• Harnessing Artificial Intelligence to Identify Natural Lipid-Lowering Agents Targeting Lipin-1
  • Zahra Zarinfar,1,* Shima Zarinfard,2 Maryam Musavi,3 Amir Abbas Momtazi-Borojeni,4
    1. Students Research Committee, Neyshabur University of Medical Sciences, Neyshabur, Iran
    2. Students Research Committee, Neyshabur University of Medical Sciences, Neyshabur, Iran
    3. : Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran
    4. Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran


  • Introduction: Lipin-1, a critical protein involved in triglyceride synthesis and fatty acid oxidation, has been linked to atherogenic processes. Lipin-1 inhibition has been found to prevent and inhibit the progression of atherosclerosis plaques. Artificial intelligence (AI) techniques can provide a cost-benefit approach for drug prediction to treat the disease. The present in silico study aimed to predict Lipin-1 inhibitors among a list of phytochemical compounds by using AI approaches.
  • Methods: In this study, several natural compounds with previously reported therapeutic impacts have been selected by a literature review. Then, the structure files of natural compounds were obtained from the PubChem site (https://pubchem.ncbi.nlm.nih.gov) and The structure of the Lipin-1 protein was obtained from the AlphaFold Protein Structure Database (https://alphafold.ebi.ac.uk/entry/Q14693) with the ID: AF-Q14693-F1. The interaction between these natural compounds and the Lipin-1 protein was examined by PyRx software.
  • Results: A comprehensive literature review provided natural compounds with approved therapeutic effects. Results from the PyRx analysis indicated that among the screened compounds, ten were selected for docking with Lipin-1, of which three showed the highest interaction affinity, represented by the lowest binding free energy measured in kilocalories per mole. These compounds and their binding free energy are as follows: (Epigallocatechin gallate (EGCG)): -7.6, (Curcumin): -7.2, (Phytosterols): -7.0, (Capsaicin): -6.7, (Quercetin): -6.5, (Beta-glucans): -6.2, (Resveratrol): -5.9, (Cannabidiol (CBD)): -5.8, (Melatonin): -5.5, (Caffeine): -5.4.
  • Conclusion: The prediction of Lipin-1-inhibiting natural compounds opens a novel avenue for research and treatment in cardiovascular health. By leveraging the protective properties of natural compounds alongside an understanding of Lipin-1's role in lipid metabolism, researchers aim to develop new therapeutic approaches for the management of atherosclerosis, especially in patients who do not respond to conventional treatments.
  • Keywords: Lipin-1, atherosclerosis, natural compounds, cardiovascular health