Gastrointestinal symptoms in Parkinson's disease treated in a controlled trial using traditional Chinese medicine (Jia-Wei-Ji-Chuan-Jian decoction) with network pharmacology analysis of active agents and mechanism of action.

BACKGROUND

Gastrointestinal symptoms in Parkinson's disease (PD), in particular chronic constipation, are common and are treated in China using the traditional Chinese medicine (Jia-Wei-Ji-Chuan-Jian decoction) (JWJCJ)). However, information on therapeutic targets and the underlying mechanism is limited.

MATERIALS AND

METHODS

A total of 72 PD patients with constipation attending Departments of Neurology in Shanghai, China (Shanghai Pudong New Area Gongli Hospital and Shuguang Hospital Affiliated to Shanghai University) were recruited into the study and allocated to a Treatment group (n = 36) and a Control group (n = 36). Patients in the Control group received a combination treatment comprising anti-Parkinson agents (Western drug regimen) with the addition of a traditional Chinese patent medicine (Huang-Xing Run-Chang Tablets*) over a period of 5 weeks, whereas patients in the Treatment group received the same anti-PD Western drug regimen together with the JWJCJ decoction, also for a period of 5 weeks. An evaluation using clinical efficacy scores was carried out together with network pharmacology analysis. Identified drug targets for JWJCJ using the traditional Chinese medicine Swiss Target Prediction database (TCMSP) and disease targets for chronic constipation in PD were obtained from Genecards and the OMIM database. Therapeutic targets for JWJCJ in the treatment of chronic constipation were identified by intersecting drug targets and disease targets. GO functional enrichment analysis, KEGG pathway analysis, and disease association analysis were carried out using the DAVID database and visualized using Cytoscape 3.9.1 software.

RESULTS

CSS efficacy scores in the Treatment group were higher than that in the Control group (88.57 vs. 52.94%, p < 0.001). No significant differences were seen prior to treatment in the CSS, PDQ-39 and MDS-UPDRS scores and the corresponding total scores for the two groups. After treatment, CSS values for patients in the Treatment group were higher than values before treatment (p < 0.01). Network pharmacology analysis identified 172 active components, 9,542 drug targets, and 421 intersecting target genes for JWJCJ. PPI analysis identified 10 main and possibly key targets for JWJCJ in the treatment of chronic constipation. KEGG analysis identified 198 signaling pathways, where pathways in cancer, specific cancer pathways such as prostate cancer and non-small cell lung cancer, lipid and atherosclerosis, hepatitis B, and the AGE-RAGE signaling pathway in diabetic complications were among the pathways most significantly enriched. These findings are evidence that the active ingredients in JWJCJ in the treatment of chronic constipation in PD mainly target TP53, SRC, AKT1, PIK3R1, and PIK3CA.

CONCLUSION

The efficacy of JWJCJ in treating chronic constipation in PD involves the targets SRC, PIK3R1, JUN, TP53, STAT3, PIK3CA, EGFR, ESR1, MAPK1, and AKT1 domains. These findings provide theoretical basis for the clinical application of JWJCJ decoction in the treatment of chronic constipation in PD.