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Drug Res (Stuttg) 2018; 68(05): 286-295
DOI: 10.1055/s-0043-123686
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Kolaviron and Garcinia kola Seed Extract Protect Against Ischaemia/Reperfusion Injury on Isolated Rat Heart

Ademola Adetokunbo Oyagbemi
1   Department of Veterinary Physiology and Biochemistry, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Nigeria
2   Drug Metabolism and Toxicology Unit, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria
3   Oxidative Stress Research Centre, Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Bellville, South Africa
,
Dirk Bester
3   Oxidative Stress Research Centre, Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Bellville, South Africa
,
Johan Esterhuyse
3   Oxidative Stress Research Centre, Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Bellville, South Africa
,
Ebenezer Olatunde Farombi
2   Drug Metabolism and Toxicology Unit, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria
› Author Affiliations
Further Information

Publication History

received 23 August 2017

accepted 22 November 2017

Publication Date:
08 January 2018 (online)

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Abstract

Background The incidence of cardiovascular diseases and its associated complications have increased greatly in the past three decades. The purpose of this study was to evaluate the acute cardioprotective effects of Garcinia kola (GK) seed extract and Kolaviron (KV) and determine mechanisms of action involving RISK signalling pathways.

Methods Male Wistar rats were used in this study. Hearts were excised and mounted on the Langendorff perfusion system. The control, group 1 was perfused with dimethyl sulfoxide (DMSO), group II with KV and group III with GK respectively. Western blot analyses were performed on frozen heart tissues.

Results Isolated rat hearts perfused with KV and GK attenuated apoptotic pathways with significant reduction in p38 MAPK protein phosphorylation, as well as reduction in total caspase 3, cleaved caspase 3 (Asp 175) and PARP cleavage. KV and GK also down-regulated p-JNK1 (Tyr 185) and p-JNK 2 (Thr 183) protein expression at the 10 min reperfusion time ponit. Cardioprotection was achieved in part, by enhancement of the reperfusion injury signalling kinase (RISK) pathway; as evidenced by significant increases in protein expresion of Akt/PKB and p-Akt/PKB (Ser 473) in KV and GK respectively.

Conclusions KV and GK supplementation led to significant increases in the expressions of survival proteins. It is noteworthy that both KV and GK supplementation offered cardioprotection in ischaemic/reperfusion injury rat heart model. In all, GK showed better cardioprotective effect that KV.

Key words

Kolaviron (KV) - Garcinia kola (GK) seed extract - antioxidant - reperfusion injury - cardio-protection

Supporting Information

    Supporting Information for this article is available online at http://www.thieme-connect.de/products
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  • References

