β-Amyrin and Benzene-1,2,4-trimethyl from Euphorbia hirta L. and Nauclea latifolia (Smith) Leaves Induce Dauer Diapause via Antagonist Inhibition of daf-12 Receptor

http://www.doi.org/10.26538/tjnpr/v7i7.38

Authors

  • Olayinka T. Ogunmefun Department of Biological Sciences, College of Sciences, Afe Babalola University, Ado-Ekiti, Nigeria
  • Oladotun A. Ogunojemite Department of Biological Sciences, College of Sciences, Afe Babalola University, Ado-Ekiti, Nigeria
  • Oluwasegun A. Adedokun Department of Pharmacognosy and Natural products, College of Pharmacy, Afe Babalola University,Ado-Ekiti, Nigeria
  • Peter T. Olagbemide Department of Biological Sciences, College of Sciences, Afe Babalola University, Ado-Ekiti, Nigeria
  • Ibrahim O. Kehinde Department of Pharmaceutical and Medicinal Chemistry, College of Pharmacy, Afe Babalola University,Ado-Ekiti, Nigeria
  • Mahmoud Soliman Department of Pharmaceutical Science, School of Health Sciences, University of Kwazulu Natal, Durban, South Africa

Abstract

Drug development begins with medicinal plants as valuable materials. Euphorbia hirta (EH) and
Nauclea latifolia (NL) are important medicinal plants having applications in the management of
infectious diseases. This research aimed at evaluating EH and NL leaves for their anthelmintic
property and establishment of probable dauer diapause effect induced via interaction with daf-12
nuclear receptor in worms using standard procedures. Powdered plant samples were extracted
using cold maceration for 72h. Qualitative, quantitative phytochemicals and antioxidants were
determined using standard procedures. Metal concentrations were determined using Atomic
Absorption Spectrophotometer. Anthelmintic assay was done by observing paralysis and death
times of worms. Molecular docking of compounds isolated from plants was done using PyRxVirtual Screening Tool workspace. SwissADME of the most promising compound was done with
online tool. Molecular Dynamics simulation done using UCSF Chimera and graphic processor
unit (GPU) version of the PMEMD.CUDA having AMBER package. Different concentrations
(10, 30, and 50 mg/mL) of methanol and hexane leaf extracts of EH and NL displayed appreciable
anthelmintic activity against Pheritima pasthuma, Taenia solium and Fasciola gigantica in the
following order, P. pasthuma >F. gigantica >T. solium. The antagonist effect of Beta amyrin and
Benzene-1,2,4-trimethyl on the key Amino acid residues in the binding site of Daf-12 nuclear
receptor confer a pronounced dauer diapause effect in EH and NL. In silico assay showed Betaamyrin having promising activity and appreciable stability in the binding site of the target and low
bioavailability. This study justifies the reasons behind EH and NL usage as anthelmintic drugs
locally
Keywords: Anthelmintic, daf-12 receptor, Dauer diapause, Euphorbia hirta, Nauclea latifolia
quadrifida

Author Biographies

Olayinka T. Ogunmefun, Department of Biological Sciences, College of Sciences, Afe Babalola University, Ado-Ekiti, Nigeria

Department of Pharmacognosy and Natural products, College of Pharmacy, Afe Babalola University,Ado-Ekiti, Nigeria

Ibrahim O. Kehinde, Department of Pharmaceutical and Medicinal Chemistry, College of Pharmacy, Afe Babalola University,Ado-Ekiti, Nigeria

Department of Pharmaceutical Science, School of Health Sciences, University of Kwazulu Natal, Durban, South Africa

References

Charlier J, Bartley DJ, Sotiraki S, Martinez-Valladares M, Claerebout E, von Samson-Himmelstjerna G, Thamsborg SM, Hoste H, Morgan ER, Rinaldi L. Anthelmintic

resistance in ruminants: challenges and solutions. Adv Parasitol. 2022 ;115:171-227. doi: 10.1016/bs.apar.2021.12.002

Wolstenholme AJ. Ion channels and receptor as targets for the control of parasitic nematodes. Vol. 1, International Journal for Parasitology: Drugs and Drug Resistance. 2011.

p. 2–13.

