Abstract
Stachydrine, a major bioactive alkaloid extracted from Leonurus heterophyllus, is a key component of traditional herbal medicine, recognized for its anti-inflammatory and antioxidant properties. In this study, we investigated the gastroprotective effects of stachydrine and its underlying mechanisms in a mouse model of indomethacin (IND)-induced gastric injury. Mice were intragastrically administered IND at a dose of 40 mg/kg, followed 30 min later by treatment with varying doses of stachydrine (0, 5, and 10 mg/kg). Six hours post-IND administration, animals were sacrificed for further analysis. The results demonstrated that stachydrine treatment effectively attenuated IND-induced acute gastric injury, as evidenced by reduced gastric myeloperoxidase activity, and pro-inflammatory cytokine production (TNF-α, IL-6, and IL-1β). Stachydrine also significantly decreased gastric malondialdehyde activity while enhancing superoxide dismutase activity. Furthermore, it suppressed the expression of extracellular signal-regulated kinase (ERK), protein kinase B (AKT), and inducible nitric oxide synthase (iNOS) expressions. These findings indicate that stachydrine confers gastroprotection against IND-induced gastric injury, potentially by suppressing inflammatory and oxidative stress responses, inhibiting the ERK, AKT and iNOS signaling pathways. Thus, stachydrine may serve as a promising candidate for the treatment of IND-induced gastric injury.
Data availability
All data supporting the findings of this study are available within the paper and its Supplementary Information.
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Funding
This work was supported in part by grants from the National Science Council (MOST 112-2314-B-182 A-137-) and Chang Gung Memorial Hospital (CMRPG3L1661-3, CMRPG3M1631-3) to Fu-Chao Liu, and Chang Gung Memorial Hospital (CMRPG3M1831) to Chia-Chih Liao.
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L.F.C., Y.H.P. and L.C.C. conceived and designed the experiments; L H.C. and L.H.T. performed the experiments; L.F.C and L.H.C. contributed to the statistical data analysis; L.F.C., Y.H.P, L.H.T. and L.C.C. wrote the manuscript; L.C.C. corrected the manuscript. All authors have read and approved the manuscript for publication.
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All animal procedures were reviewed and approved by the Institutional Animal Care and Use Committee of Chang Gung Memorial Hospital (Approval number: 2024120402). The experiments were conducted in strict compliance with the Animal Welfare Act and the National Institutes of Health Guide for the Care and Use of Laboratory Animals, and the study was conducted in accordance with the ARRIVE 2.0 guidelines.
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Liu, FC., Yu, HP., Lee, HC. et al. Gastroprotective and antioxidant effects of stachydrine against indomethacin-induced gastric injury via ERK, AKT and iNOS signaling pathways. Sci Rep (2026). https://doi.org/10.1038/s41598-026-38072-y
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DOI: https://doi.org/10.1038/s41598-026-38072-y
