The identification of natural, plant-derived compounds with pesticidal properties is crucial for developing environmentally sustainable alternatives to synthetic pesticides. In this study, four major lignans—dihydroclusin, cubebin, clusin, and yatein—were isolated from the crude extract of Piper cubeba fruit. Phytotoxicity assays revealed herbicidal activity against Agrostis stolonifera, with dihydroclusin and clusin exhibiting the highest efficacy, inhibiting seed germination by 50% and showing IC50 values of 2.9 μM and 45 μM, respectively, against Lemna paucicostata. Additionally, all compounds, except dihydroclusin, demonstrated fungicidal activity against the strawberry anthracnose pathogen Colletotrichum fragariae. Moreover, only dihydroclusin exhibited larvicidal activity against Aedes aegypti, causing 96% mortality of mosquito larvae at the 100-ppm concentration tested. These findings highlight the broad-spectrum bioactivity of Piper cubeba lignans, suggesting their potential as alternative agents of synthetic pesticides for managing agricultural pests.
References
[1]
El-Baky, N.A. and Amara, A.A.A.F. (2021) Recent Approaches Towards Control of Fungal Diseases in Plants: An Updated Review. Journal of Fungi, 7, Article No. 900. https://doi.org/10.3390/jof7110900
[2]
Gaines, T.A., Duke, S.O., Morran, S., Rigon, C.A.G., Tranel, P.J., Küpper, A., et al. (2020) Mechanisms of Evolved Herbicide Resistance. Journal of Biological Chemistry, 295, 10307-10330. https://doi.org/10.1074/jbc.rev120.013572
[3]
Ribeiro, V.P., Bajsa-Hirschel, J., Bastos, J.K., Reichley, A., Duke, S.O. and Meepagala, K.M. (2024) Characterization of the Phytotoxic Potential of Seven Copaifera Spp. Essential Oils: Analyzing Active Compounds through Gas Chromatography-Mass Spectrometry Molecular Networking. Journal of Agricultural and Food Chemistry, 72, 18528-18536. https://doi.org/10.1021/acs.jafc.4c04586
[4]
Sparks, T.C., Sparks, J.M. and Duke, S.O. (2023) Natural Product-Based Crop Protection Compounds-Origins and Future Prospects. Journal of Agricultural and Food Chemistry, 71, 2259-2269. https://doi.org/10.1021/acs.jafc.2c06938
[5]
Duke, S.O. (2011) Why Have No New Herbicide Modes of Action Appeared in Recent Years? Pest Management Science, 68, 505-512. https://doi.org/10.1002/ps.2333
[6]
McLaughlin, M.S., Roy, M., Abbasi, P.A., Carisse, O., Yurgel, S.N. and Ali, S. (2023) Why Do We Need Alternative Methods for Fungal Disease Management in Plants? Plants, 12, Article No. 3822. https://doi.org/10.3390/plants12223822
[7]
Benelli, G. (2015) Research in Mosquito Control: Current Challenges for a Brighter Future. Parasitology Research, 114, 2801-2805. https://doi.org/10.1007/s00436-015-4586-9
[8]
Dwita, L.P., Iwo, M.I., Mauludin, R. and Elfahmi (2022) Neuroprotective Potential of Lignan-Rich Fraction of Piper cubeba L. by Improving Antioxidant Capacity in the Rat's Brain. Brazilian Journal of Biology, 82, e266573. https://doi.org/10.1590/1519-6984.266573
[9]
Wu, B., Kashiwagi, T., Kuroda, I., Chen, X.H., Tebayashi, S. and Kim, C. (2008) Antifeedants against Locusta migratoria from the Japanese Cedar, Cryptomeria japonica II. Bioscience, Biotechnology, and Biochemistry, 72, 611-614. https://doi.org/10.1271/bbb.70610
[10]
