{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T10:55:58Z","timestamp":1790592958357,"version":"4.1.0"},"reference-count":38,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T00:00:00Z","timestamp":1783209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003787","name":"Natural Science Foundation of Hebei Province","doi-asserted-by":"publisher","award":["H2023423003"],"award-info":[{"award-number":["H2023423003"]}],"id":[{"id":"10.13039\/501100003787","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Chronic atrophic gastritis (CAG) is a prevalent precancerous gastric disorder characterized by persistent inflammation, glandular atrophy, and progressive mucosal damage, for which effective multi-target therapeutic strategies remain insufficient. The Lian-Huo-Hua-Zhuo formula (LHHZ), a traditional Chinese herbal prescription, has demonstrated potential anti-inflammatory and gastrointestinal protective effects in clinical practice; however, its active constituents and mechanisms of action against CAG remain undefined. This study aimed to clarify the absorbed bioactive components of LHHZ and explore its therapeutic mechanism for CAG. Methods: Ultra-high-performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry was employed to identify the absorbed components of LHHZ in the gastric and intestinal tissues of mice. The therapeutic effects of LHHZ on CAG were assessed through histopathological staining, ultrastructural observation, and evaluation of serum and gastric functional indicators. Network pharmacology, molecular docking, and molecular dynamics simulations were integrated to predict the core targets and key signaling pathways, while the regulatory effects on the interleukin-17 (IL-17) signaling pathway were further validated by immunofluorescence staining, real-time quantitative polymerase chain reaction, and Western blotting. Additionally, 16S ribosomal RNA gene sequencing and targeted metabolomics were applied to investigate the effects of LHHZ on gut microbiota composition and short-chain fatty acid (SCFA) metabolism. Results: The results revealed that 55 and 48 absorbed components were identified in the gastric and intestinal tissues, respectively, predominantly derived from Coptis chinensis Franch. and Pogostemon cablin (Blanco) Benth. LHHZ significantly alleviated gastric mucosal lesions, reduced intestinal metaplasia, restored the ultrastructure of gastric mucosal cells, improved gastric functional indicators including pepsinogen I (PG I), pepsinogen II (PG II), and gastrin-17 (GAS-17), and decreased the levels of pro-inflammatory cytokines. Network pharmacology combined with in vitro and in vivo experiments demonstrated that the core bioactive components of LHHZ can target and regulate interleukin-1 beta (IL-1\u03b2) and tumor necrosis factor-alpha (TNF-\u03b1), attenuate activation of the IL-17 signaling pathway, and suppress the secretion of downstream pro-inflammatory factors. Furthermore, LHHZ enhanced the alpha diversity of gut microbiota, reduced the Firmicutes to Bacteroidetes (F\/B) ratio, restored the abundance of SCFA-producing bacteria such as Bacteroidales and Oscillospirales, and normalized the aberrant levels of eight SCFAs. Significant correlations were also observed between gut microbiota composition and SCFA metabolism. Conclusions: These findings suggest that LHHZ alleviates CAG by inhibiting inflammation via the IL-17 signaling pathway and by modulating the gut microbiota\u2013SCFA axis, thereby providing preclinical evidence supporting its further investigation and development for multi-target therapeutic strategies against CAG.<\/jats:p>","DOI":"10.3390\/ph19071043","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T08:05:38Z","timestamp":1783325138000},"page":"1043","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanism of Lian-Huo-Hua-Zhuo Formula in Alleviating Gastric Mucosal Inflammation in a Mouse Model of Chronic Atrophic Gastritis by Inhibiting the IL-17 Signaling Pathway"],"prefix":"10.3390","volume":"19","author":[{"given":"Xiaoxuan","family":"Mo","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, China"},{"name":"Hebei Technology Innovation Center of TCM Formula Preparations, Shijiazhuang 050200, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Fan","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, China"},{"name":"Hebei Technology Innovation Center of TCM Formula Preparations, Shijiazhuang 050200, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Jiaye","family":"Tian","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, China"},{"name":"Hebei Technology Innovation Center of TCM Formula Preparations, Shijiazhuang 050200, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Fengyue","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, China"},{"name":"Hebei Technology Innovation Center of TCM Formula Preparations, Shijiazhuang 050200, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Zeyang","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Hongyan","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, China"},{"name":"Hebei Technology Innovation Center of TCM Formula Preparations, Shijiazhuang 050200, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Jinhu","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, China"},{"name":"Hebei Technology Innovation Center of TCM Formula Preparations, Shijiazhuang 050200, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Jianming","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Guoxing","family":"Deng","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, China"},{"name":"Hebei Technology Innovation Center of TCM Formula Preparations, Shijiazhuang 050200, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Qiuhong","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, China"},{"name":"Hebei Technology Innovation Center of TCM Formula Preparations, Shijiazhuang 050200, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"25309","DOI":"10.1038\/s41598-024-75912-1","article-title":"Proteomic and serological markers for diagnosing cardia gastric cancer and precursor lesions in a Chinese population","volume":"14","author":"Li","year":"2024","journal-title":"Sci. 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