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Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Research Article

The Bioactive Potential of Culturable Fungal Endophytes Isolated From the Leaf of Catharanthus roseus (L.) G. Don

Author(s): Sucheta Singh*, Surjeet Verma, Dharmendra K. Yadav, Anant Kumar, Rekha Tyagi, Priyanka Gupta, Dnyaneshwar U. Bawankule, Mahendra P. Darokar, Santosh K. Srivastava and Alok Kalra

Volume 21, Issue 10, 2021

Published on: 26 April, 2021

Page: [895 - 907] Pages: 13

DOI: 10.2174/1568026621666210426123437

Price: $65

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Abstract

Introduction: Endophyte is considered a source of natural bioactive secondary metabolites that provides an array of bioactive lead compounds. The present study was aimed to determine the antimicrobial and anti-inflammatory potential of fungal endophytes isolated from Catharanthus roseus.

Methods: A total of seven fungal endophytes crude extract were screened against bacterial pathogens. Of these, Curvularia geniculata CATDLF7 crude extract exhibited the most potent inhibitory activity against bacterial pathogens. Hence, CATDLF7 crude extract was subjected to chromatographic separation. This purification leads to the isolation of six pure compounds (1PS - 6PS). Of these, 3PS was found to be a major constituent and most effective against clinical isolates of methicillin- resistant Staphylococcus aureus (MRSA) with minimum inhibitory concentration (MIC) values ranging from 100 to 200 μg/ml. Based on the spectroscopic data, 3PS was characterized as α,β- dehydrocurvularin. This compound also showed synergistic interaction with norfloxacin and reduced its MIC up to 32-folds with a fractional inhibitory concentration index (FICI) of 0.09.

Results: To understand the possible antibacterial mechanism of action, α,β-dehydrocurvularin alone (100 μg/ml) exhibited efflux pump inhibitory potential by 0.84 fold decreasing in ethidium bromide (EtBr) fluorescence. In addition, α,β-dehydrocurvularin inhibited inflammatory cytokines TNF-α and IL-6 production, which is further validated by molecular docking scores -4.921 and -5.641, respectively, for understanding orientation and binding affinity.

Conclusion: Overall, the results highlighted identifying bioactive compound α,β-dehydrocurvularin, which could be used as an antimicrobial and anti-inflammatory agent.

Keywords: α, β-Dehydrocurvularin, Endophyte, Molecular docking, Minimum inhibitory concentration, Anti-inflammatory agents, Antimicrobial.

