Rauwolfia vomitoria extract suppresses benign prostatic hyperplasia by reducing expression of androgen receptor and 5α-reductase in a rat model

Fang, Tian; Xue, Zhaoli; Li, Jia-xuan; Liu, Jiakuan; Wu, Di; Li, Meiqian; Song, Yuting; Su, Yun; Yan, Jun

doi:10.1016/j.joim.2020.12.002

Cited by 7 publications

(8 citation statements)

References 32 publications

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“…Testosterone generated in the testicle and spread to the prostate is converted into DHT, a more potent male sex hormone, by 5α-reductase (5AR) . The biological effect of DHT is achieved by binding to the androgen receptor (AR), a member of the steroid and nuclear receptor superfamily .…”

Section: Introductionmentioning

confidence: 99%

“…Testosterone generated in the testicle and spread to the prostate is converted into DHT, a more potent male sex hormone, by 5α-reductase (5AR). 3 The biological effect of DHT is achieved by binding to the androgen receptor (AR), a member of the steroid and nuclear receptor superfamily. 4 DHT combined with AR promotes the transcriptional activation of AR, leading to the proliferation of prostate cells and increased expression of the prostate-specific antigen (PSA).…”

Section: ■ Introductionmentioning

confidence: 99%

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Purple Corn Extract Improves Benign Prostatic Hyperplasia by Regulating Prostate Cell Proliferation and Apoptosis

Kim

Kim²,

Jin

et al. 2022

J. Agric. Food Chem.

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Purple corn (Zea mays L.), utilized as a natural pigment in food production and processing, has been used to treat obesity, cystitis, and urinary tract infections. However, no reports of its use for benign prostatic hyperplasia (BPH) exist. Purple corn extract (PCE) contains anthocyanins, particularly cyanidin-3-O-glucoside, which have various pharmacological characteristics. Therefore, this study sought to elucidate the ameliorative effect of PCE on BPH in dihydrotestosterone (DHT)-stimulated WPMY-1 cells and testosterone propionate (TP)-induced rats. Expression levels of the upregulated androgen receptor (AR) and its related genes in DHT-stimulated WPMY-1 cells were reduced by PCE, and proapoptotic gene expression increased by modulating the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling cascade. PCE reduced the weight of the enlarged prostate by inhibiting the androgen/AR signaling-related markers. Histological variations in the prostate epithelium caused by TP injection were restored by PCE. Thus, PCE alleviates BPH by modulating prostate cell proliferation and apoptosis.

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Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Purple Corn Extract Improves Benign Prostatic Hyperplasia by Regulating Prostate Cell Proliferation and Apoptosis

Kim

Kim²,

Jin

et al. 2022

J. Agric. Food Chem.

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“…The RWF extract contains bioactive monoterpene and beta-carboline alkaloids, and is reported to treat many diseases, such as impaludism, gastrointestinal diseases, and cancer [12,13]. Recently, we found that RWF extract could reverse the development of BPH by suppressing 5α-reductase and androgen receptor in a BPH rat model, similar to finasteride [14]. Interestingly, its side effects were milder than finasteride, with significantly lower toxicity to sperm development in comparison to finasteride [14].…”

Section: Introductionmentioning

confidence: 99%

Rauwolfia vomitoria extract suppresses benign prostatic hyperplasia by inducing autophagic apoptosis through endoplasmic reticulum stress

