Insights on the Anti-inflammatory Mechanism of the Polyphenolic-Rich Fraction of Glyphaea brevis (Spreng.) Monachino (Tiliaceae) Leaves

Document Type : Research Paper

Authors

1 Department of Chemical Sciences (Biochemistry Program), Godfrey Okoye University, Enugu State, Nigeria.

2 Department of Pharmacology & Toxicology, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, Enugu State 410001, Nigeria

3 Department of Biochemistry, Faculty of Biological Sciences, University of Nigeria, Nsukka, Enugu State 410001, Nigeria Natural Science Unit, School of General Studies, University of Nigeria, Nsukka, Enugu State 410001, Nigeria Natural Science Unit, School of General Studies, University of Nigeria, Nsukka, Enugu State 410001, Nigeria

4 Department of Biochemistry, Faculty of Biological Sciences, University of Nigeria, Nsukka, Enugu State 410001, Nigeria

5 Deparment of Pharmaceutical Microbiology & Biotechnology, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, Enugu State 410001, Nigeria

6 Department of Pharmaceutical Microbiology and Biotechnology, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka

Abstract

Glyphaea brevis (Spreng.) Monachino has been employed folklorically in West Africa for decades to manage inflammatory disorders such as peptic ulcer, edema, dyspepsia, and worm infestations; however, these pharmacological activities have not been scientifically proven. The study investigated the chemical composition and in-vitro/in-vivo anti-inflammatory capabilities of the polyphenolic-rich fraction of G. brevis leaves (PREG). In-vitro anti-inflammatory indices were evaluated using the human red blood cell (HRBC) methods. The acute lethality (LD50) test was demonstrated in mice with graded dosages (10 to 5000 mg/kg body weight of PREG) via oral intubation. While in-vivo anti-inflammatory activity was determined using a mice model inflicted with an intraperitoneal injection of 0.1ml of undiluted fresh egg albumin paw edema using egg albumin. All parameters were assayed according to standard protocols. High levels of tannins, phenols, flavonoids, and minimum amounts of terpenoids, steroids, alkaloids, and saponins were observed in PREG. The LD50 test demonstrated no toxicity and mortality in mice up to 5.0 g/kg bw p.o. PREG. The anti-inflammatory assays showed that at the different concentrations (0.2 - 1.0 mg/ml), PREG effectively inhibited albumin denaturation, platelet aggregation, hypotonicity-induced hemolysis, protease, and phospholipase A2 activity, as the standard drugs (Aspirin and Prednisolone). Also, PREG suppressed significantly (p< 0.05) the progression of egg albumin-induced mice paw edema, and these increased with time (0.5 - 5h). The maximum percentage of edema inhibition (91.4%) was observed in mice administered with 400 mg/kg bw PREG, and this was close to that (94.49%) obtained in the group administered with the reference drug (Indomethacin). These give insights into the anti-inflammatory potential of PREG.

