Modulatory effect of ethylacetate fraction from Theobroma cacao pod husk on blood pressure in L-NAME-induced hypertensive rats using in vivo and in silico approaches

Abstract

Hypertension related diseases are public health concerns due to their high incidence and mortality. However, the inability of the synthetic drugs to normalize blood pressure (BP) to acceptable range has motivated the search for safer and effective alternatives. This study investigated the antihypertensive activity of ethyl acetate fraction of Theobroma cacao pod husk (EAF-TCPH) in L-nitro-arginine-methyl-ester (L-NAME)-induced hypertensive male rats. Methanol extract of Theobroma cacao pod husk (TCPH) was partitioned to obtain the EAF-TCPH fraction. Hypertension was induced by oral administration of 40 mg/kg body weight (bw) L-NAME; while BP was checked by tail plethysmography. Wistar rats were assigned into groups 1–6. Group 1 received 1.0 ml of paraffin oil, while groups 2–6 were hypertensive rats and received 1.0 ml of paraffin oil, 12.5, 25 and 50 mg/kg bw of the EAF-TCPH and 25 mg of captopril respectively for 6 weeks. The compounds in EAF-TCPH were identified using high performance liquid chromatography and were docked against angiotensin converting enzyme (ACE). Elevated BP of 180.17 (systolic) and 125.79 mmHg (diastolic) in the hypertensive rats was lowered to 125.33 and 88.00 mmHg, respectively in the 25 mg/kg bw EAF-TCPH treated group. The major compounds in EAF-TCPH were theaflavin, epigallocatechin, procyanidin, epicatechin and cianidanol. Theaflavin binds to ACE better than captopril (standard drug) with binding energy of −10.8 and −5.8 kcal/mol, respectively. This study therefore suggests that EAF-TCPH could have demonstrated potential antihypertensive activities in L-NAME-induced hypertensive rats due to the available bioactive components in EAF-TCPH that probably interacted in a beneficial way with ACE.