Cardiovascular diseases remain the single leading cause of deaths globally. Diet rich in fruits and vegetables is highly important in the maintenance of best possible cardiovascular health. Malaysia has a variety and large quantity of underutilized fruits which are rich in phenolic compounds. In the present study, cardiovascular protective effects of an underutilized Baccaurea angulata fruit were studied using a cholesterol-fed rabbit model. The study was divided into 5 parts. The objective of part one was to identify and quantify some phenolic compounds in the methanolic extracts of B. angulata whole fruit (WF), skin (SK) and pulp (PL). By using the ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC/MS-MS) based approach, a total of 17 compounds were detected and characterized on the basis of their chromatographic retention time, UV-vis spectra and mass spectra in the negative-ion mode and data from the literature. Part two was aimed at evaluating the effects of WF, SK and PL juices of B. angulata administered at a nutritional dose of 1 ml/kg/day on malondialdehyde (MDA) levels and antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) as well as on total antioxidant capacity (TAC) in rabbits fed with high-cholesterol diet for 12 weeks. The results showed that B. angulata fruit had modulating effects on lipid peroxidation and antioxidant enzyme activities in rabbits fed with high-cholesterol diet. It significantly (p<0.05) lowered the concentrations of plasma MDA. SOD, GPX, CAT and TAC decreased with cholesterol feeding and recovered with B. angulata juice administrations. The purpose of part three was to evaluate and compare the effects of three different B. angulata WF juice doses administered at nutritional doses of 0.5 ml/kg/day, 1 ml/kg/day and 1.5 ml/kg/day on serum, aorta & liver MDA levels, antioxidant enzymes (SOD, GPx and CAT) as well as on total antioxidant capacity in rabbits fed with cholesterol diet for 12 weeks. The results showed that higher doses (1 ml/kg/day and 1.5 ml/kg/day) of B. angulata WF juice exerted better antioxidant activity. Part four of the study was aimed at evaluating and comparing the effects of three different B. angulata WF juice concentrations administered at nutritional doses of 0.5 ml/kg/day, 1 ml/kg/day and 1.5 ml/kg/day on 12 serum, aorta & liver inflammatory biomarkers of atherosclerosis such as vascular cell adhesion molecule 1 (VCAM-1), intercellular cell adhesion molecule 1 (ICAM-1), P-selectin, C-reactive protein (CRP), IL-1, IL-2, IL-6, IL-7, IL-8, IL-10, IL-18, and tumor necrosis factor α (TNF- α) in rabbits fed with cholesterol diet for 12 weeks. The results showed that B. angulata inhibited inflammatory biomarkers of atherosclerosis. Lastly, the aim of part five was to investigate the plaque-reducing activities of B. angulata fruit as a new anti-atherogenic plant in high-cholesterol fed rabbits for 12 weeks. Rabbits fed with cholesterol diet only successfully developed severe, extensive and more densely distributed human-like atherosclerotic lesions. However, supplementation of B. angulata fruit juice to rabbits fed with cholesterol diet significantly (p<0.001) reduced atherosclerotic lesions. In conclusion, B. angulata fruit was shown to enhance plasma antioxidant enzyme activities, inhibit inflammatory biomarkers and reduce progression of atherosclerotic plaque in cholesterol-fed rabbits. Thus, B. angulata fruit plays a favorable role on several mechanisms involved in combating atherosclerosis.

Atherosclerosis is the underlying disease process in the blood vessels that usually results in coronary heart disease (CHD) and cerebrovascular disease, which are the most common forms of cardiovascular disease (CVD). A high level of serum cholesterol is mainly identified as an important risk factor in the development and progression of premature atherosclerosis. Previous studies on Baccaurea angulata (BA), a Malaysian underutilized fruit, showed that it is very rich in fiber and antioxidants. The present study was thus undertaken to evaluate the potential health benefits of BA fruit juice on cardiovascular disease biomarkers in diet-induced atherosclerotic rabbits. The studies were carried out in three distinct phases. In phase one, the effect of solvents [methanol and phosphate buffered saline (PBS)] using cold extraction was examined on the total phenolic content (TPC), total flavonoid content (TFC), and total carotene content (TCC), free radical scavenging activities and lipid peroxidation inhibition activities of the various fruit parts (skin, pulp and whole fruit) using spectrophotometer. The results indicated that the methanol crude extracts significantly (p<0.01) contained higher TPC, TFC and TCC than PBS extracts in all the fruits parts. The edible portion had the highest and most significant (p<0.01) TPC (15357.77±150.72 µg gallic acid equivalence (GAE)/g), TFC (37.32±0.55 mg quercetin equivalence (QE)/g), and TCC (6571.43±185.86 µg ?-carotene equivalence (BC)/100 g) [dry weight sample] among the methanol crude extracts. In phase two, thirty-five healthy male adult rabbits (Oryctolagus cuniculus; New Zealand White strain) with a body weight of 2300–2800 g were used. The rabbits were randomly assigned to one of the seven rabbit groups. Four groups were fed cholesterol diet (1% cholesterol) and 0, 0.5, 1.0, and 1.5 mL of juice per kg of rabbit daily (hypercholesterolemic groups), while the other three groups were fed commercial rabbit pellet and 0, 0.5, and 1.0 mL of juice per kg of rabbit per day (normocholesterolemic groups) for 90 days. Blood samples were taken before and after the experimental period. The serum, aorta and liver homogenates were also analyzed for biochemical biomarkers. The results showed that the physiological dysfunctions of the hemopoietic system, caused by the high-cholesterol diet, were significantly (p<0.01) normalized by the administration of BA whole fruit juice, especially at the highest dose (1.5 mL/kg/day). In phase three, histopathological studies were carried out to evaluate the percentage of atherosclerotic lesion accrued using different staining techniques (Hematoxylin & eosin, van Gieson and Sudan IV). The result showed that the supplementation of high-cholesterol diet of the hypercholesterolemic rabbits with only 0.5 mL BA per kg rabbit per day significantly (p<0.001) attenuated aortic fatty streak development. Higher BA fruit juice doses used (1.0 and 1.5 mL per kg rabbit per day) also significantly decreased further the development of aortic fatty streaks. Therefore, the phytochemical composition and antioxidant properties of BA whole fruit juice have substantially proved its potential health benefits as an effective hypocholesterolemic, anti-inflammatory and anti-atherosclerotic agent for the management of CVD biomarkers. Further studies may be needed to corroborate these facts.