Study On The Inhibitory Effect And Mechanism Of Two Kinds Of Natural Edible Pigments On Benign Prostatic Hyperplasia In Rats

Backgroud:Benign prostatic hyperplasia（BPH）is one of the most common progressive urinary system disease in elderly men.It can cause lower urinary tract symptoms,affect the quality of life of patients,and even threaten the life and health of patients in severe cases.Its histological definition refers to the excessive growth and proliferation of cells in the epithelial and mesenchymal transition zone and the anterior urethra of the prostate.At present,because of unclear molecular mechanism of BPH,the side-effect of therapeutic drugs for BPH and the increasing and younger incidence of BPH,the research of this disease is of great practical significance.There are two main drugs for the treatment of BPH.One type isα1-receptor antagonist,which can quickly relieve lower urinary tract symptoms,but does not inhibit the progression of BPH.Another is 5α-reductase inhibitors,such as finasteride,which can significantly inhibit the progression of BPH,but can affect male physiological functions and have drug resistance after long-term use.Therefore,plant preparations for BPH have attracted more and more attention.Through this research,it is found that active substances with strong antioxidant and anti-inflammatory effects can make good performance on prostate diseases.At the same time,many studies have also reported that a large number of natural edible pigments such as carotene,carotenoids,and flavonoids can not only impart attractive colors to food and drugs,but also exert powerful biological activities（such as antioxidant,anti-inflammatory,anti-proliferative,and antibacterial activities,etc）.Purpose:This topic is to study the inhibitory effect of two kinds of natural edible pigments（lycopene and curcuma）on BPH from vitro and vivo,and to explore its mechanism of this therapy.From the research,I hope it can provide new raw materials for medicines or health products for BPH,and provides a theoretical basis for the prevention and treatment of BPH.Contents and results:（1）Literature research:Through literature research,the pathogenesis of BPH and the current research status of treatment drugs for BPH were reviewed,and the target natural edible pigments lycopene and curcuma（curcumin and curcuma oil）were determined.And I also outline the structure and biological activity of lycopene（Ly）,curcumin（Cur）and curcuma oil（CO）.（2）Cell experiment:The CCK-8 kits were used to determine the inhibitory effects of Ly,Cur and CO on the proliferation of BPH-1 cells.The three substances have obvious inhibitory effects on BPH-1 cells,IC₅₀（Ly）is 400μg/m L,IC₅₀（Cur）is7.5μg/m L,IC₅₀（CO）is 40μg/m L.At the same time,compared with Hacat cells（representing normal cells）,none of the three substances showed obvious toxicity to Hacat cells at their half-inhibitory concentration.The Annexin V/PI assay was used to determine the inducing effect of CO on apoptosis of BPH-1 cell.When the concentration of CO is 40μg/m L,the total apoptosis rate of BPH-1 cells is 62.0±4.7%.（3）Animal experiment:250-300 g SD male rats were used for the experiment,After castration,we build a benign prostatic hyperplasia model by subcutaneous injection of testosterone propionate（5 mg/kg/sc）for 4 consecutive weeks.Then we treated the rats with Ly,Cur and CO by intragastric administration for another 4weeks,while the modeling operation is uninterrupted.Results:Through calculation of prostate index and histopathological analysis,it is proved that Ly,Cur and CO have obvious effects of inhibiting benign prostatic hyperplasia in vivo.（4）Mechanism research:Enzyme-linked immunosorbent assay,proteochemistry and immunoblotting experiments are mainly used to study the therapeutic mechanism.In this experiment,we detected many indicators including the hormone pathway indicators（dihydrotestosterone,5α-reductase）,proliferation and apoptosis pathway indicators（Ki67,CASP-8,-9,-3,Bc L-2,Bax）inflammation pathway indicators（IL-1β,IL-6,COX-2,i NOS,TNF-α）and NF-κB signaling pathway（P65,p-P65）.It is finally determined that Ly can regulate cell proliferation and apoptosis to inhibit the progression of BPH.Cur can reduce inflammation to inhibit the progression of BPH.And for CO,it can regulate hormones in the body and inhibit 5α-reductase pathway and NF-κB signaling pathway to treat BPH.