ünay , Irem Aktay , Belma Turan

https://doi.org/10.18229/kocatepetip.1302307

Öz

OBJECTIVE: It has been shown that to use Magnolia tree bark extract as supplement nutrient provided an anti-oxidative effect in various mammalian tissues and organs by several studies, however, there is no data associated with its cardioprotective role in physiological aging-related heart disorders. Therefore, here, we aimed to investigate whether Magnolia tree bark extract, containing magnolol and honokiol components (MAHO-C), has positive effects on heart dysfunction from aged mice (24-month-old).
MATERIAL AND METHODS: One group of aged mice (male BALB/c) was fed with a standard mouse chow plus MAHO-C (400 mg/kg/day, for 12 weeks with intragastrical), while the second group of aged mice was fed only with the standard chow. Following the end of the supplementation period, in situ electrocardiogram (ECG) measurements and biochemical analyzes associated oxidative stress and antioxidant system parameters of the isolated heart tissues from all mice were performed.
RESULTS: When compared to the nonsupplemented aged mice, the analysis performed in the ECGs of the aged mice supplemented with MAHO-C showed statistically significant decreases in the durations of P-waves, QRS-complexes, and QT-intervals as well as increases in the heart rates. The biochemical analysis of the heart tissues showed that the activity of arylesterase and total antioxidant levels in the heart tissues of the aged mice supplemented with MAHO-C were significantly high compared to those of untreated aged mice. In addition, when compared to the nonsupplemented group, there were significant decreases in the activity of the mitochondrial enzyme succinate dehydrogenase, one of source of reactive oxygen species (ROS) and the total oxidant level with a significant increase in the ratio of ATP to ADP in the heart samples of the aged mice supplemented with MAHO-C.
CONCLUSIONS: Overall, our data suggest that MAHO-C supplementation provides significant positive effects on both electrical and biochemical properties of the insufficiently functioning hearts from the physiological aged mice, particularly through affecting the antioxidant defense system and mitochondria.