Graphical Abstract
[1]
Tian, X.R.; Feng, G.T.; Ma, Z.Q.; Xie, N.; Zhang, J.; Zhang, X.; Tang, H.F. Three new glycosides from the whole plant of Clematis lasiandra Maxim and their cytotoxicity. Phytochem. Lett., 2014, 10, 168-172.
[http://dx.doi.org/10.1016/j.phytol.2014.09.004]
[2]
Van Wyk, B.E.; Wink, M. Medicinal Plants of the World: An illustrated scientific guide to important medicinal plants and their uses; Timber press: Portland, OR, USA, 2004.
[3]
Kharwar, R.N.; Verma, V.C.; Strobel, G.; Ezra, D. The endophytic fungal complex of Catharanthus roseus (L.) G Don. Curr. Sci., 2008, 95, 228-233.
[4]
Pandey, S.S.; Singh, S.; Babu, C.S.; Shanker, K.; Srivastava, N.K.; Kalra, A. Endophytes of opium poppy differentially modulate host plant productivity and genes for the biosynthetic pathway of benzylisoquinoline alkaloids. Planta, 2016, 243(5), 1097-1114.
[http://dx.doi.org/10.1007/s00425-016-2467-9] [PMID: 26794966]
[5]
Mishra, A.; Singh, S.P.; Mahfooz, S.; Singh, S.P.; Bhattacharya, A.; Mishra, N.; Nautiyal, C.S. Endophyte mediated modulation of defense-responsive genes and systemic resistance in Withania somnifera (L.) Dunal under Alternaria alternata stress. Appl. Environ. Microbiol., 2018, 84(8), e02845-e17.
[http://dx.doi.org/10.1128/AEM.02845-17] [PMID: 29453255]
[6]
Golinska, P.; Wypij, M.; Agarkar, G.; Rathod, D.; Dahm, H.; Rai, M. Endophytic actinobacteria of medicinal plants: diversity and bioactivity. Antonie van Leeuwenhoek, 2015, 108(2), 267-289.
[http://dx.doi.org/10.1007/s10482-015-0502-7] [PMID: 26093915]
[7]
Aly, A.H.; Debbab, A.; Proksch, P. Fungal endophytes: unique plant inhabitants with great promises. Appl. Microbiol. Biotechnol., 2011, 90(6), 1829-1845.
[http://dx.doi.org/10.1007/s00253-011-3270-y] [PMID: 21523479]
[8]
Gunatilaka, A.A.L. Natural products from plant-associated microorganisms: distribution, structural diversity, bioactivity, and implications of their occurrence. J. Nat. Prod., 2006, 69(3), 509-526.
[http://dx.doi.org/10.1021/np058128n] [PMID: 16562864]
[9]
Verma, V.C.; Kharwar, R.N.; Strobel, G.A. Chemical and functional diversity of natural products from plant associated endophytic fungi. Nat. Prod. Commun., 2009, 4(11), 1511-1532.
[http://dx.doi.org/10.1177/1934578X0900401114] [PMID: 19967984]
[10]
Zhang, H.W.; Song, Y.C.; Tan, R.X. Biology and chemistry of endophytes. Nat. Prod. Rep., 2006, 23(5), 753-771.
[http://dx.doi.org/10.1039/b609472b] [PMID: 17003908]
[11]
Strobel, G.A. Rainforest endophytes and bioactive products. Crit. Rev. Biotechnol., 2002, 22(4), 315-333.
[http://dx.doi.org/10.1080/07388550290789531] [PMID: 12487423]
[12]
Strobel, G.; Daisy, B. Bioprospecting for microbial endophytes and their natural products. Microbiol. Mol. Biol. Rev., 2003, 67(4), 491-502.
[http://dx.doi.org/10.1128/MMBR.67.4.491-502.2003] [PMID: 14665674]
[13]
Kusari, S.; Spiteller, M. Are we ready for industrial production of bioactive plant secondary metabolites utilizing endophytes? Nat. Prod. Rep., 2011, 28(7), 1203-1207.
[http://dx.doi.org/10.1039/c1np00030f] [PMID: 21629952]
[14]
Kusari, S.; Spiteller, M. Metabolomics of endophytic fungi producing associated plant secondary metabolites: progress, challenges and opportunities. In: Metabolomics; Roessner, U., Ed.; InTech: Rijeka, 2012; pp. 241-266.
[http://dx.doi.org/10.5772/31596]
[15]
