Combination of Metformin and Magnesium Citrate Reduces TNF-α, NF-κB p65, IL-6, CD4, and MMP-9 Expressions in Diabetic Model Rats
BACKGROUND: Diabetes, which causes various complications, involves pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B p65 (NF-κB p65), interleukin-6 (IL-6), cluster of differentiation 4 (CD4), and matrix metalloproteinase-9 (MMP-9). Magnesium has demonstra...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Secretariat of The Indonesian Biomedical Journal
2024-12-01
|
| Series: | Indonesian Biomedical Journal |
| Online Access: | https://inabj.org/index.php/ibj/article/view/3360 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841558859262459904 |
|---|---|
| author | Rachmi Fauziah Rahayu Adi Prayitno Bambang Purwanto Widiastuti Soewondo Ida Nurwati Eti Poncorini Pamungkasari Paramasari Dirgahayu |
| author_facet | Rachmi Fauziah Rahayu Adi Prayitno Bambang Purwanto Widiastuti Soewondo Ida Nurwati Eti Poncorini Pamungkasari Paramasari Dirgahayu |
| author_sort | Rachmi Fauziah Rahayu |
| collection | DOAJ |
| description | BACKGROUND: Diabetes, which causes various complications, involves pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B p65 (NF-κB p65), interleukin-6 (IL-6), cluster of differentiation 4 (CD4), and matrix metalloproteinase-9 (MMP-9). Magnesium has demonstrated anti-diabetic properties, but its anti-inflammatory effects in preventing cardiovascular complications remain unclear. This study aimed to evaluate the anti-inflammatory effects of magnesium citrate, alone and in combination with metformin, by measuring TNF-α, NF-κB p65, IL-6, CD4, and MMP-9 expression in diabetic model rats.
METHODS: Thirty male Wistar rats were divided into five groups: normal control, diabetes control, metformin (treated with 9 mg/200 g/day metformin), magnesium citrate (treated with 3.6 mg/200 g/day magnesium citrate), and combination therapy (treated with 4.5 mg/200 g/day metformin + 1.8 mg/200 g/day magnesium citrate). Diabetes was induced in all groups except the normal control group using streptozotocin (STZ) and nicotinamide (NA). TNF-α, NF-κB p65, IL-6, CD4, and MMP-9 expression levels were measured using enzyme-linked immunosorbent assay (ELISA).
RESULTS: Significant differences in TNF-α, NF-κB p65, IL-6, CD4, and MMP-9 expression levels were observed across all groups (p<0.001). The combination therapy group demonstrated the most significant reduction in all parameters compared to the diabetic control group (p<0.001) and other therapy groups. Both metformin and magnesium citrate monotherapies showed moderate reductions in cytokine levels but were less effective than combination therapy.
CONCLUSION: Combination therapy with metformin and magnesium citrate exhibited the most potent anti-inflammatory effects, significantly reducing TNF-α, NF-κB p65, IL-6, CD4, and MMP-9 expressions in diabetic Wistar rats. This combination has potential as a therapeutic approach for managing diabetes and its complications.
KEYWORDS: diabetes mellitus, inflammation, cytokines, metformin, magnesium citrate |
| format | Article |
| id | doaj-art-ac52a15a2d7e4700b4844eab24a7b192 |
| institution | Kabale University |
| issn | 2085-3297 2355-9179 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Secretariat of The Indonesian Biomedical Journal |
| record_format | Article |
| series | Indonesian Biomedical Journal |
| spelling | doaj-art-ac52a15a2d7e4700b4844eab24a7b1922025-01-06T02:04:18ZengSecretariat of The Indonesian Biomedical JournalIndonesian Biomedical Journal2085-32972355-91792024-12-011665465210.18585/inabj.v16i6.3360609Combination of Metformin and Magnesium Citrate Reduces TNF-α, NF-κB p65, IL-6, CD4, and MMP-9 Expressions in Diabetic Model RatsRachmi Fauziah Rahayu0Adi Prayitno1Bambang Purwanto2Widiastuti Soewondo3Ida Nurwati4Eti Poncorini Pamungkasari5Paramasari Dirgahayu6Doctoral Program of Medical Science, Faculty of Medicine, Universitas Sebelas Maret, Jl. Ir. Sutami 36A, Surakarta 57126Doctoral Program of Medical Science, Faculty of Medicine, Universitas Sebelas Maret, Jl. Ir. Sutami 36A, Surakarta 57126Department of Internal Medicine, Faculty of Medicine, Universitas Sebelas Maret, Jl. Ir. Sutami 36A, Surakarta 57126Department of Radiology, Faculty of Medicine, Universitas Sebelas Maret, Jl. Kolonel Sutarto No.132, Surakarta 57126Department of Biochemistry Sciences, Faculty of Medicine, Universitas Sebelas Maret, Jl. Ir. Sutami 