Arjunolic acid modulate pancreatic dysfunction by ameliorating pattern recognition receptor and canonical Wnt pathway activation in type 2 diabetic rats

  • Life Sci. 2023 Aug 15:327:121856. doi: 10.1016/j.lfs.2023.121856.
Khurram Aamir  1 ,  Gautam Sethi  2 ,  Mst Rejina Afrin  3 ,  Chowdhury Faiz Hossain  3 ,  Patricia Regina Jusuf  4 ,  Satyajit D Sarker  5 ,  Aditya Arya  6
Affiliations
  • 1. School of Pharmacy, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, Malaysia; Akhtar Saeed College of Pharmacy, Canal Campus, Lahore, Pakistan.
  • 2. Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  • 3. Department of Pharmacy, Faculty of Sciences and Engineering, East West University, Dhaka 1212, Bangladesh.
  • 4. School of Biosciences, Faculty of Sciences, University of Melbourne, Parkville, VIC, Australia.
  • 5. Centre for Natural Product Discovery, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, James Parsons Building, Byrom Street, Liverpool L3 3AF, United Kingdom.
  • 6. School of Biosciences, Faculty of Sciences, University of Melbourne, Parkville, VIC, Australia; Centre for Natural Product Discovery, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, James Parsons Building, Byrom Street, Liverpool L3 3AF, United Kingdom; Department of Pharmacology & Therapeutics, School of Medicine, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, Malaysia. Electronic address: [email protected].
PMID: 37307966 DOI: 10.1016/j.lfs.2023.121856
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.

Keywords
Arjunolic acid; Insulin signaling; TLR-4; Type 2 diabetes mellitus; Wnt.
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