International Journal of Drug Delivery Technology
Volume 15, Issue 1

Prediction of the Mechanism of Nephrolepis cordifolia (L) C. Presl against Disorders of Increased Blood Sugar and Lipid Levels using the Network Pharmacology Approach

Samsul Hadi1*, Noer Komari2, Adi Rahmadi3, Askur Rahman4, Hamzah Fansuri4

1Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Lambung Mangkurat University, Banjarbaru, South Kalimantan, Indonesia, 70714

2Department of Chemistry, Faculty of Mathematics and Natural Sciences, Lambung Mangkurat University, Banjarbaru, South Kalimantan, Indonesia, 70714

3Departmnet of Forestry, Lambung Mangkurat University, Banjarbaru, South Kalimantan, Indonesia, 70714

4Departement Agricultural Industrial Technology, Faculty of Agriculture, Trunojoyo Madura Universiy, Bankalan, East Java, Indonesia, 69162 

Received: 29th Nov, 2024; Revised: 20th Jan, 2025; Accepted: 27th Feb, 2025; Available Online: 25th Mar, 2025 

ABSTRACT

Elevated blood sugar and lipid levels are a growing global health concern and N. Cordelia presents potential therapeutic benefits. Therefore, this study aimed to identify active compounds and mechanisms in N. cordifolia using a network pharmacology method. Active compounds were screened for target proteins associated with elevated blood sugar and lipids through PPI networks, enrichment analysis, docking, and MM/GB (PB) SA. The results showed 6 compounds from N. cordifolia, and 24 proteins were obtained using Cluster One analysis at the PPI network stage. An important mechanism, such as the PPAR signaling pathway was identified through enrichment. The proteins in this mechanism were FABP, PPARα, and PPARλ, obtained by docking and MMGB (PB) A. The key compounds were 9-Oxo-10 (E) and 12 (E)-octadecadienoic acid, suggesting the potential of N. cordifolia to overcome increased blood sugar and lipids.

Keywords: N. cordifolia; Network Pharmacology; Blood sugar; Lipid.

How to cite this article: Samsul Hadi, Noer Komari, Adi Rahmadi, Askur Rahman, Hamzah Fansuri. Prediction of the Mechanism of Nephrolepis cordifolia (L) C. Presl against Disorders of Increased Blood Sugar and Lipid Levels using the Network Pharmacology Approach. International Journal of Drug Delivery Technology. 2025;15(1): 1-10. doi: 10.25258/ijddt.15.1.1

