Sinomenine Hydrochloride Can Ameliorate Benign Prostatic Hyperplasia by Lowering the 5α-Reductase 2 Level and Regulating the Balance between the Proliferation and Apoptosis of Cells

Abstract

Benign prostatic hyperplasia (BPH) is a chronic disease that affects the quality of life of older males. Sinomenine hydrochloride (SIN) is the major bioactive alkaloid isolated from the roots of the traditional Chinese medicinal plant Sinomenium acutum Rehderett Wilson. We wondered if the SIN administration exerted a regulatory effect on BPH and its potential mechanism of action. Mice with testosterone propionate-induced BPH subjected to bilateral orchiectomy were employed for in vivo experiments. A human BPH cell line (BPH-1) was employed for in vitro experiments. SIN administration inhibited the proliferation of BPH-1 cells (p < 0.05) by regulating the expression of androgen-related proteins (steroid 5-alpha reductase 2 (SRD5A2), androgen receptors, prostate-specific antigen), apoptosis-related proteins (B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax)) and proliferation-related proteins (proliferating cell nuclear antigen (PCNA), mammalian target of rapamycin, inducible nitric oxide synthase) in vitro. SIN administration decreased the prostate-gland weight coefficient (p < 0.05) and improved the histological status of mice suffering from BPH. The regulatory effects of SIN administration on SRD5A2, an apoptosis-related protein (Bcl-2), and proliferation-related proteins (PCNA, matrix metalloproteinase-2) were consistent with in vitro data. SIN exerted a therapeutic effect against BPH probably related to lowering the SRD5A2 level and regulating the balance between the proliferation and apoptosis of cells. Our results provide an important theoretical basis for the development of plant medicines for BPH therapy.

Effect of Gynerium sagittatum methanol extract on testosterone-induced benign prostatic hyperplasia in rats compared with finasteride.

“…SIN therapy significantly reduced protein expression of Bcl-2 and PCNA in the PG tissues of mice with TP-induced BPH in vivo, indicating that SIN treatment alleviated BPH via the apoptotic pathway, which was consistent with in vitro data. These findings suggest that SIN treatment may improve BPH via the apoptotic pathway [32,33]. Inflammation is another mechanism for the development of BPH, which is also an important clue.…”

Bioactivities and Mechanisms of Action of Sinomenine and Its Derivatives: A Comprehensive Review

“…M. S. Fan et al reported that SH (25, 50, and 100 µM) inhibited BcL-2 and increased Bax protein expression, thereby suppressing the proliferation of BPH-1 cells. SH at doses of 0.5, 1, and 2 mg/kg decreased steroid 5-alpha reductase 2 (SRD5A2), PCNA, BcL-2, and MMP-2 [ 222 ]. The various other bioactivities of SIN are detailed in Table 15 .…”