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Khurram, A, Sethi, G, Afrin, MR, Hossain, CF, Jusuf, PR, Sarker, S and Arya, A (2023) Arjunolic acid modulate pancreatic dysfunction by ameliorating pattern recognition receptor and canonical Wnt pathway activation in type 2 diabetic rats. Life Sciences. ISSN 0024-3205
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Arjunolic acid modulate pancreatic dysfunction by ameliorating pattern recognition receptor .pdf - Accepted Version Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (2MB) | Preview |
Abstract
Background: Arjunolic acid (AA) is a potent phytochemical with multiple therapeutics effects. In this study, AA is evaluated on type 2 diabetic (T2DM) rats to understand the mechanism of β-cell linkage with Toll-like receptor 4 (TLR-4) and canonical Wnt signaling. However, its role in modulating TLR-4 and canonical Wnt/β-catenin crosstalk on insulin signaling remains unclear during T2DM. Aim: The current study is aimed to examine the potential role of AA on insulin signaling and TLR-4-Wnt crosstalk in the pancreas of type 2 diabetic rats. Method: Multiple methods were used to determine molecular cognizance of AA in T2DM rats, when treated with different dosage levels. Histopathological and histomorphometry analysis was conducted using masson trichrome and H&E stains. While, protein and mRNA expressions of TLR-4/Wnt and insulin signaling were assessed using automated Western blotting (jess), immunohistochemistry, and RT-PCR. Results: Histopathological findings revealed that AA had reversed back the T2DM-induced apoptosis and necrosis caused to rats pancreas. Molecular findings exhibited prominent effects of AA in downregulating the elevated level of TLR-4, MyD88, NF-κB, p-JNK, and Wnt/β-catenin by blocking TLR-4/MyD88 and canonical Wnt signaling in diabetic pancreas, while IRS-1, PI3K, and pAkt were all upregulated by altering the NF-κB and β-catenin crosstalk during T2DM. Conclusion: Overall results, indicate that AA has potential to develop as an effective therapeutic in the treatment of T2DM associated meta-inflammation. However, future preclinical research at multiple dose level in a long-term chronic T2DM disease model is warranted to understand its clinical relevance in cardiometabolic disease.
| Item Type: | Article |
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| Uncontrolled Keywords: | 0601 Biochemistry and Cell Biology; 1115 Pharmacology and Pharmaceutical Sciences; Pharmacology & Pharmacy |
| Subjects: | Q Science > QH Natural history > QH301 Biology R Medicine > R Medicine (General) R Medicine > RS Pharmacy and materia medica |
| Divisions: | Pharmacy & Biomolecular Sciences |
| Publisher: | Elsevier |
| SWORD Depositor: | A Symplectic |
| Date Deposited: | 12 Jun 2023 15:38 |
| Last Modified: | 10 Jun 2024 00:50 |
| DOI or ID number: | 10.1016/j.lfs.2023.121856 |
| URI: | https://researchonline.ljmu.ac.uk/id/eprint/19742 |
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