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ORIGINAL RESEARCH ARTICLE

Potential antiviral and immunomodulatory activity of Amazonian medicinal plant compounds

Sarah Maria da Silva Napoleão1 ,  João Paulo Romualdo Alarcão Bernardes2 ,  Bernardo Guerra Tenório2 ,  Calisto Moreno Cardenas3 ,  Bruno Stéfano Lima Dallago4 ,  Serhat Sezai Çiçek3,5 ,  Roberto Messias Bezerra6 ,  Jorge Federico Orellana Segovia7 ,  Elida Cleyse Gomes da Mata Kanzaki8 ,  Isamu Kanzaki8*
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1 Human Immunology Laboratory, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo. Av. Prof. Lineu Prestes, 1730. Butantã, São Paulo, SP, Brazil
2 Tropical Medicine Center, Faculty of Medicine, Darcy Ribeiro University Campus, University of Brasília, Brasília, DF, Brazil
3 Department of Pharmaceutical Biology, Kiel University, Gutenbergstraße 76, Kiel, Germany
4 Interdisciplinary Laboratory of Biosciences, Faculty of Medicine, University of Brasília, Darcy Ribeiro University Campus, Brasília, DF, Brazil
5 Department of Biotechnology, Hamburg University of Applied Sciences, Ulmenliet 20, Hamburg, Germany
6 Laboratory of Bioprospection and Atomic Absorption, Federal University of Amapá, Rod. JK, Macapá, AP, Brazil
7 Ecoregional Research Unit, Brazilian Agricultural Research Corporation, Rod. JK, Km 5, Macapá, AP, Brazil
8 Laboratory of Bioprospection, Darcy Ribeiro University Campus, University of Brasilia, Brasilia, DF, Brazil
MI, 8367 https://doi.org/10.36922/mi.8367
Submitted: 2 January 2025 | Revised: 1 February 2025 | Accepted: 3 March 2025 | Published: 25 March 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Novel antiretroviral drugs are constantly needed for human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients to confront the continuously emerging resistance to the commonly prescribed combination of anti-HIV synthetic agents and their side effects. Amazonian medicinal plants, Licania macrophylla (LM) (Chrysobalanaceae) and Ouratea hexasperma (OH) (Ochnaceae), were assayed for antiretroviral and immunomodulatory activity, by utilizing an established human leukocyte cell line and the simian immunodeficiency virus (SIV). Interleukin (IL)-4, IL-6, IL-8, IL-10, and interferon-gamma were quantified after leukocyte culture was stimulated with ethanolic plant extracts and subsequently challenged with lentivirus infection. Mitotic activity induced by OH extract was significantly more pronounced than that of LM extract. Cytokine modulation was observed in SIV-infected cells under independent treatment with OH and LM extracts. Betulinic acid, niruriflavone, (-)-epigallocatechin, (-)-gallocatechin, and 4’-O-methyl-epigallocatechin were isolated from LM. In summary, the tested extracts hold application potential in the therapy of HIV/AIDS pathology by regulating cellular proliferative activity and cytokine levels, as the isolated compounds from these plants have been reported to exhibit antiviral activity.

Keywords
Simian immunodeficiency virus
Human leukocytes
Ouratea hexasperma
Licania macrophylla
Funding
This research work was funded by FAP DF (grant number 00193-00000210/2019-60) and the University of Brasilia/ FINATEC (grant number SEI 23106.103923/2021-72).
Conflict of interest
The authors declare that they have no competing interests.
References
  1. Atanasov AG, Waltenberger B, Pferschy-Wenzig EM, et al. Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnol Adv. 2015;33(8):1582-1614. doi: 10.1016/j.biotechadv.2015.08.001

 

  1. Arribas P, Andújar C, Bidartondo MI, et al. Connecting high-throughput biodiversity inventories: Opportunities for a site-based genomic framework for global integration and synthesis. Mol Ecol. 2021;30(5):1120-1135. doi: 10.1111/mec.15797

 

  1. Duarte EA, Novella IS, Weaver SC, et al. RNA virus quasispecies: Significance for viral disease and epidemiology. Infect Agents Dis. 1994;3(4):201-214.

