{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T14:29:29Z","timestamp":1779892169852,"version":"3.53.1"},"reference-count":79,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundamental Research Funds for the Central Public Welfare Research Institutes","award":["ZZ13-YQ-048"],"award-info":[{"award-number":["ZZ13-YQ-048"]}]},{"name":"Fundamental Research Funds for the Central Public Welfare Research Institutes","award":["ZZ15-WT-08"],"award-info":[{"award-number":["ZZ15-WT-08"]}]},{"name":"Fundamental Research Funds for the Central Public Welfare Research Institutes","award":["ZXKT21008"],"award-info":[{"award-number":["ZXKT21008"]}]},{"name":"Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences","award":["CI2023E001TS12"],"award-info":[{"award-number":["CI2023E001TS12"]}]},{"name":"Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences","award":["CI2024E003"],"award-info":[{"award-number":["CI2024E003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Chronic gastritis (CG) involves gastric mucosal imbalance, with H. pylori (&gt;90% cases), acid-pepsin imbalance, and bile reflux as druggable mechanisms. FDA-approved drugs show limited efficacy against antibiotic-resistant strains and fail to target undruggable pathways (e.g., inflammation, autoimmune atrophy). Traditional Chinese Medicine (TCM), particularly Qing-Wei-Zhi-Tong micro-pills (QWZT), offers multi-target advantages, though its mechanisms remain poorly understood. Methods: The dual-algorithm integration framework predicts QWZT\u2019s pharmacological effects to treat gastritis. For druggable processes (pathways targeted by existing drugs), the structure\u2013target\u2013pathway similarity algorithm quantifies QWZT similar activities to FDA drugs, validated by gastrointestinal smooth muscle experiments. For undruggable processes (novel biological mechanisms not addressed by current therapies), the multi-target perturbation algorithm predicts QWZT\u2019s unique capacity to undruggable processes and is validated via LPS-induced inflammation in RAW264.7 and GES-1 cells. Results: Structure\u2013target\u2013pathway similarity algorithm identified QWZT compounds sharing prokinetic mechanisms with FDA drugs, validated by dopamine-induced relaxations and acetylcholine-induced contractions in gastrointestinal smooth muscle. Multi-target perturbation algorithm quantified QWZT\u2019s superior disruption of undruggable immune\/inflammation networks, confirmed by restored cell viability in LPS-injured GES-1 cells and significantly reduced the expression of NO, IL-6, and TNF-\u03b1 in RAW264.7 cells via key compounds (paeoniflorin and berberine). Conclusions: QWZT may exert its regulatory effects on gastrointestinal smooth muscle by mediating muscarinic and dopamine receptor D2 (DRD2), and reduce the expression of NO, IL-6, and TNF-\u03b1 to achieve anti-inflammatory effects, thereby effectively treating CG. The integration strategy that integrates algorithms and experiments to reveal the common and distinct mechanisms of QWZT compared to FDA-approved drugs, offering a novel approach for studying Traditional Chinese Medicine mechanisms.<\/jats:p>","DOI":"10.3390\/ph18111743","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T14:04:07Z","timestamp":1763388247000},"page":"1743","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Dual-Algorithm Integration Framework Reveals Qing-Wei-Zhi-Tong\u2019s Dual Mechanisms in Chronic Gastritis"],"prefix":"10.3390","volume":"18","author":[{"given":"Zhijie","family":"Shu","sequence":"first","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Huang","sequence":"additional","affiliation":[{"name":"Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Xi","sequence":"additional","affiliation":[{"name":"Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jiangxi Province Key Laboratory of Traditional Chinese Medicine Pharmacology, Institute of Traditional Chinese Medicine Health Industry, China Academy of Chinese Medical Sciences, Nanchang 330115, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Cai","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3624-4704","authenticated-orcid":false,"given":"Feifei","family":"Guo","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"ref_1","first-page":"5189797","article-title":"Protective Effect of Ultraviolet C Irradiation on the Gastric Mucosa of Rats with Chronic Gastritis Induced by Physicochemical Stimulations","volume":"2021","author":"Wang","year":"2021","journal-title":"Evid.-Based Complement. 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