Sains Malaysiana 49(10)(2020): 2499-2506

http://dx.doi.org/10.17576/jsm-2020-4910-15

 

Hibiscus sabdariffa Linn. (Roselle) Polyphenols-Rich Extract Prevents Hyperglycemia-Induced Cardiac Oxidative Stress and Mitochondrial Damage in Diabetic Rats

(Ekstrak Kaya-Polifenol Hibiscus sabdariffa Linn. (Roselle) Mencegah Tekanan Oksidatif dan Kerosakan Mitokondria Jantung Aruhan Hiperglisemia pada Tikus Diabetes)

 

NUR LIYANA MOHAMMED YUSOF1, TENGKU NURUL TASNIM TENGKU AFFENDI1, FATIN FARHANA JUBAIDI1, SATIRAH ZAINALABIDIN2 & SITI BALKIS BUDIN1*

 

1Centre for Diagnostic, Therapeutic and Investigative Studies, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, 50300 Kuala Lumpur, Federal Territory, Malaysia

 

2Centre for Toxicology and Health Risk Studies, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, 50300 Kuala Lumpur, Federal Territory, Malaysia

 

Received: 18 January 2020/Accepted: 18 April 2020

 

ABSTRACT

Cardiac mitochondrial damage plays a crucial role in the initiation of diabetic cardiomyopathy. Hibiscus sabdariffa Linn. (roselle) has been proven to prevent various pathological conditions, however it remains unclear whether roselle extract can attenuate diabetes-induced mitochondrial damage. This study aimed to investigate whether roselle polyphenol-rich extract (HPE) is able to ameliorate hyperglycemia-induced oxidative stress and mitochondrial damage in diabetic rats. Diabetes was induced by a single dose of streptozotocin (55 mg kg-1, intraperitoneally); and diabetic rats were then orally fed with 100 mg kg-1 of HPE (DM+Roselle) or 150 mg kg-1 of Metformin (DM+MET) daily for 4 weeks. Meanwhile, the control and untreated diabetic (DM) groups were only orally given normal saline. After 4 weeks of treatment, the results showed that DM+Roselle group significantly improved blood glucose level and lipid profile status (p<0.05) compared to the DM group. DM+Roselle group also had significantly (p<0.05) lower the level of thiobarbituric acid reactive substances (TBARS) and advanced oxidation protein product (AOPP) in cardiac homogenate than the DM group. HPE supplementation also significantly improved activities of total superoxide dismutase (SOD), SOD-2, catalase (CAT) and level of reduced glutathione (GSH) of the cardiac homogenate. Complex I activity of mitochondria respiratory chain also decreased significantly (p<0.05) in DM+Roselle group as compared to the DM group. Observations using electron microscope showed that mitochondria in the DM+Roselle group appeared more organized compared to the DM group. In conclusion, these results highlight the potential of HPE as a protective agent against oxidative stress and mitochondrial damage in diabetic condition.

 

Keywords: Hyperglycemia; mitochondria; myocardial damage; ROS; roselle

 

ABSTRAK

Kerosakan mitokondria jantung memainkan peranan yang penting dalam permulaan kardiomiopati diabetis. Walaupun Hibiscus sabdariffa Linn. (rosel) terbukti berupaya mencegah pelbagai keadaan patologi, keupayaan ekstrak rosel dalam memulihkan kerosakan mitokondria aruhan diabetis melitus masih lagi belum diketahui. Kajian ini mengkaji sama ada ekstrak rosel kaya polifenol (HPE) mampu mencegah tekanan oksidatif dan kerosakan aruhan hiperglisemia pada tikus diabetis. Diabetis diaruh dengan suntikan tunggal streptozotosin (55 mg kg-1, intraperitonial); dan tikus diabetis kemudiannya diberi 100 mg kg-1 HPE (DM+Roselle) atau 150 mg kg-1 Metformin (DM+MET) setiap hari selama 4 minggu. Tikus kawalan normal (NDM) dan diabetis tanpa rawatan (DM) hanya diberikan salin normal. Selepas 4 minggu suplementasi, hasil kajian menunjukkan kumpulan DM+Roselle mempunyai aras glukosa darah dan status profil lipid yang lebih baik secara signifikan (p<0.05) berbanding kumpulan DM. Kumpulan DM+Roselle juga turut menunjukkan aras bahan reaktif asid tiobarbiturik (TBARS) dan produk oksidasi protein lanjutan (AOPP) homogenat jantung yang lebih rendah (p<0.05) berbanding kumpulan DM. Suplementasi HPE turut membaik pulih aktiviti jumlah superoksida dismutase (SOD), SOD-2, katalase (CAT) dan aras glutation terturun (GSH) pada homogenat jantung tikus. Aktiviti Kompleks I pada rantaian pernafasan mitokondria turut menurun dengan ketara pada kumpulan DM+Roselle berbanding kumpulan DM. Pemerhatian dengan mikroskop elektron menunjukkan mitokondria pada jantung tikus kumpulan DM+Roselle kelihatan lebih teratur berbanding kumpulan DM. Kesimpulannya, hasil kajian ini mencadangkan potensi HPE sebagai agen perlindungan tekanan oksidatif serta mencegah kerosakan mitokondria dalam keadaan diabetis. 