Venugopalan, A.; Srivastava, S. Endophytes as in vitro production platforms of high value plant secondary metabolites. Biotechnol. Adv., 2015, 33(6 Pt 1), 873-887.
[http://dx.doi.org/10.1016/j.biotechadv.2015.07.004] [PMID: 26225453]
[16]
Brakhage, A.A. Regulation of fungal secondary metabolism. Nat. Rev. Microbiol., 2013, 11(1), 21-32.
[http://dx.doi.org/10.1038/nrmicro2916] [PMID: 23178386]
[17]
van Wezel, G.P.; McDowall, K.J. The regulation of the secondary metabolism of Streptomyces: new links and experimental advances. Nat. Prod. Rep., 2011, 28(7), 1311-1333.
[http://dx.doi.org/10.1039/c1np00003a] [PMID: 21611665]
[18]
Stierle, A.; Strobel, G.; Stierle, D. Taxol and taxane production by Taxomyces andreanae, an endophytic fungus of Pacific yew. Science, 1993, 260(5105), 214-216.
[http://dx.doi.org/10.1126/science.8097061] [PMID: 8097061]
[19]
Kusari, S.; Verma, V.C.; Lamshoeft, M.; Spiteller, M. An endophytic fungus from Azadirachta indica A. Juss. that produces azadirachtin. World J. Microbiol. Biotechnol., 2012, 28(3), 1287-1294.
[http://dx.doi.org/10.1007/s11274-011-0876-2] [PMID: 22805849]
[20]
Kusari, S.; Lamshöft, M.; Spiteller, M. Aspergillus fumigatus Fresenius, an endophytic fungus from Juniperus communis L. Horstmann as a novel source of the anticancer pro-drug deoxypodophyllotoxin. J. Appl. Microbiol., 2009, 107(3), 1019-1030.
[http://dx.doi.org/10.1111/j.1365-2672.2009.04285.x] [PMID: 19486398]
[21]
Puri, S.C.; Verma, V.; Amna, T.; Qazi, G.N.; Spiteller, M. An endophytic fungus from Nothapodytes foetida that produces camptothecin. J. Nat. Prod., 2005, 68(12), 1717-1719.
[http://dx.doi.org/10.1021/np0502802] [PMID: 16378360]
[22]
Kusari, S.; Kosuth, J.; Cellarova, E.; Spiteller, M. Survival-strategies of endophytic Fusarium solani against indigenous camptothecin biosynthesis. Fungal Ecol., 2011, 4, 219-223.
[http://dx.doi.org/10.1016/j.funeco.2010.11.002]
[23]
Kusari, S.; Zühlke, S.; Spiteller, M. An endophytic fungus from Camptotheca acuminata that produces camptothecin and analogues. J. Nat. Prod., 2009, 72(1), 2-7.
[http://dx.doi.org/10.1021/np800455b] [PMID: 19119919]
[24]
Shweta, S.; Zuehlke, S.; Ramesha, B.T.; Priti, V.; Mohana Kumar, P.; Ravikanth, G.; Spiteller, M.; Vasudeva, R.; Uma Shaanker, R. Endophytic fungal strains of Fusarium solani, from Apodytes dimidiata E. Mey. ex Arn (Icacinaceae) produce camptothecin, 10-hydroxycamptothecin and 9-methoxycamptothecin. Phytochemistry, 2010, 71(1), 117-122.
[http://dx.doi.org/10.1016/j.phytochem.2009.09.030] [PMID: 19863979]
[25]
Kusari, S.; Lamshöft, M.; Zühlke, S.; Spiteller, M. An endophytic fungus from Hypericum perforatum that produces hypericin. J. Nat. Prod., 2008, 71(2), 159-162.
[http://dx.doi.org/10.1021/np070669k] [PMID: 18220354]
[26]
Kumar, A.; Patil, D.; Rajamohanan, P.R.; Ahmad, A. Isolation, purification and characterization of vinblastine and vincristine from endophytic fungus Fusarium oxysporum isolated from Catharanthus roseus. PLoS One, 2013, 8(9), e71805.
[http://dx.doi.org/10.1371/journal.pone.0071805] [PMID: 24066024]
[27]
Eyberger, A.L.; Dondapati, R.; Porter, J.R. Endophyte fungal isolates from Podophyllum peltatum produce podophyllotoxin. J. Nat. Prod., 2006, 69(8), 1121-1124.
[http://dx.doi.org/10.1021/np060174f] [PMID: 16933860]
[28]
