In Silico Evaluation of Diterpenoids from Jatropha curcas Roots as Potential HMG-CoA Reductase Inhibitors for Hyperlipidemia Management
DOI:
https://doi.org/10.22270/ajprd.v14i3.1765Abstract
Hyperlipidemia is a major metabolic disorder characterized by elevated levels of cholesterol and triglycerides, predisposing individuals to atherosclerosis and cardiovascular diseases. Although statins remain the first-line therapy through inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, their long-term use is associated with adverse effects, including hepatotoxicity and myopathy. This has fueled interest in identifying safer, plant-derived alternatives. Jatropha curcas, a medicinal plant traditionally used for various ailments, is particularly rich in bioactive diterpenoids in its root extracts. These secondary metabolites exhibit a wide spectrum of pharmacological properties, yet their potential in lipid-lowering therapy remains underexplored.The present study aimed to evaluate the binding affinity and interaction profile of selected diterpenoids from J. curcas roots against HMG-CoA reductase using molecular docking. Ligands were retrieved from published phytochemical reports and optimized, while the crystal structure of HMG-CoA reductase (PDB ID: 1HWK) was prepared by removing water molecules and heteroatoms. Docking was performed using AutoDock Vina, and results were visualized with Discovery Studio. Among the tested compounds, [ Curcusone B] exhibited the lowest binding energy (-9.1 kcal/mol), forming stable hydrogen bonds with key active site residues such as Lys735, Glu559, and Ser684, comparable to the reference drug atorvastatin. Other diterpenoids such as [Jatropholone B (-8.9 kcal/mol)] also demonstrated favorable interactions, suggesting their potential as natural HMG-CoA reductase inhibitors. These findings highlight the promise of J. curcas diterpenoids as lead candidates for hyperlipidemia management, providing a strong rationale for further in vitro and in vivo validation. Overall, this study emphasizes the relevance of in silico approaches in accelerating the discovery of plant-based lipid-lowering agents.
Downloads
References
Chen, M., Hou, L., & Zhang, G. (1988). The diterpenoids from Jatropha curcas L. Journal of Integrative Plant Biology, 30(2), 123-130.
De Souza, T. A., Pereira, T. N. S., & da Silva, V. C. (2007). Diterpenoids from Jatropha curcas. Phytochemistry, 68(12), 1990-1996.
Kim, S. et al. (2023). PubChem Database. National Center for Biotechnology Information.
ChemDraw Professional, PerkinElmer, USA (2023).
Chem3D Software, PerkinElmer, USA (2023).
Allinger, N. L. (1977). Conformational analysis. MM2 Force Field. Journal of the American Chemical Society, 99(25), 8127-8134.
Halgren, T. A. (1996). Merck molecular force field (MMFF94). Journal of Computational Chemistry, 17(5-6), 490-519.
Brooks, B. R., et al. (1983). CHARMM: A program for macromolecular energy minimization and dynamics calculations. Journal of Computational Chemistry, 4(2), 187-217.
Raval MA, Suthar MA, Durani MB, Thakar MN, Zankhwala MF, Kushkiwala MA, Rathod MS. Smart Co-Processed Excipient Platforms: A Novel Strategy for Multifunctional Optimization of Ibuprofen Tablet Formulations. practice.;1:2.
Daina, A., Michielin, O., & Zoete, V. (2017). SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7, 42717.
Lipinski, C. A., et al. (2001). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews, 46(1-3), 3-26
Istvan, E. S., & Deisenhofer, J. (2001). Structural mechanism for statin inhibition of HMG-CoA reductase. Science, 292(5519), 1160-1164. https://doi.org/10.1126/science.1059344
Tobert, J. A. (2003). Lovastatin and beyond: The history of the HMG-CoA reductase inhibitors. Nature Reviews Drug Discovery, 2(7), 517-526. https://doi.org/10.1038/nrd1112
Morris, G. M., Huey, R., Lindstrom, W., et al. (2009). AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. Journal of Computational Chemistry, 30(16), 2785-2791. https://doi.org/10.1002/jcc.21256
Trott, O., & Olson, A. J. (2010). AutoDock Vina: Improving the speed and accuracy of docking. Journal of Computational Chemistry, 31(2), 455-461. https://doi.org/10.1002/jcc.21334
Ferreira, L. G., Dos Santos, R. N., Oliva, G., & Andricopulo, A. D. (2015). Molecular docking and structure-based drug design strategies. Molecules, 20(7), 13384-13421. https://doi.org/10.3390/molecules200713384
Lionta, E., Spyrou, G., Vassilatis, D. K., & Cournia, Z. (2014). Structure-based virtual screening for drug discovery. Current Topics in Medicinal Chemistry, 14(16), 1923-1938.
