Study On The Mechanism Of Jie Yu Xing Yang Tang Improving Erectile Dysfunction Induced By Risperidone Based On Metabolomics

ObjectiveSchizophrenia(SP)is one of the most serious psychiatric disorders with a global prevalence of nearly 1% and a lifetime prevalence of 25%,with a higher prevalence in men than in women.Antipsychotic drugs(APDs)are the main clinical treatment for SP.A common side effect of APDs is erectile dysfunction(ED)in men.Studies have shown that82% of male SP patients taking APDs experience sexual dysfunction,the most significant symptom of which is ED.ED associated with APDs increases the psychological burden of patients,decreases compliance with APDs and increases the risk of disease recurrence.This study was conducted to further clarify the possible mechanism of action of Jie Yu Xing Yang Tang in the treatment of ED by plasma metabolomics analysis,so as to improve the quality of life of SP patients,improve the compliance of APDs medication,and provide scientific basis for the clinical application of Jie Yu Xing Yang Tang.MethodsAll subjects were from 27 male schizophrenic patients on risperidone admitted to the closed male ward of the Affiliated Brain Hospital of Guangzhou Medical University,Guangzhou City,Guangdong Province,China,from May 2020 to September 2022.All schizophrenia patients who met the inclusion criteria were treated with risperidone and were stable on the basis of taking Jie Yu Xing Yang Tang Chinese herbal soup for 4weeks.Nocturnal Penile Tumescence(NPT),Positive and Negative Symptom Scale(PANSS),and plasma metabolite LC-MS/MS assays were performed at 0 and 4 weeks of herbal treatment.Subjects were divided into 2 groups for further analysis of improvement in erectile function after 4 weeks of treatment with Jie Yu Xing Yang Tang.The group with improvement in both erection strength and frequency was divided into the superior remission(SR)group and the group with improvement in erection frequency only was the inferior remission(IR)group.SPSS 22.0 software was used to analyze the data.The Kolmogorov-Smirnov method was used to test the normality of the data.Data conforming to a normal or approximately normal distribution were expressed as ?± using the t-test,and data not conforming to a normal distribution were expressed as M(P25,P75)using the nonparametric test.Frequency and proportional data were tested using the chi-square test.Differential metabolites were screened using partial least squares discriminant analysis(PLS-DA),orthogonal partial least squares discriminant analysis(OPLS-DA),and differential metabolites were analyzed using Fold Change Analysis(FC Analysis),Hierarchical Clustering,and Pearson correlation analysis.Resultsa.All subjects were monitored for NPT at 0 and 4 weeks,and the erection strength in the out-group was greater than the median erection strength in the in-group at(50% vs40%),and the difference between the two groups was statistically significant(Z=-2.392,p=0.017<0.05),and the number of erections in the out-group was also better than the median number of erections in the in-group at(5 vs 4),and the difference between the two groups was also statistically significant(Z=4.322,p<0.0001);b.Partial least squares discriminant analysis(PLS-DA)and orthogonal partial least squares discriminant analysis(OPLS-DA)showed that after 4 weeks of treatment with Jie Yu Xing Yang Tang,the subjects had significant changes in plasma differential metabolites,and the difference in plasma differential metabolites between the SR,and IR groups was significant;c.The data were screened and processed using MSDIAL software,and the data were analyzed according to the multiplicity of variance(FC Analysis),t-test,and the number of erections.analysis(FC Analysis),t-test,and OPLS-DA model to obtain variable weight values(VIP)to screen metabolites and analyze metabolite changes,and determine that the nicotinamide metabolic pathway and the pentose phosphate pathway may be associated with Risperidone-induced erectile dysfunction treated with Jie Yu Xing Yang Tang.Conclusionsa.Jie Yu Xing Yang Tang can improve the generation of erectile dysfunction in male patients with schizophrenia caused by risperidone.b.The plasma metabolites LC-MS/MS suggest that Jie Yu Xing Yang Tang may play a role in regulating erectile function in schizophrenia patients by modulating the nicotinamide pathway and pentose phosphate pathway in patients.