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1.
Biomed Pharmacother ; 135: 111197, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33433362

ABSTRACT

Prostatitis, defined as a pathological inflammatory change in the prostate tissue, is one of the most prevalent urological conditions in men. However, optimal management of prostatitis remains unclear, and treatment outcomes are unsatisfactory owing to adverse effects. Carica papaya leaf extract (PAL) is known for its antioxidant, immunomodulatory, and anticancer properties; however, evidence of its anti-inflammatory effect in prostatic tissues remains elusive. In this study, the therapeutic effects and underlying molecular mechanisms of PAL in mice with experimental autoimmune prostatitis (EAP) and a prostatic cell line (RWPE-1 cells) exposed to inflammatory conditioned medium were investigated. PAL suppressed pathological alterations in EAP and markedly reduced prostate weight in EAP mice. Histological analysis revealed that PAL alleviates prostatic hyperplasia. Furthermore, PAL significantly reduced cyclooxygenase-2 mRNA and protein expression; production of inflammatory cytokines, including interleukin-6, tumor necrosis factor-α, and transforming growth factor-ß; and TRAF6/TAK1/MEK/ERK and NF-κB pathway-related protein expression. TRAF6/TAK1/MEK/ERK and NF-κB pathway-related proteins were upregulated in inflammatory conditioned medium-stimulated RWPE-1 cells, but PAL reduced the expression of these markers. Particularly, PAL treatment suppressed the nuclear translocation of NF-κB p65 and phosphorylation of p65 in RWPE-1 cells exposed to the inflammatory conditioned medium. Collectively, the results demonstrate the anti-proliferative and anti-inflammatory effects of PAL in the experimental prostatitis model, which highlights the potential of PAL as a new therapeutic agent in the treatment of prostatic disease.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Carica , MAP Kinase Kinase Kinases/metabolism , NF-kappa B/metabolism , Plant Extracts/pharmacology , Prostate/drug effects , Prostatic Hyperplasia/prevention & control , Prostatitis/drug therapy , TNF Receptor-Associated Factor 6/metabolism , Animals , Anti-Inflammatory Agents/isolation & purification , Carica/chemistry , Cell Line , Cell Proliferation/drug effects , Cytokines/metabolism , Disease Models, Animal , Finasteride/pharmacology , Inflammation Mediators/metabolism , Male , Mice, Inbred BALB C , Plant Extracts/isolation & purification , Plant Leaves , Prostate/enzymology , Prostate/pathology , Prostatic Hyperplasia/enzymology , Prostatic Hyperplasia/pathology , Prostatitis/enzymology , Prostatitis/pathology , Rats, Wistar , Signal Transduction
2.
Biomed Res Int ; 2019: 3101987, 2019.
Article in English | MEDLINE | ID: mdl-31467880

ABSTRACT

There has been a remarkable interest in finding lipid inhibitors from natural products to replace synthetic compounds, and a variety of oriental medicinal herbs are reported to have biological activity with regard to lipid inhibition. Buginawa (Bugi) is a novel combined formula that contains twelve medicinal herbs with potential for weight loss induction. We hypothesized that Bugi may have antiobesity effects in 3T3-L1 preadipocytes and in a high-fat diet- (HFD-) induced mouse model. In this study, 3T3-L1 cells were treated with varied concentrations of Bugi (62.5, 125, or 250 µg/mL). Bugi treatment inhibited adipocyte differentiation by suppressing adipogenic transcription genes, including peroxisome proliferator-activated receptor γ protein (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), sterol regulatory element-binding protein 1 (SREBP1), and CCAAT/enhancer-binding protein ß (C/EBPß). Mice were fed a normal diet or an HFD for 11 weeks, and Bugi was simultaneously administered at 50 or 100 mg/kg. Bugi administration significantly reduced body weight gain and white adipose tissue (WAT) weight and effectively inhibited lipid droplet accumulation in epididymal white adipose tissue (eWAT) and liver tissue. Further, Bugi treatment suppressed mRNA levels of PPARγ, C/EBPα, and SREBP1 in eWAT and liver tissue. Our findings demonstrate that Bugi could be an effective candidate for preventing obesity and related metabolic disorders.