Gu, H., Cheng, S., Huang, C., Chen, W. and Chang, S. (2009) Mosquito Larvicidal Activities of Extractives from Black Heartwood-Type Cryptomeria Japonica. Parasitology Research, 105, 1455-1458. https://doi.org/10.1007/s00436-009-1550-6
[11]
Agrawal, N., Goyal, D. and Goyal, A. (2023) A Review on Multi-Therapeutic Potential of (−)-Cubebin: Experimental Evidences. Natural Product Research, 37, 4290-4301. https://doi.org/10.1080/14786419.2023.2177849
[12]
Drissi, B., Mahdi, I., Yassir, M., Ben Bakrim, W., Bouissane, L. and Sobeh, M. (2022) Cubeb (Piper cubeba L. f.): A Comprehensive Review of Its Botany, Phytochemistry, Traditional Uses, and Pharmacological Properties. Frontiers in Nutrition, 9, Article ID: 1048520. https://doi.org/10.3389/fnut.2022.1048520
[13]
Fan, D., Zhou, C., Chen, C., Li, X., Ma, J., Hu, Y., et al. (2023) Lignans from the Genus piper L. and Their Pharmacological Activities: An Updated Review. Fitoterapia, 165, Article ID: 105403. https://doi.org/10.1016/j.fitote.2022.105403
[14]
Alqadeeri, F., Rukayadi, Y., Abbas, F. and Shaari, K. (2019) Antibacterial and Antispore Activities of Isolated Compounds from Piper cubeba L. Molecules, 24, Article No. 3095. https://doi.org/10.3390/molecules24173095
[15]
Fazly, A.Z. and Rukayadi, Y. (2019) Antibacterial Activity of Ethanolic Piper cubeba L. Extract against Escherichia coli and Its Effect on Microbiological Quality of Raw Chicken Meat during Storage. International Food Research Journal, 26, 933-944.
[16]
Gomes, A.C., Borges, A., Zoca, D.G., Silva, M.L.A.e., Machado, A.R.d.S.R., Machado, A.M., et al. (2022) Larvicidal Potential of Extracts and Isolated Compounds from Piper cubeba Fruits against Aedes aegypti (Diptera: Culicidae) Larvae. Natural Product Research, 37, 2787-2794. https://doi.org/10.1080/14786419.2022.2131784
[17]
Arruda, C., Mejía, J.A.A., Pena Ribeiro, V., Costa Oliveira, L., e Silva, M.L.A. and Bastos, J.K. (2018) Development of a Validated High-Performance Liquid Chromatography Method and Optimization of the Extraction of Lignans from Piper cubeba. Journal of Agricultural and Food Chemistry, 67, 753-759. https://doi.org/10.1021/acs.jafc.8b05359
[18]
Enders, D., Lausberg, V., Signore, G.D. and Berner, O.M. (2002) A General Approach to the Asymmetric Synthesis of Lignans: (−)-Methyl Piperitol, (−)-Sesamin, (−)-Aschantin, (+)-Yatein, (+)-Dihydroclusin, (+)-Burseran, and (−)-isostegane. Synthesis, 2002, 515-522. https://doi.org/10.1055/s-2002-20967
[19]
Arruda, C., Eugênio, D.d.S., Moreira, M.R., Símaro, G.V., Bastos, J.K., Martins, C.H.G., et al. (2017) Biotransformation of (−)-Cubebin by Aspergillus spp. into (−)-Hinokinin and (−)-Parabenzlactone, and Their Evaluation against Oral Pathogenic Bacteria. Natural Product Research, 32, 2803-2816. https://doi.org/10.1080/14786419.2017.1380017
[20]
Koul, S.K., Taneja, S.C., Dhar, K.L. and Atal, C.K. (1983) Lignans of Piper clusii. Phytochemistry, 22, 999-1000. https://doi.org/10.1016/0031-9422(83)85040-7
[21]
Dayan, F.E., Romagni, J.G. and Duke, S.O. (2000) Investigating the Mode of Action of Natural Phytotoxins. Journal of Chemical Ecology, 26, 2079-2094. https://doi.org/10.1023/a:1005512331061
[22]
Ribeiro, V.P., Bajsa-Hirschel, J., Tamang, P., Meepagala, K. and Duke, S.O. (2023) Antifungal and Phytotoxic Activities of Isolated Compounds from Heliettaparvifolia Stems. Molecules, 28, Article No. 7930. https://doi.org/10.3390/molecules28237930
