Study On Pharmacodynamics And Mechanism Of Inhibitory Effect Of Xanthoceras Sorbifolium Flower Extract On Benign Prostatic Hyperplasia In Rats

AIM:A quantitative analysis method for the chemical constituents of Water Extract?WE?and Ethanol Extract?EE?of Xanthoceras Sorbifolia Flower was established,the half Lethal Dose?LD50?and the maximum dose was determined,at the same time,evaluate the mechanism of WE and EE inhibition of prostate hyperplasia as a whole.METHODS:1.Quantitative analysis of chemical constituents:Extracts of Xanthoceras Sorbifolia flowers were extracted with distilled water and ethanol,respectively.UV-Vis was used to determine the polysaccharides and total flavonoids in WE and EE.2.Acute toxicology test:The general acute toxicology test method is used to evaluate the toxicity of WE and EE,and the LD₅₀ is predicted according to different gradient design doses.The maximum dose is estimated by combining with the LD₅₀ data.3.Study on the pharmacodynamics and preliminary molecular mechanism of water extract and alcohol extract of Xanthoceras Sorbifolia flower on BPH animal models:66 male Wistar rats were induced by subcutaneous injection of Testosterone Propionate?TP?in rats Model,the prostate index and serum DHT evaluation model were used for 4 consecutive weeks.Rats with successful modeling were randomly divided into model group?M?,positive control group?P,10mg/kg?,Xanthoceras Sorbifolia flower water extract high dose group?WEH,480mg/kg?,Xanthoceras Sorbifolia flower water Low-dose extract group?WEL,120mg/kg?,high-dose ethanol extract group?EEH,550mg/kg?,high-dose ethanol extract group?EEL,140mg/kg?.Normal rats were the normal control group?N?,with 8 rats in each group.After 1 week of modeling,preventive administration was given by intragastric administration once a day for 28 consecutive days.On day 29,mice in each group were anesthetized with chloral hydrate,and serum and prostate tissues were taken.The detection indicators are as follows:?1?Record the trend of weight change during administration;?2?Compare the prostate tissue of each group visually and observe the changes of the prostate index?PI?;?3?HE staining to observe the epithelium and interstitial of prostate tissue in each group;?4?Determination of DHT content in serum and prostate homogenate by enzyme-linked immunoassay?ELISA?;?5?Determination of inflammatory factors such as IL-6,IL-8,TNF-?in prostate homogenate by ELISA method;?6?ELISA method to determine prostate specific antigen?PSA?content;?7?Immunohistochemistry?IHC?analysis of the distribution of VEGF-A and b FGF in prostate tissues,and semi-quantitative prediction of their content in each group;?8?Western blotting?WB?was used to detect the expression of proliferating cell nuclear antigen?PCNA?in prostate tissue of each group.RESULTS:1.UV-Vis analysis results:WE polysaccharide content was 9.12%,total flavonoid content was 4.30%;EE polysaccharide content was 4.68%,total flavonoid content was 5.67%.2.The results of the acute toxicology test showed that maximum dose is greater than 30g/kg,and WE and EE are considered to have no significant toxicity at this dose.3.The efficacy and preliminary molecular mechanism of WE and EE on BHP rats are as follows:?1?The weight generally increased with the extension of the administration period.Compared with the N group,the weight of the M group showed an upward trend,but the weight change was not statistically significant?P>0.05?.Compared with the M group,each group also showed There was an upward trend,but there was a downward trend in the P group,WEH group,WEL group,and EEL group at the fourth week.The EEL group was statistically significant?P<0.05?,and the other groups were not statistically significant?P>0.05?.?2?Compared with the N group,TP can significantly increase the prostate index of rats,and there is a significant difference?P<0.01?,indicating that the modeling was successful;compared with the M group,each extract group of Fructus Xanthoceras flower inhibited the prostate index.And significant difference?P<0.01,P<0.05?.?3?Compared with the N group,the interstitial components of the M group were significantly increased,the acinar volume was increased,the glandular epithelial cells were disordered,and the nodular tissue proliferation was obvious;compared with the M group,the interstitial components of the WEH and Eeh groups were reduced The disorder of small,glandular epithelial cell sorting is alleviated to varying degrees,and there are a small number of densely arranged acinar cells.?4?Compared with the N group,the DHT in serum and prostate tissues of the M group were increased and statistically significant?P<0.01?.This result indicates that the modeling was successful;compared with the M group,the DHT content of each extract was reduced.And there was statistical significance?P<0.01,P<0.05?.?5?Compared with the N group,the levels of IL-6,IL-8 and TNF-?in the M group were all increased and statistically significant?P<0.01?;compared with the M group,the P group and EEE group The IL-6 levels in the EEL and EEL groups had a downward trend and were statistically significant?P<0.05?,and the other groups were not statistically significant?P>0.05?.Compared with the M group,the IL-The content of 6 decreased significantly and was statistically significant?P<0.01?,and the rest of the groups were not statistically significant?P>0.05?.Compared with the M group,the TNF-?content in the P group,WEH group,and EEE group decreased and showed a trend.Statistical significance?P<0.05?,the other groups were not statistically significant?P>0.05?.?6?Compared with the N group,the PSA content in the M group was higher than that in the N group and was statistically significant?P<0.05?;compared with the M group,the PSA levels in the other groups had a downward trend,but there was no statistical significance?P>0.05?.?7?Compared with the N group,the positive expression of VEGF-A protein in the M group was significantly increased and the difference was statistically significant?P<0.01?;compared with the M group,the P group,WEH group,WEL group,Eeh group and The positive expression of VEGF-A protein in the EEL group decreased significantly,all with statistical significance?P<0.05?.Compared with the N group,the positive expression of b GFG protein in the M group was significantly increased and the difference was statistically significant?P<0.001?;compared with the M group,the b GFG protein was positive in the P group,WEH group,WEL group,Eeh group,and EEL group The expression levels were significantly decreased and were statistically significant?P<0.05,P<0.01,P<0.001?.?8?Compared with the N group,the expression of PCNA protein in the prostate tissue of the M group increased significantly and was statistically significant?P<0.01?;compared with the M group,the expression of PCNA protein in the prostate tissue of each group will now trend,The P group,WEH group,and EEE group showed a significant downward trend,with statistical significance?P<0.01,P<0.05?,and the other groups were not statistically significant?P>0.05?.CONCLUSION:Xanthoceras Sorbifolia Flower is a non-medicinal part other than the traditional medicinal parts of Mongolian medicine.Based on the research of folk medicine,the new medicinal value of Xanthoceras Sorbifolia Flower not only makes the Mongolian medicine resources sustainable,but also expands its medicinal value and reduces non-medicine waste of parts.Related studies have also found that extracts of Xanthoceras Sorbifolia Flower can play a medicinal effect by inhibiting prostate hyperplasia,there by providing a preliminary scientific basis for the treatment or prevention of BPH.