Berberine Improves Benign Prostatic Hyperplasia via Suppression of 5 Alpha Reductase and Extracellular Signal-Regulated Kinase in Vivo and in Vitro

Abstract

Benign prostate hyperplasia (BPH) is a common disease in elderly men, characterized by proliferated prostate and urinary tract symptoms. The hormonal cascade starting by the action of 5-alpha-reductase (5AR) is known to be one of the pathways responsible for the pathogenesis of BPH. Present investigation evaluated the capacity of berberine (BBR), a nature-derived compound abundant in Coptis japonica, in testosterone-induced BPH rats. Experimental BPH was induced by inguinal injection with testosterone propionate (TP) for 4 weeks. BBR or finasteride, a 5AR inhibitor as positive control, was treated for 4 weeks during BPH. BPH induced by TP evoked weight gaining and histological changes of prostate and BBR treatment improved all the detrimental effects not only weight reduction and histological changes but also suppression of prostate-specific antigen (PSA), which is elevated during BPH. Additionally, BBR suppressed TP-associated increase of 5AR, androgen receptor (AR) and steroid coactivator-1 (SRC-1), the key factors in the pathogenesis of BPH. To evaluate the underlying molecular mechanisms responsible for beneficial effects of BBR, we investigated whether these effects were associated with the mitogen-activated protein kinase pathway. BPH induced by TP showed increased phosphorylation of extracellular signal-regulated kinase (ERK), whereas this was suppressed by BBR treatment. On the other hand, c-jun-N-terminal kinase (JNK) and p38 mitogen-activated protein kinase was not changed in BPH rats. In in vitro study using RWPE-1 cells, a human prostate epithelial cell line. TP increased cell proliferation and BPH-related key factors such as PSA, AR, and 5AR in RWPE-1 cells, and those factors were significantly decreased in the presence of BBR. Furthermore, these proliferative effects in RWPE-1cells were attenuated by treatment with U0126, an ERK inhibitor, confirming BBR can relieve overgrowth of prostate via ERK-dependent signaling. The cotreatment of U0126 and BBR did not affect the change of 5AR nor proliferation compared with U0126 alone, suggesting that the effect of BBR was dependent on the action of ERK. In conclusion, this study shows that BBR can be used as a therapeutic agent for BPH by controlling hyperplasia of prostate through suppression of ERK mechanism.

Phytochemicals in Cancer Treatment: From Preclinical Studies to Clinical Practice

“…(Berberidaceae) has long been a part of traditional Chinese and Ayurvedic medicine. Preclinical efficacy of berberine has been established in various cancers including colon , breast (Zhao et al, 2017), gastrointestinal (Hesari et al, 2018), oral , liver (Tsang et al, 2015), pancreas (Abrams et al, 2019), prostate (Youn et al, 2018), ovarian (Hou et al, 2017), and cervical (Mahata et al, 2011) cancers. Despite large preclinical efficacy data, clinical trials related to the evaluation of true potential of berberine as an anticancer agent are limited.…”

Berberine Ameliorates Prenatal Dihydrotestosterone Exposure-Induced Autism-Like Behavior by Suppression of Androgen Receptor

“…BBR is one of the herbal medicine that has been employed for the management of neurodegenerative diseases such as AD and PD due to its multi-faceted defensive capabilities, such as its protective role in atherosclerosis-related to lipid-and glucoselowering properties (Jiang et al, 2015;Cai et al, 2016). Also, BBR has been reported to inhibit the AR signaling pathway (Li et al, 2011;Tian et al, 2016;Youn et al, 2018), while the related mechanism remains unclear. Besides, BBR has been used for the treatment of PCOS to improve pregnancy outcomes through its effect on insulin resistance (Li et al, 2013;Chen et al, 2017) and normalizing the endocrine and metabolic parameters in PCOS women Arentz et al, 2014;Wang et al, 2016), while there have been no reports on the effect of BBR on PCOS-mediated ASD development.…”

“…It passes through the bloodbrain barrier (BBB) and has many positive effects against some neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD; Jiang et al, 2015;Cai et al, 2016). Also, BBR has been reported to suppress the androgen receptor (AR) signaling pathway (Li et al, 2011) and prostatic hyperplasia (Youn et al, 2018), and has many potential effects on PCOS (Li et al, 2013;An et al, 2014;Arentz et al, 2014;Wang et al, 2016), although the detailed mechanism remains unclear and there have been no reports on the effect of BBR on ASD development.…”

Peanut Sprout Extracts Cultivated with Fermented Sawdust Medium Inhibits Benign Prostatic Hyperplasia In Vitro and In Vivo

“…Binding of DHT to the androgen receptor (AR) induces conformational changes that lead to abnormal growth of the prostate through subsequent molecular events [7,8]. During the progression of BPH, prostatic cells including epithelial cells and stromal cells proliferate via critical steps involving dysregulated cell-cycle progression, altered signaling pathways, and enhanced transcription factors expression [9][10][11]. Therefore, such molecular changes that occur during BPH progression are other potential targets for developing preventive or therapeutic agents.…”