Network Pharmacology and Serum Nontargeted Metabolomics Reveal the Protective Effects of Propionate Against Liver Damage Induced by a High-Fat and AGE-Rich Diet in Diabetic Mice
Diabetic liver injury is a leading cause of mortality in diabetes, with no specific treatment available. Sodium propionate (NaP) has anti-inflammatory and antioxidant properties, but its effectiveness in treating diabetic liver injury is still lacking research. The study employed network pharmacolog...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-01-01
|
| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/jdr/3955893 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849702930671730688 |
|---|---|
| author | Liang Wu Jiajun Tan Wen Sun Xueyun Dong Jiayuan He Asmaa Ali Min Chen Leilei Zhang Pingping Wang |
| author_facet | Liang Wu Jiajun Tan Wen Sun Xueyun Dong Jiayuan He Asmaa Ali Min Chen Leilei Zhang Pingping Wang |
| author_sort | Liang Wu |
| collection | DOAJ |
| description | Diabetic liver injury is a leading cause of mortality in diabetes, with no specific treatment available. Sodium propionate (NaP) has anti-inflammatory and antioxidant properties, but its effectiveness in treating diabetic liver injury is still lacking research. The study employed network pharmacology to identify potential targets of NaP for Type 2 diabetes treatment, using oleic acid (OA) and advanced glycation end products (AGEs) to induce diabetic liver injury in HepG2 cells in vitro. Post-NaP intervention, Oil Red O staining assessed cellular lipid deposition, while Western blotting analyzed protein expression associated with oxidative stress, autophagy, and bile acid synthesis. NaP was administered to mice with diabetic liver injury induced by a high-fat and AGEs diet, and qPCR analysis was conducted to assess the expression of genes associated with inflammation, oxidative stress, and bile acid synthesis in the liver. HE staining was used to observe the liver injury, and nontargeted metabolomics analysis was used to analyze the effect of NaP on serum metabolic pathways. Network pharmacology analysis showed that NaP has anti-inflammatory and antioxidant effects, mainly involving multiple targets such as mitochondrial function, insulin resistance, and glucose metabolism. Experimental results in cells and animals demonstrated that NaP reduces lipid accumulation and inflammation in liver cells; decreases inflammatory markers like NLRP3, IL-1β, and TNF-α; enhances antioxidant factors such as serum SOD and liver Nrf2; increases the expression of the bile acid synthesis enzyme CYP7A1; and upregulates autophagy in liver cells. Serum nontargeted metabolomics indicated that NaP enhances anti-inflammatory and antioxidant metabolites, including proline and N-Acetyl-L-leucine, in diabetic liver injury mice. It potentially influences purine metabolism, amino acid synthesis (e.g., arginine, tryptophan, and tyrosine), and steroid hormone biosynthesis. This study indicates that NaP may serve as a preventive and therapeutic agent for diabetic liver injury. |
| format | Article |
| id | doaj-art-81406ab55be2476d9e4953aa4cd57fdd |
| institution | DOAJ |
| issn | 2314-6753 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-81406ab55be2476d9e4953aa4cd57fdd2025-08-20T03:17:27ZengWileyJournal of Diabetes Research2314-67532025-01-01202510.1155/jdr/3955893Network Pharmacology and Serum Nontargeted Metabolomics Reveal the Protective Effects of Propionate Against Liver Damage Induced by a High-Fat and AGE-Rich Diet in Diabetic MiceLiang Wu0Jiajun Tan1Wen Sun2Xueyun Dong3Jiayuan He4Asmaa Ali5Min Chen6Leilei Zhang7Pingping Wang8Department of Laboratory MedicineDepartment of Laboratory MedicineJurong Hospital Affiliated to Jiangsu UniversityDepartment of Laboratory MedicineHealth Testing CenterDepartment of Laboratory MedicinePublic Experiment and Service CenterDepartment of Laboratory MedicineDepartment of Laboratory MedicineDiabetic liver injury is a leading cause of mortality in diabetes, with no specific treatment available. Sodium propionate (NaP) has anti-inflammatory and antioxidant properties, but its effectiveness in treating diabetic liver injury is still lacking research. The study employed network pharmacology to identify potential targets of NaP for Type 2 diabetes treatment, using oleic acid (OA) and advanced glycation end products (AGEs) to induce diabetic liver injury in HepG2 cells in vitro. Post-NaP intervention, Oil Red O staining assessed cellular lipid deposition, while Western blotting analyzed protein expression