 

Kata kunci: Hiperglisemia; kecederaan mitokondria; mitokondria; ROS; rosel

 

REFERENCES

Beyer, W.F. & Fridovich, I. 1987. Assaying for superoxide dismutase activity: Some large consequences of minor changes in conditions. Analytical Biochemistry 161(2): 559-566.

Brownlee, M. 2001. Biochemistry and molecular cell biology of diabetic complications.  Nature 414(6865): 813.

Budin, S.B., Sharifuddin, N.A., Jubaidi, F.F. & Zainalabidin, S. 2019. The potential of Hibiscus sabdariffa Linn. (roselle) polyphenol-rich extract as a cardioprotective agent in myocardial infarction model. Jurnal Teknologi 81(5): 25-31.

Budin, S.B., Abdul Rahman, W.A., Jubaidi, F.F., Mohammed Yusof, N.L., Taib, I.S. & Zainalabidin, S. 2018. Roselle (Hibiscus sabdiriffa) polyphenol-rich extract prevents testicular damage of diabetic rats. Journal of Applied Pharmaceutical Science 8(2): 65-70.

Carvajal-Zarrabal, O., Hayward-Jones, P., Orta-Flores, Z., Nolasco-Hipólito, C., Barradas-Dermitz, D., Aguilar-Uscanga, M. & Pedroza-Hernández, M. 2009. Effect of Hibiscus sabdariffa L. dried calyx ethanol extract on fat absorption-excretion, and body weight implication in rats.  BioMed Research International 2009: 394592.

Chen, C.C., Hsu, J.D., Wang, S.F., Chiang, H.C., Yang, M.Y., Kao, E.S., Ho, Y.C. & Wang, C.J. 2003. Hibiscus sabdariffa extract inhibits the development of atherosclerosis in cholesterol-fed rabbits. Journal of Agricultural and Food Chemistry 51(18): 5472-5477.

Coughlan, M.T., Thorburn, D.R., Penfold, S.A., Laskowski, A., Harcourt, B.E., Sourris, K.C., Tan, A.L., Fukami, K., Thallas-Bonke, V. & Nawroth, P.P. 2009. Rage-induced cytosolic ROS promote mitochondrial superoxide generation in diabetes. Journal of the American Society of Nephrology 20(4): 742-752.

Dai, D.F., Johnson, S.C., Villarin, J.J., Chin, M.T., Nieves-Cintrón, M., Chen, T., Marcinek, D.J., Dorn, G.W., Kang, Y.J. & Prolla, T.A. 2011. Mitochondrial oxidative stress mediates angiotensin ii-induced cardiac hypertrophy and gαq overexpression-induced heart failure.  Circulation Research108(7): 837-846.

Duncan 2011

El-Gendy, K.S., Aly, N.M., Mahmoud, F.H., Kenawy, A. & El-Sebae, A.K.H. 2010. The role of vitamin C as antioxidant in protection of oxidative stress induced by imidacloprid.  Food and Chemical Toxicology 48(1): 215-221.

Ellman, G.L. 1959. Tissue sulfhydryl groups.  Archives of Biochemistry and Biophysics 82(1): 70-77.

