Modulatory Effects of Aqueous Leaf Extract of Gongronema latifolium (asclepiadaceae) on Some Natural and Adaptive Immune Responses in Rodents http://www.doi.org/10.26538/tjnpr/v7i6.23
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Abstract
Gongronema latifolium (GL) is widely used by indigenous communities in southern Nigeria as a food spice and is known for its rich natural compounds with significant biological and pharmacological properties. This prompted the investigation into the effects of the aqueous G. latifolium leaf extract (AGL) on several specific and non-specific immune responses in rodent (mice) models and in vitro essay. The effects of AGL on delayed-type hypersensitivity (DTH) response, phagocytic activities of monocytic cells using carbon clearance assay, haemolytic complement activation test, antibody expression studies, and cyclophosphamide-induced neutropenia assay were examined. Administration of AGL (100, 200, or 400 mg/kg) significantly (p<0.05) increased footpad inflammation in a dose-related manner at 24 hours after antigen challenge in DTH studies. In a homologous prime-boost immunization strategy with tetanus toxoid (TT) or ovalbumin (OVA) antigens, there was a significant (p<0.05) elevation of total immunoglobulin, IgG, and IgG1. The mean phagocytic indices of carbon clearance were significantly (p < 0.05) greater after oral delivery in treated groups, even at the lowest dose of 100 mg AGL/kg. In immunocompromised mice, after cyclophosphamide-induced immunosuppression, short-term daily supplementation of AGL (100, 200, or 400 mg/kg) produced a significant increase in total neutrophil count and affected other leukocyte differential counts. At all concentrations greater than 125 g/ml in the in vitro assay, AGL inhibited the classical complement system. These findings indicate that the aqueous extract of Gongronema latifolium may enhance both cellular and humoral immune responses. Consequently, further research will be needed to learn more about the immune system's strengthening effects and mechanisms.
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References
Hutchison, J. and Dalziel, J.M. (1963) Flora of West Tropical Africa. Vol. II, Crown Agents for Overseas Government and Administration, London, 435-436.
Chattopadhyah RR. A comparative evaluation of some blood sugar lowering agents of plant origin. J. Ethnopharmacol. 1999; 67:367-372.
Edim EH, Egomi UG, Ekpo UF, Archibong EU. A review on Gongronema latifolium (Utasi): A novel antibiotic against Staphylococcus aureus related infections. Int. J. Biochem. Biotechnol. 2012; 1(8):204-208
Morebise O, Fafunso MA, Makinde JM. Membrane stabilizing activity: A possible mechanism of action for the antiinflammatory property of Gongronema latifolium leaves. Int J Biomed Health Sci., 1998; 1(1):15-19.
Morebise O, Fafunso, MA, Makinde JM, Olajide OA. Evaluation of the bioactivity of Gongronema latifolium leaf extract in rodents. Sci. Focus 2006; 11(1):27-30.
Edet EE, Akpanabiatu MI, Uboh FE, Edet TE, Eno AE, Itam EH, Umoh IB. Gongronema latifolium crude leaf extract reverses alterations in haematological indices and weight loss in diabetic rats. J Pharmacol Toxicol., 2011; 6(2):174- 181.
Mosango DM. Gongronema latifolium Benth. Record from PROTA4U. Schmelzer GH, Gurib-Fakim A (eds.). Plant Resources of Tropical Africa (PROTA); 2002. Available: https://prota4u.org/database/protav8.asp?g=pe&p=Gongron ema+latifolium+Benth.
Oliver-Bever B. Medicinal plants in tropical West Africa. Cambridge University Press, London., 1986; 89-90.
Iwu MM. Dietary plants and masticatories as sources of biologically active substances. In, 4th OAU/ STRC INTERAFRICAN symposium on traditional pharmacopoeia and African medicinal plants. Abuja-Nigeria. 1988; pp: 70 and 379
Morebise O, Fafunso MA, Makinde JM, Olajide OA, Awe EO. Antiinflammatory property of the leaves of Gongronema latifolium. Phytother. Res. 2002; 16:75-77.
Eleyinmi AF (2007). Chemical composition and antibacterial activity of J. Zhejiang Univ. Sci. B 8(5), 352-358.
Ugochukwu NH, Babady NE. Antioxidant effects of Gongronema latifolium in hepatocytes or rat models of noninsulin dependent diabetes mellitus. Fitoterapia 2002; 73(7-8): 612-618.
Nwanjo HU, Okafor MC, Oze GO. Anti-lipd peroxidative activity of Gongronema latifolium in Streptozotocin-induced diabetic rats. Nig. J. Physiol. Sci. 2006; 21(1-2):61- 65
Eze SO, Nwanguma BC. Effects of tannin extract from Gongronema latifolium leaves on lipoxygenase Cucumeropsis manii seeds. J. Chem., 2013 (Article ID 864095), 1-7. http://www.doi.org/10.1155/2013/864095
Iweala EEJ, Liu F, Cheng R, Li Y. Anticancer and free radical scavenging activity of some Nigerian food plants in vitro. Int J Cancer Res. 2015; 11(1):41-51.
