Corni Fructus attenuates testosterone-induced benign prostatic hyperplasia by suppressing 5α-reductase and androgen receptor expression in rats

Hwangbo, Hyun; Kwon, Da Hye; Choi, Eun Ok; Kim, Min Yeong; Ahn, Kyu Im; Ji, Seon Yeong; Kim, Jong Sik; Kim, Kyung-Il; Park, No-Jin; Kim, Bum Hoi; Kim, Gi‐Young; Hong, Su‐Hyun; Park, Cheol; Jeong, Ji-Suk; Choi, Yung Hyun

doi:10.4162/nrp.2018.12.5.378

Cited by 15 publications

(19 citation statements)

References 42 publications

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“…61,62 This event results in the rise of PSA levels in prostate cancer patients as well as in the serum of BPH patients. 7 Therefore, alleviation in PSA levels may be a representative of the mitigation of BPH. We also studied how diosmin treatment against TP-induced hyperplasia could decrease the level of PSA.…”

Section: Discussionmentioning

confidence: 99%

“…5 In addition, the serum level of the prostate-specific antigen (PSA) is elevated in BPH patients compared with unaffected men since PSA production is promoted by binding DHT to the androgen receptor (AR). 6,7 The important characteristics involved are gush in the smooth muscle tone and nonmalignant enlargement of the gland. 8 This may lead to recurrent urinary withholding, urinary tract infections, and erratic postrenal failure.…”

Section: Introductionmentioning

confidence: 99%

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Protective role of diosmin against testosterone propionate-induced prostatic hyperplasia in Wistar rats: Plausible role of oxidative stress and inflammation

et al. 2019

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Benign prostatic hyperplasia (BPH) is an important key health concern for aging men. Polyphenolic compounds have been found to possess important roles in the inhibition of numerous ailments that involve reactive oxygen species and inflammation. Diosmin is a citrus flavone that possesses antioxidant, anti-inflammatory, antiproliferative, and anticancer activities, so based on these properties of diosmin, we decided to evaluate its effect on testosterone propionate (TP)-induced BPH. A total of 30 Wistar rats were randomly assigned to five groups having six animals in each. This study was of 28 days in which TP (5 mg kg−1) was administered to induce BPH in the last 10 days of the study. It was found that diosmin at the doses of 20 and 40 mg kg−1 significantly reduced malondialdehyde and xanthine oxidase formation in a dose-dependent manner; however, it replenished catalase, glutathione (GSH), and GSH-dependent enzymes, that is, glutathione peroxidase, glutathione reductase, and glutathione- S-transferase significantly against TP-induced BPH. Further, immunohistochemical study showed that diosmin alleviated inflammatory markers (nuclear factor kappa-light-chain-enhancer of activated B cells, cyclooxygenase-2, and interleukin-6). It was also found that diosmin downregulated the expression of androgen receptor and decreased the prostate-specific antigen concentration dose-dependently, significantly against TP-induced BPH. Diosmin also restored histoarchitecture of the prostate in a dose-dependent manner. Findings from the present study revealed the protective role of diosmin against TP-induced BPH in Wistar rats.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Protective role of diosmin against testosterone propionate-induced prostatic hyperplasia in Wistar rats: Plausible role of oxidative stress and inflammation

et al. 2019

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“…officinalis , called the SC extract. According to their pharmacological properties and a prior report [ 9 ] together with our previous study [ 10 ], a combination of these two plants may benefit from a synergistic effect and consequently promises to be an effective treatment for BPH.…”

Section: Introductionmentioning

confidence: 95%

Protective effects of combination of Stauntonia hexaphylla and Cornus officinalis on testosterone-induced benign prostatic hyperplasia through inhibition of 5α- reductase type 2 and induced cell apoptosis