Newman, D. J., & Cragg, G. M. (2020). Natural products as sources of new drugs over nearly four decades. Journal of Natural Products, 83(3), 770-803. https://doi.org/10.1021/acs.jnatprod.9b01285
Atanasov, A. G., Zotchev, S. B., Dirsch, V. M., et al. (2021). Natural products in drug discovery: Advances and opportunities. Nature Reviews Drug Discovery, 20, 200-216. https://doi.org/10.1038/s41573-020-00114-z
Raval AM, Ratnakar BP, Utpalkumar PF, Utpalkumar PV, Development and Evaluation of Multifunctional Co-Processed Excipients for Fast Dissolving Tablet Formulation, Asian Journal of Pharmaceutical Research and Development. 2026; 14(2):226-233, DOI: http://dx.doi.org/10.22270/ajprd.v14i2.1751
Patel PS, Raval AM, Patel A A K, Patel P D, Prajapati T G, Patel P B, A Comprehensive Review of Antibiotic Resistance: Mechanisms, Causes, and Novel Therapeutic Approaches, Asian Journal of Pharmaceutical Research and Development. 2026; 14(2):117-128, DOI: http://dx.doi.org/10.22270/ajprd.v14i2.1739
Wink, M. (2015). Modes of action of herbal medicines and plant secondary metabolites. Medicines, 2(3), 251-286. https://doi.org/10.3390/medicines2030251
Raval AM, Bhavsar PR, Pandya FU, Patel DK, Co-Processed Excipients in Pharmaceutical Formulation: Advances, Characterization, and Applications, Asian Journal of Pharmaceutical Research and Development. 2026; 14(1):105-113, DOI: http://dx.doi.org/10.22270/ajprd.v14i1.1705
Prasad, S., Gupta, S. C., Tyagi, A. K., & Aggarwal, B. B. (2017). Curcumin and related compounds in cancer and inflammatory diseases. Biotechnology Advances, 32(6), 1053-1064.
Verma, N., & Khosa, R. L. (2012). Phytochemistry and pharmacological studies on Jatropha curcas. Journal of Medicinal Plants Research, 6(6), 1077-1085.
Devappa, R. K., Makkar, H. P. S., & Becker, K. (2010). Jatropha toxicity-A review. Journal of Toxicology and Environmental Health, 13(6), 476-507.
Chandragirivar PC, Banu A, Raval AM, Kusuma R, Srinidhi G, Yashwanth HB, Suheel A. Improved Dissolution Performance of Fenoprofen Calcium Using PEG 6000 Solid Dispersions: Preparation by Fusion Method and Physicochemical Characterization. Int J Drug Deliv Technol. 2026;16(36s): 771-781. DOI: 10.25258/ijddt.16.36s.87
Raval AM, Verma AR, Prajapati DS, Efficacy and Safety of Major Antihypertensive Drug Classes in Adults with Hypertension: A Systematic Review, Asian Journal of Pharmaceutical Research and Development. 2026; 14(2):216-225, DOI: http://dx.doi.org/10.22270/ajprd.v14i2.1750
Kumar, A., Sharma, S. (2008). An evaluation of multipurpose oil seed crop for industrial uses (Jatropha curcas L.). Industrial Crops and Products, 28(1), 1-10.
Falwariya R, Jethva T, Raval AM, Lokhande D. Comprehensive review: Microneedle patches–A painless revolution in transdermal drug delivery. World J Pharm Med Res. 2026;12(1):199-207.
Mevada J, Patel K, Raval AM. Role of pharmacovigilance in drug safety monitoring. World J Pharm Med Res. 2025;11(11):235-40.
Rathi S. Physicochemical Characterization and In-Vitro Dissolution Enhancement of Ranolazine Using Solid Dispersion Method. Available at SSRN 3507970. 2019 Dec 21.
Patel, N. and Raval, A.M., 2026. Gastro-retentive drug delivery system: A review. Int J Pharm Sci, 4(1), pp.734-42.
Raval AM, Bhavsar PR, Pandya FU, Patel D. Co-processed excipients in pharmaceutical formulation: advances, characterization, and applications. Asian Journal of Pharmaceutical Research and Development. 2026 Feb 16;14(01):105-13.
kumar Patel PB, Raval AM, Patel HB, Patel KH, Poorv P, Vaidya PA, Kahar KH. A comprehensive review of polycystic ovary syndrome (PCOS): pathophysiology, diagnosis and management. Asian Journal of Pharmaceutical Research and Development. 2026 Apr 15;14(2):32-41.