 

  1. Ben-Shabat S, Yarmolinsky L, Porat D, Dahan A. Antiviral effect of phytochemicals from medicinal plants: Applications and drug delivery strategies. Drug Deliv Transl Res. 2020;10(2):354-367. doi: 10.1007/s13346-019-00691-6

 

  1. Carr A, Mackie NE, Paredes R, Ruxrungtham K. HIV drug resistance in the era of contemporary antiretroviral therapy: A clinical perspective. Antivir Ther. 2023;28(5):13596535231201162. doi: 10.1177/13596535231201162

 

  1. Menéndez-Arias L, Delgado R. Update and latest advances in antiretroviral therapy. Trends Pharmacol Sci. 2022;43(1):16-29. doi: 10.1016/j.tips.2021.10.004

 

  1. Berrut G, de Decker L. Immunosénescence: Une revue [Immunosenescence: A review]. Geriatr Psychol Neuropsychiatr Vieil. 2015;13 Suppl 2:7-14. doi: 10.1684/pnv.2015.0548

 

  1. Sun L, Wang X, Saredy J, Yuan Z, Yang X, Wang H. Innate-adaptive immunity interplay and redox regulation in immune response. Redox Biol. 2020;37:101759. doi: 10.1016/j.redox.2020.101759

 

  1. Wautier JL, Wautier MP. Pro- and anti-inflammatory prostaglandins and cytokines in humans: A mini review. Int J Mol Sci. 2023;24(11):9647. doi: 10.3390/ijms24119647

 

  1. Chang Y, Durante KM. Why consumers have everything but happiness: An evolutionary mismatch perspective. Curr Opin Psychol. 2022;46:101347. doi: 10.1016/j.copsyc.2022.101347

 

  1. Chang J, Jiang T, Shan X, et al. Pro-inflammatory cytokines in stress-induced depression: Novel insights into mechanisms and promising therapeutic strategies. Prog Neuropsychopharmacol Biol Psychiatry. 2024;131:110931. doi: 10.1016/j.pnpbp.2023.110931

 

  1. Zindel J, Kubes P. DAMPs, PAMPs, and LAMPs in immunity and sterile inflammation. Annu Rev Pathol. 2020;15:493-518. doi: 10.1146/annurev-pathmechdis-012419-032847

 

  1. Çiçek SS, Pfeifer Barbosa AL, Wenzel-Storjohann A, et al. Chemical and biological evaluation of amazonian medicinal plant Vouacapoua Americana Aubl. Plants (Basel). 2022;12(1):99. doi: 10.3390/plants12010099

 

  1. Pavi CP, Prá ID, Cadamuro RD, et al. Amazonian medicinal plants efficiently inactivate Herpes and Chikungunya viruses. Biomed Pharmacother. 2023;167:115476. doi: 10.1016/j.biopha.2023.115476

 

  1. Çiçek SS, Galarza Pérez M, Wenzel-Storjohann A, et al. Antimicrobial prenylated isoflavones from the leaves of the Amazonian medicinal plant Vatairea guianensis Aubl. J Nat Prod. 2022;85(4):927-935. doi: 10.1021/acs.jnatprod.1c01035

 

  1. Oliveira AA, Segovia JF, Sousa VY, et al. Antimicrobial activity of amazonian medicinal plants. Springerplus. 2013;2:371. doi: 10.1186/2193-1801-2-371

 

  1. da Mata EC, Gonçalves MC, Segovia JF, Bezerra RM, Carvalho JC, Kanzaki LI. Antiretroviral activity of Amazonian plants. Retrovirology. 2011;8(Suppl 2):P87. doi: 10.1186/1742-4690-8-S2-P87

 

  1. Sothers CA, Prance GT. Hymenopus macrophyllus (Benth). Kew Bull. 2016;71(4)-58:20.

 

  1. Queiróz JA, Mochiuti S, Machado SA. Características silviculturais e potencial de uso da espécie arbórea Licania macrophylla Benth (anoerá/anauerá). Macapá: Embrapa Amapá[Forestry characteristics and potencial utilization of the arboreal species Licania macrophylla Benth]; 2005. Available from: https://www.infoteca.cnptia.embrapa.br/ infoteca/handle/doc/341761

 

  1. Medeiros FA, Medeiros AA, Tavares JF, Barbosa Filho JM, Lima EO, Silva MS. Licanol, um novo flavanol, e outros constituintes de Licania macrophylla Benth [Licanol, a new flavanol, and Other constituents from the Licania macrophylla Benth]. Quím Nova. 2012;35(6):1179-1183. doi: 10.1590/S0100-40422012000600021

 

  1. Correia AF, Segovia JF, Gonçalves MC, et al. Amazonian plant crude extract screening for activity against multidrug-resistant bacteria. Eur Rev Med Pharmacol Sci. 2008;12(6):369-380.