Huang

Xue

et al. 2022

BMC Complement Med Ther

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Background The current drug treatments for benign prostatic hyperplasia (BPH) have negative side effects. Therefore, it is important to find effective alternative therapies with significantly fewer side effects. Our previous study revealed that Rauwolfia vomitoria (RWF) root bark extract reversed BPH development in a rat model. However, the molecular mechanism of its inhibitory effects on BPH remains largely unknown. Methods BPH-1 and WPMY-1 cell lines derived from BPH epithelial and prostatic stromal compartments were selected to investigate how RWF extract inhibits BPH in vitro by MTT and flow cytometry assays. Microarray, quantitative real-time PCR, immunoblotting, and GFP-LC3 immunofluorescence assays were performed to evaluate the effects of RWF extract on endoplasmic reticulum stress (ER stress) and autophagic apoptosis pathways in two cell lines. A human BPH ex vivo explant assay was also employed for validation. Results RWF extract treatment decreased cell viability and induced apoptotic cell death in both BPH-1 and WPMY-1 cells in a concentration-dependent manner with the increase of pro-apoptotic PCDC4 protein. RWF extract induced autophagy by enhancing the levels of autophagic genes (ULK2 and SQSTM1/p62) and the LC3II:LC3I ratio, with the increase of GFP-LC3 puncta. Moreover, RWF extract activated PERK- and ATF6-associated ER stress pathways by inducing the transcriptional levels of EIF2AK3/PERK, DDIT3/CHOP and ATF6, accompanied by the reduction of BiP protein level, but not its mRNA level. Another ER stress pathway was not induced by RWF extract, as manifested by the lack of XBP1 splicing. Pharmacological inhibition of autophagy by 3-methyladenine abrogated apoptosis but not ER stress; while inhibition of ER stress by 4-phenylbutyrate alleviated the induction of autophagy and apoptosis. In addition, pretreatments with either 3-methyladenine or 4-phenylbutyrate suppressed RWF extract-induced cytotoxicity. Notably, the inductions of PERK- and ATF6-related stress pathways and autophagic apoptosis were confirmed in a human BPH ex vivo explant. Conclusions Our data have demonstrated that RWF extract significantly suppressed the viabilities of BPH epithelial cells and BPH myofibroblasts by inducing apoptosis via upregulating ER stress and autophagy. These data indicate that RWF extract is a potential novel alternative therapeutic approach for BPH.

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“…(Uckert et al, 2020). At present, 5α‐reductase inhibitors and α‐blockers are the most commonly used medications for BPH (Fang et al, 2021). Nevertheless, 5α‐reductase inhibitors and α‐blockers show several adverse reactions, such as depression, erectile dysfunction, dizziness, hypotension, and so on (Traish, 2017).…”

Section: Introductionmentioning

confidence: 99%

Quercetin in Tonglong Qibi decoction ameliorates testosterone‐induced benign prostatic hyperplasia in rats by regulating Nrf2 signalling pathways and oxidative stress

Chen

Zhang

et al. 2022

Andrologia

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Benign prostatic hyperplasia (BPH) is a common urological disease in older males. Existing pharmacotherapy shows several side effects, and the exploration of new therapeutic strategies is of high significance. Tonglong Qibi (TQ) decoction was proved to ameliorate BPH, while the underlying mechanisms are still unclear. In the current study, we explored the anti-BPH effects of TQ in vivo and identified its main therapeutic component and the underlying mechanisms in vitro. We demonstrated that TQ mitigated BPH in rats and showed no toxicity to the liver and reproductive system. Network pharmacology identified quercetin as the main component in TQ treating BPH. Quercetin reduced proliferation, oxidative stress, and increased Nrf2 expression in hyperplastic prostate epithelial cells. These findings indicate that quercetin in TQ alleviates BPH via inhibiting oxidative stress and activating the Nrf2 signalling pathway.

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Rauwolfia vomitoria extract suppresses benign prostatic hyperplasia by reducing expression of androgen receptor and 5α-reductase in a rat model

Cited by 7 publications

References 32 publications

Purple Corn Extract Improves Benign Prostatic Hyperplasia by Regulating Prostate Cell Proliferation and Apoptosis

Purple Corn Extract Improves Benign Prostatic Hyperplasia by Regulating Prostate Cell Proliferation and Apoptosis

Rauwolfia vomitoria extract suppresses benign prostatic hyperplasia by inducing autophagic apoptosis through endoplasmic reticulum stress

Quercetin in Tonglong Qibi decoction ameliorates testosterone‐induced benign prostatic hyperplasia in rats by regulating Nrf2 signalling pathways and oxidative stress

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