Pharmacological and Toxicological Evaluation of Stem Extracts of Croton Membranaceus in Benign Prostatic Hyperplasia and Prostate Cancer Models

Abstract

Phytotherapeutic studies on some extracts have revealed promising anti-prostatic growth or anticancer activities. In this study, the pharmacological and toxicological activities of the aqueous stem (CMASE) and sequential stem fractions (SECM) of Croton membranaceus were evaluated in; testosterone-induced benign prostatic hyperplasia (BPH) Sprague-Dawley (S-D) male rats and prostate cancer lines (PC3 and LNCaP). Phytochemical screening of CMASE revealed presence of phenols, alkaloids, saponins, terpenoids and tannins. Gas chromatography-mass spectrometry analysis of CMASE showed the presence of n-hexadeconoic acid and 6-octadecanoic acid, known for their anti-androgenic, antioxidant, and 5-alpha reductase inhibitory properties. All extracts (SECM and CMASE) exhibited mild antioxidant potentials, and antiproliferative activities against PC3 and LNCaP cells. Sequential aqueous fraction and CMASE exhibited selective indices for PC3 (SI=75.41, 85.11) and LNCaP (SI=2.2, 2.07) cells, respectively. CMASE induced key apoptotic hallmarks in PC3 cells. Acute (1000, 2500, 5000 mg/kg) and sub-chronic (30, 150 and 300 mg/kg for 90 days) toxicity studies of CMASE in male S-D rats revealed, it was relatively safe, possessed nephroprotective, mild hepatotoxic activity, and had LD50 value greater than 5 g/kg. CMASE caused significant (p<0.001) reduction in prostatic prostate specific antigens levels, significant (p<0.01 and p<0.05) reductions in 5- alpha reductase activity, marked reduction in prostatic androgens levels, and size of prostates (between 48.1-70.4%) in BPH-induced rats. Also, CMASE caused marked elevation of prostatic and liver antioxidant enzymes. In conclusion, CMASE was relatively safe, had apoptotic, mild antioxidant potential, anti-prostate growth and anti-cancer activity, and is a 5-alpha reductase inhibitor.