Neferine attenuates development of testosterone-induced benign prostatic hyperplasia in mice by regulating androgen and TGF-β/Smad signaling pathways.

Content Provider	Europe PMC
Author	Liu, Chi-Ming Shao, ZiChen Chen, XuZhou Chen, HanWu Su, MengQiao Zhang, ZiWen Wu, ZhengPing Zhang, Peng An, LiJie Jiang, YinJie Ouyang, Ai-Jun
Copyright Year	2023
Abstract	Benign prostatic hyperplasia (BPH) is a common urinary disease among the elderly, characterized by abnormal prostatic cell proliferation. Neferine is a dibenzyl isoquinoline alkaloid extracted from Nelumbo nucifera and has antioxidant, anti-inflammatory and anti-prostate cancer effects. The beneficial therapeutic effects and mechanism of action of neferine in BPH remain unclear.A mouse model of BPH was generated by subcutaneous injection of 7.5 mg/kg testosterone propionate (TP) and 2 or 5 mg/kg neferine was given orally for 14 or 28 days. Pathological and morphological characteristics were evaluated. Prostate weight, prostate index (prostate/body weight ratio), expression of type Ⅱ 5α-reductase, androgen receptor (AR) and prostate specific antigen were all decreased in prostate tissue of BPH mice after administration of neferine. Neferine also downregulated the expression of pro-caspase-3, uncleaved PARP, TGF-β1, TGF-β receptor Ⅱ (TGFBR2), p-Smad2/3, N-cadherin and vimentin. Expression of E-cadherin, cleaved PARP and cleaved caspase-3 was increased by neferine treatment.1–100 μM neferine with 1 μM testosterone or 10 nM TGF-β1 were added to the culture medium of the normal human prostate stroma cell line, WPMY-1, for 24 h or 48 h. Neferine inhibited cell growth and production of reactive oxygen species (ROS) in testosterone-treated WPMY-1 cells and regulated the expression of androgen signaling pathway proteins and those related to epithelial-mesenchymal transition (EMT). Moreover, TGF-β1, TGFBR2 and p-Smad2/3, N-cadherin and vimentin expression were increased but E-cadherin was decreased after 24 h TGF-β1 treatment in WPMY-1 cells. Neferine reversed the effects of TGF-β1 treatment in WPMY-1 cells. Neferine appeared to suppress prostate growth by regulating the EMT, AR and TGF-β/Smad signaling pathways in the prostate and is suggested as a potential agent for BPH treatment.
ISSN	13190164
Journal	Saudi Pharmaceutical Journal : SPJ
Volume Number	31
PubMed Central reference number	PMC10244910
Issue Number	7
PubMed reference number	37293563
e-ISSN	22137475
DOI	10.1016/j.jsps.2023.05.004
Language	English
Publisher	Elsevier
Publisher Date	2023-05-11
Access Restriction	Open
Rights License	This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). © 2023 The Author(s)
Subject Keyword	Benign prostatic hyperplasia (BPH) Androgen receptor (AR) TGF-β/Smad Neferine Epithelial-mesenchymal transition (EMT) Apoptosis
Content Type	Text
Resource Type	Article
Subject	Pharmacology Pharmaceutical Science