Ameliorative effect of Annona muricata seed extract on testosterone-induced benign prostatic hyperplasia in rats: biochemical, histopathological, and in silico evidence of 5-alpha reductase inhibition.

Abstract

Background: Annona muricata L., known for its medicinal properties, has been explored for its potential in treating benign prostatic hyperplasia (BPH). While previous studies have noted its numerous health benefits, this research evaluated the therapeutic potential of seed extract of Annona muricata (SEAM) against BPH in rats by exploring in vivo and in silico approaches.

Methods: SEAM extraction, phytochemical analysis, in vitro antioxidant activities, and acute toxicity were achieved using standard methods. Thirty male Wistar rats (weight: 158-192 g) were randomly divided into six groups of five rats each. The groups were assigned as follows: (1) normal control, (2) negative control, (3) positive control, and (4-6) experimental groups. BPH was induced in rats of groups (2-6) by subcutaneous injection of 3 mg/kg body weight (b.w) testosterone for 28 days, followed by daily oral treatment with 5 mg/kg b.w. Finasteride, 200, 400 and 600 mg/kg b.w SEAM, respectively for 21 days. The effect of SEAM treatment on changes in rats' biochemical, hematological, and histological indices was assessed.

Results: Extraction of 3000 g of A. muricata seeds yielded 255.6 g SEAM. GC-MS analysis of SEAM revealed flavonoids, alkaloids, polyphenols, and saponins. SEAM exhibited strong radical scavenging activity in vitro. BPH induction in rats triggered significant (p < 0.05) alterations in some biochemical, hematological and histological profiles of test rats. Notably, SEAM significantly (p <0.05) normalized altered levels of prostate-specific antigen, testosterone, antioxidant enzymes, and hematological parameters of treated rats, and is comparable to the standard drug, Finasteride. Molecular docking studies revealed strong binding interactions between SEAM phytochemicals and 5-alpha reductase, suggesting inhibition of this enzyme as a key mechanism of SEAM action.

Conclusions: Our study not only confirms the therapeutic potential of SEAM in BPH management but also provides insights into novel biochemical pathways and molecular interactions. These findings indicate that SEAM possess significant anti-BPH property through antioxidant activity and 5-alpha reductase inhibitory activity, providing scientific validation for its potential as a natural remedy for BPH, and setting the stage for further mechanistic studies and clinical trials.