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References

  1. Ahmed A.U. An overview of inflammation: mechanism and consequences. Front in Biol. 2011;6. http://dx.doi.org/10.1007/s11515-011-1123-9
  2. Guo H., Callaway J.B., Ting J.P. Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat Med. 2015;21:677-687. https://doi.org/10.1038/nm.3893.
  3. Wu T. The effect of Psidium guajava hydroalcoholic extract on reducing the expression of Resistin and TNF-α genes in articular chondrocytes of patients with knee osteoarthritis. Cell and mol biol (Noisy-le-Grand, France). 2022;67(6): 74-81. https://doi.org/10.14715/cmb/2021.67.6.11
  4. Larson E. Social and economic impact of infectious diseases--United States. Clin Perform Qual Healt Car. 1997;5:31-37.
  5. Furman D., Campisi J., Verdin E., Carrera-Bastos P., Targ S., Franceschi C., Ferrucci L.W., Gilroy D., Fasano M.A., Miller G.W., Mantovani A.H., Weyand A., Barzilai C.M., Goronzy N., Rando J.J., Effros T.A.R.B.,  Lucia A., Kleinstreuer N., Slavich G.M. Chronic inflammation in the etiology of disease across the life span. Nat Med. 2019;25:1822-1832. https://doi.org/10.1038/s41591-019-0675-0 
  6. Chen L., Deng H., Cui H., Fang J., Zuo Z., Deng J., Li Y., Wang X., Zhao L. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 2017;9(6):7204-7218. https://doi.org/10.18632/oncotarget.23208
  7. Kragballe K. Topical corticosteroids: mechanisms of action. Acta Derm Venereol Suppl (Stockh). 1989;151:7-10.
  8. Zhu L., Zhang C., Chuck R.S. Topical steroid and non-steroidal anti-inflammatory drugs inhibit inflammatory cytokine expression on the ocular surface in the botulinum toxin B-induced murine dry eye model. Mol Vis. 2012;18:1803-1812.
  9. Mpofu S. Steroids, non-steroidal anti-inflammatory drugs, and sigmoid diverticular abscess perforation in rheumatic conditions. Ann Rheum Dis. 2004;63:588-590. https://doi.org/10.1136/ard.2003.010355
  10. Fürst R., Zündorf I. Plant-derived anti-inflammatory compounds: hopes and disappointments regarding the translation of preclinical knowledge into clinical progress. Mediat of Inflamm. 2014;1-9. http://dx.doi.org/10.1155/2014/146832
  11. Osafo N., Boakye Y. Glyphaea brevis (Spreng.) Monach: A review of the ethno-medical, phytochemical and pharmacological investigations. Br J Pharm Res 2016;12:1-18. https://doi.org/10.9734/bjpr/2016/26689.
  12. Obiri D.D., Osafo N., Abotsi R.E. Antiallergic and antiarthritic effects of stem bark extract of Glyphaea brevis (Spreng) Monachino (Tiliaceae) in murine models. ISRN Pharmacol. 2013;1–13. https://doi.org/10.1155/2013/874263.
  13. Dickson R.A., Ekuadzi E., Annan K., Komlaga G. Antibacterial, anti-inflammatory, and antioxidant effects of the leaves and stem bark of Glyphaea brevis (Spreng) Monachino (Tiliaceae): a comparative study. Phcog Res. 2011;3:166-172.
  14. Anjuwon T.M., Adepoju O.A., Adeniran S.M. A comparative study of antimalarial and toxicological effects of aqueous and methanol extracts of glphaea brevis leaves in mice. Afr J Biomed Res. 2019;22:309-314.
  15. Olugbodi J.O., David O., Ojo O.A., Akinmoladun A.C. Influence of Glyphaea brevis twig extract on nucleus , tight junctions and expression of inhibin - β, stem cell factor, and androgen binding protein in TM4 Sertoli cells. Asia Pac J of Rep. 2019;8(4):157–166. https://doi.org/10.4103/2305-0500.262832
  16. Mbosso E.J.T., Wintjensa R., Bruno Ndjakou Lentac B.N., Ngouelad S., Rohmere M., Tsamod E. Chemical constituents from Glyphaea brevis and Monodora myristica: chemotaxonomic significance. Chemist and Biodiver. 2013;10:224-232.
  17. Oloruntobi J.A., Olusola J.O. Analysis of bioactive components in ethanolic extract of Glyphaea brevis leaves. J of EmergTren in Engineer and App Sci. 2015;6(4):263-266.
  18. Chu Y.F., Sun J., Wu X., Liu R.H. Antioxidant and antiproliferative activities of common fruits. J Agric Food Chem. 2002;50:7449-7454.
  19. Jesumani V., Du H., Pei P., Aslam M., Huang N. Comparative study on skin protection activity of polyphenol-rich extract and polysaccharide-rich extract from Sargassum vachellianum. PLo On. 2020;15(1): e0227308. https://doi.org/10.1371/journal.pone.0227308
  20. Vane J.R. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol 1971;231:232–235. https://doi.org/10.1038/newbio231232a00
  21. Oyedepo O.O., Femurewas A.J. Anti-protease and membrane stabilizing activities of extracts of Fagra zanthoxiloides, Olax subscorpioides and Tetrapleura tetraptera. In J Pharm. 1995;33: 65-69.