Wang Z, Schaffer NE, Kliewer SA, Mangelsdorf DJ. Nuclear receptors: Emerging drug targets for parasitic diseases. J. Clin Invest. 2017; 127(4):1165–71.

Williamson SM, Robertson AP, Brown L, Williams T, Woods DJ, Martin RJ, et al. The nicotinic acetylcholine receptors of the parasitic nematode Ascaris suum: Formation

of two distinct drug targets by varying the relative expression levels of two subunits. PLoS Pathog. 2009;5(7):e1000517.

Frayha GJ, Smyth JD, Gobert JG, Savel J. The mechanisms of action of antiprotozoal and anthelmintic drugs in man. Gen Pharmacol. 1997; 28(2):273–99.

Rose VH, Morgan ER, Hertzberg H, Bartley DJ, Bosco A, Charlier J, Chartier C, Claerebout E, de Waal T, Hendrickx G, Hinney B, Höglund J, Ježek J, Kašný M, Keane OM,

Martínez-Valladares M, Mateus TL, McIntyre J, Mickiewicz M, Munoz AM, Phythian CJ, Ploeger HW, Rataj AV, Skuce PJ, Simin S, Sotiraki S, Spinu M, Stuen S, Thamsborg SM,

Vadlejch J, Varady M, von Samson-Himmelstjerna G, Rinaldi L. Increasing importance of anthelmintic resistance in European livestock: creation and meta-analysis of an open

database. Parasite. 2020; 27:69. doi: 10.1051/parasite/2020062

Ghosh P, Ghosh C, Das S, Das C, Mandal S, Chatterjee S. Botanical Description, Phytochemical Constituents and Pharmacological Properties of Euphorbia hirta Linn: A

Review. Int J Heal Sci Res. 2019;9.

Abiodun F, Igwe A, Osahon O. Anti-microbial evaluation of a herbal dental remedy: Stem bark of Nuclea latifolia-family rubiaceae. J. Appl Sci. 2007;7(18): 2696-2700.

Oshadie G, Silva D, Abeysundara AT, Minoli M, Aponso W. Extraction methods, qualitative and quantitative techniques for screening of phytochemicals from plants. ~ 29 ~ Am JEssent Oils Nat Prod. 2017;5(2): 29-32.

Gospel Ajuru M. Qualitative and Quantitative Phytochemical Screening of Some Plants Used in Ethnomedicine in theNiger Delta Region of Nigeria. J Food Nutr Sci. 2017;5(5):

Oluwasegun A. In Vitro Free Radical Scavenging Activity and Total Phenolic Content of Kigelia Africana (LAM). Int J Sci Res. 2014;3(1): 368-70.

Cardoso-Gutierrez E, Aranda-Aguirre E, Robles-Jimenez LE, Castelán-Ortega OA, Chay-Canul AJ, Foggi G, AngelesHernandez JC, Vargas-Bello-Pérez E, González-RonquilloM. Effect of tannins from tropical plants on methane

production from ruminants: A systematic review. Vet Anim Sci. 2021; 9;14:100214. doi: 10.1016/j.vas.2021.100214

Christiana Jesumirhewe, Adaobi Sandra Okoro, Oluwasegun Adedokun. The phytochemical constituents and antibacterial activity of methanolic and ethanolic leaf and

stem extracts of Eucalyptus torelliana, Nigeria. GSC Biol Pharm Sci. 2021; 16(2): 306-311. https://doi.org/10.30574/gscbps.2021.16.2.0246

Nasiru A, Oluwasegun A. Phytochemical, nutritional and amino acid composition of Citrullus lanatus (Cucurbitaceae) seeds cultivated in South-South Nigeria. ~ 3738 ~ J

Pharmacogn Phytochem. 2019;8(3):3738–40.

