Antidiabetic Activity and in silico Molecular Docking of GC-MS- Identified Compounds in Chromatographic Fractions of Tephrosia bracteolata Guill. & Perr. (Fabaceae) Leaves

Authors

  • Precious A. Idakwoji Department of Biochemistry, Faculty of Natural Sciences, Prince Abubakar Audu University, Anyigba, Kogi State, PMB 1008, Nigeria.
  • Joan M. Oniemola Department of Science Laboratory Technology, School of Applied Sciences, Kogi State Polytechnic, Lokoja, Kogi State, Nigeria
  • David A. Zakari Department of Microbiology, Faculty of Natural Sciences, Prince Abubakar Audu University, Anyigba, Kogi State, PMB 1008, Nigeria
  • Fatima A. Sule Department of Biochemistry, Faculty of Natural Sciences, Prince Abubakar Audu University, Anyigba, Kogi State, PMB 1008, Nigeria
  • Ummulkhairi Tukur Independent Researcher, Ankara, Turkey. (Formerly at Middle East Technical University, Ankara) 
  • Endaline A. Madu Department of Biochemistry, Faculty of Biological Sciences, University of Nigeria, Nsukka, Enugu State, Nigeria
  • Obumneme C. Ogbonnaya Department of Biochemistry, Faculty of Biological Sciences, University of Nigeria, Nsukka, Enugu State, Nigeria
  • Abubakar R. Mannir Department of Biochemistry, Faculty of Natural and Applied Sciences, Umaru Musa Yar’adua University, Katsina, Katsina State, Nigeria
  • Samson C. Onoyima Department of Biochemistry, Faculty of Biological Sciences, University of Nigeria, Nsukka, Enugu State, Nigeria

DOI:

https://doi.org/10.26538/tjnpr/v9i8.31

Keywords:

Antidiabetic activity, Molecular docking, Tephrosia bracteolata, Diabetes, Chromatographic fraction

Abstract

Recent efforts for the complementary treatment of diabetes have focused on medicinal plants and their bioactive compounds. This study evaluated the antidiabetic activity of chromatographic subfractions of ethylacetate fraction (EAF) of Tephrosia bracteolata leaves. Also, to carry out molecular docking of some GC-MS-identified compounds in the subfraction with the highest antidiabetic activity against key targets in the pathophysiology of diabetes. The EAF (5 g) was subjected to silica gel column chromatography using gradient elution with hexane, chloroform, ethyl acetate, methanol and water. Approximately 100 fractions (100 mL each) were collected and monitored via TLC, resulting in 7 major sub-fractions (SF1-SF7). The antidiabetic activity of the sub-fractions was evaluated (at doses of 200 and 400 mg/kg) against alloxan-induced diabetes in mice. GC-MS analysis was carried out on the subfraction with the highest activity. Subsequently, some of the identified active compounds were docked against key targets in the pathology of diabetes using AutoDock Vina. Phytochemical analysis revealed the presence of several phytochemicals in varying proportions in the subfractions.  SF5 (400 mg/kg) produced the most significant (p< 0.05) decrease in FBS (35.29 and 38.37 %) at 12 h and 24 h- post-treatment respectively. GC-MS analysis of SF5 revealed the presence of 36 compounds among which are Mome inositol, 2-methoxy-4-vinylphenol, 1-D-thio-glucitol and 4-Piperidinone. Molecular docking showed that Mome inositol and 1-D-thio-glucitol have a strong affinity for alpha-glucosidase and sodium-glucose co-transporter 2 (SGLT 2). These findings suggest that the antidiabetic activity of the extract maybe attributed to the bioactive compounds identified in SF5.

Author Biography

  • Abubakar R. Mannir, Department of Biochemistry, Faculty of Natural and Applied Sciences, Umaru Musa Yar’adua University, Katsina, Katsina State, Nigeria

    Nanomaterials for Biomedical Applications Research Group, Italian Institute of Technology, Genova, Italy.

References

1. American Diabetes Association Professional Practice Committee. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2022. Diabetes Care. 2022; 45(Supplment_1): S17–S38. https://doi.org/10.2337/dc22-S002.

2. Basit A, Fawwad A, Qureshi H, Shera AS, NDSP Members. Prevalence of diabetes, pre-diabetes and associated risk factors: second National Diabetes Survey of Pakistan (NDSP), 2016–2017. BMJ Open. 2018; 8(8): e020961. https://doi.org/10.1136/bmjopen-2017-020961.