Omodale P, Enitan S, Adejumo E, Akinleye W, Bella A. Protective effect of aqueous root extract of Gongronema latifolium against paracetamol induced hepatotoxicity and chloroquine induced nephrotoxicity in rats. Int J Herb Med. 2017; 5(3):115-120.
Nworu CS, Akah PA, Esimone CO, Okoli CO, Okoye FBC. Immunomodulatory activities of Kolaviron, a mixture of three related biflavonoids of Garcinia kola Heckel. Immunopharmacol. Immunotoxicol. 2008; 30(2):317-332.
Nworu CS, Akah PA, Okoye FBC, Esimone CO. Aqueous extract of Phyllanthus niruri (Euphorbiaceae) enhances the phenotypic and functional maturation of bone marrowderived dendritic cells and their antigen presentation function. Immunopharmacol. Immunotoxicol. 2010; 32(3):393-401
Nworu CS, Akah PA, Okoye FBC, Esimone CO. Supplementation with aqueous leaf extract of Morinda lucida enhances immunorestoration and upregulates the expression of cytokines and immunostimulatory markers. Immunol. Investig. 2012; 4(8):799-819.
Nworu CS, Akah PA, Okoye FBC, Esimone CO. Aqueous extract of Phyllanthus niruri (Euphorbiaceae) enhances the phenotypic and functional maturation of bone marrowderived dendritic cells and their antigen presentation function. Immunopharmacol. Immunotoxicol. 2010; 32(3):393-401.
Nworu CS, Akah PA, Okoye FBC, Proksch P, Esimone CO. The effects of Phyllanthus niruri aqueous extract on the activation of murine lymphocytes and bone marrow-derived macrophages. Immunol. Investig. 2010; 39 (3):245-267.
Agwaramgbo A, Ilodigwe EE, Ajaghaku DL, Onuorah MU, Mbagwu SI. Evaluation of antioxidant, immunomodulatory activities, and Safety of ethanol extract and fractions of Gongronema latifolium Fruit, Int. Sch. Res. Not., 2014, 695272, https://doi.org/10.1155/2014/695272
Evans WC. Trease and Evans’ Pharmacognosy: Sixteenth Edition. Trease Evans’ Pharmacogn Sixt Ed.; 2009; 1–603.
National Research Council. Guide for the care and use of laboratory animals. 8th ed.; 2011; 1-246.
Lorke D. A new approach to practical acute toxicity testing. Arch Toxicol, 1983; 54(4):275–287. Available from: https://link.springer.com/article/10.1007/BF01234480
Nworu CS, Ihim SA, Okoye FBC, Esimone CO, Adikwu MU, Akah PA. Immunomodulatory and immunorestorative activities of β-D-glucan-rich extract and polysaccharide fraction of mushroom, Pleurutus tuberregium. Pharm Biol. 2015; 53(11):1555-1566.
Beck L, Spiegelberg HL. The polyclonal and antigenspecific IgE and IgG subclass response of mice injected with ovalbumin in alum or complete Freund’s adjuvant. Cell Immunol. 1989; 123(1):1-8.
Kanase V, Patil DT. Evaluation of in vivo immunomodulatory activity of aqueous and ethanolic extract of Eulophia nuda l. Asian J Pharm Clin Res. 2018; 11(12):374-379.
Tamokou JD, Kuete V. 7—toxic plants used in african traditional medicine, in Toxicological survey of african medicinal plants. Editor V. Kuete (Elsevier), 2014: 135-180. http://www.doi:10.1016/B978-0-12-800018-2.00007-8
Anywar G, Kakudidi E, Byamukama R, Mukonzo J, Schubert A, Oryem-Origa H, Jassoy CA. Review of the Toxicity and Phytochemistry of Medicinal Plant Species Used by Herbalists in Treating People Living With HIV/AIDS in Uganda. Front Pharmacol. 2021; 12:615147. http://www.doi: 10.3389/fphar.2021.615147
Ladics GS. Primary immune response to sheep red blood cells (SRBC) as the conventional T-cell dependent antibody response (TDAR) test. J. Immunotoxicol. 2007; 4(2):149- 152.
