Effets des extraits de Vitex doniana Sweet, Trichoscypha acuminata et Detarium microcarpum sur la santé cardiométabolique chez les rats

Abstract

Obesity and hyperglycemia are the genesis of several metabolic disorders responsible for various vascular alterations. The present study aimed at evaluating the effects of Vitex doniana (V. doniana), Trichoscypha acuminata (T. acuminata), and Detarium microcarpum (D. microcarpum) extracts on cardiometabolic health in rats. First, the hydroethanolic extracts of V. doniana fruits, aqueous extracts of T. acuminata and aqueous extracts of D. microcarpum barks were prepared, followed by the evaluation of their total polyphenol and flavonoid contents. Then, the identification of the most active extract based on the effects on oxidative stress, carbohydrate and lipid homeostasis in STZ-induced hyperglycemic rats, and the evaluation of some modes of action via the antiradical, reducing and glucophagic power were performed. Subsequently, the cardioprotective effects of the most active extract were evaluated in rats fed with the atherogenic diet (DESF). After characterization of this extract by HPLC-DAD, docking was used to predict some of its modes of action. Finally, acute and subacute toxicity studies of the most active extract were conducted. The contents of total polyphenols were 737.78, 777.50 and 2226.00 µg EC/g DM for the extracts of T. acuminata, D. microcarpum and V. doniana respectively. Those in total flavonoids were 6.18, 8.06 and 53.62 µg EQ/g DM for V. doniana, T. acuminata and D. microcarpum extract respectively. Regarding the effect on glucose homeostasis, all three extracts resulted in a significant and progressive decrease of fasting blood glucose in the short and medium term. This hypoglycemic potential of the three extracts was associated with their glucophagic power. In terms of oxidative stress, D. microcarpum extract lowered Thiobarbituritic Acid Reactive Substance (TBARS) levels in liver, heart and plasma, while T. acuminata extract decreased TBARS levels only in plasma. For catalase, T. acuminata and V. doniana extract decreased erythrocyte activity of the enzyme, while D. microcarpum extract resulted in an increase in erythrocyte catalase activity. The ability of the extracts to protect tissues from the action of pro-oxidants was associated with their ability to scavenge the DPPH radical and to reduce phosphomolybdenum VI to V. The effects on lipid homeostasis revealed that only D. microcarpum extract had beneficial effects on HDL-c and triglycerides, while T. acuminata extract was the only extract that decreased total cholesterol. From these results, D. microcarpum extract showed the best efficacy. In rats subjected to the atherogenic diet, D. microcarpum extract showed a cardioprotective effect via improvement of endothelial function (increase in cardiac NO and decrease in plasma NO), protection against cardiac cytolysis (increase in cardiac ASAT) and decrease in cardiac risk, and improvement of the cardioprotective index. The extract showed hypotriglyceridemic, hypocholesterolemic, hypo LDL-c, hypo VLDL-c, hypo non xxxviii HDL-c and hyper HDL-c properties. The extract resulted in a reduction of atherogenic risk (decrease of IR, AC and AIP), of hepatic fat accumulation and increase of vascular protection. The characterization of the extract revealed the presence of catechin, epicatechin and quercetin 3-O-rhamnoside. Molecular docking showed that these compounds had the ability to bind to the active sites of ACLY and CETP enzymes, and inhibit their activities. Finally, the toxicity studies of D. microcarpum revealed that the LD50 is > 2000 mg/kg, but this extract showed signs of hepatotoxicity. The extracts of V. doniana and T. acuminata fruits, and D. microcarpum bark have beneficial effects on oxidative stress, carbohydrate and lipid homeostasis. The aqueous extract of D. microcarpum bark was the most active and improved cardiometabolic health. However, it was potentially hepatotoxic.