Subject(s)
Adipose Tissue, White/drug effects , Lipid Metabolism/genetics , Obesity/drug therapy , Plant Preparations/pharmacology , Plants, Medicinal , 3T3-L1 Cells , Adipocytes/drug effects , Adipogenesis/drug effects , Adipose Tissue, White/growth & development , Animals , Body Weight/drug effects , Body Weight/genetics , CCAAT-Enhancer-Binding Proteins/genetics , Cell Differentiation/drug effects , Diet, High-Fat/adverse effects , Gene Expression Regulation/drug effects , Humans , Lipid Metabolism/drug effects , Mice , Obesity/metabolism , Obesity/pathology , PPAR gamma/genetics
3.
Nutrients ; 11(5)2019 May 24.
Article in English | MEDLINE | ID: mdl-31137609

ABSTRACT

Obesity is one of major health challenges in the industrial world. Although rice hull has been reported to show various bioactivities, no studies have evaluated its anti-obesity effect. We hope to demonstrate the anti-obesity effect of rice hull extract (RHE) and the underlying mechanism in high-fat diet (HFD)-induced obese mice and 3T3-L1 preadipocytes. Serum lipid profiles were determined by enzymatic methods. Histological analysis of liver and epididymis fat tissues was carried out with hematoxylin and eosin stain. The mRNA expression of adipogenic markers was analyzed with qRT-PCR and western blotting. Oral administration of RHE reduced body weight gain and fat accumulation in HFD-fed mice. RHE also reduced lipid accumulation by inhibiting the mRNA expression of adipogenic-related genes in HFD-fed obese mice and differentiated preadipocytes. The downregulation of adipogenesis by RHE was mediated through the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC). In addition, RHE induced the phosphorylation of c-Jun N-terminal kinases (JNK) and extracellular-signal-regulated kinases (ERK) in liver and epididymis adipose tissues of HFD-fed obese mice. Taken together, these findings indicate that RHE could inhibit the differentiation of adipose cell and prevent HFD-induced obesity, suggesting its potential in the prevention of obesity and metabolic syndrome and related-disorders.


Subject(s)
Adipocytes/drug effects , Adipogenesis/drug effects , Adiposity/drug effects , Anti-Obesity Agents/pharmacology , Diet, High-Fat , Obesity/prevention & control , Oryza , Plant Extracts/pharmacology , Seeds , 3T3-L1 Cells , AMP-Activated Protein Kinases/metabolism , Adipocytes/metabolism , Adipocytes/pathology , Adipogenesis/genetics , Animals , Anti-Obesity Agents/isolation & purification , Disease Models, Animal , Lipids/blood , Male , Mice , Mice, Inbred C57BL , Mitogen-Activated Protein Kinases/metabolism , Obesity/blood , Obesity/pathology , Obesity/physiopathology , Oryza/chemistry , Phosphorylation , Plant Extracts/isolation & purification , Seeds/chemistry , Signal Transduction , Weight Gain/drug effects
4.
Mol Med Rep ; 14(5): 4692-4698, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27748836

ABSTRACT

Alternative medicine is a widely accepted therapeutic approach for the management of various diseases. The Korean medicine, musulju (MSJ), has been traditionally used to improve vital energy in men with reduced physical strength and a weakened urinary system. The present study determined the mechanisms underlying the protective effect of MSJ against benign prostatic hyperplasia (BPH), a common disorder in elderly men that involves inflammation­mediated imbalance between cell proliferation and death. MSJ treatment was demonstrated to decrease prostate weight, cell proliferation, and the protein expression of proliferating cell nuclear antigen in a rat model of BPH. In addition, MSJ markedly reduced serum testosterone levels, 5α­reductase2 mRNA expression and BPH­associated upregulation of inflammatory proteins, inducible nitric oxide synthase and cyclooxygenase 2. Furthermore, MSJ induced apoptosis by regulating B­cell lymphoma (Bcl)­2 protein expression and the Bcl­2:Bax ratio, leading to caspase 3 activation. Taken together, MSJ demonstrated antiproliferative effects in BPH model rats by regulating the expression levels of proteins involved in inflammation and apoptosis. The effects of MSJ may be attributed to its alternative therapeutic properties.


Subject(s)
Apoptosis/drug effects , Inflammation/metabolism , Inflammation/pathology , Medicine, Korean Traditional , Plant Extracts/pharmacology , Prostatic Hyperplasia/metabolism , Prostatic Hyperplasia/pathology , 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/metabolism , Animals , Cell Proliferation/drug effects , Inflammation/drug therapy , Inflammation Mediators/metabolism , Male , Organ Size/drug effects , Prostatic Hyperplasia/drug therapy , Rats , Testosterone/blood , Testosterone/metabolism
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