Adedokun O, Gbolade A, Ayinde B. 13, 14-Epoxyoleanan- 3-ol-acetate: A male fertility enhancing constituent from hexane fraction of Momordica charantia Linn

(Curcubitaceae). Turkish J Pharm Sci. 2021; 0(0): 180-186. doi: 10.4274/tjps.galenos.2021.48264

Ayofe AM, Oluwasegun A, Adesina AB, Ogochukwu U. Comparative studies on In-vitro radical scavenging potential of methanol extracts of Garcinia kola heck (Clusiaceae)

seeds, Conyza sumatrensis retz (Asteraceae) and Mitracarpus scaber zucc (Rubiaceae) leaves. ~ 33 ~ Am J Essent Oils Nat Prod. 2017; 5(2):33–6.

Samatha T, Srinivas P, Shyamsundarachary R, Rajinikanth M, Rama Swamy N. Phytochemical analysis of seeds, stem bark and root of an endangered medicinal forest tree

OROXYLUM INDICUM(L)kurz. Int J Pharma Bio Sci. 2012; 3(3):B1063-B1075.

Mansor N, Herng HJ, Samsudin SJ, Sufian S, Uemura Y. Quantification and Characterization of Allicin in Garlic Extract. J Med Bioeng. 2016; 5(1):24–7.

Khanal S. Qualitative and Quantitative Phytochemical Screening of Azadirachta indica Juss. Plant Parts. Int J Appl Sci Biotechnol. 2021;9(2): 122-127.

DOI: 10.3126/ijasbt.v9i2.38050

Harris R. Anglo-Saxon aromatherapy: its evolution and current situation. Int J Aromather. 2003;13(1): 9-17.

Evans WC. Trease and Evans Pharmacognosy. 15th edtion. Edinburgh, Saunders. 2002.

Ogunmefun OT, Fasola TR, Saba AB, Oridupa OA. The ethnobotanical, phytochemical and mineral analyses of Phragmanthera Incana (Klotzsch), a species of mistletoe

growing on three plant hosts in South-western Nigeria. Int J Biomed Sci. 2013; 9(1):33-40.

Oluwasegun A, Ume O, Nasiru A, Peter A, Benjamin G. Evaluation of antidiabetic and anti-lipid peroxidation potentials of leaves crude and solvent fractions of Annona

muricata Linn ( Annonaceae ). 2019; 8(3):3973–7.

Boly1 AG., Belemlilga M., Traore A, S Ouedraogo E, Guissou I. Phytochemical Study and In vitro Anthelminthic Properties Studies of the Trunk Barks Aqueous Extract from

Acacia Nilotica Var. Adansonii (Guill & Perr). O Ktze (Mimosaceae). Int J Pharmacogn Phytochem Res. 2018;10(1):5-10.

Oliveira Santos F, Ponce Morais Cerqueira A, Branco A, José Moreira Batatinha M, Borges Botura M. Anthelmintic activity of plants against gastrointestinal nematodes of goats:

A review. Vol. 146, Parasitology. 2019. 158pp.

Ngouateu Teufack SE, NMbogning Tayo G, Ngangout Alidou M, Yondo J, Djiomene AF, Wabo Poné J, Faùily Mpoame Mbida. Anthelminthic properties of Methylene chloridemethanol (1:1) extracts of two Cameroonians medicinal

plants on Heligmosomoides bakeri (Nematoda: Heligmosomatidea). BMC Complement Altern Med. 2017;17(1):630-634. https://doi.org/10.1186/s12906-017-

-8

Ajayeoba OO, Diehl DL. Pneumatic dilation for achalasia: new techniques to improve an old procedure. VideoGIE. 2020;5(10).

Bintari YR, Risandiansyah R. In Silico Study to Assess Antibacterial Activity from Cladophora Sp. on Peptide Deformylase: Molecular Docking Approach. Borneo J

Pharm. 2019;2(1):20-23.

Simon L, Imane A, Srinivasan KK, Pathak L, Daoud I. In Silico Drug-Designing Studies on Flavanoids as Anticolon Cancer Agents: Pharmacophore Mapping, Molecular

Docking, and Monte Carlo Method-Based QSAR Modeling. Interdiscip Sci Comput Life Sci. 2017 Sep 1;9(3):445–58.