Anahtar Kelimeler

Antioxidant, MAHO-C, Phenolic compounds, Aging, Oxidative stress

Proje Numarası

202AP404-2022

Kaynakça

• 1. Prasad S, Sung B, Aggarwal BB. Age-associated chronic diseases require age-old medicine: role of chronic inflammation. Prev Med. 2012;54: 29-37.
• 2. Lakatta EG, Sollott SJ, Pepe S, The old heart: operating on the edge. Novartis Found Symp. 2001;235: 172-96.
• 3. Dillin A, Gottschling DE, Nyström T. The good and the bad of being connected: the integrons of aging. Curr Opin Cell Biol. 2014;(26):107-12.
• 4. Rodgers JL, Jones J, Bolleddu SI, et al. Cardiovascular Risks Associated with Gender and Aging. J Cardiovasc Dev Dis. 2019;6(2):1-19.
• 5. Lazzarini E Lodrini AM, Arici M, et al. Stress-induced premature senescence is associated with a prolonged QT interval and recapitulates features of cardiac aging. Theranostics. 2022;12(11):5237-57.
• 6. Lesnefsky EJ, Chen Q, Hoppel CL, Mitochondrial metabolism in aging heart. Circulation Research. 2016;118(10):1593-611.
• 7. Chason KD, Jaspers I, Parker J, et al. Age-Associated Changes in the Respiratory Epithelial Response to Influenza Infection. Journals of Gerontology. Series A: Biological Sciences and Medical Sciences. 2018;73(12):1643-50.
• 8. Ormazabal V, Nair S, Elfeky O, et al. Association between insulin resistance and the development of cardiovascular disease. Cardiovascular Diabetology. 2018;17(1):1-14.
• 9. Boudina S. Cardiac aging and insulin resistance: could insulin/insulin-like growth factor (IGF) signaling be used as a therapeutic target? Current Pharmaceutical Design. 2013;19(32):5684-94.
• 10. Olgar Y, Billur D, Tuncay E, Turan B. MitoTEMPO provides an antiarrhythmic effect in aged-rats through attenuation of mitochondrial reactive oxygen species. Exp Gerontol. 2020;136:110961.
• 11. Izzo NJ, Yuede CM, LaBarbera KM, et al. Preclinical and clinical biomarker studies of CT1812: A novel approach to Alzheimer's disease modification. Alzheimers Dement. 2021;17(8):1365-82.
• 12. Conti V, Izzo V, Corbi G, et al. Antioxidant supplementation in the treatment of aging-associated diseases. Frontiers in pharmacology. 2016;7:24.
• 13. Howlett SE. Age-associated changes in excitation-contraction coupling are more prominent in ventricular myocytes from male rats than in myocytes from female rats. Am J Physiol Heart Circ Physiol. 2010;298(2):659-70.
• 14. Thomàs-Moyà E, Gianotti M, Proenza AM, Lladó I. The age-related paraoxonase 1 response is altered by long-term caloric restriction in male and female rats. J Lipid Res. 2006;47(9):2042-8.
• 15. Goszcz K, Deakin SJ, Duthie GG, et al. Antioxidants in cardiovascular therapy: panacea or false hope?. Front Cardiovasc Med. 2015;2:29-50.
• 16. Duan J, Xiao J, Chen Y, et al. Inhibition of magnolol and honokiol on cytochrome P450 enzymes in rat and human liver microsomes. Chinese Herbal Medicines. 2015;7(2):167-72.
• 17. Jiang Y, Zhao Q, Li L, et al. Effect of Traditional Chinese Medicine on the Cardiovascular Diseases. Front Pharmacol. 2022;13:806300.
• 18. Xie Z, Zhao J, Wang H, et al. Magnolol alleviates Alzheimer's disease-like pathology in transgenic C. elegans by promoting microglia phagocytosis and the degradation of beta-amyloid through activation of PPAR-γ. Biomedicine & Pharmacotherapy. 2020; 124:109886.
• 19. Zhang GS, Wang RJ, Zhang HN, et al. Effects of chronic treatment with honokiol in spontaneously hypertensive rats. Biol Pharm Bull. 2010;33(3): 427-31.
• 20. Zhao C, Liu ZQ. Comparison of antioxidant abilities of magnolol and honokiol to scavenge radicals and to protect DNA. Biochimie. 2011;93(10):1755-60.
• 21. Oh S, Gadde UD, Bravo D, et al. Growth-promoting and antioxidant effects of magnolia bark extract in chickens uninfected or co-infected with Clostridium perfringens and Eimeria maxima as an experimental model of necrotic enteritis. Current Developments in Nutrition. 2018;2(4):9.
• 22. Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem. 2004;37(2):112-9.
• 23. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005;38(12):1103-11.
