title: Modulatory effect of silymarin on inflammatory mediators in experimentally induced benign prostatic hyperplasia: emphasis on PTEN, HIF-1α, and NF-κB.
abstract: The current study aimed to investigate the potential role of the anti-inflammatory effects of silymarin (SIL) in inhibiting experimentally induced benign prostatic hyperplasia (BPH) in rats. Rats were injected testosterone (3 mg/kg/day, subcutaneously (s.c.)) for 2 weeks. In the treatment group, SIL (50 mg/kg, per orally (p.o.)) was administered daily to rats concomitantly with testosterone. Rats were killed 72 h after the last testosterone injection. Then, prostate tissues were dissected out, weighed, and subjected to histological, immunohistochemical, and biochemical examinations. Rats treated with testosterone showed marked increase in prostate weight and prostate weight/body weight with histopathological picture of inflammation and hyperplasia as well as increased collagen deposition. Co-treatment with SIL significantly alleviated these pathological changes. Further, SIL attenuated testosterone-induced nuclear factor-kappa B (NF-κB), cyclooxygenase-II (COX-II), and inducible nitric oxide synthase (iNOS) upregulation, and blunted testosterone-mediated increase in nitric oxide level and messenger RNA (mRNA) expression of interleukin-6 (IL-6) and IL-8. Testosterone-induced downregulation of phosphatase and tensin homolog (PTEN) and upregulation of hypoxia-inducible factor 1α (HIF-1α) were alleviated by SIL. Our findings highlight the anti-inflammatory properties of SIL as a crucial mechanism of its preventive actions against experimental BPH. This can be attributed to, at least partly, attenuating the expression of NF-kB and the subsequent inflammatory cascade, ameliorating the expression of PTEN, and mitigating that of HIF-1α. These data warrant further investigations for the potential use of SIL in the management of BPH.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Abbasia, Cairo, Egypt.
authors.forename: Reem T
authors.initials: RT
authors.lastname: Atawia
authors.forename: Hala H
authors.initials: HH
authors.lastname: Mosli
authors.forename: Mariane G
authors.initials: MG
authors.lastname: Tadros
authors.forename: Amani E
authors.initials: AE
authors.lastname: Khalifa
authors.forename: Hisham A
authors.initials: HA
authors.lastname: Mosli
authors.forename: Ashraf B
authors.initials: AB
authors.lastname: Abdel-Naim
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012838:Silymarin / Q000494:pharmacology*; D013739:Testosterone / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018836:Inflammation Mediators; D016328:NF-kappa B; D012333:RNA, Messenger; D012838:Silymarin; D013739:Testosterone; D051059:PTEN Phosphohydrolase; C487216:Pten protein, rat