Tormentic acid, a triterpenoid isolated from the fruits of Chaenomeles speciose, protected indomethacin-induced gastric mucosal lesion via modulating miR-139 and the CXCR4/CXCL12/PLC/PKC/Rho a/MLC pathway
CONTEXT: Tormentic acid (TA), an effective triterpenoid isolated from Chaenomeles speciosa (Sweet) Nakai (Rosaceae) fruits, exerts an effective treatment for gastric damage.
OBJECTIVE: To investigate the gastroprotective effect of TA on indomethacin (IND) damaged GES-1 cells and rats, and explore potential mechanisms.
MATERIALS AND METHODS: TA concentrations of 1.563-25 µM were used. Cell proliferation, apoptosis and migration were performed using MTT, colony formation, wound healing, migration, Hoechst staining assays. SD rats were divided into control, IND, TA (1, 2 and 4 mg/kg) + IND groups, once a day for 21 continuous days. Twenty-four hours after the last administration, all groups except the control group were given IND (100 mg/kg) by gavage. Gastric juice parameters, gastric ulcer, gastric blood flow (GBF), blood biochemical parameters and cytokine analysis and gastric mucosal histopathology were detected for 2 h and 6 h after IND oral administration. The mRNA and protein expression of miR-139 and the CXCR4/CXCL12/PLC/PKC/Rho A/MLC pathway were analyzed in the IND-damaged GES-1 cells and gastric tissue of rats.
RESULTS: TA might ameliorate the gastric mucosal injury by accelerating the IND-damaged GES-1 cell proliferation and migration, ameliorating GBF, ulcer area and pathologic changes, the redox system and cytokine levels, the gastric juice parameters, elevating the gastric pH in IND damaged rats; suppressed miR-139 mRNA expression, elevated CXCR4 and CXCL12 mRNA and protein expression, p-PLC, p-PKC, Rho A, MLCK and p-MLC protein expression.
DISCUSSION AND CONCLUSIONS: TA may have potential use as a clinical drug candidate for gastric mucosal lesion treatment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:61 |
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| Enthalten in: |
Pharmaceutical biology - 61(2023), 1 vom: 12. Dez., Seite 1343-1363 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
He, Jun-Yu [VerfasserIn] |
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| Links: |
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| Themen: |
CXCL12 protein, rat |
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| Anmerkungen: |
Date Completed 28.08.2023 Date Revised 30.08.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.1080/13880209.2023.2249526 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM361215614 |
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| 100 | 1 | |a He, Jun-Yu |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Tormentic acid, a triterpenoid isolated from the fruits of Chaenomeles speciose, protected indomethacin-induced gastric mucosal lesion via modulating miR-139 and the CXCR4/CXCL12/PLC/PKC/Rho a/MLC pathway |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 28.08.2023 | ||
| 500 | |a Date Revised 30.08.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a CONTEXT: Tormentic acid (TA), an effective triterpenoid isolated from Chaenomeles speciosa (Sweet) Nakai (Rosaceae) fruits, exerts an effective treatment for gastric damage | ||
| 520 | |a OBJECTIVE: To investigate the gastroprotective effect of TA on indomethacin (IND) damaged GES-1 cells and rats, and explore potential mechanisms | ||
| 520 | |a MATERIALS AND METHODS: TA concentrations of 1.563-25 µM were used. Cell proliferation, apoptosis and migration were performed using MTT, colony formation, wound healing, migration, Hoechst staining assays. SD rats were divided into control, IND, TA (1, 2 and 4 mg/kg) + IND groups, once a day for 21 continuous days. Twenty-four hours after the last administration, all groups except the control group were given IND (100 mg/kg) by gavage. Gastric juice parameters, gastric ulcer, gastric blood flow (GBF), blood biochemical parameters and cytokine analysis and gastric mucosal histopathology were detected for 2 h and 6 h after IND oral administration. The mRNA and protein expression of miR-139 and the CXCR4/CXCL12/PLC/PKC/Rho A/MLC pathway were analyzed in the IND-damaged GES-1 cells and gastric tissue of rats | ||
| 520 | |a RESULTS: TA might ameliorate the gastric mucosal injury by accelerating the IND-damaged GES-1 cell proliferation and migration, ameliorating GBF, ulcer area and pathologic changes, the redox system and cytokine levels, the gastric juice parameters, elevating the gastric pH in IND damaged rats; suppressed miR-139 mRNA expression, elevated CXCR4 and CXCL12 mRNA and protein expression, p-PLC, p-PKC, Rho A, MLCK and p-MLC protein expression | ||
| 520 | |a DISCUSSION AND CONCLUSIONS: TA may have potential use as a clinical drug candidate for gastric mucosal lesion treatment | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Gastric mucosal epithelial cells | |
| 650 | 4 | |a cell proliferation and migration | |
| 650 | 7 | |a tormentic acid |2 NLM | |
| 650 | 7 | |a Triterpenes |2 NLM | |
| 650 | 7 | |a Cytokines |2 NLM | |
| 650 | 7 | |a MicroRNAs |2 NLM | |
| 650 | 7 | |a CXCL12 protein, rat |2 NLM | |
| 650 | 7 | |a Chemokine CXCL12 |2 NLM | |
| 650 | 7 | |a MIRN139 microRNA, rat |2 NLM | |
| 700 | 1 | |a Li, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yuan-Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a He, Hai-Bo |e verfasserin |4 aut | |
| 700 | 1 | |a He, Yu-Min |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Dao-Xiang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xiao |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Hao-Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Ji-Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Jahid, Hasan |e verfasserin |4 aut | |
| 700 | 1 | |a Sadia, Akter |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Hui-Fan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jun-Zhi |e verfasserin |4 aut | |
| 700 | 1 | |a Zou, Kun |e verfasserin |4 aut | |
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