title: Chrysophanic acid reduces testosterone-induced benign prostatic hyperplasia in rats by suppressing 5α-reductase and extracellular signal-regulated kinase.
abstract: Benign prostatic hyperplasia (BPH) is one of the most common chronic diseases in male population, of which incidence increases gradually with age. In this study, we investigated the effect of chrysophanic acid (CA) on BPH. BPH was induced by a 4-week injection of testosterone propionate (TP). Four weeks of further injection with vehicle, TP, TP + CA, TP + finasteride was carried on. In the CA treatment group, the prostate weight was reduced and the TP-induced histological changes were restored as the normal control group. CA treatment suppressed the TP-elevated prostate specific antigen (PSA) expression. In addition, 5α-reductase, a crucial factor in BPH development, was suppressed to the normal level close to the control group by CA treatment. The elevated expressions of androgen receptor (AR), estrogen receptor α and steroid receptor coactivator 1 by TP administration were also inhibited in the CA group when compared to the TP-induced BPH group. Then we evaluated the changes in three major factors of the mitogen-activated protein kinase chain during prostatic hyperplasia; extracellular signal-regulated kinase (ERK), c-Jun-N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38). While ERK was elevated in the process of BPH, JNK and p38 was not changed. This up-regulated ERK was also reduced as normal by CA treatment. Further in vitro studies with RWPE-1 cells confirmed TP-induced proliferation and elevated AR, PSA and p-ERK were all reduced by CA treatment. Overall, these results suggest a potential pharmaceutical feature of CA in the treatment of BPH.
authors.affiliation: Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Dongdaemun-Gu, Seoul, 02447, Republic of Korea.
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Youn
authors.affiliation: Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Dongdaemun-Gu, Seoul, 02447, Republic of Korea.
authors.forename: Jinbong
authors.initials: J
authors.lastname: Park
authors.affiliation: College of Korean Medicine, Basic Research Laboratory for Comorbidity Regulation, Kyung Hee University, Dongdaemun-Gu, Seoul, 02447, Republic of Korea.
authors.forename: Hye-Lin
authors.initials: HL
authors.lastname: Kim
authors.affiliation: Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Dongdaemun-Gu, Seoul, 02447, Republic of Korea.
authors.forename: Yunu
authors.initials: Y
authors.lastname: Jung
authors.affiliation: Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Dongdaemun-Gu, Seoul, 02447, Republic of Korea.
authors.forename: JongWook
authors.initials: J
authors.lastname: Kang
authors.affiliation: College of Korean Medicine, Basic Research Laboratory for Comorbidity Regulation, Kyung Hee University, Dongdaemun-Gu, Seoul, 02447, Republic of Korea.
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Jeong
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117600, Singapore.
authors.forename: Gautam
authors.initials: G
authors.lastname: Sethi
authors.affiliation: College of Korean Medicine, Basic Research Laboratory for Comorbidity Regulation, Kyung Hee University, Dongdaemun-Gu, Seoul, 02447, Republic of Korea.
authors.forename: Kwang
authors.initials: K
authors.lastname: Seok Ahn
authors.affiliation: Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Dongdaemun-Gu, Seoul, 02447, Republic of Korea.|College of Korean Medicine, Basic Research Laboratory for Comorbidity Regulation, Kyung Hee University, Dongdaemun-Gu, Seoul, 02447, Republic of Korea.
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Um
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D058891:5-alpha Reductase Inhibitors / Q000494:pharmacology*; D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D004195:Disease Models, Animal; D015536:Down-Regulation; D047628:Estrogen Receptor alpha / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D018120:Finasteride / Q000494:pharmacology; D008297:Male; D056920:Nuclear Receptor Coactivator 1 / Q000378:metabolism; D009929:Organ Size; D010766:Phosphorylation; D011467:Prostate / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D043343:Testosterone Propionate; D013997:Time Factors
chemical_list: D058891:5-alpha Reductase Inhibitors; D000880:Anthraquinones; D047628:Estrogen Receptor alpha; D011944:Receptors, Androgen; D018120:Finasteride; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D056920:Nuclear Receptor Coactivator 1; D048049:Extracellular Signal-Regulated MAP Kinases; D017430:Prostate-Specific Antigen; C027113:chrysophanic acid; D043343:Testosterone Propionate
keywords: 5α-reductase; benign prostatic hyperplasia-BPH; chrysophanic acid; extracellular signal-regulated kinase; prostate specific antigen