Atkinson SM, Usher PA, Kvist PH, Markholst H, Haase C, Nansen A. Establishment and characterization of a sustained delayed-type hypersensitivity model with arthritic manifestations in C57BL/6J mice. Arthritis Res. Ther. 2012; 14(3):R134; http://www.doi.org/10.1186/ar3867
Li G, Kolan SS, Guo S, Marciniak K, Kolan P, Malachin G, Grimolizzi F, Haraldsen G, Skålhegg BS. Activated, ProInflammatory Th1, Th17, and Memory CD4+ T Cells and B Cells Are Involved in Delayed-Type Hypersensitivity Arthritis (DTHA) Inflammation and Paw Swelling in Mice. Front. Immunol. 2021; 12, 689057. http://www.doi.org/10.3389/fimmu.2021.689057
Allenspach EJ, Torgerson TR. Immunogenetics, in S. Maloy & K. Hughes (Eds.), Brenner's Encyclopedia of Genetics (Second Edition) (pp. 25–28). Academic Press., 2013; http://www.doi.org/10.1016/B978-0-12-374984-0.00770-1
Slauch JM. How does the oxidative burst of macrophages kill bacteria? Still an open question. Mol Microbiol. 2011; 80(3): 580-3. http://www.doi: 10.1111/j.1365-2958.2011.07612. x.
Austermann J, Roth J, Barczyk-Kahlert K. The Good and the Bad: Monocytes' and Macrophages' Diverse Functions in Inflammation. Cells 2022; 11(12):1979.
Arango Duque G, Descoteaux A. Macrophage cytokines: involvement in immunity and infectious diseases. Front. Immunol. 2014; 5:491-505;
http://www.doi.org/10.3389/fimmu.2014.00491
Palmieri EM, McGinity C, Wink DA, McVicar DW. Nitric Oxide in Macrophage Immunometabolism: Hiding in Plain Sight. Metabolites 2020; Article 429; 10(11):1-34; http://www.doi: 10.3390/metabo10110429.
Bertók L. New Prospect for the Enhancement of Natural Immunity; In NeuroImmune Biology (Eds. Lóránd Bertók, Donna A. Chow); Elsevier 2005; 5:289-307, ISBN 9780444517555. http://www.doi.org/10.1016/S1567- 7443(05)80019-5.
Bao L, Hao C, Wang J, Wang D, Zhao Y, Li Y, Yao W. HighDose Cyclophosphamide Administration Orchestrates Phenotypic and Functional Alterations of Immature Dendritic Cells and Regulates Th Cell Polarization; Front. Pharmacol. 2020; Article 775; 11:1-11; http://www.doi:
3389/fphar.2020.00775
Murphy K, Weaver C, Berg L. The complement system and innate immunity; In Janeways’s Immunobiology: The Immune System in Health and Disease. 10th edition. New York: Garland; Science; 2022; ISBN: 978-0-393-88487-6
Akah PA, Uzodinma SU, Okolo, CE. Antidiabetic activity of aqeous and methanol extract and fraction of Gongronema latifolium (Aselepidaceae) leaves in Alloxan diabetic rats. J. Appl. Pharm. Sci. 2011; 1(9):99-102.
Robert AE, Luke UO, Udosen EO, Ufot SU, Effiong AE, Ekam VS. Antidiabetic and anti-hyperlipidemic properties of ethanol root extract of Gongronema latifolium (utazi) on streptozotocin (STZ) induced diabetic rats. ARPN J. Food Sci. Technol. 2013; 3(10):995-998.
Onuoha SC, Chinaka NC. Carbon tetrachloride induced renal toxicity and the effect of aqueous extract of Gongronema latifolium in wistar rats. Drug Discov. 2013; 4(11):15-16.
Ezeonwu VU. Effects of Ocimum gratissimum and Gongronema latifolium on fertility parameters: a case for biherbal formulations. Asian J. Biochem. Pharm. 2013; 1(3):142-147.
Owu DU, Nwokocha CR, Obembe AO, Essien AD, Ikpi DE, Osim EE. Effect of Gongronema latifolium leaf extract on gastric acid secretion and cytoprotection in streptozotocininduced diabetic rats. West Indian Med J 2012; 61(9):853- 860
Morebise O, Fafunso MA. Antimicrobial and phytotoxic activities of saponin extracts from two Nigerian edible medicinal plants. Biokemistri 1998; 8(2):69-77.
Nwinyi OC, Chinedu NS, Ajani OO. Evaluation of antibacterial activity of Psidium guajava and Gongronema latifolium. J. Med. Plants Res. 2008; 2(8):189-192.
Palu AK, Kim AH, West BJ, Deng S, Jensen J, White L. The effects of Morinda citrifolia L. (noni) on the immune system: Its molecular mechanisms of action. J Ethnopharmacol. 2008; 115(3):502-506.
Shorinwa OA, Out VS. Immunomodulatory Activity of the Aqueous Extract of the pith of Citrus limon L. (Rutaceae) Using Cyclophosphamide Induced Myelosuppression. Trop. J. Nat. Prod. Res. 2023; 7(3):2660–2664. http://www.doi.org/10.26538/tjnpr/v7i3.29.