A Study Of Yunnan Baiyao’ Effect On Rats With Chronic Prostatitis And Its Underling Mechanisms

Background Chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS)may be one of most common problem in men younger than 50 years old in urology out-patient.CP/CPPS approximately account for 90-95% of prostatitis.Approximately 8.2% of men of all ages suffer from CP/CPPS,which has caused severe effect on quality of life and great economic burden for society.The real reason of CP/CPPS is unknown,multiple etiology theory is common acknowledged.Infection,inflammation and aberrant pelvic muscle tense cause nerve change.The traditional marker of CP/CPPS,small particles of lecithine and white blood cell count in EPS,didn’t reveal the disease quite well.NF-k B,one kind nucleus transcriptional factor,is extensively involved in to inflammation response and immune system.NF-k B accepts stimulus and turns to activation which accelerates secretion of pro-inflammation cytokine,such as TNF-αand IL-1β.Cytokines,such as IL-6,IL-8,IL-1β and TNF-α et al were found excessive in semen and expressed prostate secretions(EPS)in CP/CPPS patients,which means unbalance of cytokine may be involved into CP/CPPS.Because of undefined pathogenesis,the therapeutic choice is limited for CP/CPPS.Objective Here we try to figure out the effect of Yunnan Baiyao on chronic prostatitis and its underlying mechanisms.To determine whether cytokines in urine or EPS are good marker for CP/CPPS.Materials and Methods: The first part: because CP/CPPS is one of main reasons for elevated PSA level in young men.Besides,Yunnan Baiyao is supposed to have function of anti-inflammation.Therefore,we applied creatively PSA as marker of treatment.In this randomized,prospective and non-blinded clinical trial,we recruited eligible 96 CP/CPPS patients who were with PSA level of 4-20ng/ml for non-malignant disease in our center.All patients were treated with Yunnan Baiyao for 6 months.PSA tests,digital rectal examination(DRE)and ultrasonography(US)were conducted and compared in the following 1,2,3,6 month。 The second part:48 adult male Sprague Dawley rats were equally randomized assigned to group A and B.Group A and B were further divided into control,prostatitis model,high dose and low dose four subgroups respectively.Rats in the latter three subgroups were induced chronic non-bacteria prostatitis by injecting completely Freund’s adjuvant into prostates and treated with saline,800mg/kg and 400mg/kg Yunnan Baiyao per day accordingly.Rats in group A and B were retained for 2 and 4 weeks respectively.Pathology results of prostates and expressions of IL-1β,IL-6,TNF-α and COX-2 in prostate tissue were evaluated.THP-1 cells were stimulated with 1ug/ml LPS to induce inflammation and subsequently treated with a series concentration of 10ug/ml,50ug/ml,100ug/ml and 200ug/ml Yunnan Baiyao.NF-k B,Phospho-NF-k B,IL-1β and TNF-α were evaluated by western blot.Results: The first part: The average level of PSA before treatment with Yunnan Baiyao is 9.166+4.091ng/ml.PSA level was reduced to 7.988+3.326 ug/ml、8.718+4.803 ug/ml、7.390+2.703 ug/ml、7.110+2.525 ug/ml after treated with Yunnan Baiyao for 1,2,3,6 months.The average PSA decreased significantly compared with baseline value after a course of 6 months treatment,with a change of-2.05ng/ml,about a reduction rate of 22.2%(p<0.05).The second part: Injecting CFA into prostate lead to amounts of leucocytes,macrophages and fibroblasts infiltrating to the stroma of prostates.After treatment with YNBY,the number of inflammatory cells decreased significantly.YNBY treatment also lead to inhibition of IL-1β,IL-6 and TNF-a expressions in prostate tissue.LPS caused up-regulation of Phospho-NF-k B,IL-1β and TNF-α in THP-1 cells.However,YNBY down-regulated Phospho-NF-k B and IL-1β and TNF-α expressions in THP-1 cells.Conclusion: 1.CP/CPPS is one of main reason for elevated PSA level in young men.Yunnan Baiyao may contribute to decline of elevated PSA about 20% caused by non-malignant lesions,which may be due to its function of anti-inflammation property 2.Yunnan Baiyao can alleviate chronic inflammation in rats’ prostates by suppression of cytokine expressions(TNF-α,IL-1β and IL-6).Meanwhile,Yunnan Baiyao inhibits activation of NF-k B in THP-1 induced with LPS,which may be the underling mechanism of Yunnan Baiyao’ anti-inflammation property.3.Geven that pro-inflammation cytokines such as TNF-α,IL-1β and IL-6 were detected higher in prostate of rats with CP/CPPS,it means that cytokines in EPS or urine may be promising maker to evaluate CP/CPPS in clinical practice in the future.