• 24. Cakmak A, Zeyrek D, Atas A, Erel O. Paraoxonase activity in athletic adolescents. Pediatr Exerc Sci. 2010;22(1):93-104.
• 25. Degirmenci S, Olgar Y, Durak A, Tuncay E, Turan B. Cytosolic increased labile Zn2+ contributes to arrhythmogenic action potentials in left ventricular cardiomyocytes through protein thiol oxidation and cellular ATP depletion. J Trace Elem Med Biol. 2018; 48:202-12.
• 26. Merentie M, Lipponen JA, Hedman M, et al. Mouse ECG findings in aging, with conduction system affecting drugs and in cardiac pathologies: Development and validation of ECG analysis algorithm in mice. Physiol Rep. 2015;3(12):e12639.
• 27. Xing S, Tsaih SW, Yuan R, Svenson KL, Jorgenson LM, et al. Genetic influence on electrocardiogram time intervals and heart rate in aging mice. Am J Physiol Heart Circ Physiol. 2009;296(6):1907-13.
• 28. Herrmann S, Fabritz L, Layh B, Kirchhof P, Ludwig A. Insights into sick sinus syndrome from an inducible mouse model. Cardiovasc Res. 2011;90(1):38-48.
• 29. Liu Y, Jansen HJ, Krishnaswamy PS, Bogachev O, Rose RA. Impaired regulation of heart rate and sinoatrial node function by the parasympathetic nervous system in type 2 diabetic mice. Sci Rep. 2021;14;11(1):12465.
• 30. Billur D, Aktay I, Bayram P, Bitirim CV, Turan B, Morphological and functional analysis of cardiac ameliorations in elderly rats supplemented with a magnolol extract complex. Int. J. Morphol. 2023;41(3):915-25.
• 31. Bou-Teen D, Kaludercic N, Weissman D, et al. Mitochondrial ROS and mitochondria-targeted antioxidants in the aged heart. Free Radical Biology and Medicine. 2021;167: 109-24.
• 32. Huang L, Zhang K, Guo, Y, et al. Honokiol protects against doxorubicin cardiotoxicity via improving mitochondrial function in mouse hearts. Scientific Reports. 2017;7(1): 1-12.
• 33. Lo YC, Che-Ming T, Chieh-Fu C, et al. Magnolol and honokiol isolated from Magnolia officinalis protect rat heart mitochondria against lipid peroxidation. Biochemical Pharmacology. 1994;47(3):549-53.
• 34. Leopold JA, Antioxidants and coronary artery disease: from pathophysiology to preventive therapy. Coronary Artery Disease. 2015;26(2):176.
• 35. Magnani JW, Gorodeski EZ, Johnson VM, et al. P wave duration is associated with cardiovascular and all-cause mortality outcomes: the National Health and Nutrition Examination Survey. Heart Rhythm. 2011;8(1):93-100.
• 36. Luo X, Yu W, Liu Z, et al. Ageing Increases Cardiac Electrical Remodelling in Rats and Mice via NOX4/ROS/CaMKII-Mediated Calcium Signalling. Oxid Med Cell Longev. 2022;8538296.
• 37. Lee YM, Hsiao G, Chen HR, et al. Magnolol reduces myocardial ischemia/reperfusion injury via neutrophil inhibition in rats. European Journal of Pharmacology. 2011;422(1-3):159-67.
• 38. Pillai VB, Samant S, Sundaresan NR, et al. Honokiol blocks and reverses cardiac hypertrophy in mice by activating mitochondrial Sirt3. Nature Communications. 2015;6(1): 1-16.
• 39. Yan M, Sun S, Xu K, et al. Cardiac aging: from basic research to therapeutics. Oxidative Medicine and Cellular Longevity. 2021;1:1-13.
• 40. Tsai YC, Cheng PY, Kung CW, et al. Beneficial effects of magnolol in a rodent model of endotoxin shock. European Journal of Pharmacology. 2010;641(1):67-73.
• 41. Hong TD, Ellis RH, A protocol to determine seed storage behaviour (No. 1). Bioversity International. 1996;1-62.
• 42. Kim GD, Oh J, Park HJ, et al. Magnolol inhibits angiogenesis by regulating ROS-mediated apoptosis and the PI3K/AKT/mTOR signaling pathway in mES/EB-derived endothelial-like cells. International Journal of Oncology. 2013;43(2): 600-10.
• 43. Yuan Y, Zhou X, Wang Y, et al. Cardiovascular modulating effects of Magnolol and Honokiol, two polyphenolic compounds from traditional Chinese medicine-Magnolia officinalis. Current Drug Targets. 2020;21(6): 559-72.
• 44. Du K, Wang Y, Tang K, et al. A study on the relationship between succinate dehydrogenase and mitoKATPC in the mechanism of ischemic postconditioning protecting against MIRI under CPB in adult rats. Research Square. 2022;(8):1-21.

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