Puri, S.C.; Nazir, A.; Chawla, R.; Arora, R.; Riyaz-Ul-Hasan, S.; Amna, T.; Ahmed, B.; Verma, V.; Singh, S.; Sagar, R.; Sharma, A.; Kumar, R.; Sharma, R.K.; Qazi, G.N. The endophytic fungus Trametes hirsuta as a novel alternative source of podophyllotoxin and related aryl tetralin lignans. J. Biotechnol., 2006, 122(4), 494-510.
[http://dx.doi.org/10.1016/j.jbiotec.2005.10.015] [PMID: 16375985]
[29]
Pandey, S.S.; Singh, S.; Babu, C.S.; Shanker, K.; Srivastava, N.K.; Shukla, A.K.; Kalra, A. Fungal endophytes of Catharanthus roseus enhance vindoline content by modulating structural and regulatory genes related to terpenoid indole alkaloid biosynthesis. Sci. Rep., 2016, 6, 26583.
[http://dx.doi.org/10.1038/srep26583] [PMID: 27220774]
[30]
Singh, S.; Pandey, S.S.; Shanker, K.; Kalra, A. Endophytes enhance the production of ajmalicine and serpentine content by modulating the terpenoid indole alkaloid pathway in Catharanthus roseus roots. J. Appl. Microbiol., 2020, 128(4), 1128-1142.
[http://dx.doi.org/10.1111/jam.14546] [PMID: 31821696]
[31]
Strobel, G.A. Endophytes as sources of bioactive products. Microbes Infect., 2003, 5(6), 535-544.
[http://dx.doi.org/10.1016/S1286-4579(03)00073-X] [PMID: 12758283]
[32]
Owen, N.L.; Hundley, N. Endophytes--the chemical synthesizers inside plants. Sci. Prog., 2004, 87(Pt 2), 79-99.
[http://dx.doi.org/10.3184/003685004783238553] [PMID: 15782772]
[33]
CLSI (Clinical and Laboratory Standards Institute). Methods for dilution Antimicrobial susceptibility tests for bacteria that grow aerobically, Approved standard-tenth edition; Clinical Laboratory and Standards Institute: Wayne, PA, USA, 2015. CLSI document M07-A10.
[34]
Sun, S.; Li, Y.; Guo, Q.; Shi, C.; Yu, J.; Ma, L. In vitro interactions between tacrolimus and azoles against Candida albicans determined by different methods. Antimicrob. Agents Chemother., 2008, 52(2), 409-417.
[http://dx.doi.org/10.1128/AAC.01070-07] [PMID: 18056277]
[35]
Iten, F.; Saller, R.; Abel, G.; Reichling, J. Additive antimicrobial [corrected] effects of the active components of the essential oil of Thymus vulgaris--chemotype carvacrol. Planta Med., 2009, 75(11), 1231-1236.
[http://dx.doi.org/10.1055/s-0029-1185541] [PMID: 19347798]
[36]
Fu, Y.; Zu, Y.; Chen, L.; Shi, X.; Wang, Z.; Sun, S.; Efferth, T. Antimicrobial activity of clove and rosemary essential oils alone and in combination. Phytother. Res., 2007, 21(10), 989-994.
[http://dx.doi.org/10.1002/ptr.2179] [PMID: 17562569]
[37]
Carson, C.F.; Mee, B.J.; Riley, T.V. Mechanism of action of Melaleuca alternifolia (tea tree) oil on Staphylococcus aureus determined by time-kill, lysis, leakage, and salt tolerance assays and electron microscopy. Antimicrob. Agents Chemother., 2002, 46(6), 1914-1920.
[http://dx.doi.org/10.1128/AAC.46.6.1914-1920.2002] [PMID: 12019108]
[38]
Oonmetta-aree, J.; Suzuki, T.; Gasaluck, P.; Eumkeb, G. Antimicrobial properties and action of galangal (Alpinia galanga Linn.) on Staphylococcus aureus. Lebensm. Wiss. Technol., 2006, 39, 1214-1220.
[http://dx.doi.org/10.1016/j.lwt.2005.06.015]
[39]
Kalia, N.P.; Mahajan, P.; Mehra, R.; Nargotra, A.; Sharma, J.P.; Koul, S.; Khan, I.A. Capsaicin, a novel inhibitor of the NorA efflux pump, reduces the intracellular invasion of Staphylococcus aureus. J. Antimicrob. Chemother., 2012, 67(10), 2401-2408.
[http://dx.doi.org/10.1093/jac/dks232] [PMID: 22807321]
[40]