  • 1 Iwu MM, Igboko OA, Onwuchekwa U. et al. Evaluation of the anti-hepatotoxicity of the biflavonoids of Garcinia kola seeds. J Ethnopharmacol 1987; 21: 127-142
    CrossrefPubMedGoogle Scholar
  • 2 Farombi EO, Alabi MC, Akuru TO. Kolaviron modulates cellular redox status and impairment of membrane protein activities induced by potassium bromate (KBrO(3)) in rats. Pharmacol Res 2002; 45: 63-68
    CrossrefPubMedGoogle Scholar
  • 3 Adaramoye OA, Nwaneri VO, Anyanwu KC. et al. Possible anti-atherogenic effect of kolaviron (a Garcinia kola seed extract) in hypercholesterolaemic rats. Clin Expt Pharmacol Physiol 2005; 32: 40-46
    PubMedGoogle Scholar
  • 4 Adaramoye OA, Kehinde AO, Adefisan A. et al. Ameliorative Effects of Kolaviron, a Biflavonoid Fraction from Garcinia Kola Seed, on Hepato-renal Toxicity of Anti-tuberculosis Drugs in Wistar Rats. Tokai J Exp Clin Med 2016; 41: 14-21
    PubMedGoogle Scholar
  • 5 Onasanwo SA, Velagapudi R, El-Bakoush A. et al. Inhibition of neuroinflammation in BV2 microglia by the biflavonoid Kolaviron is dependent on the Nrf2/ARE antioxidant protective mechanism. Mol Cell Biochem 2016; 414: 23-36
    CrossrefPubMedGoogle Scholar
  • 6 Adedara IA, Owoeye O, Aiyegbusi MA. et al. Kolaviron protects against benzo[a]pyrene-induced functional alterations along the brain-pituitary-gonadal axis in male rats. Environ Toxicol Pharmacol 2015; 40: 459-470
    CrossrefPubMedGoogle Scholar
  • 7 Awogbindin IO, Olaleye DO, Farombi EO. Kolaviron improves morbidity and suppresses mortality by mitigating oxido-inflammation in balb/c mice infected with influenza virus. Viral Immunol 2015; 28: 367-377
    CrossrefPubMedGoogle Scholar
  • 8 Akinmoladun AC, Akinrinola BL, Olaleye MT. et al. Kolaviron, a Garcinia kola biflavonoid complex, protects against ischemia/reperfusion injury: Pertinent mechanistic insights from biochemical and physical evaluations in rat brain. Neurochem Res 2015; 40: 777-487
    CrossrefPubMedGoogle Scholar
  • 9 Farombi EO, Abarikwu SO, Adedara IA. et al. Curcumin and Kolaviron ameliorate di-n-butylphthalate-induced testicular damage in rats. Basic Clin Pharmacol Toxicol 2007; 100: 43-48
    CrossrefPubMedGoogle Scholar
  • 10 Adaramoye OA. Protective effect of kolaviron, a biflavonoid from Garcinia kola seeds, in brain of Wistar albino rats exposed to gamma-radiation. Biol Pharmaceut Bulletin 2010; 33: 260-266
    PubMedGoogle Scholar
  • 11 Adaramoye OA, Nwaneri VO, Anyanwu KC. et al. Possible anti-atherogenic effect of kolaviron (a Garcinia kola seed extract) in hypercholesterolaemic rats. Clin Expt Pharmacol Physiol 2005; 32: 40-46
    PubMedGoogle Scholar
  • 12 Adaramoye OA, Adeyemi EO. Hepatoprotection of D-galactosamine-induced toxicity in mice by purified fractions from Garcinia kola seeds. Basic and Clinical Pharmacol Toxicol 2006; 98: 135-141
    PubMedGoogle Scholar
  • 13 Olaleye SB, Farombi EO. Attenuation of indomethacin and HCl/ethanol-induced oxidative gastric mucosa damage in rats by Kolaviron, a natural biflavonoid of Garcinia kola seed. Phytother Res 2006; 20: 14-20
    CrossrefPubMedGoogle Scholar
  • 14 Farombi EO, Alabi MC, Akuru TO. Kolaviron modulates cellular redox status and impairment of membrane protein activities induced by potassium bromate (KBrO(3)) in rats. Pharmacol Res 2002; 45: 63-68
    CrossrefPubMedGoogle Scholar
  • 15 Farombi EO, Møller P, Dragsted LO. Ex-vivo and in vitro protective effects of kolaviron against oxygen-derived radical-induced DNA damage and oxidative stress in human lymphocytes and rat liver cells. Cell Biol Toxicol 2004; 20: 71-82
    CrossrefPubMedGoogle Scholar
  • 16 Farombi EO, Adepoju BF, Ola-Davies OE. et al. Chemoprevention of aflatoxin B1-induced genotoxicity and hepatic oxidative damage in rats by kolaviron, a natural bioflavonoid of Garcinia kola seeds. Eur J Cancer Prev 2005; 14: 207-214
    CrossrefPubMedGoogle Scholar
  • 17 Farombi EO, Nwaokeafor IA. Anti-oxidant mechanisms of Kolaviron: studies on serum lipoprotein oxidation, metal chelation and oxidative membrane damage in rats. Clin Exp Pharmacol Physiol 2005; 32: 667-674
