Hovenia dulcis Honey Suppresses Androgen‐Induced Epithelial–Mesenchymal Transition in Benign Prostatic Hyperplasia
ABSTRACT Benign prostate hyperplasia (BPH) is characterized by abnormal prostate epithelial and stromal cell growth, which leads to bladder outlet obstruction (BOO) and lower urinary tract symptoms (LUTS). BPH pathogenesis involves key signaling pathways, including androgen/androgen receptor (AR) an...
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| Format: | Article |
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Wiley
2025-05-01
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| Series: | Food Frontiers |
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| Online Access: | https://doi.org/10.1002/fft2.70026 |
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| author | Buyun Kim Young‐Eun Kim Eun‐Bin Kwon Wei Li Hye Jin Yang Sung‐Joon Na Sang Mi Han Soon Ok Woo Hong Min Choi Siwon Moon Young Soo Kim Jang‐Gi Choi |
| author_facet | Buyun Kim Young‐Eun Kim Eun‐Bin Kwon Wei Li Hye Jin Yang Sung‐Joon Na Sang Mi Han Soon Ok Woo Hong Min Choi Siwon Moon Young Soo Kim Jang‐Gi Choi |
| author_sort | Buyun Kim |
| collection | DOAJ |
| description | ABSTRACT Benign prostate hyperplasia (BPH) is characterized by abnormal prostate epithelial and stromal cell growth, which leads to bladder outlet obstruction (BOO) and lower urinary tract symptoms (LUTS). BPH pathogenesis involves key signaling pathways, including androgen/androgen receptor (AR) and transforming growth factor‐beta (TGF‐β)/Smad, which contribute to cell proliferation, transformation, and epithelial–mesenchymal transition (EMT). To date, the effect of Hovenia dulcis honey (HH) on BPH has not been reported. Herein, in vivo and in vitro BPH models were used to determine whether HH has therapeutic effects and its underlying mechanisms, if present. To evaluate the anti‐BPH effect of HH in vivo, mice were treated with testosterone propionate (TP; 10 mg/kg, s.c.), finasteride (Fi; 10 mg/kg, i.p.), or HH (600 mg/kg, p.o.) for 4 weeks. Additionally, HH in vitro efficacy was evaluated using a dihydrotestosterone (DHT)‐stimulated RWPE‐1 prostate cell model. HH significantly reduced prostate size, epithelial thickness, and markers of AR signaling (prostate‐specific antigen [PSA], proliferating cell nuclear antigen [PCNA], and DHT) as well as exhibited anti‐inflammatory effects by lowering the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase‐2 (COX‐2), interleukin‐6 (IL‐6), and tumor necrosis factor‐α (TNF‐α) and inhibited the EMT process by decreasing α‐smooth muscle actin (α‐SMA), neural cadherin (N‐cadherin), and vimentin levels while restoring epithelial cadherin (E‐cadherin) expression. These findings suggest that HH inhibits the androgen/AR and TGF‐β/Smad signaling pathways and may offer a novel therapeutic approach for BPH treatment. |
| format | Article |
| id | doaj-art-b8aeb7938909431bb1c0a58e3410b3dc |
| institution | Kabale University |
| issn | 2643-8429 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Food Frontiers |
| spelling | doaj-art-b8aeb7938909431bb1c0a58e3410b3dc2025-08-20T03:48:22ZengWileyFood Frontiers2643-84292025-05-01631362137510.1002/fft2.70026Hovenia dulcis Honey Suppresses Androgen‐Induced Epithelial–Mesenchymal Transition in Benign Prostatic HyperplasiaBuyun Kim0Young‐Eun Kim1Eun‐Bin Kwon2Wei Li3Hye Jin Yang4Sung‐Joon Na5Sang Mi Han6Soon Ok Woo7Hong Min Choi8Siwon Moon9Young Soo Kim10Jang‐Gi Choi11Korean Medicine (KM) Application Center Korea Institute of Oriental Medicine (KIOM) Daegu Republic of KoreaKorean Medicine (KM) Application Center Korea Institute of Oriental Medicine (KIOM) Daegu Republic of KoreaKorean Medicine (KM) Application Center Korea Institute of Oriental Medicine (KIOM) Daegu Republic of KoreaKorean Medicine (KM) Application Center Korea Institute of Oriental Medicine (KIOM) Daegu Republic of KoreaKorean Medicine (KM) Application Center Korea Institute of Oriental Medicine (KIOM) Daegu Republic of KoreaSpecial Forest Resources Division National Institute of Forest Science Suwon