Raval AM, Rana T, Joshi SY, Buch S, Arora B, Patel VS. Artificial intelligence in pharmacy and healthcare: applications in drug discovery, precision medicine, clinical practice, and future perspectives. Asian Journal of Pharmaceutical Research and Development. 2026 Apr 15;14(2):62-9.
Thakor AD, Dharajiya RM, Shaikh MZ, Raval AM. A review on neuropharmacology: mechanisms, drug classes, and clinical applications. Asian Journal of Pharmaceutical Research and Development. 2026 Feb 15;14(01):114-21.
Goswami V, Shukla R, Patel B, Suthar A, Patel P, Raval AM. HPTLC Method Development and Validation for Simultaneous Estimation of Rifaximin and Metronidazole Benzoate in Combined Tablet Dosage Form. Int J Drug Deliv Technol. 2026;16(46s): 257-265. DOI: 10.25258/ijddt.16.46s.27
Amar M. Raval AMR, Krina N Chaudhari KNC, Dr. Bhoomi Arora DBA, Dr. Aastha Ukani DAU, Riddhi Modh RM, Dr. Kuldeep Choubisa DKC, Dr. Ashok Kumar DAK. Emerging Role of GLP-1 and Dual Incretin Agonists in the Management of Type 2 Diabetes Mellitus: Mechanisms, Clinical Evidence, Dosing Strategies, and Future Perspectives. International Journal of Medical and Pharmaceutical Research. 2026 May;7(3):357-370.
Dallakyan, S., & Olson, A. J. (2015). Small-molecule library screening by docking with PyRx. In Chemical Biology (Methods in Molecular Biology, vol 1263). Humana Press.
Meng, X. Y., Zhang, H. X., Mezei, M., & Cui, M. (2011). Molecular docking: A powerful approach for structure-based drug discovery. Current Computer-Aided Drug Design, 7(2), 146-157.
Lipinski, C. A. (2004). Lead- and drug-like compounds: The rule-of-five revolution. Drug Discovery Today: Technologies, 1(4), 337-341.
Veber, D. F., Johnson, S. R., Cheng, H. Y., et al. (2002). Molecular properties that influence oral bioavailability. Journal of Medicinal Chemistry, 45(12), 2615-2623.
Pires, D. E. V., Blundell, T. L., & Ascher, D. B. (2015). pkCSM: Predicting small-molecule pharmacokinetic properties. Journal of Medicinal Chemistry, 58(9), 4066-4072.
World Health Organization. (2021). Cardiovascular diseases (CVDs). Retrieved from https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)
Benet, L. Z., Hosey, C. M., Ursu, O., & Oprea, T. I. (2016). BDDCS and drug disposition classification. The AAPS Journal, 18(5), 1265-1276.
Kitchen, D. B., Decornez, H., Furr, J. R., & Bajorath, J. (2004). Docking and scoring in virtual screening. Nature Reviews Drug Discovery, 3(11), 935-949.
Endo, A. (1992). The discovery and development of HMG-CoA reductase inhibitors. Journal of Lipid Research, 33(11), 1569-1582.
Joseph L. Goldstein, & Michael S. Brown (2015). A century of cholesterol and coronaries: From plaques to genes to statins. Cell, 161(1), 161-172. https://doi.org/10.1016/j.cell.2015.01.036
Kumar, S., & Pandey, A. K. (2013). Chemistry and biological activities of flavonoids: An overview. The Scientific World Journal, 2013, 162750. https://doi.org/10.1155/2013/162750
Meng, X. Y., Zhang, H. X., Mezei, M., & Cui, M. (2011). Molecular docking: A powerful approach for structure-based drug discovery. Current Computer-Aided Drug Design, 7(2), 146-157. https://doi.org/10.2174/157340911795677602
Sogame, Y., Kitazato, K., & Kobayashi, H. (2009). Natural compounds as potential HMG-CoA reductase inhibitors. Mini-Reviews in Medicinal Chemistry, 9(5), 564-576.
Aiyelaagbe, O. O., Adeniyi, B. A., Fatunsin, O. F., & Arimah, B. D. (2011). In vitro antimicrobial activity and phytochemical analysis of Jatropha curcas roots. International Journal of Pharmacognosy and Phytochemical Research, 3(2), 30-33.
Published
How to Cite
Issue
Section
Copyright (c) 2026 Ritu Kumari Singh, Nitesh Chandel, Dr. Dhaval Patel, Dr. Pankti Dalwadi, Ketan Rathod
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
AUTHORS WHO PUBLISH WITH THIS JOURNAL AGREE TO THE FOLLOWING TERMS:
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 Unported License. that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
. 