    CrossrefPubMedGoogle Scholar
  • 18 Farombi EO, Shrotriya S, Surh YJ. Kolaviron inhibits dimethyl nitrosamine-induced liver injury by suppressing COX-2 and iNOS expression via NF-kappaB and AP-1. Life Sci 2009; 84: 149-155
    CrossrefPubMedGoogle Scholar
  • 19 Zhao ZQ, Morris CD, Budde JM. et al. Inhibition of myocardial apoptosis reduces infarct size and improves regional contractile dysfunction during reperfusion. Cardiovasc Res 2003; 59: 132-142
    CrossrefPubMedGoogle Scholar
  • 20 Hausenloy DJ, Yellon DM. New directions for protecting the heart against ischaemia-reperfusion injury: Targeting the Reperfusion Injury Salvage Kinase (RISK)-pathway. Cardiovasc Res 2004; 61: 448-460
    CrossrefPubMedGoogle Scholar
  • 21 Hausenloy DJ, Yellon DM. Reperfusion Injury Salvage Kinase signaling: Taking a RISK for cardioprotection. Heart Fail Rev 2007; 12: 217-234
    CrossrefPubMedGoogle Scholar
  • 22 Hausenloy DJ, Tsang A, Yellon DM. The reperfusion injury salvage kinase pathway: A common target for both ischemic preconditioning and postconditioning. Trends Cardiovasc Med 2005; 15: 69-75
    CrossrefPubMedGoogle Scholar
  • 23 Davidson SM, Hausenloy D, Duchen MR. et al. Signalling via the Reperfusion Injury Signalling Kinase (RISK) pathway links closure of the mitochondrial permeability transition pore to cardioprotection. Int J Biochem Cell Biol 2006; 38: 414-419
    CrossrefPubMedGoogle Scholar
  • 24 Abdallah Y, Gkatzoflia A, Gligorievski D. et al. Insulin protects cardiomyocytes against reoxygenation-induced hypercontracture by a survival pathway targeting SR Ca2+ storage. Cardiovasc Res 2006; 70: 346-353
    CrossrefPubMedGoogle Scholar
  • 25 Pantos C, Mourouzis I, Saranteas T. et al. Thyroid hormone improves postischaemic recovery of function while limiting apoptosis: A new therapeutic approach to support hemodynamics in the setting of ischaemia–reperfusion?. Basic Res Cardiol 2009; 104: 69-77
    CrossrefPubMedGoogle Scholar
  • 26 Galang N, Sasaki H, Maulik N. Apoptotic cell death during ischemia/reperfusion and its attenuation by antioxidant therapy. Toxicol 2000; 148: 111-118
    CrossrefPubMedGoogle Scholar
  • 27 Ma X, Gao F, Lopez B. et al. Peroxynitrate, a two-edged sword in post-ischemic myocardial njurydichotomy of action in crystalloid- versus blood- perfused hearts. J Pharmacol Expt Ther 2000; 292: 912-920
    PubMedGoogle Scholar
  • 28 Piao CS, Gao S, Lee GH. et al. Sulforaphane protects ischemic injury of hearts through antioxidant pathway and mitochondrial K(ATP) channels. Pharmacol Res 2010; 61: 342-348
    CrossrefPubMedGoogle Scholar
  • 29 Adedara IA, Vaithinathan S, Jubendradass R. et al. Kolaviron prevents carbendazim-induced steroidogenic dysfunction and apoptosis in testes of rats. Environ Toxicol Pharmacol 2013; 35: 444-453
    CrossrefPubMedGoogle Scholar
  • 30 Farombi EO, Adedara IA, Oyenihi AB. et al. Hepatic, testicular and spermatozoa antioxidant status in rats chronically treated with Garcinia kola seed. J Ethnopharmacol. 2013; 146: 536-542
    CrossrefPubMedGoogle Scholar
  • 31 Guidolin D, Agnati LF, Tortorella C. et al. Neuroglobin as a regulator of mitochondrial-dependent apoptosis: A bioinformatics analysis. Int J Mol Med 2014; 33: 111-116
    CrossrefPubMedGoogle Scholar
  • 32 Valen G. 2003; The basic biology of apoptosis and its implications for cardiac function and viability. Ann Thorac Surg 2003 75: S656-S6560
    PubMedGoogle Scholar
  • 33 Watts JA, Kline JA. Bench to bedside: The role of mitochondrial medicine in the pathogenesis and treatment of cellular injury. Acad Emerg Med 2003; 10: 985-997
    CrossrefPubMedGoogle Scholar
  • 34 Guo J, Wang SB, Yuan TY. et al. Coptisine protects rat heart against myocardial ischemia/reperfusion injury by suppressing myocardial apoptosis and inflammation. Atherosclerosis 2013; 231: 384-391
    CrossrefPubMedGoogle Scholar
  • 35 Lan R, Zhang Y, Xiang J. et al. Xiao-Xu-Ming decoction preserves mitochondrial integrity and reduces apoptosis after focal cerebral ischemia and reperfusion via the mitochondrial p53 pathway. J Ethnopharmacol 2014; 151: 307-316
