{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T20:20:09Z","timestamp":1778617209939,"version":"3.51.4"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T00:00:00Z","timestamp":1672790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Parkinson\u2019s disease is a neurodegenerative disorder involving loss of dopaminergic neurons. Multiple studies implicate the microbiota-gut-brain axis in Parkinson\u2019s disease pathophysiology. <jats:italic>Ping-wei-san plus<\/jats:italic> Herbal Decoction, a traditional Chinese medicine composition with beneficial effects in Parkinson\u2019s disease, may have a complex array of actions. Here we sought to determine whether gut microbiota and metabolic pathways are involved in <jats:italic>Ping-wei-san plus<\/jats:italic> herbal therapy for Parkinson\u2019s disease and to identify functional pathways to guide research.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>The model of Parkinson\u2019s disease were induced with the rotenone. The <jats:italic>Ping-wei-san plus<\/jats:italic> group received the PWP herbal decoction for 90 days, after which all groups were analyzed experimentally. PWP herbal treatment improved motor behavior and emotional performance, balanced gut microbiota, and benefited dietary metabolism. Tandem Mass Tags mass spectrometry identified many differentially expressed proteins (DEPs) in the substantia nigra and duodenum in the PWP group, and these DEPs were enriched in pathways such as those involving cAMP signaling, glutamatergic synapses, dopaminergic synapses, and ribosome-rich functions in the gut. The PWP group showed increases in recombinant tissue inhibitors of metalloproteinase 3, and nucleotide-binding oligomerization domain, leucine rich repeat, and pyrin domain containing proteins 6 in the substantia nigra and decreased parkin, gasdermin D, recombinant tissue inhibitors of metalloproteinase 3, and nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing proteins 6 in the duodenum.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>In conclusion, this study combined gut microbiota, metabolomics, and proteomics to evaluate the mechanism of action of <jats:italic>Ping-wei-san plus<\/jats:italic> on Parkinson\u2019s disease and revealed that PWP herbal treatment modulated gut microbiota, altered metabolite biological pathways, and affected functional pathway protein expression in Parkinson\u2019s disease mice, resulting in therapeutic 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