et al. 2020

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Benign prostatic hyperplasia (BPH) is a progressive pathological condition associated with proliferation of prostatic tissues, prostate enlargement, and lower-urinary tract symptoms. However, the mechanism underlying the pathogenesis of BPH is unclear. The aim of this study was to investigate the protective effects of a combination of Stauntonia hexaphylla and Cornus officinalis (SC extract) on a testosterone propionate (TP)-induced BPH model. The effect of SC extract was examined in a TP-induced human prostate adenocarcinoma cell line. Male Sprague-Dawley rats were randomly divided into 5 groups (n = 6) for in vivo experiments. To induce BPH, all rats, except those in the control group, were administered daily with subcutaneous injections of TP (5 mg/kg) and orally treated with appropriate phosphate buffered saline/drugs (finasteride/saw palmetto/SC extract) for 4 consecutive weeks. SC extract significantly downregulated the androgen receptor (AR), prostate specific antigen (PSA), and 5α-reductase type 2 in TP-induced BPH in vitro . In in vivo experiments, SC extract significantly reduced prostate weight, size, serum testosterone, and dihydrotestosterone (DHT) levels. Histologically, SC extract markedly recovered TP-induced abnormalities and reduced prostatic hyperplasia, thereby improving the histo-architecture of TP-induced BPH rats. SC extract also significantly downregulated AR and PSA expression, as assayed using immunoblotting. Immunostaining revealed that SC extract markedly reduced the 5α-reductase type 2 and significantly downregulated the expression of proliferating cell nuclear antigen. In addition, immunoblotting of B-cell lymphoma 2 (Bcl-2) family proteins indicated that SC extract significantly downregulated anti-apoptotic Bcl-2 and markedly upregulated pro-apoptotic B cell lymphoma-associated X (Bax) expression. Furthermore, SC treatment significantly decreased the Bcl-2/Bax ratio, indicating induced prostate cell apoptosis in TP-induced BPH rats. Thus, our findings demonstrated that SC extract protects against BPH by inhibiting 5α-reductase type 2 and inducing prostate cell apoptosis. Therefore, SC extract might be useful in the clinical treatment of BPH.

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“…In contrast, previous studies have shown that ursolic acid, oleanolic acid, and triterpenoids derived from C. officinalis , effectively suppressed the development of BPH in animal model [ 26 , 27 ]. In addition, the aqueous extract of C. officinalis inhibited testosterone-induced BPH, raising the intriguing concerns that the pharmacological functions of C. officinalis could not be described by only the major components [ 14 ]. Although many studies have implied the anti-BPH effect of C. officinalis and its compounds, neither the anti-proliferative effect of standardized C. officinalis on BPH nor the understanding of molecular mechanism could be considered in much detail.…”

Section: Discussionmentioning

confidence: 99%

“…These biological activities are consistent with those reported for the C. officinalis used as traditional medicine, which are TCM formulae to treat urinary frequency and seminal emission [ 13 ]. Furthermore, recent study has shown that aqueous extract of C. officinalis attenuates testosterone-induced benign prostatic hyperplasia (BPH) by suppressing androgen signaling pathway [ 14 ]. However, no study has investigated the exact molecular mechanism(s) underlying the anti-proliferative effects of standardized C. officinalis on prostatic cells.…”

Section: Introductionmentioning

confidence: 99%

Anti-Proliferative Effects of Standardized Cornus officinalis on Benign Prostatic Epithelial Cells via the PCNA/E2F1-Dependent Cell Cycle Pathway

Jin

Cheon

Kim

et al. 2020

IJMS

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Cornus officinalis, widely used in traditional Chinese medicine, exhibits pharmacological effects against erectile dysfunction and pollakisuria, which are pathological symptoms of benign prostatic hyperplasia (BPH). Although traditional usage and a study on BPH have been reported, to our knowledge, no study has investigated the exact molecular mechanism(s) underlying the anti-proliferative effects of standardized C. officinalis on prostatic cells. We standardized C. officinalis 30% ethanol extract (COFE) and demonstrated the therapeutic effects of COFE on human BPH epithelial cells and testosterone-induced BPH in rats. In vitro studies using BPH-1 cells demonstrated an upregulation of BPH-related and E2F Transcription Factor 1(E2F1)-dependent cell cycle markers, whereas treatment with COFE clearly inhibited the proliferation of BPH epithelial cells and reduced the overexpression of G1 and S checkpoint genes. Additionally, COFE administration alleviated the androgen-dependent prostatic enlargement in a testosterone-induced BPH animal model. COFE exerted these anti-BPH effects by the inhibition of anti-apoptotic markers, suppression of PCNA expression, and regulation of E2F1/pRB-dependent cell cycle markers in rats with BPH. These results suggest that COFE exerts anti-proliferative effect by regulating PCNA/E2F1-dependent cell cycle signaling pathway both in vivo and in vitro. These findings reveal the therapeutic potential of COFE, which could be used as a substitute for BPH treatment.

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Corni Fructus attenuates testosterone-induced benign prostatic hyperplasia by suppressing 5α-reductase and androgen receptor expression in rats

Cited by 15 publications

References 42 publications

Protective role of diosmin against testosterone propionate-induced prostatic hyperplasia in Wistar rats: Plausible role of oxidative stress and inflammation

Protective role of diosmin against testosterone propionate-induced prostatic hyperplasia in Wistar rats: Plausible role of oxidative stress and inflammation

Protective effects of combination of Stauntonia hexaphylla and Cornus officinalis on testosterone-induced benign prostatic hyperplasia through inhibition of 5α- reductase type 2 and induced cell apoptosis

Anti-Proliferative Effects of Standardized Cornus officinalis on Benign Prostatic Epithelial Cells via the PCNA/E2F1-Dependent Cell Cycle Pathway

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