  22. Mizushima Y., Kobayashi M. Interaction of anti‐inflammatory drugs with serum proteins, especially with some biologically active proteins. J Pharm Pharmacol. 1968;20:169-173. https://doi.org/10.1111/j.2042-7158.1968.tb09718.x.
  23. Born G.V.R., Cross M.J. The aggregation of blood platelets. J Physiol. 1963;168:178-195.
  24. Oyedepo O.O., Akindele V.R., Okunfolami OK. Effect of extracts of Parham, P. The immune system. New York (NY): Garland Publishing. 1997.
  25. Ezekwesili C.N., Nwodo O.F.C. Anti-inflammatory properties of Vigna unguiculata seed extract. J Med Lab Sci. 2000; 9:141-145.
  26. National Institutes of Health (US), author Guide for the Care and Use of Laboratory Animals. NIH Publication No. 85-23. Revised 1985.
  27. Lorke D. A new approach to practical acute toxicity testing. Arch Toxicol. 1983;53:275-289.
  28. Okokon J.E., Nwafor P.A. Antiinflammatory, analgesic and antipyretic activities of ethanolic root extract of Croton zambesicus. Pak J Pharm Sci. 2010;23:383-390.
  29. Anosike C.A., Onyechi O., Ezeanyika L.U.S. The anti-inflammatory activity of garden egg (Solanum aethiopicum) on egg albumin-induced oedema and granuloma tissue formation in rats. Asian Pac J Trop Biomed. 2012;1:62-66.
  30. Ekor M. The growing use of herbal medicines : issues relating to adverse reactions and challenges in monitoring safety. Front in Pharmacolo. 2014;4(January):1-10. https://doi.org/10.3389/fphar.2013.00177.
  31. Šantić Ž., Pravdić N., Bevanda M., Galić K. The historical use of medicinal plants in traditional and scientific medicine. Medici Academi Mostariens. 2017;5(1-2):69-74.
  32. Lim X.Y., Teh B.P., Tan T.Y.C. Medicinal plants in COVID-19: potential and limitations. Front. Pharmacol. 2021;12:611408. https://doi.org/10.3389/fphar.2021.611408
  33. Di Marco G., Gismondi A., Panzanella L., Canuti L., Impei S., Leonardi D., Canini A. Botanical influence on phenolic profile and antioxidant level of Italian honeys. J Food Sci Technol. 2018;55:4042-4050.
  34. Farooq S., Shaheen G., Asif H.M., Aslam M.R., Zahid R., Rajpoot S.R., Jabbar S., Zafar F. Preliminary phytochemical analysis: in-vitro comparative evaluation of anti-arthritic and anti-inflammatory potential of some traditionally used medicinal plants. Dos Respon. 2022;20(1):15593258211069720. http://dx.doi.org/10.1177/15593258211069720
  35. Yang N.N., Zhang Y.F., Zhang H.T., Ma X.H., Shen J.H., Li P., Zhang Y.H. The in vitro and in vivo anti-inflammatory activities of triterpene saponins from Clematis florida. Nat Prod Res. 2020;1-4.
  36. Yang T., Hu Y., Yan Y., Zhou W., Chen G., Zeng X., Cao Y. Characterization and evaluation of antioxidant and anti-inflammatory activities of flavonoids from the fruits of Lyciumbarbarum. Foods. 2022;11:306.
  37. Waghole R.J., Misar A.V., Kulkarni N.S., Khan F., Naik D.G., Jadhav SH. In vitro and in vivo anti-inflammatory activity of Tetrastigmasulcatum leaf extract, pure compound and its derivatives. Inflammopharmaco. 2022;30:291-311.
  38. Schauss A.G. Polyphenols and Inflammation. In: Watson RR and Preedy VR (eds.) Bioactive Food as Dietary Interventions for Arthritis and Related Inflammatory Diseases. San Diego: Academic Press, 2013, pp. 379-392.
  39. Selma M.V., Espín J.C., Tomás-Barberán F.A. Interaction between phenolics and gut microbiota: role in human health. J Agric Food Chem 2009;12(57)(15):6485-6501. https://doi.org/10.1021/jf902107d
  40. Gross G., Jacobs D.M., Peters S., Possemiers S., Duynhoven J.V., Vaughan E.E., Wiele T.V.D. In vitro bioconversion of polyphenols from black tea and red wine/ grape juice by human intestinal microbiota displays strong interindividual variability. J Agric Food Chem A-J. 2010. https://doi.org/10.1021/jf101475m
  41. Attiq A., Jalil J., Husain K., Ahmad W. Raging the war against inflammation with natural products. Front in Pharmaco. 2018;9. http://dx.doi.org/10.3389/fphar.2018.00976
  42. Mozaffarian D., Wu J.H.Y. Flavonoids, dairy foods, and cardiovascular and metabolic health. Circulat Res. 2018;122:369-384.
  43. Timmermans S., Souffriau J., Libert C. A general introduction to glucocorticoid biology. Front Immunol. 2019;4(10):1545. https://doi.org/10.3389/fimmu.2019.01545
  44. Gunathilake K.D.P.P., Ranaweera K.K.D.S., Rupasinghe H.P.V. In vitro anti-inflammatory properties of selected green leafy vegetables. Biomedicin. 2018;6:107 http://dx.doi.org/10.3390/biomed icines6040107