REFERENCE

  1. Moreno-Fernández S, Garcés-Rimón M, Vera G, Astier J, Landrier JF, Miguel M. High fat/high glucose diet induces metabolic syndrome in an experimental rat model. Nutrients. 2018 Oct;10(10):1502.
  2. Chen X, Hou C, Yao L, Li J, Gui M, Wang M, et al. Dietary inflammation index is associated with dyslipidemia: evidence from national health and nutrition examination survey, 1999–2019. Lipids Health Dis [Internet]. 2023;22(1):149. https://doi.org/10.1186/s12944-023-01914-z.
  3. Śliwińska-Mossoń M, Bil-Lula I, Marek G. The cause and effect relationship of diabetes after acute pancreatitis. Biomedicines. 2023 Feb;11(3):667.
  4. Okura T, Ito Y, Anno M, Endo S, Kitao S, Nakamura R, et al. Postprandial fatty acid-binding protein 4 is associated with muscle insulin resistance. Diabetologia [Internet]. 2024;67(10):2304–15. https://doi.org/10.1007/s00125-024-06222-4.
  5. Konopelnyuk V, Yurchenko A, Karpovets T, Ostapchenko L. The development of obesity and prediabetes under conditions of longterm consumption of fructose solution in rats. J Appl Pharm Sci. 2015 Jan 30;5:1–5.
  6. Pal R, Teli G, Sharma B, Kumar B, Chawla PA. In vitro anti-inflammatory and antioxidant activity of Nephrolepis cordifolia and molecular docking of its active chemical constituent. Pharmaspire. 2021;13:21–7.
  7. Rajasekaran A, Vellaichamy S. Evaluation of diuretic potential of Nephrolepis cordifolia Rhizome juice in Wistar rats. Sains Malays. 2009 Feb 1;38:57–9.
  8. Chettri U, Kumari S, Chettri B. A review on antimicrobial and hepatoprotective properties of Himalayan wild fern Nephrolepis cordifolia (Pani Amla). J Pharm Innov J. 2020 Aug 30;9:572–7.
  9. Widiono ES, Setyadi A, Prasetyo A, Sadhana U, Subagio A. Protective effects of Nephrolepsis exaltata mask against blood glucose level (A study of Wistar rats with chronic exposure to nanosilica). Indian J Sci Technol. 2019 Sep 20;12(36):1–5.
  10. Anthony E O, Joseph C M, Simon O, Chijiokwu E A. Hypoglycemic and hypolipidemic indices of ethanolic leaf extract of Nephrolepis undulata in alloxan induced diabetic Wistar rats. Biomed Pharmacol J. 2020 Sep 28;13(3):1423–9.
  11. Ojieh AE. Evaluation of antidiabetic and Antioxidant potential of Nephrolepis unduranta leaves extract in streptozotocin Induced Diabetic Wistar rats. Int J Forensic Med Investig. 2019;5(1):34–41.
  12. Ossai N, Richard AE, Nwogueze BC, Olowe G, Eyituoyo A. Ameliorative potentials of methanolic leaf extract of Nephrolepis undulate in streptozotocin-induced diabetic Wistar rats. Plant Cell Biotechnol Mol Biol. 2021 Jan 1;22:41–53.
  13. Hadi S, Setiawan D, Komari N, Rahmadi A, Rahman A, Fansuri H, et al. Network pharmacology and docking of Nephrolepis cordifolia as Type-2 antidiabetic agent. Trop J Nat. Prod Res. 2024;8(9).
  14. Komari N, Hadi E, Bhusari S, Mustikasari K, Putera GMP. Antihypertensive Activity of Peptides Derived from Toman Fish albumin (Channa micropeltes): in-silico angiotensin-converting enzyme Inhibitory Study. Int J Drug Deliv Technol. 2024 Sep 25;14(3):1505–10.
  15. Sable V, Ahire G. Network pharmacology and molecular docking technology-based strategy to explore the potential mechanism of Diabecon formulation botanicals. Int J Drug Deliv Technol. 2024;14(1):274–80.
  16. Zeena F, Sahana KD, Dattatreya KS. A network pharmacology approach to explore the potential mechanism of Ficus religiosa against Alzheimer’s disease. Int J Drug Deliv Technol. 2022 Jun 30;12(3):996–1003.
  17. Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010 Jan;31(2):455–61.
  18. Yang M, Bo Z, Xu T, Xu B, Wang D, Zheng H. Uni-GBSA: an open-source and web-based automatic workflow to perform MM/GB(PB)SA calculations for virtual screening. Brief Bioinform. 2023 Jul;24(4):bbad218.
  19. Glatz JFC, Luiken JJFP. From fat to FAT (CD36/SR-B2): understanding the regulation of cellular fatty acid uptake. Biochimie. 2017 May;136:21–6.
  20. Hotamisligil GS, Bernlohr DA. Metabolic functions of FABPs--mechanisms and therapeutic implications. Nat Rev Endocrinol. 2015 Oct;11(10):592–605.
  21. Lavudi K, Nuguri SM, Olverson Z, Dhanabalan AK, Patnaik S, Kokkanti RR. Targeting the retinoic acid signaling pathway as a modern precision therapy against cancers. Front Cell Dev Biol. 2023;11:1254612.
  22. Xu Y, Jin J, Zhang W, Zhang Z, Gao J, Liu Q, et al. EGFR/MDM2 signaling promotes NF-κB activation via PPARγ degradation. Carcinogenesis. 2016 Feb;37(2):215–22.
  23. Jung JY, Choi Y, Suh CH, Yoon D, Kim HA. Effect of fenofibrate on uric acid level in patients with gout. Sci Rep. 2018 Nov;8(1):16767.
  24. Chen YQ, Zhao SP, Ye HJ. Efficacy and safety of coenzyme A versus fenofibrate in patients with hyperlipidemia: a multicenter, double-blind, double-mimic, randomized clinical trial. Curr Med Res Opin. 2020 Jun;36(6):941–5.
  25. Park MK, Kim TE, Kim J, Kim C, Yoon SH, Cho JY, et al. Tolerability and pharmacokinetics of lobeglitazone, a novel peroxisome proliferator-activated receptor-γ agonist, after a single oral administration in healthy female subjects. Clin Drug Investig. 2014 Jul;34(7):467–74.
  26. Musso G, Cassader M, Paschetta E, Gambino R. Thiazolidinediones and advanced liver fibrosis in nonalcoholic steatohepatitis: A meta-analysis. JAMA Intern Med. 2017 May;177(5):633–40.
  27. Liu CH, Lee TH, Lin YS, Sung PS, Wei YC, Li YR. Pioglitazone and PPAR-γ modulating treatment in hypertensive and type 2 diabetic patients after ischemic stroke: a national cohort study. Cardiovasc Diabetol [Internet]. 2020;19(1):2. https://doi.org/10.1186/s12933-019-0979-x.
  28. Yabut KCB, Martynova A, Nath A, Zercher BP, Bush MF, Isoherranen N. Drugs form ternary complexes with human liver fatty acid binding protein (FABP1) and FABP1 binding alters drug metabolism. bioRxiv: the preprint server for biology. United States; 2024.
  29. Umaru BA, Kagawa Y, Ohsaki Y, Pan Y, Chen CT, Chen DK, et al. Oleic acid-bound FABP7 drives glioma cell proliferation through regulation of nuclear lipid droplet formation. FEBS Journal. 2023 Apr;290(7):1798–821.