    CrossrefPubMedGoogle Scholar
  • 36 Murray J, Renslo AR. Modulating caspase activity: Beyond the active site. Curr Opin Struct Biol 2013; 23: 812-819
    CrossrefPubMedGoogle Scholar
  • 37 Belizário JE, Alves J, Occhiucci JM. et al. Mechanistic view of mitochondrial death decision pores. Braz J Med Biol Res 2007; 40: 1011-1024
    CrossrefPubMedGoogle Scholar
  • 38 Banafa AM, Roshan S, Liu YY. et al. Fucoidan induces G1 phase arrest and apoptosis through caspases-dependent pathway and ROS induction in human breast cancer MCF-7 cells. J Huazhong Univ Sci Technolog Med Sci 2013; 33: 717-724
    CrossrefPubMedGoogle Scholar
  • 39 Abarikwu SO, Farombi EO, Pant AB. Kolaviron biflavanoids of Garcinia kola seeds protect atrazine-induced cytotoxicity in primary cultures of rat Leydig cells. Int J Toxicol 2012; 31: 407-415
    CrossrefPubMedGoogle Scholar
  • 40 Yadav HN, Singh M, Sharma PL. Pharmacological inhibition of GSK-3β produces late phase of cardioprotection in hyperlipidemic rat: Possible involvement of HSP 72. Mol Cell Biochem 2012; 369: 227-233
    CrossrefPubMedGoogle Scholar
  • 41 Zhao ZQ, Morris CD, Budde JM. et al. Inhibition of myocardial apoptosis reduces infarct size and improves regional contractile ysfunction during reperfusion. Cardiovasc Res 2003; 59: 132-142
    CrossrefPubMedGoogle Scholar
  • 42 Nishizawa K, Yanagida S, Yamagishi T. et al. Continuous inhibition of poly (ADP-ribose) polymerase does not reduce reperfusion injury in isolated rat heart. J Cardiovasc Pharmacol 2013; 62: 99-105
    CrossrefPubMedGoogle Scholar
  • 43 Song ZF, Ji XP, Li XX. et al. Inhibition of the activity of poly (ADP-ribose) polymerase reduces heart ischaemia/reperfusion injury via suppressing JNK-mediated AIF translocation. J Cell Mol Med 2008; 12: 1220-1228
    CrossrefPubMedGoogle Scholar
  • 44 Izumi M, Masaki M, Hiramoto Y. et al. Cross-talk between bone morphogenetic protein 2 and leukemia inhibitory factor through ERK 1/2 and Smad1 in protection against doxorubicininduced injury of cardiomyocytes. J Mol Cell Cardiol 2006; 40: 224-233
    CrossrefPubMedGoogle Scholar
  • 45 Wang M, Zhang W, Crisostomo P. et al. Enothelial STAT3 plays a critical role in generalized myocardial proinflammatory and proapoptotic signaling. Am J Physiol Heart Circ Physiol 2007; 293: H2101-H2108
    CrossrefPubMedGoogle Scholar
  • 46 Manukyan MC, Alvernaz CH, Poynter JA. et al. Interleukin-10 protects the ischemic heart from reperfusion injury via the STAT3 pathway. Surgery 2011; 150: 231-239
    CrossrefPubMedGoogle Scholar
  • 47 Stephanou A. Role of STAT-1 and STAT-3 in ischaemia/reperfusion injury. J Cell Mol Med 2004; 8: 519-525
    CrossrefPubMedGoogle Scholar
  • 48 Zhan X, Kook S, Gurevich EV. et al. Arrestin-Dependent Activation of JNK Family Kinases. Handbook Expt Pharmacol 2014; 219: 259-280
    PubMedGoogle Scholar
  • 49 Jeong CW, Yoo KY, Lee SH. et al. Curcumin protects against regional myocardial ischemia/reperfusion injury through activation of RISK/GSK-3β and inhibition of p38 MAPK and JNK. J Cardiovasc Pharmacol Therapeut 2012; 17: 387-394
    CrossrefPubMedGoogle Scholar
  • 50 Engelbrecht AM, Esterhuyse J, du Toit EF. et al. p38-MAPK and PKB/Akt, possible role players in red palm oil-induced protection of the isolated perfused rat heart?. J Nutr Biochem 2006; 17: 265-271
    CrossrefPubMedGoogle Scholar
  • 51 Arslan F, Lai RC, Smeets MB. et al. Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia/reperfusion injury. Stem Cell Res 2013; 10: 301-312
    CrossrefPubMedGoogle Scholar
  • 52 Guo J, Wang SB, Yuan TY. et al. Coptisine protects rat heart against myocardial ischemia/reperfusion injury by suppressing myocardial apoptosis and inflammation. Atherosclerosis 2013; 231: 384-391
    CrossrefPubMedGoogle Scholar
  • 53 Li J, Shao ZH, Xie JT. et al. The effects of ginsenoside Rb1 on JNK in oxidative injury in cardiomyocytes. Arch Pharmaceut Res 2012; 35: 1259-1267
    PubMedGoogle Scholar