Citrus reticulata fruit peel extract ameliorates testesterone-induced benign prostatic hyperplasia-like phenotypes in rats

Abstract

Benign prostatic hyperplasia is a major pathophysiologic event that presents a high risk for prostate cancer (the second most frequently diagnosed cancer in men). The prognosis of conventional therapy for BPH remains poor due to treatment failures. Thus, natural remedies such as botanical drugs remain a promising alternative therapy to be explored for the treatment of BPH and prostate cancer. Citrus fruits, specifically fruit peels of Citrus reticulata (CRE) contain bioactive compounds that exhibit anti-inflammatory properties and have been used in crude form in traditional settings to manage benign prostatic hyperplasia and prostate cancer, however, scientific scrutiny of this ethnobotanical claim remains incomplete. This study assessed the protective effect of CRE in testosterone-induced benign prostatic hyperplasia-like phenotypes in rats. Male Wistar rats (n = 30, 150-200 g) were randomly assigned into six groups (n = 5), and treated for 28 days as follows: control group (normal saline, 5 mg/kg s.c.), model group (testosterone,5 mg/kg, i.p.), the finasteride (1 mg/kg, p.o.), and CRE (50, 100, and 200 mg/kg, p.o.) groups received testosterone (5 mg/kg, i.p.) in the morning and their respective treatments (either finasteride or CRE). All rats were given chow and water ad libitum. On the 28th day, the rats were sacrificed following deep anesthesia. Blood and the prostate gland were collected. Full blood count, serum levels of prostate-specific antigen (PSA), testosterone, C-reactive protein (CRP), and histology of the prostate gland were assessed. Compared to the model, treatment with C. reticulata peel extracts markedly reduced prostate weight, attenuated atresia of the prostatic glands, stromal fibrosis, and mast cell infiltration, and increased glandular secretion. Additionally, serum levels of testosterone, CRP, PSA, and white blood count were reduced in the high-dose C. reticulata peel extract-treated group. Fruit peels of C. reticulata exhibited a protective effect against BPH partly by attenuating inflammatory activity. Thus, this finding provides a rationale for further exploration of CRE for novel anti-BPH molecules that could be used to develop therapeutics against prostate cancer.