Gomes, A.P., Price, N.L., Ling, A.J., Moslehi, J.J., Montgomery, M.K., Rajman, L., White, J.P., Teodoro, J.S., Wrann, C.D. & Hubbard, B.P. 2013. Declining NAD+ induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging.  Cell 155(7): 1624-1638.

Hansawasdi, C., Kawabata, J. & Kasai, T. 2000. Α-amylase inhibitors from roselle (Hibiscus sabdariffa Linn.) tea.  Bioscience, Biotechnology, and Biochemistry 64(5): 1041-1043.

Hussan et al. 2015

Huynh, K., Bernardo, B.C., Mcmullen, J.R. & Ritchie, R.H. 2014. Diabetic cardiomyopathy: mechanisms and new treatment strategies targeting antioxidant signaling pathways.  Pharmacology & Therapeutics 142(3): 375-415.

Iglesias-González, J., Sánchez-Iglesias, S., Beiras-Iglesias, A., Soto-Otero, R. & Méndez-Álvarez, E. 2013. A simple method for isolating rat brain mitochondria with high metabolic activity: Effects of EDTA and EGTA. Journal of Neuroscience Methods 213(1): 39-42.

Lee, S.C. & Pervaiz, S. 2007. Apoptosis in the pathophysiology of diabetes mellitus. The International Journal of Biochemistry & Cell Biology 39(3): 497-504.

Li, L., Peng, M., Ge, C., Yu, L. & Ma, H. 2017. (-)-Hydroxycitric acid reduced lipid droplets accumulation via decreasing acetyl-COA supply and accelerating energy metabolism in cultured primary chicken hepatocytes. Cellular Physiology and Biochemistry 43(2): 812-831.

Li, Y.W. & Aronow, W.S. 2011. Diabetes mellitus and cardiovascular disease. Journal of Clinical and Experimental Cardiology 2(2): 1-9.

Lim, Y.C., Budin, S.B., Othman, F., Latip, J. & Zainalabidin, S. 2017. Roselle polyphenols exert potent negative inotropic effects via modulation of intracellular calcium regulatory channels in isolated rat heart. Cardiovascular Toxicology 17(3): 251-259.

Liu, Q., Wang, S. & Cai, L. 2014. Diabetic cardiomyopathy and its mechanisms: Role of oxidative stress and damage. Journal of Diabetes Investigation 5(6): 623-634.

Madsen-Bouterse, S.A., Zhong, Q., Mohammad, G., Ho, Y.S. & Kowluru, R.A. 2010. Oxidative damage of mitochondrial DNA in diabetes and its protection by manganese superoxide dismutase. Free Radical Research 44(3): 313-321.

Mannervik, B., Helena Danielson, U. & Ketterer, B. 1988. Glutathione transferases - structure and catalytic activity. Critical Reviews in Biochemistry 23(3): 283-337.

Matough, F.A., Budin, S.B., Hamid, Z.A., Alwahaibi, N. & Mohamed, J. 2012. The role of oxidative stress and antioxidants in diabetic complications. Sultan Qaboos University Medical Journal 12(1): 5-18.

Mohammed Yusof, N.L., Zainalabidin, S., Mohd Fauzi, N. & Budin, S.B.  2018a.   Hibiscus sabdariffa (Roselle) polyphenol-rich extract averts cardiac functional and structural abnormalities in type 1 diabetic rats. Applied Physiology, Nutrition and Metabolism 43(12): 1224-1232.

Mohammed Yusof, N.L., Jubaidi, F.F., Mohamad Nasir, S.N., Yusoff, N.A., Mohd Fauzi, N., Zainalabidin, S. & Budin, S.B. 2018b. Hibiscus sabdariffa (Roselle) polyphenol-rich extract prevents the aortic oxidative damage in type 1 diabetic rats. Jurnal Teknologi 80(2): 1-8.

Nishikawa et al. 2000

Nisoli, E., Falcone, S., Tonello, C., Cozzi, V., Palomba, L., Fiorani, M., Pisconti, A., Brunelli, S., Cardile, A. & Francolini, M. 2004. Mitochondrial biogenesis by no yields functionally active mitochondria in mammals. Proceedings of the National Academy of Sciences 101(47): 16507-16512.

