Efficacy and potential mechanisms of jatrorrhizine on MNNG-induced chronic atrophic gastritis in rats based on serological metabolomics and molecular docking
Abstract Jatrorrhizine (JATR), a natural isoquinoline alkaloid from Coptidis Rhizoma, exhibits various pharmacological activities, including antibacterial, anti-inflammatory, and antitumor effects. While JATR is known to treat chronic gastritis, its therapeutic potential for chronic atrophic gastrit...
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Nature Portfolio
2025-07-01
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| author | Zong-ge Sha Sen Lin Zhi-liang Fan Ze-Chun Yang Ye-tao Gong Tao Qin Rong Yu Yong He |
| author_facet | Zong-ge Sha Sen Lin Zhi-liang Fan Ze-Chun Yang Ye-tao Gong Tao Qin Rong Yu Yong He |
| author_sort | Zong-ge Sha |
| collection | DOAJ |
| description | Abstract Jatrorrhizine (JATR), a natural isoquinoline alkaloid from Coptidis Rhizoma, exhibits various pharmacological activities, including antibacterial, anti-inflammatory, and antitumor effects. While JATR is known to treat chronic gastritis, its therapeutic potential for chronic atrophic gastritis (CAG) and its underlying mechanisms are not fully understood. This study induced CAG in rats using N-Methyl-N′-nitro-N-nitrosoguanidine (MNNG) for 12 weeks through free drinking and force-feeding. Serological metabolomics identified 23 core targets of JATR related to CAG improvement. Reverse transcription-quantitative polymerase chain reaction and western blotting confirmed the involvement of these targets. Molecular docking revealed interactions between JATR and IL-1β and Caspase-3. JATR significantly alleviated gastric inflammation and atrophy, with Kyoto Encyclopedia of Genes and Genomes analysis showing enrichment in the “Nod-like receptor-related pyroptosis pathway”. JATR also enhanced GES-1 cell proliferation and reduced MNNG-induced cell damage. Additionally, JATR downregulated pyroptosis-related (Gasdermin D, NLRP3, Caspase-1) and apoptosis-related (Bcl-2, Bax, Caspase-3) markers. These findings suggest that JATR may ameliorate MNNG-induced CAG by inhibiting the activation of the Nod-like receptor-related pyroptosis pathway, supporting its potential as a therapeutic intervention for CAG. |
| format | Article |
| id | doaj-art-020708476a6f46b0b5845fa82c15c640 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
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| spelling | doaj-art-020708476a6f46b0b5845fa82c15c6402025-08-20T03:03:37ZengNature PortfolioScientific Reports2045-23222025-07-0115111410.1038/s41598-025-05502-2Efficacy and potential mechanisms of jatrorrhizine on MNNG-induced chronic atrophic gastritis in rats based on serological metabolomics and molecular dockingZong-ge Sha0Sen Lin1Zhi-liang Fan2Ze-Chun Yang3Ye-tao Gong4Tao Qin5Rong Yu6Yong He7Basic Medical School, Guizhou University of Traditional Chinese MedicineDepartment of Pharmacy, Chongqing Rongchang Hospital of Traditional Chinese MedicineBasic Medical School, Guizhou University of Traditional Chinese MedicineDepartment of Pharmacy, Chongqing Rongchang Hospital of Traditional Chinese MedicineDepartment of Pharmacy, Chongqing Rongchang Hospital of Traditional Chinese MedicineDepartment of Pharmacy, Chongqing Rongchang Hospital of Traditional Chinese MedicineDepartment of Obstetrics and Gynecology, Chongqing Rongchang Hospital of Traditional Chinese MedicineDepartment of Pharmacy, Chongqing Rongchang Hospital of Traditional Chinese MedicineAbstract Jatrorrhizine (JATR), a natural isoquinoline alkaloid from Coptidis Rhizoma, exhibits various pharmacological activities, including antibacterial, anti-inflammatory, and antitumor effects. While JATR is known to treat chronic gastritis, its therapeutic potential for chronic atrophic gastritis (CAG) and its underlying mechanisms are not fully understood. This study induced CAG in rats using N-Methyl-N′-nitro-N-nitrosoguanidine (MNNG) for 12 weeks through free drinking and force-feeding. Serological metabolomics identified 23 core targets of JATR related to CAG improvement. Reverse transcription-quantitative polymerase chain reaction and western blotting confirmed the involvement of these targets. Molecular docking revealed interactions between JATR and IL-1β and Caspase-3. JATR significantly alleviated gastric inflammation and atrophy, with Kyoto Encyclopedia of Genes and Genomes analysis showing enrichment in the “Nod-like receptor-related pyroptosis pathway”. JATR also enhanced GES-1 cell proliferation and reduced MNNG-induced cell damage. Additionally, JATR downregulated pyroptosis-related (Gasdermin D, NLRP3, Caspase-1) and apoptosis-related (Bcl-2, Bax, Caspase-3) markers. These findings suggest that JATR may ameliorate MNNG-induced CAG by inhibiting the activation of the Nod-like receptor-related pyroptosis pathway, supporting its potential as a therapeutic intervention for CAG.https://doi.org/10.1038/s41598-025-05502-2JatrorrhizineNL family pyrin domain containing 3Caspase-3Chronic atrophic gastritisMNNGMolecular docking |
| spellingShingle | Zong-ge Sha Sen Lin Zhi-liang Fan Ze-Chun Yang Ye-tao Gong Tao Qin Rong Yu Yong He Efficacy and potential mechanisms of jatrorrhizine on MNNG-induced chronic atrophic gastritis in rats based on serological metabolomics and molecular docking Scientific Reports Jatrorrhizine NL family pyrin domain containing 3 Caspase-3 Chronic atrophic gastritis MNNG Molecular docking |
| title | Efficacy and potential mechanisms of jatrorrhizine on MNNG-induced chronic atrophic gastritis in rats based on serological metabolomics and molecular docking |
| title_full | Efficacy and potential mechanisms of jatrorrhizine on MNNG-induced chronic atrophic gastritis in rats based on serological metabolomics and molecular docking |
| title_fullStr | Efficacy and potential mechanisms of jatrorrhizine on MNNG-induced chronic atrophic gastritis in rats based on serological metabolomics and molecular docking |
| title_full_unstemmed | Efficacy and potential mechanisms of jatrorrhizine on MNNG-induced chronic atrophic gastritis in rats based on serological metabolomics and molecular docking |
| title_short | Efficacy and potential mechanisms of jatrorrhizine on MNNG-induced chronic atrophic gastritis in rats based on serological metabolomics and molecular docking |
| title_sort | efficacy and potential mechanisms of jatrorrhizine on mnng induced chronic atrophic gastritis in rats based on serological metabolomics and molecular docking |
| topic | Jatrorrhizine NL family pyrin domain containing 3 Caspase-3 Chronic atrophic gastritis MNNG Molecular docking |
| url | https://doi.org/10.1038/s41598-025-05502-2 |
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