associated with oxidative stress, autophagy, and bile acid synthesis. NaP was administered to mice with diabetic liver injury induced by a high-fat and AGEs diet, and qPCR analysis was conducted to assess the expression of genes associated with inflammation, oxidative stress, and bile acid synthesis in the liver. HE staining was used to observe the liver injury, and nontargeted metabolomics analysis was used to analyze the effect of NaP on serum metabolic pathways. Network pharmacology analysis showed that NaP has anti-inflammatory and antioxidant effects, mainly involving multiple targets such as mitochondrial function, insulin resistance, and glucose metabolism. Experimental results in cells and animals demonstrated that NaP reduces lipid accumulation and inflammation in liver cells; decreases inflammatory markers like NLRP3, IL-1β, and TNF-α; enhances antioxidant factors such as serum SOD and liver Nrf2; increases the expression of the bile acid synthesis enzyme CYP7A1; and upregulates autophagy in liver cells. Serum nontargeted metabolomics indicated that NaP enhances anti-inflammatory and antioxidant metabolites, including proline and N-Acetyl-L-leucine, in diabetic liver injury mice. It potentially influences purine metabolism, amino acid synthesis (e.g., arginine, tryptophan, and tyrosine), and steroid hormone biosynthesis. This study indicates that NaP may serve as a preventive and therapeutic agent for diabetic liver injury.http://dx.doi.org/10.1155/jdr/3955893 |
| spellingShingle | Liang Wu Jiajun Tan Wen Sun Xueyun Dong Jiayuan He Asmaa Ali Min Chen Leilei Zhang Pingping Wang Network Pharmacology and Serum Nontargeted Metabolomics Reveal the Protective Effects of Propionate Against Liver Damage Induced by a High-Fat and AGE-Rich Diet in Diabetic Mice Journal of Diabetes Research |
| title | Network Pharmacology and Serum Nontargeted Metabolomics Reveal the Protective Effects of Propionate Against Liver Damage Induced by a High-Fat and AGE-Rich Diet in Diabetic Mice |
| title_full | Network Pharmacology and Serum Nontargeted Metabolomics Reveal the Protective Effects of Propionate Against Liver Damage Induced by a High-Fat and AGE-Rich Diet in Diabetic Mice |
| title_fullStr | Network Pharmacology and Serum Nontargeted Metabolomics Reveal the Protective Effects of Propionate Against Liver Damage Induced by a High-Fat and AGE-Rich Diet in Diabetic Mice |
| title_full_unstemmed | Network Pharmacology and Serum Nontargeted Metabolomics Reveal the Protective Effects of Propionate Against Liver Damage Induced by a High-Fat and AGE-Rich Diet in Diabetic Mice |
| title_short | Network Pharmacology and Serum Nontargeted Metabolomics Reveal the Protective Effects of Propionate Against Liver Damage Induced by a High-Fat and AGE-Rich Diet in Diabetic Mice |
| title_sort | network pharmacology and serum nontargeted metabolomics reveal the protective effects of propionate against liver damage induced by a high fat and age rich diet in diabetic mice |
| url | http://dx.doi.org/10.1155/jdr/3955893 |
| work_keys_str_mv | AT liangwu networkpharmacologyandserumnontargetedmetabolomicsrevealtheprotectiveeffectsofpropionateagainstliverdamageinducedbyahighfatandagerichdietindiabeticmice AT jiajuntan networkpharmacologyandserumnontargetedmetabolomicsrevealtheprotectiveeffectsofpropionateagainstliverdamageinducedbyahighfatandagerichdietindiabeticmice AT wensun networkpharmacologyandserumnontargetedmetabolomicsrevealtheprotectiveeffectsofpropionateagainstliverdamageinducedbyahighfatandagerichdietindiabeticmice AT xueyundong networkpharmacologyandserumnontargetedmetabolomicsrevealtheprotectiveeffectsofpropionateagainstliverdamageinducedbyahighfatandagerichdietindiabeticmice AT jiayuanhe networkpharmacologyandserumnontargetedmetabolomicsrevealtheprotectiveeffectsofpropionateagainstliverdamageinducedbyahighfatandagerichdietindiabeticmice AT asmaaali networkpharmacologyandserumnontargetedmetabolomicsrevealtheprotectiveeffectsofpropionateagainstliverdamageinducedbyahighfatandagerichdietindiabeticmice AT minchen networkpharmacologyandserumnontargetedmetabolomicsrevealtheprotectiveeffectsofpropionateagainstliverdamageinducedbyahighfatandagerichdietindiabeticmice AT leileizhang networkpharmacologyandserumnontargetedmetabolomicsrevealtheprotectiveeffectsofpropionateagainstliverdamageinducedbyahighfatandagerichdietindiabeticmice AT pingpingwang networkpharmacologyandserumnontargetedmetabolomicsrevealtheprotectiveeffectsofpropionateagainstliverdamageinducedbyahighfatandagerichdietindiabeticmice |