Ochani, P.C. & D’mello, P. 2009. Antioxidant and antihyperlipidemic activity of Hibiscus sabdariffa Linn. leaves and calyces extracts in rats. Indian Journal of Experimental Biology 47(4): 276-282.  

Packer, M., Pitt, B., Rouleau, J.L., Swedberg, K., Demets, D.L. & Fisher, L. 2017. Long-term effects of flosequinan on the morbidity and mortality of patients with severe chronic heart failure: Primary results of the profile trial after 24 years. JACC: Heart Failure 5(6): 399-407.

Peng, C.H., Chyau, C.C., Chan, K.C., Chan, T.H., Wang, C.J. & Huang, C.N. 2011. Hibiscus sabdariffa polyphenolic extract inhibits hyperglycemia, hyperlipidemia, and glycation-oxidative stress while improving insulin resistance. Journal of Agricultural and Food Chemistry 59(18): 9901-9909.

Shen, G.X. 2010. Oxidative stress and diabetic cardiovascular disorders: Roles of mitochondria and NADPH oxidase. Canadian Journal of Physiology and Pharmacology 88(3): 241-248.

Si, L.Y.N., Ali, S.A.M., Latip, J., Fauzi, N.M., Budin, S.B. & Zainalabidin, S. 2017a. Roselle is cardioprotective in diet-induced obesity rat model with myocardial infarction. Life Sciences 191: 157-165.

Si, L.Y.N., Kamisah, Y., Ramalingam, A., Lim, Y.C., Budin, S.B. & Zainalabidin, S. 2017b. Roselle supplementation prevents nicotine-induced vascular endothelial dysfunction and remodelling in rats. Applied Physiology, Nutrition, and Metabolism42(7): 765-772. 

Srivastava, A., Akoh, C.C., Yi, W., Fischer, J. & Krewer, G. 2007. Effect of storage conditions on the biological activaty of phenolic compounds of blueberry extract packed in glass bottles. Journal of Agricultural and Food Chemistry 55: 2705-2713.

Stocks, J. & Dormandy, T. 1971. The autoxidation of human red cell lipids induced by hydrogen peroxide.  British Journal of Haematology 20(1): 95-111.

Tandler, B. 1990. Improved uranyl acetate staining for electron microscopy. Microscopy Research and Technique 16(1): 81-82.

Vanessa Fiorentino, T., Prioletta, A., Zuo, P. & Folli, F. 2013. Hyperglycemia-induced oxidative stress and its role in diabetes mellitus related cardiovascular diseases. Current Pharmaceutical Design 19(32): 5695-5703.

Verma, R.S., Mehta, A. & Srivastava, N. 2007. In vivo chlorpyrifos induced oxidative stress: Attenuation by antioxidant vitamins. Pesticide Biochemistry and Physiology 88(2): 191-196.

Witko-Sarsat, V., Friedlander, M., Capeillère-Blandin, C., Nguyen-Khoa, T., Nguyen, A.T., Zingraff, J., Jungers, P. & Descamps-Latscha, B. 1996. Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney International 49(5): 1304-1313.

Yusof, N.L.M., Jubaidi, F.F., Nasir, S.N.M., Yusoff, N.A., Fauzi, N.M., Zainalabidin, S. & Budin, S.B. 2018. Hibiscus sabdariffa (roselle) polyphenol-rich extract prevents the aortic oxidative damage in type 1 diabetic rats.  Jurnal Teknologi 80(2): 1-8.

Yusof, N.M., Zainalabidin, S., Fauzi, N.M. & Budin, S. 2017. Cardioprotective effects of roselle (Hibiscus sabdariffa Linn.) polyphenol-rich extract in streptozotocin-induced diabetic rats.  International Journal of Cardiology 249: S4.

Zainalabidin, S., Budin, S.B., Anuar, N.N.M., Yusoff, N.A. & Yusof, N.L.M. 2018. Hibiscus sabdariffa Linn. improves the aortic damage in diabetic rats by acting as antioxidant.  Journal of Applied Pharmaceutical Science 8(01): 108-114.

 

*Corresponding author; email: balkis@ukm.edu.my

 

 

 

previous