Sharma, S.; Chattopadhyay, S.K.; Yadav, D.K.; Khan, F.; Mohanty, S.; Maurya, A.; Bawankule, D.U. QSAR, docking and in vitro studies for anti-inflammatory activity of cleomiscosin A methyl ether derivatives. Eur. J. Pharm. Sci., 2012, 47(5), 952-964.
[http://dx.doi.org/10.1016/j.ejps.2012.09.008] [PMID: 23022518]
[41]
Singh, M.; Hamid, A.A.; Maurya, A.K.; Prakash, O.; Khan, F.; Kumar, A.; Aiyelaagbe, O.O.; Negi, A.S.; Bawankule, D.U. Synthesis of diosgenin analogues as potential anti-inflammatory agents. J. Steroid Biochem. Mol. Biol., 2014, 143, 323-333.
[http://dx.doi.org/10.1016/j.jsbmb.2014.04.006] [PMID: 24816230]
[42]
Chen, S.; Feng, Z.; Wang, Y.; Ma, S.; Hu, Z.; Yang, P.; Chai, Y.; Xie, X. Discovery of novel ligands for TNF-α and TNF receptor-1 through structure based virtual screening and biological assay. J. Chem. Inf. Model., 2017, 57(5), 1101-1111.
[http://dx.doi.org/10.1021/acs.jcim.6b00672] [PMID: 28422491]
[43]
Somers, W.; Stahl, M.; Seehra, J.S. 1.9 A crystal structure of interleukin 6: implications for a novel mode of receptor dimerization and signaling. EMBO J., 1997, 16(5), 989-997.
[http://dx.doi.org/10.1093/emboj/16.5.989] [PMID: 9118960]
[44]
Yadav, D.K.; Dhawan, S.; Chauhan, A.; Qidwai, T.; Sharma, P.; Bhakuni, R.S.; Dhawan, O.P.; Khan, F. QSAR and docking based semi-synthesis and in vivo evaluation of artemisinin derivatives for antimalarial activity. Curr. Drug Targets, 2014, 15(8), 753-761.
[http://dx.doi.org/10.2174/1389450115666140630102711] [PMID: 24975562]
[45]
Yadav, D.K.; Kalani, K.; Singh, A.K.; Khan, F.; Srivastava, S.K.; Pant, A.B. Design, synthesis and in vitro evaluation of 18β-glycyrrhetinic acid derivatives for anticancer activity against human breast cancer cell line MCF-7. Curr. Med. Chem., 2014, 21(9), 1160-1170.
[http://dx.doi.org/10.2174/09298673113206660330] [PMID: 24180274]
[46]
Yadav, D.K.; Kumar, S.; Saloni, ; Singh, H.; Kim, M.H.; Sharma, P.; Misra, S.; Khan, F. Molecular docking, QSAR and ADMET studies of withanolide analogs against breast cancer. Drug Des. Devel. Ther., 2017, 11, 1859-1870.
[http://dx.doi.org/10.2147/DDDT.S130601] [PMID: 28694686]
[47]
Yadav, D.K.; Rai, R.; Kumar, N.; Singh, S.; Misra, S.; Sharma, P.; Shaw, P.; Pérez-Sánchez, H.; Mancera, R.L.; Choi, E.H.; Kim, M.H.; Pratap, R. New arylated benzo[h]quinolines induce anti-cancer activity by oxidative stress-mediated DNA damage. Sci. Rep., 2016, 6, 38128.
[http://dx.doi.org/10.1038/srep38128] [PMID: 27922047]
[48]
Bisht, R.; Bhatt, A.; Agarwal, P.K. Antimicrobial, antioxidant activity and phytochemical analysis of an endophytic fungi Penicillium oxalicum isolated from a gymnosperm tree Cupressus torulosa D. Don. of garhwal region. Int. J. Sci. Eng. Manag., 2016, 1(2), 90-96.
[http://dx.doi.org/10.1617/vol1iss2pid0010022]
[49]
Tong, X.; Shen, X.Y.; Hou, C.L. Antimicrobial Activity of Fungal Endophytes from Vaccinium dunalianum var. urophyllum. Sains Malays., 2018, 47(8), 1685-1692.
[http://dx.doi.org/10.17576/jsm-2018-4708-07]
[50]
Priyadharsini, P.; Muthukumar, T. The root endophytic fungus Curvularia geniculata from Parthenium hysterophorus roots improves plant growth through phosphate solubilisation and phytohormone production. Fungal Ecol., 2017, 27, 69-77.
[http://dx.doi.org/10.1016/j.funeco.2017.02.007]
[51]
