Kolaviron, a biflavonoid of Garcinia kola seed mitigates ischemic/reperfusion injury by modulation of pro-survival and apoptotic signaling pathways

Abstract

Objective: The study was designed to investigate the ameliorative effect of Kolaviron (KV) on ischemic/reperfusion injury in experimental animal models.

Materials and methods: Male Wistar rats were randomly divided into two groups: Group 1 received corn oil as a vehicle and rats in Group 2 were administered KV at 200 mg/kg for 4 weeks. The rats were fed with rat standard chow pellet and water administered ad libitum. After 4 weeks of KV administration, hearts were excised and mounted on the working heart perfusion system. Western blot analysis for protein expression was carried out on frozen heart samples.

Results: There was significant (P < 0.05) reduction in the activity of catalase, superoxide dismutase, and glutathione peroxidase with concomitant reduction in oxygen radical absorbance capacity in ischemic rat heart of control compared to group pre-treated with KV, respectively. Similarly, intracellular reactive oxygen species and malondialdehyde were significantly elevated in control compared to KV pre-treated rats. KV significantly increased total Akt/protein kinase B (PKB), phosphorylated Akt/PKB at serine 473 and also caused a significant reduction in p38 mitogen-activated protein kinase, Caspase 3, and cleaved poly adenosine diphosphate ribose polymerase.

Conclusion: Taken together, KV offered significant cardioprotection via free radical scavenging activity and upregulation of pro-survival pathway.

Keywords: Antioxidant; Kolaviron; chemoprevention; ischemic/reperfusion injury; oxidative stress.

Figure 1

Structure of kolaviron

Chart 1

Heart perfusion protocol

Figure 2

The effect Kolaviron (KV) on plasma reduced glutathione (GSH), oxidize GSH (GSSG) and GSH/GSSG ratio in 20 min reperfusion time point. Values are mean ± standard deviation, n = 10. Kolaviron; KV (200 mg/kg bodyweight), corn oil (2 mL/kg)

Figure 3

The effect of Kolaviron (KV) on total Akt/PKB and phosphorylated Akt/PKB at 20 min perfusion and 25 min reperfusion time point. Values are mean ± standard deviation, n = 10, *P < 0.05 compared with control. KV (200 mg/kg bodyweight), corn oil (2 mL/kg)

Figure 4

The effect of Kolaviron (KV) on p38 MAPK at 20 min perfusion and 25 min reperfusion time points. Values are mean ± standard deviation, n = 10, **P < 0.05 compared with control. KV (200 mg/kg bodyweight), corn oil (2 mL/kg)

Figure 5

The effect Kolaviron on Caspase 3 and cleaved Caspase 3 at 20 min perfusion and 25 min reperfusion time points. Values are mean ± standard deviation, n = 10, *P < 0.05 compared with control

Figure 6

The effect of Kolaviron (KV) on apoptotic marker (cleaved Caspase 3) at 20 min perfusion and 25 min reperfusion time points. Values are mean ± standard deviation, n = 10, *P < 0.05 compared with control. KV (200 mg/kg bodyweight), corn oil (2 mL/kg)