Oso BJ, Adeoye AO, Olaoye IF. Pharmacoinformatics and hypothetical studies on allicin, curcumin, and gingerol as potential candidates against COVID-19-associated

proteases. J Biomol Struct Dyn. 2022;40(1):1 -7.

Muh’d M baba, Uzairu A, Shallangwa GA, Uba S. Molecular docking and quantitative structure-activity relationship study of anti-ulcer activity of quinazolinone derivatives. J King

Saud Univ - Sci [Internet]. 2020;32(1).657–666 Available from:https://doi.org/10.1016/j.jksus.2018.10.003

Saeed M, Shoaib A, Tasleem M, Alabdallah NM, Alam MJ, El Asmar Z, et al. Assessment of antidiabetic activity of the shikonin by allosteric inhibition of protein-tyrosine

phosphatase 1b (Ptp1b) using state of art: An in silico and in vitro tactics. Molecules. 2021;26(13). 10.3390/molecules26133996

Abdul-Hammed M, Adedotun IO, Olajide M, Irabor CO, Afolabi TI, Gbadebo IO, et al. Virtual screening, ADMET profiling, PASS prediction, and bioactivity studies of

potential inhibitory roles of alkaloids, phytosterols, and flavonoids against COVID-19 main protease (Mpro). Nat Prod Res. 2022; 36(12):23 -33.

Wongsinlatam W, Remsungnen T. Molecular dynamics simulations of CO2 molecules in ZIF-11 using refined AMBER force field. J Chem. 2013; 1-10.

Pabis A, Geronimo I, York DM, Paneth P. Molecular dynamics simulation of nitrobenzene dioxygenase using AMBER force field. J Chem Theory Comput. 2014;10(6):2246 - 2254.

Najib A, Handayani V, Ahmad AR, Hikmat S. Insilico screening chemical compounds a-glucosidase inhibitor fromcordia myxa L. Int J Res Pharm Sci. 2019;10(3):1 - 3.

Pióro-Jabrucka E, Pawelczak A, Przybyl JL, Baczek K, Weglarz Z. Accumulation of phenolic and sterol compounds in Euphorbia hirta (L.). Herba Pol. 2011; 57(2):1-26.

Olalere OA, Gan CY. Microwave-assisted extraction of phenolic compounds from Euphorbia hirta leaf and characterization of its morphology and thermal stability. Sep

Sci Technol. 2021; 56(11):444-476.

Susiloningrum D, Permanasari AA, Adianti M, Tumewu L, Wahyuni TS, Tanjung M, et al. The alkaloid fraction from melicope latifolia leaves inhibits hepatitis C Virus.

Pharmacogn J. 2020; 12(3):535 - 540.

Gbolade A, Adedokun O, Igbinomwanhia E, Alli M. Lethality of Bryophyllum pinnatum (Lam) Oken (Crassulaceae ) Leaf Methanol Extract and Fractions against

Naja nigricollis and Bitis arietans Lethality of Bryophyllum pinnatum ( Lam .) Oken (Crassulaceae) Leaf Methanol Extract and Fractions against N. 2020;8(July):6–11.

Parul R, Kundu SK, Saha P. In Vitro Nitric Oxide Scavenging Activity of Methanol Extracts of Three Bangladeshi Medicinal Plants. Pharma Innov. 2012;

(12):83–88.

Kumar S, Malhotra R, Kumar D. Euphorbia hirta: Its chemistry, traditional and medicinal uses, and pharmacological activities. Vol. 4, Pharmacognosy Reviews.

:273-286.

Isyaku Y, Uzairu A, Uba S. Computational studies of a series of 2-substituted phenyl-2-oxo-, 2-hydroxyl- and 2-acylloxyethylsulfonamides as potent anti-fungal agents.

Heliyon. 2020;6(4): e03724 - 37.

Han G, Lee DG. Antibacterial Mode of Action of ß-Amyrin Promotes Apoptosis-Like Death in Escherichia coli by Producing Reactive Oxygen Species. J Microbiol

Biotechnol. 2022; 28;32(12):1547-1552. doi: 10.4014/jmb.2209.09040.