  45. Dhama K., Latheef S.K., Dadar M., Samad H.A., Munjal A., Khandia R., Karthik K., Tiwari R., Yatoo M.I., Bhatt P., Chakraborty S., Singh K.P., Iqbal H.M.N., Chaicumpa W., Joshi S.K. Biomarkers in stress related diseases/disorders: diagnostic, prognostic, and therapeutic values. Front in Mol Biosci. 2019;6. http://dx.doi.org/10.3389/fmolb.2019.00091
  46. Osman N.I., Sidik N.J., Awal A., Mara T. In vitro xanthine oxidase and albumin denaturation inhibition assay of Barringtonia racemosa L . and total phenolic content analysis for potential anti-inflammatory use in gouty arthritis. J of Intercult Ethnopharmaco. 2016;5(4). https://doi.org/10.5455/jice.20160731025522
  47. Raju M.G., Srilakshmi S., Suvarchala NVLR. Anti-inflammatory, in-silico docking and adme analysis of some isolated compounds of Tageteserecta flower heads. Int J Pharm Sci Res. 2019;11:1358-1366.
  48. Rosales C. Neutrophil: a cell with many roles in inflammation or several cell types? Front in Physiol. 2018;9. https://doi.org/10.3389/fphys.2018.00113
  49. Chanchal S., Mishra A., Singh M.K., Ashraf M.Z. Understanding inflammatory responses in the manifestation of prothrombotic phenotypes. Front in Cell and Develop Bio. 2020;8. http://dx.doi.org/10.3389/fcell.2020.00073
  50. Hirayama D., Iida T., Nakase H. The phagocytic function of macrophage-enforcing innate immunity and tissue homeostasis. Intern J of Molecu Sci. 2017;19(1):92. https://doi.org/10.3390/ijms19010092
  51. Bermúdez-Humarán L.G., Motta J.P., Aubry C. Serine protease inhibitors protect better than IL-10 and TGF-β anti-inflammatory cytokines against mouse colitis when delivered by recombinant lactococci. Microb Cell Fact. 2015;14:26.
  52. Enechi O.C., Okeke E.S., Abonyi U.C., Nwankwo N.E., Ndimele U.J., Benneth M.E. Evaluation of in vitro anti-inflammatory and antioxidant potentials of methanol leaf extract of Fagarazanthoxyloides. Indo Am J Pharm Sci 2019;6:14365-14371.
  53. Hanna V.S., Hafez E. Synopsis of arachidonic acid metabolism: A review. J of Adv Res. 2018;11:23-32. https://doi.org/10.1016/j.jare.2018.03.005
  54. Wang B., Wu L., Chen J. Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets. Sig Transduct Target Ther. 2021;6:94 https://doi.org/10.1038/s41392-020-00443-w
  55. Ricciotti E., FitzGerald G.A. Prostaglandins and inflammation. Arteriosclero, Thrombo, and Vascul Biolo. 2011;31(5):986-1000. https://doi.org/10.1161/ATVBAHA.110.207449
  56. Takeuchi K. Pathogenesis of NSAID-induced gastric damage: importance of cyclooxygenase inhibition and gastric hypermotility. World J of Gastroenterol. 2012;18(18):2147–2160. https://doi.org/10.3748/wjg.v18.i18.2147
  57. Fabre J., Gurney M.E. Limitations of current therapies to prevent thrombosis : a need for novel strategies. Mol Biosyst. 2010;6:305-315. https://doi.org/10.1039/b914375k
  58. Umapathy E., Ndebia E.J., Meeme A., Adam B., Menziura P., Nkeh-Chungag B.N., Iputo J.E. An experimental evaluation of Albucasetosa aqueous extract on membrane stabilization, protein denaturation and white blood cell migration during acute inflammation. J Med Plant Res. 2010;4:789-795.
  59. Kardile M.V., Mohamad A.S., Israf D.A. Membrane Stabilization assay for anti-inflammatory activity yields false positive results for samples containing traces of ethanol and methanol. World J Pharm Pharm Sci. 2016;5:493-497.
  60. Yoganandam G.P., Mohamad A.S., Israf D.A. Evaluation of anti-inflammatory and membrane stabilizing properties of various extracts of Punicagranatum L. (Lythraceae). Int J Pharmtech Res. 2010;2:1260-1263.
  61. Enechi O.C., Amah C.C., Okagu I.U., Ononiwu CP, Azidiegwu VC,  Ugwuoke EO, Ndukwe EE. Methanol extracts of Fagara zanthoxyloides leaves possess antimalarial effects and normalizes haematological and biochemical status of Plasmodium berghei-passaged mice. Pharm Bio. 2010;57:577-585. http://dx.doi.org/10.1080/13880209.2019.165675 
  62. Omkar A., Jeeja T., Chhaya G. Evaluation of anti-inflammatory activity of Nyctanthes arbour-tristis and Onosma echioides. Pharmacogn Mag. 2007;2:258-260.
  63. Kang H.S., Lee J.Y., Kim C.J. Anti-inflammatory activity of arctigenin from Forsythiae fructus. J Ethnopharmacol. 2008;116:305-310.
Journal of Medicinal plants and By-Products
Volume 13, Issue 1
March 2024
Pages 219-232

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