Anti-hyperplastic effects of Acmella oleracea flower and leaf extracts in prostate cell lines and in spontaneously hypertensive rats

Benign prostatic hyperplasia (BPH) is a highly prevalent age-associated disorder and a leading cause of lower urinary tract symptoms in men worldwide. Given the limitations of current therapies, there is increasing interest in phytotherapeutic compounds as sources of biologically active agents. Acmella oleracea, a medicinal plant rich in the alkamide spilanthol, has been traditionally associated with urogenital effects; however, the biological impact of distinct plant organs on prostate hyperplasia remains poorly defined. In this study, we investigated the effects of flower (A.Fl) and leaf (A.Le) extracts of A. oleracea using human prostate cell lines (RWPE-1 and PC-3) and a spontaneously hypertensive rat (SHR) model of BPH. In vitro analyses included cell viability assays and immunofluorescence for androgen receptor (AR), estrogen receptor alpha (ERα), and proliferating cell nuclear antigen (PCNA). In vivo, SHR were treated orally with A.Fl or A.Le (100 mg/kg/day for 21 days), followed by morphological, immunohistochemical, ultrastructural, and oxidative stress analyses of the ventral prostate. A.Fl displayed lower cytotoxicity than A.Le in both prostate cell lines and preferentially increased ERα immunoreactivity, whereas A.Le more strongly modulated AR without affecting cell proliferation. In SHR, both extracts attenuated prostatic hyperplasia, although A.Fl produced a more pronounced reduction in epithelial proliferation and stromal remodeling. These effects occurred independently of changes in systemic blood pressure or antioxidant activity. Collectively, these findings demonstrate that flower and leaf extracts of A. oleracea exert distinct biological and endocrine-modulatory effects on prostate tissue. The present data provide experimental evidence that different plant organs differentially influence epithelial-stromal dynamics and steroid receptor signaling in prostatic hyperplasia, supporting further mechanistic and translational investigations.