 

  1. Lemos JR. Morfoanatomia de Plantas do Semiárido (Morphoanatomy of Semiarid Plants). 1st ed. São Paulo: Blucher Open Access; 2020. p. 84. Available from: https://pdf. blucher.com.br/openaccess/9786555060485/completo.pdf

 

  1. Daniel JF, Carvalho MG, Cardoso RS, Agra MF, Eberlin MN. Others flavonoids from Ouratea hexasperma (Ochnaceae). J Braz Chem Soc. 2005;16(3b):634-638. doi: 10.1590/S0103-50532005000400022

 

  1. Fidelis QC, Faraone I, Russo D, et al. Chemical and biological insights of Ouratea hexasperma (A. St.-Hil.) Baill.: A source of bioactive compounds with multifunctional properties. Nat Prod Res. 2019;33(10):1500-1503. doi: 10.1080/14786419.2017.1419227

 

  1. Grynberg NF, Carvalho MG, Velandia JR, et al. DNA topoisomerase inhibitors: Biflavonoids from Ouratea species. Braz J Med Biol Res. 2002;35(7):819-822. doi: 10.1590/s0100-879x2002000700009

 

  1. Da Mata EC, Kanzaki LI. A Simple method to immortalize human leukocytes and its potential applications. Microbiol Infect Dis. 2019;3(2):1-3.

 

  1. Da Mata EC, Ombredane A, Joanitti GA, Kanzaki LI, Schwartz EF. Antiretroviral and cytotoxic activities of Tityus obscurus synthetic peptide. Arch Pharm (Weinheim). 2020;353(11):e2000151. doi: 10.1002/ardp.202000151

 

  1. Gazdar AF, Carney DN, Bunn PA, et al. Mitogen requirements for the in vitro propagation of cutaneous T-cell lymphomas. Blood. 1980;55(3):409-417.

 

  1. Qiu S, Shao S, Zhang Y, et al. Comparison of protective effects of nicotinamide mononucleotide and nicotinamide riboside on DNA damage induced by cisplatin in HeLa cells. Biochem Biophys Rep. 2024;37:101655. doi: 10.1016/j.bbrep.2024.101655

 

  1. Rudd H, Toborek M. Pitfalls of antiretroviral therapy: Current status and long-term CNS toxicity. Biomolecules. 2022;12(7):894. doi: 10.3390/biom12070894

 

  1. D’Orso I, Forst CV. Mathematical models of HIV-1 dynamics, transcription, and latency. Viruses. 2023;15(10):2119. doi: 10.3390/v15102119

 

  1. Da Mata ECG. Avaliação da Atividade Antiretroviral de Plantas Amazônicas Utilizando como Modelo o Vírus da Imunodeficiência Símia. [Antiretroviral Activity Evaluation of Amazonian Plants Utilizing the Simian Immunodeficiency Virus as a Model]. Dissertation. University of Brasilia; 2011. Available from: http://repositorio2.unb.br/jspui/ handle/10482/9185 [Last acessed on 2025 Jan 31].

 

  1. Tandon N, Yadav SS. Contributions of Indian Council of Medical Research (ICMR) in the area of medicinal plants/ traditional medicine. J Ethnopharmacol. 2017;197:39-45. doi: 10.1016/j.jep.2016.07.064

 

  1. Roux P, Alfieri C, Hrimech M, Cohen EA, Tanner JE. Activation of transcription factors NF-kappaB and NF-IL-6 by human immunodeficiency virus type 1 protein R (Vpr) induces interleukin-8 expression. J Virol. 2000;74(10):4658-4665. doi: 10.1128/jvi.74.10.4658-4665.2000

 

  1. Ellwanger JH, Valverde-Villegas JM, Kaminski VL, et al. Increased IL-8 levels in HIV-infected individuals who initiated ART with CD4+ T cell counts <350 cells/mm3- A potential hallmark of chronic inflammation. Microbes Infect. 2020;22(9):474-480. doi: 10.1016/j.micinf.2020.05.019

 

  1. Cummings MJ, Bakamutumaho B, Price A, et al. HIV infection drives pro-inflammatory immunothrombotic pathway activation and organ dysfunction among adults with sepsis in Uganda. AIDS. 2023;37(2):233-245. doi: 10.1097/QAD.0000000000003410

 

  1. Dwivedi AK, Gornalusse GG, Siegel DA, et al. A cohort-based study of host gene expression: Tumor suppressor and innate immune/inflammatory pathways associated with the HIV reservoir size. PLoS Pathog. 2023;19(11):e1011114. doi: 10.1371/journal.ppat.1011114

 

  1. Schonhofer C, Yi J, Sciorillo A, et al. Flavonoid-based inhibition of cyclin-dependent kinase 9 without concomitant inhibition of histone deacetylases durably reinforces HIV latency. Biochem Pharmacol. 2021;186:114462. doi: 10.1016/j.bcp.2021.114462

 

  1. Ka’e AC, Nanfack AJ, Ambada G, et al. Inflammatory profile of vertically HIV-1 infected adolescents receiving ART in Cameroon: A contribution toward optimal pediatric HIV control strategies. Front Immunol. 2023;14:1239877. doi: 10.3389/fimmu.2023.1239877

 