3. Ansari P, Akther S, Hannan JMA, Seidel V, Nujat NJ, Abdel-Wahab YHA. Pharmacologically Active Phytomolecules Isolated from Traditional Antidiabetic Plants and Their Therapeutic Role for the Management of Diabetes Mellitus. Molecules. 2022; 27(13): 4278. https://doi.org/10.3390/molecules27134278.

4. Asante DB, Wiafe GA. Therapeutic Benefit of Vernonia amygdalina in the Treatment of Diabetes and Its Associated Complications in Preclinical Studies. J. Diabetes Res. 2023; 1: 3159352. https://doi.org/10.1155/2023/3159352

5. Ning C Jiao, Y, Wang Y, Li W, Zhou J, Lee YC. Recent advances in the management of type 2 diabetes mellitus and natural hypoglycemic substances. Food Sci Hum Well. 2022; 11(5):1121–1133. https://doi.org/10.1016/j.fshw.2022.04.004.

6. Ansari P, Samia JF, Khan JT, Rafi MR, Rahman MS, Rahman AB, Abdel-Wahab YHA, Seidel V. Protective Effects of Medicinal Plant-Based Foods Against Diabetes: A Review on Pharmacology, Phytochemistry and Molecular Mechanisms. Nutr. 2023; 15(14): 3266. https://doi.org/10.3390/nu15143266.

7. Bidulka P, Lugo-Palacios DG, Carroll O, O’Neill S, Adler AI, Basu A, Silverwood RJ, Bartlett JW, Nitsch D, Charlton P. Comparative effectiveness of second-line oral antidiabetic treatments among people with type 2 diabetes mellitus: Emulation of a target trial using routinely collected health data. BMJ Open. 2024; 385: e077097. https://doi.org/10.1136/bmj-2023-077097.

8. Chhabria S, Mathur S, Vadakan S, Sahoo DK, Mishra P, Paital B. A Review on Phytochemical and Pharmacological Facets of Tropical Ethnomedicinal Plants as Reformed DPP-IV Inhibitors to Regulate Incretin Activity. Front. Endocrinol (Lausanne). 2022; 13: 1027237. https://doi.org/10.3389/fendo.2022.1027237.

9. Karigidi KO, Olaiya CO. Antidiabetic activity of corn steep liquor extract of Curculigo pilosa and its solvent fractions in streptozotocin-induced diabetic rats. J. Traditional. Complem. Med. 2019; 10(6): 555–564. https://doi.org/10.1016/j.jtcme.2019.06.005.

10. Dalziel JM. The Useful Plants of West Tropical Africa. The Crown Agents for the Colonies, London. 1937; Pp 52-560. https://doi.org/10.12691/ajbr-2-4-1.

11. Burkill HM. The Useful Plants of West Tropical Africa. Royal Botanical Gardens, Kew, 1985 1:319.

12.Onaolapo MAO, Nzelibe HC, Aduadi AO, Ayo JO. Toxicity and antipyretic studies of the crude extract of Tephrosia bracteolata leaves. JOPAT. 2004; 9: 15-19. https://doi.org/10.4314/jopat.v9i1.48589.

13. Idakwoji PA, Oguche M, Sule FA, Oniwon WO, Shaibu IE, Edogbo E, Onoja AO, Ukwubile II. In vitro Antidiabetic Activity and Sub-chronic Toxicity Profile of Ethanol Extract of Tephrosia bracteolata Leaves. Trop. J. Nat. Prod. Res. 2024; 8(4): 7012-7019. https://doi.org/10.26538/tjnpr/v8i4.37.

14. Egharevba GO, Dosumu OO, Oguntoye SO, Njinga NS, Dahunsi SO, Hamid AA, Anand A, Amtul Z, Ukkujuri P. Antidiabetic, antioxidant and antimicrobial activities of extracts of Tephrosia bracteolata leaves. Heliyon. 2019; 5:1-6. https://doi.org/10.1016/j.heliyon.2019.e02481.

15. Derrell C, Gerald FG, Janet CG, Michale EK, Dennis FK. The 1996 Guide for Care and Use of Laboratory Animals. ILAR Journal. 1997; 1:41-48. https://doi.org/10.1093/ilar.38.1.41.

16. Uzor PF, Osadebe PO, Omeje EO, Agbo MO. Bioassay Guided Isolation and Evaluation of the Antidiabetic Principles of Combretum dolichopetalum Root, Br. J. Pharm. Res. 2014; 18: 2155-2171.

