COMPARATIVE BIOCHEMICAL ACTIVITIES OFMOBOLA PLUl\1 (Parinari curatellifolia Bent-h) SEEDS EXTRACT AND " FLAVONOIDS (RUTIN AND QUERCETIN) IN NaCI-INDUCED . HYPERTENSIVE RATS

Abstract

The effectiveness of aqueous-methanolic extract of Parinari curatellifolia and· flavonoids (rutin and quercetin) as alternative therapy in hypertension was evaluated in this study -Pocuratellifolia was investigated for its phytochemical constituents, in vitro antioxidant. potential (total phenol, total flavonoids, reducing property, and lipid peroxidation using FeS04 and FeS04 + EDT A as pro-oxidants, free radical and hydrogen < peroxide scavenging ability). Hypertension was induced in albino rats using 8% NaCl diet. The animals were divided into twelve groups of four rats each. Group 1 (control) received 1% ethanol, group 2 was given 8% salt diet alone for six weeks. Group 3 was given 8% salt diet for six weeks after which nifedipine (1.67 mg/kg) was administered for two weeks. Groups 4-6 were fed with 8% salt diet for six weeks after which varying doses (200-800 mg/kg) of Parinari curatellifolia extract administered for two weeks while groups 7-12 were fed with 8% salt diet for six weeks after which they were administered flavonoids (50-150 mg/kg) for two weeks. Twenty four hour after the last adm in istration, they were all anaesthetized with 5m IIkg urethane-ch loralose (25% urethane and 1% chloralose) after which the blood pressure was taken before they were sacrificed. The effect of the plant extract and flavonoids on salt induced hypertension, in vivo antioxidant defense (lipid peroxidation, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities), serum biochemical indices (creatinine, urea, glucose, total protein), serum lipid profiles (low density lipoprotein (LDL), high density lipoprotein (HDL), triglycerides (TAG) and total cholesterol) as well as their effect on the plasma nitric oxide concentration (NO) were evaluated. The toxicities of the extract and flavonoids were also evaluated by determining their effects on some biochemical indices (urea, uric acid, creatinine, alkaline phosphatase (ALP), total protein (TP), bilirubin, aspartate transaminase (AST), alkaline transaminase (ALT), alkaline phosphatase (ALP) and albumin) in the kidney and the liver. The phytochemical screening results revealed the presence of tannins, flavonoids, terpenoids, steroids, saponins, alkaloids and cardiac glycosides in the extract. The extract redu-ced the formation of TBARS resulting from iron sulphate and iron sulphate-EDTA induction in a concentration dependent manner. The results of the antioxidant property gave total phenolic content (12.73 mg/g tannic acid equivalent), total flavonoids (22.38 mg/g quercetin Equivalent), ferric reducing power (13.92 mg/g ascorbic acid), the percentage of hydrogen peroxide inhibition (76.38-96.85%) and % DPPH radical scavenge varied (17.05- 68.18%). The antihypertensive assay revealed that salt induction caused significant (P::;0.05) increases (174.25±9.89, 129.75±3.33, 42.5±11.12, 145±2.55, 462±8.65) in systolic, diastolic blood pressure, pulse pressure, mean arterial blood pressure and heart rate as compared with control (83±3.50, 69±3A2, 19.5±J.71, 75A±4.02, 4l4.5±5.85) respectively. P. curatellifolia extract caused a dose-dependent (200-800mg/kg) significant reduction (P::;0.05) in systolic (155± 1.91-66.25±2.53), diastolic (132±4.08-52±1.63), mean arterial (25.5±4.27-14.25±J.03) blood pressure and heart rate (420±12.00-362±0.00) as compared with the induced group. Equally, quercetin caused a dose-dependent (50-150mg/kg) significant reduction (P::;0.05) in systolic (120±J.63-67.5±4.8), diastolic (104.5±4.55-49.25±2A) and mean arterial blood pressure (109.7±3.50-55.3±3.09) as compared with the induced group. Salt induction also resulted in significant (P::;O.05) increase (45.18±4.08) in the production of thiobarbituric acid reactive substances (TBARS) in the liver as compared with the control (17.57±4.08). The activities of the antioxidant enzymes (CAT, SOD and GPx) in the liver were significantly (P::;O.05) reduced as compared with the control while the post treatment with the extract and flavonoids abolished these effects. Post treatment with theextract and flavonoids reduce the serum concentration of the biochemical indices. Salt induction increased nitric oxide concentration in the plasma as compared with the control, whereas post-treatment with the flavonoids reversed this effect; extract had no significant effect on the NO concentration. Th~ toxicological investigation revealed that administration of extracts and flavonoids significantly (P:S0.05) increased the levels of urea and bilirubin and the activities of AST, ALT and ALP in the liver as compared with the control. There was a statistical (P:S9.05) decrease in the levels of creatinine, total protein and albumin in the treated groups as compared with control but the groups treated with 50 and 100 mg/kg rutin increased the level of creatinine in the liver. There was a marked increase in the level of uric acid, urea and ALP activity and a significant (P:S0.05) reduction in the level of creatinine in the kidney of treated groups as compared with the control. The results showed that the extract and flavonoids are effective against salt induced hypertension and also exhibit little or no toxicity at the particular dosage used. The presence of the phytochemicals coupled with the recorded antioxidant potentials and antihypertensive activity (600mg/kg); would justify the use of P. curatellifolia in the treatment of hypertension. Moreover, P. curatellifolia compares favourably with quercetin in the activities investigated.