AccScience Publishing / GPD / Online First / DOI: 10.36922/gpd.0927
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ORIGINAL RESEARCH ARTICLE

Analysis of multi-disease targeting effect of phytochemicals by AMPK stimulation– diabetes: A computational approach

Richa Goyal1* ,  Manoj Kumar2 ,  Muhammad Anwar Mallick3
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1 Department of Biotechnology, Vinoba Bhave University, Hazaribagh, Jharkhand, India
2 Department of Zoology, Vinoba Bhave University, Hazaribagh, Jharkhand, India
3 Department of Botany/ Biotechnology, Vinoba Bhave University, Hazaribagh, Jharkhand, India
GPD 2023, 2(3), 0927 https://doi.org/10.36922/gpd.0927
Submitted: 8 May 2023 | Accepted: 21 August 2023 | Published: 12 September 2023
© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Diabetes is a silent killer and a metabolic syndrome characterized by hyperglycemia that has been exponentially increasing in recent years. There is a need to develop therapeutic agents to control hyperglycemia and its secondary complications as well as protect and revive beta cells in diabetic patients. The target for first-line diabetes treatment is the adenosine monophosphate protein kinase (AMPK), which participates in cellular energy metabolism through phosphorylation of metabolic enzymes and transcription regulators. This study examined the drug-related properties as well as lead preparation of Catharanthus roseus alkaloids and testing molecular interaction at the AMPK targets to confirm their anti-diabetic effect. A control drug metformin and a library of 85 molecules of C. roseus alkaloids were crossed with the ADMET test, followed by the investigation of molecular interaction tested on AMPK1 and AMPK2 targets through an in silico docking process. Vindolinine (CID: 24148538), vindoline (CID: 425978), (+)-vindorosine (CID: 261578), Cr-1 (CID: 5315746), and Cr-2 (CID: 59908094) had passed the ADMET test. Molecular interaction of the tested C. roseus alkaloids on AMPK1 and AMPK2 targets had potential energy that varied from −7.4 to −5.3 kcal/mol, whereas binding energies of −4.0 kcal/mol for AMPK1-metformin interaction and −4.2 kcal/mol for AMPK2-metformin interaction were observed. The tested C. roseus alkaloids were shown to be more potent activators of AMPK than the control drug. All five biomolecules of C. roseus acted as modulators that have the potential to stimulate AMPK, reduce glucose production, and increase glucose utilization in hepatocytes. In addition, they diminished insulin resistance and secondary complications of diabetes by inhibiting acetyl-CoA carboxylase, regulating cholesterol levels and macrophage, and reviving beta cells in Type 2 diabetes. These results provided the foundation for developing new multi-disease-targeting drugs that can treat diabetes, obesity, cardiovascular disease, cancer, and other diseases by the stimulation of AMPK1 and AMPK2 targets.

Keywords
Diabetes
Adenosine monophosphate protein kinase
Catharanthus roseus alkaloids
Metformin
Docking study
Funding
None.
Conflict of interest
All the authors declared no conflicts of interest.
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