17. Idakwoji PA, Ekpo DE, Joshua PE, Njoku OU, Nwodo OFC. Ethanol Extract of Tephrosia bracteolata Leaves & its Fractions Ameliorates Alloxan-induced Diabetes and its Complications in Wistar Rat Model. Int. J. Diabetes Dev. Ctries. 2021; 41(3): 456–468. https://doi.org/10.1007/s13410-020-00900-w.

18. Cannell RJP. Methods in Biotechnology, Natural products isolation. Human Press, New Jersey. Pp 14-36.

19. Trease GE, Evans MC. Pharmacognosy. 13th Edn. Bailiere, Tindall. 2000; pp. 200- 775.

20. Harborne JB. Phytochemical Methods. A Guide to Modern Technology of Plant Analysis. 3rd Edn. Chapman and Hall, New York. 1998; pp. 88-185.

21. Drake T, Landsteiner A, Langsetmo L, MacDonald R, Anthony M, Kalinowski C, Ullman K, Billington CJ, Kaka A, Sultan S. Newer Pharmacologic Treatments in Adults with Type 2 Diabetes: A Systematic Review and Network Meta-analysis for the American College of Physicians. Ann. Intern. Med. 2024; 177: 618–632. https://doi.org/10.7326/M23-1490.

22. Natarajan V, Smith AA, Vishwanath BA. Antidiabetic Activity of Phenolic Compounds from Drega volubilis (Benth) Leaves in Streptozotocin-induced Diabetic Rats. Global J. Pharmacol. 2020; 14:1- 7.

23. Beach EF, Turner JJ. An enzymatic method for glucose determination uptake in body fluids. Clin. Chem. 1958; 4: 462-468.

24. Stanley MP, Venugopal MP. Anti-oxidant action of Tinospora cordifolia root extract in alloxan-induced Diabetic rats. Phytother Res. 2001; 15:213-218.

25. Rheney CC, Kirk KK. Performance of three blood glucose meters. Ann Pharmacother. 2001; 34: 317-321.

26. Delano WL. The PyMOL Molecular Graphics System. Delano Scientific, San Carlos. 2002

27. Trott O, Olson AJ. AutoDock Vina: Improving the Speed and Accuracy of Docking with a New Scoring Function, Efficient Optimization, and Multithreading. J. of Comp. Chem. 2010; 31: 455–461. https://doi.org/10.1002/jcc.

28. Akter S, Ali H, Shati AA, Alfaifi MY, Elbehairi SEI, Sayyed RZ, Yeasmin T. Antidiabetic Activity of Methanolic Extract of Hibiscus sabdariffa Linn. Fruit in Alloxan-induced Swiss Albino Diabetic Mice. Open Agric. 2024; 9:2022-2043.

29. Momoh S, Yusuf OW, Adamu MM, Agwu COC, Atanu FO. Evaluation of the phytochemical composition and hypoglycaemic activity of methanolic leaves extract of Costusafer in albino rats. Br. J. Pharm. Res. 2011; 1:1-8.

30. Oliver-Bever B. Medicinal Plants in Tropical West Africa. London: Cambridge University Press.1986: pp 6. http://dx.doi.org/10.1017/cbo9780511753114.

31. Roni WS, Omri SS, Saar D, Itamar R. Overview of Oxidative Stress and Inflammation in Diabetes. J. Diabetes. 2024; 16: e70014. https://doi.org/10.1111/1753-0407.70014.

32. Idakwoji PA, Joshua PE, Asamodu RO, Njoku OU, Nwodo OFC. Antidiabetic activity, phytochemical and proximate compositions of different extracts of Tephrosia bracteolata leaves. Asian J. Plant Sci. 2021; 20:291-299.

33. Furman BL, Candasamy M, Bhattamisra SK, Veettil SK. Reduction of blood glucose by plant extracts and their use in the treatment of diabetes mellitus; discrepancies in effectiveness between animal and human studies. J. Ethnopharmacol. 2020; 247:1122-1164.

34. Roy S, Ghosh A, Majie A, Karmakar V, Das S, Dinda SC, Bose A, Gorain B. Terpenoids as potential phytoconstituent in the treatment of diabetes: From preclinical to clinical advancement. Phytomedicine. 2024; 129:155638.

35. Pak Y, Huang LC, Lilley KJ, Larner J. “In vivo conversion of [3H] myoinositol to [3H] Chiroinositol in rat tissues,” J. Biol. Chem. 1992; 267: 16904–16910.

