TTENUATIONANDCYTOTOXIC EFFECTS

BENIGN PROSTATIC HYPERPLASIA ATTENUATIONANDCYTOTOXIC EFFECTS OF Lonchocarpus grif onianus G. DON(FABACEAE) STEM AND ROOT BARKS

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Abstract
Rising incidences of benign and cancerous tumours, such as benign prostatic hyperplasia (BPH)and prostate cancer, coupled with the unpleasant side effects of current therapy, suggest a needtosearch for new drug molecules. The stem bark of Lonchocarpus grif onianus G. Don(Fabaceae) is an important medicinal plant used in Nigeria to treat BPH and other tumourrelated ailments. No pharmacological study on the use of the plant for treating BPHhas beenreported. This study aimed to investigate the protective effect of L. grif onianus (LG) on BPH. Two organs (stem and root barks) of LG were identified, collected, pulverized and extractedwithabsolute methanol (99 %) using a Soxhlet extractor. Comparative preliminary biological
evaluations were done on the L. grif onianus stem bark (LGSB) extract and root bark (LGRB)extracts using two benchtop assays (cytotoxic and antiproliferative). The acute toxicity of theLGstem bark extract was done using a modified Lorke's method. The extract was subjectedtoVacuum Liquid Chromatography (VLC) and Gravity Column Chromatography (GCC) toobtaintwo isolated compounds, LO1 and LO2. The compounds were subjected to MS and 1DNMRanalysis for identification. The isolated compounds (LO1 and LO2) were subjected to cytotoxicevaluation on human prostate (PC3) and uterine cervical cancer (Hela) cell lines using a 3-(4, 5-dimethyl thiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay. Anti-BPHevaluationwasdone on the extract and LO1 using testosterone-induced BPH in the rat model. BPHwas inducedby the administration of testosterone propionate (4 mg/kg, s.c., in olive oil) for 28 days. LGSBextract (100, 200 and 400 mg/kg), LO1 (5 mg/kg), LGSB extract (200 mg/kg)+finasteride(5mg/kg) and finasteride (5 mg/kg) were orally administered daily. On day 29, the rats weresacrificed under anaesthesia and blood was collected via the abdominal aorta. The collectedblood was centrifuged, and the serum was separated. The serum was analyzed for biochemical
parameters such as prostate-specific antigen (PSA), testosterone and estradiol. The prostatewasharvested for histological examination. The wet weight and volume of the prostate were taken. The prostate index (PI) was calculated. All data were expressed as mean ± SEM(standarderrorof the mean) and were compared using analysis of variance (ANOVA), The result of preliminary evaluations indicated that the LGSB extract has a higher activity(100±0.00% mortality at 80 µg/mL) than the LGRB extract (3.33 ± 1.29%at 80 µg/mL). Acutetoxicity results revealed no mortality in both phases after oral administration with LD50>5000mg/kg. LO1 and LO2 significantly inhibited the multiplication of PC3 and Hela cells invitro.
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