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The ancient Chinese medication for PD is Compound Dihuang Granule (CDG), and we found a neuroprotective function in treating the constipation of PD patients. Nevertheless, the mechanism of action still needs to be clarified. We predicted the probable targets of CDG against PD through Traditional Chinese medicine (TCM) network pharmacology and verified the analysis through animal experiments in vivo. The protein\u2013protein interaction (PPI) network analysis screened PD-related genes, including Toll-like receptor 4(TLR4), TANK-binding kinase 1(TBK1), Nuclear Factor- Kappa B (NF-\u03baB), and Tumor necrosis factor (TNF). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses proved that the NF-\u03baB and toll-like receptor signaling pathways serve a key function in CDG therapy of PD. Molecular docking analysis demonstrated that CDG strongly connected to TLR4\/NF-\u03baB. Experiments findings indicated that CDG improved the damage of dopaminergic neurons and gut microbial dysbiosis, ameliorated motor impairments, and suppressed the PD-associated inflammation and oxidative stress in mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahy dropyridine (MPTP). CDG suppressed the inflammatory proteins in the colon and protected the intestinal barrier. Overall, CDG improved gut microbial in PD by blocking the pathway of TLR4\/NF-\u03baB.<\/jats:p>","DOI":"10.1007\/s11064-023-04004-9","type":"journal-article","created":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T06:02:51Z","timestamp":1691647371000},"page":"3610-3624","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Compound Dihuang Granule Changes Gut Microbiota of MPTP-Induced Parkinson\u2019s Disease Mice via Inhibiting TLR4\/NF-\u03baB Signaling"],"prefix":"10.1007","volume":"48","author":[{"given":"Zhu-qing","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng-fei","family":"Huan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-cheng","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,8,10]]},"reference":[{"issue":"10291","key":"4004_CR1","doi-asserted-by":"publisher","first-page":"2284","DOI":"10.1016\/S0140-6736(21)00218-X","volume":"397","author":"BR Bloem","year":"2021","unstructured":"Bloem BR, Okun MS, Klein C (2021) Parkinson\u2019s disease. 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