36. Kamalesh, DR, Geetha KM. Role of dietary myo-inositol in diabetes and diabetic complication. J. Chem. Health Risks. 2025; 15:737–750. https://jchr.org/index.php/JCHR/article/view/7530.

37. Quaresima P, Myers SH, Pintaudi B, D’Anna R, Morelli M, Unfer V. Gestational diabetes mellitus and polycystic ovary syndrome, a position statement from EGOI-PCOS. Front. Endocrinol. 2025; 16:1501110. https://doi.org/10.3389/fendo.2025.1501110.

38. Romeo P, D’Anna R. Myoinositol and metformin in the prevention of gestational diabetes in high-risk patients: A narrative review. J. Clin. Med. 2024; 13: 53-87. https://doi.org/10.3390/jcm13185387.

39. Li C, Shi H. Inositol supplementation for the prevention and treatment of gestational diabetes mellitus: A meta-analysis of randomized controlled trials. Arch. Gynecol. Obs. 2024; 309: 1959-1969. https://doi.org/10.1007/s00404-023-07100-x.

40. Corrado FD, Anna R, di Vieste G. “The effect of myoinositol supplementation on insulin resistance in patients with gestational diabetes,” Diabet Med. 2011; 28: 972–975.

41. Lubin V, Shojai R, Darmon P, Cosson E. “A pilot study of gestational diabetes mellitus not controlled by diet alone: first line medical treatment with myoinositol may limit the need for insulin,” Diabetes Metab. 2016; 42: 192–195.

42. Chand S, Tripathi AS, Dewani AP, Sheikh NWA. Molecular targets for management of diabetes: Remodelling of white adipose to brown adipose tissue, Life Sci. 2024; 345: 122607. https://doi.org/10.1016/j.lfs.2024.122607.

43. Basilio P, Giacoma Di V, Matteo B. The Effectiveness of Myo-Inositol and D-Chiro Inositol Treatment in Type 2 Diabetes. Int. J. Endocrinol. 2016; 16: 1-5.

44. Baigent C, Emberson J, Haynes R, Herrington WG, Judge P, Landray MJ, Mayne KJ, Ng SY, Preiss D, Roddick AJ. Impact of diabetes on the effects of sodium-glucose co-transporter-2 inhibitors on kidney outcomes: Collaborative meta-analysis of large placebo-controlled trials. Lancet. 2022; 400: 1788-1801. https://doi.org/10.1016/S0140-6736(22)02074-8.

45. Palmer SC, Tendal B, Mustafa RA, Vandvik PO, Li S, Hao Q, Tunnicliffe D, Ruospo M, Natale P, Saglimbene V. Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: Systematic review and network meta-analysis of randomized controlled trials. BMJ. 2021; 372: m4573. https://doi.org/10.1136/bmj.m4573.

46. Kurosaki E, Ogasawara H. Ipragliflozin and other sodium-glucose cotransporter- 2 (SGLT2) inhibitors in the treatment of type 2 diabetes: preclinical and clinical data. Pharmacol. Ther. 2013; 139: 51-59. https://doi.org/10.1016/j.pharmthera.2013.04.003.

47. Kakinuma H, Oi T, Hashimoto-Tsuchiya Y. (1S)-1,5-anhydro-1-[5-(4- methoxybenzyl)-2-methoxy-4-methylphenyl]-1-thio-D-glucitol (TS-071) is a potent, selective sodium-dependent glucose cotransporter 2 (SGLT 2) inhibitor for type 2 diabetes treatment. J. Med. Chem. 2010; 53: 3247-61.

48. American Diabetes Association Professional Practice Committee. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes- 2025. Diabetes Care. 2025; 48: S181–S206. https://doi.org/10.2337/dc25-S009.

49. Seino Y, Sasaki T, Fukatsu A. Dose-finding study of luseogliflozin in Japanese patients with type 2 diabetes mellitus: a 12-week, randomized, double-blind, placebo-controlled, phase II study. Curr. Med. Res. Opin. 2014; 30:1238-1245.

Downloads

Published

2025-08-31

How to Cite

Antidiabetic Activity and in silico Molecular Docking of GC-MS- Identified Compounds in Chromatographic Fractions of Tephrosia bracteolata Guill. & Perr. (Fabaceae) Leaves. (2025). Tropical Journal of Natural Product Research , 9(8), 3720-3728. https://doi.org/10.26538/tjnpr/v9i8.31