Republic of KoreaDepartment of Agricultural Biology National Institute of Agricultural Sciences, Rural Development Administration Wanju Republic of KoreaDepartment of Agricultural Biology National Institute of Agricultural Sciences, Rural Development Administration Wanju Republic of KoreaDepartment of Agricultural Biology National Institute of Agricultural Sciences, Rural Development Administration Wanju Republic of KoreaDepartment of Agricultural Biology National Institute of Agricultural Sciences, Rural Development Administration Wanju Republic of KoreaKorean Medicine (KM) Application Center Korea Institute of Oriental Medicine (KIOM) Daegu Republic of KoreaKorean Medicine (KM) Application Center Korea Institute of Oriental Medicine (KIOM) Daegu Republic of KoreaABSTRACT Benign prostate hyperplasia (BPH) is characterized by abnormal prostate epithelial and stromal cell growth, which leads to bladder outlet obstruction (BOO) and lower urinary tract symptoms (LUTS). BPH pathogenesis involves key signaling pathways, including androgen/androgen receptor (AR) and transforming growth factor‐beta (TGF‐β)/Smad, which contribute to cell proliferation, transformation, and epithelial–mesenchymal transition (EMT). To date, the effect of Hovenia dulcis honey (HH) on BPH has not been reported. Herein, in vivo and in vitro BPH models were used to determine whether HH has therapeutic effects and its underlying mechanisms, if present. To evaluate the anti‐BPH effect of HH in vivo, mice were treated with testosterone propionate (TP; 10 mg/kg, s.c.), finasteride (Fi; 10 mg/kg, i.p.), or HH (600 mg/kg, p.o.) for 4 weeks. Additionally, HH in vitro efficacy was evaluated using a dihydrotestosterone (DHT)‐stimulated RWPE‐1 prostate cell model. HH significantly reduced prostate size, epithelial thickness, and markers of AR signaling (prostate‐specific antigen [PSA], proliferating cell nuclear antigen [PCNA], and DHT) as well as exhibited anti‐inflammatory effects by lowering the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase‐2 (COX‐2), interleukin‐6 (IL‐6), and tumor necrosis factor‐α (TNF‐α) and inhibited the EMT process by decreasing α‐smooth muscle actin (α‐SMA), neural cadherin (N‐cadherin), and vimentin levels while restoring epithelial cadherin (E‐cadherin) expression. These findings suggest that HH inhibits the androgen/AR and TGF‐β/Smad signaling pathways and may offer a novel therapeutic approach for BPH treatment.https://doi.org/10.1002/fft2.70026androgen receptorbenign prostatic hyperplasiadihydrotestosteroneepithelial–mesenchymal transitionHovenia dulcis honeyinflammation |
| spellingShingle | Buyun Kim Young‐Eun Kim Eun‐Bin Kwon Wei Li Hye Jin Yang Sung‐Joon Na Sang Mi Han Soon Ok Woo Hong Min Choi Siwon Moon Young Soo Kim Jang‐Gi Choi Hovenia dulcis Honey Suppresses Androgen‐Induced Epithelial–Mesenchymal Transition in Benign Prostatic Hyperplasia Food Frontiers androgen receptor benign prostatic hyperplasia dihydrotestosterone epithelial–mesenchymal transition Hovenia dulcis honey inflammation |
| title | Hovenia dulcis Honey Suppresses Androgen‐Induced Epithelial–Mesenchymal Transition in Benign Prostatic Hyperplasia |
| title_full | Hovenia dulcis Honey Suppresses Androgen‐Induced Epithelial–Mesenchymal Transition in Benign Prostatic Hyperplasia |
| title_fullStr | Hovenia dulcis Honey Suppresses Androgen‐Induced Epithelial–Mesenchymal Transition in Benign Prostatic Hyperplasia |
| title_full_unstemmed | Hovenia dulcis Honey Suppresses Androgen‐Induced Epithelial–Mesenchymal Transition in Benign Prostatic Hyperplasia |
| title_short | Hovenia dulcis Honey Suppresses Androgen‐Induced Epithelial–Mesenchymal Transition in Benign Prostatic Hyperplasia |
| title_sort | hovenia dulcis honey suppresses androgen induced epithelial mesenchymal transition in benign prostatic hyperplasia |
| topic | androgen receptor benign prostatic hyperplasia dihydrotestosterone epithelial–mesenchymal transition Hovenia dulcis honey inflammation |
| url | https://doi.org/10.1002/fft2.70026 |
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