Campos, F.F.; Rosa, L.H.; Cota, B.B.; Caligiorne, R.B.; Rabello, A.L.T.; Alves, T.M.; Rosa, C.A.; Zani, C.L. Leishmanicidal metabolites from Cochliobolus sp., an endophytic fungus isolated from Piptadenia adiantoides (Fabaceae). PLoS Negl. Trop. Dis., 2008, 2(12), e348.
[http://dx.doi.org/10.1371/journal.pntd.0000348] [PMID: 19079599]
[52]
Manamgoda, D.S.; Cai, L.; Bahkali, A.H.; Chukeatirote, E.; Hyde, K.D. Cochliobolus: an overview and current status of species. Fungal Divers., 2011, 51, 3-42.
[http://dx.doi.org/10.1007/s13225-011-0139-4]
[53]
Kumar, C.G.; Mongolla, P.; Sujitha, P.; Joseph, J.; Babu, K.S.; Suresh, G.; Ramakrishna, K.V.S.; Purushotham, U.; Sastry, G.N.; Kamal, A. Metabolite profiling and biological activities of bioactive compounds produced by Chrysosporium lobatum strain BK-3 isolated from Kaziranga National Park, Assam, India. Springerplus, 2013, 2(1), 122.
[http://dx.doi.org/10.1186/2193-1801-2-122] [PMID: 23565355]
[54]
Jeon, Y.T.; Ryu, K.H.; Kang, M.K.; Park, S.H.; Yun, H.; Kim, S.U. Alternariol monomethyl ether and α,β-Dehydrocurvularin from endophytic fungi Alternaria spp. inhibit appressorium formation of Magnaporthe grisea. J. Korean Soc. Appl. Biol. Chem., 2010, 53(1), 39-42.
[http://dx.doi.org/10.3839/jksabc.2010.007]
[55]
Gaur, R.; Gupta, V.K.; Singh, P.; Pal, A.; Darokar, M.P.; Bhakuni, R.S. Drug resistance reversal potential of Isoliquiritigenin and Liquiritigenin isolated from Glycyrrhiza glabra against Methicillin resistant Staphylococcus aureus (MRSA). Phytother. Res., 2016, 30(10), 1708-1715.
[http://dx.doi.org/10.1002/ptr.5677] [PMID: 27388327]
[56]
Gupta, V.K.; Tiwari, N.; Gupta, P.; Verma, S.; Pal, A.; Srivastava, S.K.; Darokar, M.P. A clerodane diterpene from Polyalthia longifolia as a modifying agent of the resistance of methicillin resistant Staphylococcus aureus. Phytomedicine, 2016, 23(6), 654-661.
[http://dx.doi.org/10.1016/j.phymed.2016.03.001] [PMID: 27161406]
[57]
Gupta, P.; Patel, D.K.; Gupta, V.K.; Pal, A.; Tandon, S.; Darokar, M.P. Citral, a monoterpenoid aldehyde interacts synergistically with norfloxacin against methicillin resistant Staphylococcus aureus. Phytomedicine, 2017, 34, 85-96.
[http://dx.doi.org/10.1016/j.phymed.2017.08.016] [PMID: 28899514]
[58]
Olajuyigbe, O.O.; Afolayan, A.J. Synergistic interactions of methanolic extract of Acacia mearnsii De Wild. with antibiotics against bacteria of clinical relevance. Int. J. Mol. Sci., 2012, 13(7), 8915-8932.
[http://dx.doi.org/10.3390/ijms13078915] [PMID: 22942742]
[59]
Martins, M.; McCusker, M.P.; Viveiros, M.; Couto, I.; Fanning, S.; Pagès, J.M.; Amaral, L. A simple method for assessment of MDR bacteria for over-expressed efflux pumps. Open Microbiol. J., 2013, 7, 72-82.
[http://dx.doi.org/10.2174/1874285801307010072] [PMID: 23589748]
[60]
Christiaens, I.; Zaragoza, D.B.; Guilbert, L.; Robertson, S.A.; Mitchell, B.F.; Olson, D.M. Inflammatory processes in preterm and term parturition. J. Reprod. Immunol., 2008, 79(1), 50-57.
[http://dx.doi.org/10.1016/j.jri.2008.04.002] [PMID: 18550178]
[61]
Kumar, A.; Singh, S.; Kumar, A.; Bawankule, D.U.; Tandon, S.; Singh, A.K.; Verma, R.S.; Saikia, D. Chemical composition, bactericidal kinetics, mechanism of action, and anti-inflammatory activity of Isodon melissoides (Benth.) H. Hara essential oil. Nat. Prod. Res., 2019, 35(4), 690-695.
[http://dx.doi.org/10.1080/14786419.2019.1591399] [PMID: 30964333]

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