Study On Mechanism And Active Constituents Of Zi-Shen Pill Against Benign Prostatic Hyperplasia (BPH)

Benign prostatic hyperplasia (BPH) is an extremely common medical condition that can expect to affect most men as they age and have a significant negative impact on the quality of life. Many kinds of medicines are prevalent in treating BPH, such as 5α-reductase inhibition, alpha-1-adrenoceptor antagonist. Although these drugs often achieve excellent treatment results, their side effects should not be overlooked. Thus, the prescriptions of Traditional Chinese Medicine (TCM), which may exhibit similar efficacy and have less harmful side effects, are being paid more attention.The Zi-Shen Pill (ZSP) was originally reported in the Secret Record of the Chamber of Orchids, which was wrote by Li Gao (1279~1368AD) who lived in Yuan Dynasty of China. The pill contained Anemarrhena asphodeloides Bge (Liliaceae, rhizome), Phellodendron amurense Rup. (Rutaceae, bark) and Cinnamomum cassia Presl (camphoraceae,bark) with a ration of 10 : 10 : 1 in weight.ZSP is traditionally being used to treat BPH, prostatitis or frequent urination by the kidney-tonifing and pass dredging method and has gotten a quite good effect. However, the experimental study and the mechanism of ZSP on BPH has not been reporeted.In this study, the in vivo effects of an extract of ZSP on BPH were investigated in rats induced by testosterone after castration. Also testosterone, DTH , VEGF,bFGF and TGF-βwere measured because androgens (testosterone and related hormones) and polypeptide growth factors such as VEGF,bFGF and TGF-βare considered to play important roles in the development of BPH. It was shown that ZSP significantly reduced the prostate weight, prostatic index, and serum dihydrotestosterone (DHT) levels. ZSP also suppressed the pathological changes in BPH. Concomitantly, immunohistochemical examination revealed that the expressions of VEGF and bFGF in prostate were inhibited by ZSP treatment, whereas the levels of TGF-β1 were increased.Thus ZSP has a definite inhibition effect on BPH. ZSP extracts can depress the expression of bFGF and inflammatory response. ZSP extracts also may enhance the expression of TGF-β1 to induce cell apoptosis. All of these may be the major intrinsic mechanism of ZSP inhibition on BPH.As the ration of 10 : 10 : 1 in weight, herbs combination Anemarrhena asphodeloid -es Bge and Phellodendron amurense Rupr (ZB) was considered to be a major part of ZSP. Treatments with ZB extracts decreased the prostate weight and prostate index number (p<0.05; vs. model group).Total flavonoids , total saponins and total alkaloids are major chemical constituents from ZB. In our further study, treatments with Total flavonoids, total saponins and total alkaloids(3T) decreased the prostate weight and prostate index number (p<0.05; vs. model group). Prostate tissues proliferated lightly, VEGF and bFGF was weakly expressed in epithelial cells, TGF-β1 got a high expression.It is suggested that Total flavonoids , total saponin and total alkaloid has best inhibitory effect on BPH. The results of gene array showed: Tgfb1i1 that is related apoptosis in the 3T /model group was up-regulated (ratio>2); 8 genes related proliferation in the 3T /model group was down-regulated(ratio<0.5) such as Fgf1, Fgf21; 8 genes related to inflammatory response in the 3T /model were down-regulated(ratio<0.5) such as Il1b, Il1r1, Il1r2, Il4r.These findings suggest that 3T are major active constituents from ZB.