[23]
Ribeiro, V.P., Bastos, J.K., Estep, A.S. and Meepagala, K.M. (2024) Larvicidal Activity of Constituents from the Main Brazilian Propolis Types: Green, Red, and Brown against Aedes aegypti. ACS Omega, 9, 35560-35566. https://doi.org/10.1021/acsomega.4c03132
[24]
Marsala, L., Oliveira Cunha, M.L., do Nascimento, V., Pereira Prado, E., da Silva Viana, R. and Ferrari, S. (2022) Can 2,4-D Promote the Hormesis Effect in Upland Rice? Journal of Environmental Science and Health, Part B, 57, 680-685. https://doi.org/10.1080/03601234.2022.2099687
[25]
Belz, R.G. (2007) Stimulation versus Inhibition—Bioactivity of Parthenin, a Phytochemical from Parthenium hysterophorus L. Dose-Response, 6, 80-96. https://doi.org/10.2203/dose-response.07-007.belz
[26]
Ruiz-Vásquez, L., Ruiz Mesia, L., Caballero Ceferino, H.D., Ruiz Mesia, W., Andrés, M.F., Díaz, C.E., et al. (2022) Antifungal and Herbicidal Potential of Piper Essential Oils from the Peruvian Amazonia. Plants, 11, Article No. 1793. https://doi.org/10.3390/plants11141793
[27]
Cuadros-Siguas, C.F., Herrera-Calderon, O., Batiha, G.E., Almohmadi, N.H., Aljarba, N.H., Apesteguia-Infantes, J.A., et al. (2023) Volatile Components, Antioxidant and Phytotoxic Activity of the Essential Oil of Piper acutifolium Ruiz & Pav. from Peru. Molecules, 28, Article No. 3348. https://doi.org/10.3390/molecules28083348
[28]
DellaGreca, M., Zuppolini, S. and Zarrelli, A. (2013) Isolation of Lignans as Seed Germination and Plant Growth Inhibitors from Mediterranean Plants and Chemical Synthesis of Some Analogues. Phytochemistry Reviews, 12, 717-731. https://doi.org/10.1007/s11101-013-9311-7
[29]
Oliva, A., Moraes, R.M., Watson, S.B., Duke, S.O. and Dayan, F.E. (2002) Aryltetralin Lignans Inhibit Plant Growth by Affecting the Formation of Mitotic Microtubular Organizing Centers. Pesticide Biochemistry and Physiology, 72, 45-54. https://doi.org/10.1006/pest.2002.2582
[30]
Labruzzo, A., Cantrell, C.L., Carrubba, A., Ali, A., Wedge, D.E. and Duke, S.O. (2018) Phytotoxic Lignans from Artemisia arborescens. Natural Product Communications, 13, Article No. 3. https://doi.org/10.1177/1934578x1801300302
[31]
Singh, G., Kiran, S., Marimuthu, P., Lampasona, M.P., Heluani, C.S. and Catalan, C.A.N. (2008) Chemistry, Biocidal and Antioxidant Activities of Essential Oil and Oleoresins from Piper cubeba (Seed). International Journal of Essential Oil Therapeutics, 2, 50.
[32]
De Campos, M.P., Cechinel Filho, V., Da Silva, R.Z., Yunes, R.A., Zacchino, S., Juarez, S., et al. (2005) Evaluation of Antifungal Activity of Piper solmsianum C. DC. var. Solmsianum (Piperaceae). Biological and Pharmaceutical Bulletin, 28, 1527-1530. https://doi.org/10.1248/bpb.28.1527
[33]
Aneja, K.R., Joshi, R., Sharma, C. and Aneja, A. (2010) Antimicrobial Efficacy of Fruit Extracts of Two Piper Species against Selected Bacterial and Oral Fungal Pathogens. Brazilian Journal of Oral Sciences, 9, 421-426.
[34]
Silva, M.L.A., Coímbra, H.S., Pereira, A.C., Almeida, V.A., Lima, T.C., Costa, E.S., et al. (2007) Evaluation of Piper cubeba Extract, (−)-Cubebin and Its Semi-Synthetic Derivatives against Oral Pathogens. Phytotherapy Research, 21, 420-422. https://doi.org/10.1002/ptr.2088