Emmanuel, IA, Olotu F, Agoni, C, Soliman ME, ‘Broadening the horizon: Integrative pharmacophore-based and cheminformatics screening of novel chemical

modulators of mitochondria ATP synthase towards interventive Alzheimer’s disease therapy’, Med. Hypotheses 2019; 130:109277. https://doi.org/10.1016/j.mehy.2019.109277

Bjij I, Khan S, Betz R, Cherqaoui D, Soliman ME, ‘Exploring the structural mechanism of covalently bound E3 ubiquitin ligase: Catalytic or allosteric inhibition?’, Protein J.

, 37:500–509. https://doi.org/10.1007/ s10930-018- 9795-

Ndagi U, Mhlongo NN, Soliman ME, ‘The impact of Thr91 mutation on c-Src resistance to UM-164: Molecular dynamics study revealed a new opportunity for drug design’,

Mol. BioSyst. 2017, 13, 1157–1171. https://doi.org/ 10.1039/c6mb00848h

Akher FB, Farrokhzadeh A, Olotu FA, Agoni C, Soliman ME, ‘The irony of chirality – unveiling the distinct mechanistic binding and activities of 1-(3-(4amino-5-(7-

methoxy-5-methylbenzo[b]thiophen2-yl)-7H-pyrrolo[2,3- d]pyrimidin-7-yl)pyrrolidin1-yl)prop-2-en-1-one enantiomers as irreversible covalent FGFR4 inhibitors’, Org.

Biomol. Chem. 2019; 17:1176–1190. DOI: 10.1039/c8ob02811g

Olanlokun JO, Olotu FA, David OM, Idowu TO, Soliman ME, Olorunsogo OO, ‘A novel compound purified from Alstonia boonei inhibits Plasmodium falciparum Lactate

dehydrogenase and Plasmepsin II’, J. Biomol. Struct. Dyn. 2019; 37:2193–2200. DOI: 10.1080/ 07391102.2018.1483840

Adewumi AT, Ajadi MB, Soremekun OS, Soliman ME, ‘Thompson loop: Opportunities for antitubercular demethylmenaquinone methyltransferase protein’, RSC

Adv. 2020; 10:23466–23483. https://doi.org/10.1039/D0RA03206A

Adewumi AT, Elrashedy A, Soremekun OS, Ajadi MB, Soliman ME, ‘Weak spots inhibition in the Mycobacteriumtuberculosis antigen 85 C target for antitubercular drug

design through selective irreversible covalent inhibitorSER124’, J. Biomol. Struct. Dyn. 2020. DOI: 10.1080/ 07391102.2020.1844061

Kalathiya U, Padariya M, Baginski M, ‘Structural, functional, and stability change predictions in human telomerase upon specific point mutations’, Sci. Rep. 2019,

,1–13. https://www.nature.com/articles/s41598-019-45206-y

Olotu FA, Soliman ME, ‘From mutational inactivation to aberrant gain-of-function: unraveling the structural basis of mutant p53 oncogenic transition’, J. Cell. Biochem. 2018;

: 2646–52. DOI: 10.1002/jcb.26430

Adejoro IA, Waheed SO, Adeboye OO, ‘Molecular docking studies of Lonchocarpus cyanescens Triterpenoids as Inhibitors for Malaria’, J. Phys. Chem. B 2016; 6:1–4. DOI:

4172/2161-0398.1000213

Published

2023-07-31

How to Cite

Ogunmefun, O. T., Ogunojemite, O. A., Adedokun, O. A., Olagbemide, P. T., Kehinde, I. O., & Soliman, M. (2023). β-Amyrin and Benzene-1,2,4-trimethyl from Euphorbia hirta L. and Nauclea latifolia (Smith) Leaves Induce Dauer Diapause via Antagonist Inhibition of daf-12 Receptor: http://www.doi.org/10.26538/tjnpr/v7i7.38. Tropical Journal of Natural Product Research (TJNPR), 7(7), 3546–3557. Retrieved from https://tjnpr.org/index.php/home/article/view/2259