36A, Surakarta 57126Department of Public Health, Faculty of Medicine, Universitas Sebelas Maret, Jl. Ir. Sutami 36A, Surakarta 57126Department of Parasitology and Mycology, Faculty of Medicine, Universitas Sebelas Maret, Jl. Ir. Sutami 36A, Surakarta 57126BACKGROUND: Diabetes, which causes various complications, involves pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B p65 (NF-κB p65), interleukin-6 (IL-6), cluster of differentiation 4 (CD4), and matrix metalloproteinase-9 (MMP-9). Magnesium has demonstrated anti-diabetic properties, but its anti-inflammatory effects in preventing cardiovascular complications remain unclear. This study aimed to evaluate the anti-inflammatory effects of magnesium citrate, alone and in combination with metformin, by measuring TNF-α, NF-κB p65, IL-6, CD4, and MMP-9 expression in diabetic model rats. METHODS: Thirty male Wistar rats were divided into five groups: normal control, diabetes control, metformin (treated with 9 mg/200 g/day metformin), magnesium citrate (treated with 3.6 mg/200 g/day magnesium citrate), and combination therapy (treated with 4.5 mg/200 g/day metformin + 1.8 mg/200 g/day magnesium citrate). Diabetes was induced in all groups except the normal control group using streptozotocin (STZ) and nicotinamide (NA). TNF-α, NF-κB p65, IL-6, CD4, and MMP-9 expression levels were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: Significant differences in TNF-α, NF-κB p65, IL-6, CD4, and MMP-9 expression levels were observed across all groups (p<0.001). The combination therapy group demonstrated the most significant reduction in all parameters compared to the diabetic control group (p<0.001) and other therapy groups. Both metformin and magnesium citrate monotherapies showed moderate reductions in cytokine levels but were less effective than combination therapy. CONCLUSION: Combination therapy with metformin and magnesium citrate exhibited the most potent anti-inflammatory effects, significantly reducing TNF-α, NF-κB p65, IL-6, CD4, and MMP-9 expressions in diabetic Wistar rats. This combination has potential as a therapeutic approach for managing diabetes and its complications. KEYWORDS: diabetes mellitus, inflammation, cytokines, metformin, magnesium citratehttps://inabj.org/index.php/ibj/article/view/3360 |
| spellingShingle | Rachmi Fauziah Rahayu Adi Prayitno Bambang Purwanto Widiastuti Soewondo Ida Nurwati Eti Poncorini Pamungkasari Paramasari Dirgahayu Combination of Metformin and Magnesium Citrate Reduces TNF-α, NF-κB p65, IL-6, CD4, and MMP-9 Expressions in Diabetic Model Rats Indonesian Biomedical Journal |
| title | Combination of Metformin and Magnesium Citrate Reduces TNF-α, NF-κB p65, IL-6, CD4, and MMP-9 Expressions in Diabetic Model Rats |
| title_full | Combination of Metformin and Magnesium Citrate Reduces TNF-α, NF-κB p65, IL-6, CD4, and MMP-9 Expressions in Diabetic Model Rats |
| title_fullStr | Combination of Metformin and Magnesium Citrate Reduces TNF-α, NF-κB p65, IL-6, CD4, and MMP-9 Expressions in Diabetic Model Rats |
| title_full_unstemmed | Combination of Metformin and Magnesium Citrate Reduces TNF-α, NF-κB p65, IL-6, CD4, and MMP-9 Expressions in Diabetic Model Rats |
| title_short | Combination of Metformin and Magnesium Citrate Reduces TNF-α, NF-κB p65, IL-6, CD4, and MMP-9 Expressions in Diabetic Model Rats |
| title_sort | combination of metformin and magnesium citrate reduces tnf α nf κb p65 il 6 cd4 and mmp 9 expressions in diabetic model rats |
| url | https://inabj.org/index.php/ibj/article/view/3360 |
| work_keys_str_mv | AT rachmifauziahrahayu combinationofmetforminandmagnesiumcitratereducestnfanfkbp65il6cd4andmmp9expressionsindiabeticmodelrats AT adiprayitno combinationofmetforminandmagnesiumcitratereducestnfanfkbp65il6cd4andmmp9expressionsindiabeticmodelrats AT bambangpurwanto combinationofmetforminandmagnesiumcitratereducestnfanfkbp65il6cd4andmmp9expressionsindiabeticmodelrats AT widiastutisoewondo combinationofmetforminandmagnesiumcitratereducestnfanfkbp65il6cd4andmmp9expressionsindiabeticmodelrats AT idanurwati combinationofmetforminandmagnesiumcitratereducestnfanfkbp65il6cd4andmmp9expressionsindiabeticmodelrats AT etiponcorinipamungkasari combinationofmetforminandmagnesiumcitratereducestnfanfkbp65il6cd4andmmp9expressionsindiabeticmodelrats AT paramasaridirgahayu combinationofmetforminandmagnesiumcitratereducestnfanfkbp65il6cd4andmmp9expressionsindiabeticmodelrats |