  1. Fernandes J, Castilho RO, da Costa MR, Wagner-Souza K, Coelho Kaplan MA, Gattass CR. Pentacyclic triterpenes from Chrysobalanaceae species: Cytotoxicity on multidrug resistant and sensitive leukemia cell lines. Cancer Lett. 2003;190(2):165-169. doi: 10.1016/s0304-3835(02)00593-1

 

  1. Braca A, Morelli I, Mendez J, Battinelli L, Braghiroli L, Mazzanti G. Antimicrobial triterpenoids from Licania heteromorpha. Planta Med. 2000;66(8):768-769. doi: 10.1055/s-2000-9601

 

  1. Bilia AR, Mendez J, Morelli I. Phytochemical investigations of Licania genus. Flavonoids and triterpenoids from Licania carii. Pharm Acta Helv. 1996a;71:191-197. doi: 10.1016/0031-6865(96)00010-6

 

 

  1. Estrada O, Contreras W, Acha G, et al. Chemical constituents from Licania cruegeriana and their cardiovascular and antiplatelet effects. Molecules. 2014;19(12):21215-21225. doi: 10.3390/molecules191221215

 

  1. Braca A, Sortino C, Mendez J, Morelli I. Triterpenes from Licania licaniaeflora. Fitoterapia. 2001;72(5):585-587. doi: 10.1016/s0367-326x(00)00321-x

 

  1. Carvalho MG, Costa PM. Outros constituintes isolados de Licania arianeae (Chrysobalanaceae) [Other constituents isolated from Licania arianeae (Chrysobalanaceae)]. Rev Bras Farmacogn. 2009;19(1b):290-293. doi: 10.1590/S0102-695X2009000200018

 

  1. Fujioka T, Kashiwada Y, Kilkuskie RE, et al. Anti-AIDS agents, 11. Betulinic acid and platanic acid as anti-HIV principles from Syzigium claviflorum, and the anti-HIV activity of structurally related triterpenoids. J Nat Prod. 1994;57(2):243-247. doi: 10.1021/np50104a008

 

  1. Mayaux JF, Bousseau A, Pauwels R, et al. Triterpene derivatives that block entry of human immunodeficiency virus type 1 into cells. Proc Natl Acad Sci U S A. 1994;91(9):3564-3568. doi: 10.1073/pnas.91.9.3564

 

  1. Hashimoto F, Kashiwada Y, Cosentino LM, Chen CH, Garrett PE, Lee KH. Anti-AIDS agents--XXVII. Synthesis and anti-HIV activity of betulinic acid and dihydrobetulinic acid derivatives. Bioorg Med Chem. 1997;5(12):2133-2143. doi: 10.1016/s0968-0896(97)00158-2

 

  1. Aiken C, Chen CH. Betulinic acid derivatives as HIV-1 antivirals. Trends Mol Med. 2005;11(1):31-36. doi: 10.1016/j.molmed.2004.11.001

 

  1. Than NN, Fotso S, Poeggeler B, Hardeland R, Laatsch H. Niruriflavone, a new antioxidant flavone sulfonic acid from Phyllanthus niruri. ChemInform. 2006;67(1):1-4. doi: 10.1002/chin.200625196

 

  1. Moore PS, Pizza C. Observations on the inhibition of HIV-1 reverse transcriptase by catechins. Biochem J. 1992;288 (Pt 3):717-719. doi: 10.1042/bj2880717

 

  1. Hussein G, Miyashiro H, Nakamura N, et al. Inhibitory effects of Sudanese plant extracts on HIV-1 replication and HIV-1 protease. Phytother Res. 1999;13(1):31-36. doi: 10.1002/(SICI)1099-1573(199902)13:1<31:AID-PTR 381>3.0.CO;2-C

 

  1. Lin YM, Anderson H, Flavin MT, et al. In vitro anti-HIV activity of biflavonoids isolated from Rhus succedanea and Garcinia multiflora. J Nat Prod. 1997;60(9):884-888. doi: 10.1021/np9700275

 

  1. Nath S, Bachani M, Harshavardhana D, Steiner JP. Catechins protect neurons against mitochondrial toxins and HIV proteins via activation of the BDNF pathway. J Neurovirol. 2012;18(6):445-455. doi: 10.1007/s13365-012-0122-1

 

  1. Mehla R, Bivalkar-Mehla S, Chauhan A. A flavonoid, luteolin, cripples HIV-1 by abrogation of tat function. PLoS One. 2011;6(11):e27915. doi: 10.1371/journal.pone.0027915

 

  1. Tang TT, Li SM, Pan BW, et al. Identification of flavonoids from Scutellaria barbata D. Don as Inhibitors of HIV-1 and Cathepsin L proteases and their structure-activity relationships. Molecules. 2023;28(11):4476. doi: 10.3390/molecules28114476

 

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