Evaluating the potential of Kalanchoe pinnata, Piper amalago amalago, and other botanicals as economical insecticidal synergists against Anopheles gambiae
Abstract Background Synergists reduce insecticide metabolism in mosquitoes by competing with insecticides for the active sites of metabolic enzymes, such as cytochrome P450s (CYPs). This increases the availability of the insecticide at its specific target site. The combination of both insecticides a...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | Malaria Journal |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12936-025-05254-4 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832586083851829248 |
|---|---|
| author | Sheena Francis William Irvine Lucy Mackenzie-Impoinvil Lucrecia Vizcaino Rodolphe Poupardin Audrey Lenhart Mark J. I. Paine Rupika Delgoda |
| author_facet | Sheena Francis William Irvine Lucy Mackenzie-Impoinvil Lucrecia Vizcaino Rodolphe Poupardin Audrey Lenhart Mark J. I. Paine Rupika Delgoda |
| author_sort | Sheena Francis |
| collection | DOAJ |
| description | Abstract Background Synergists reduce insecticide metabolism in mosquitoes by competing with insecticides for the active sites of metabolic enzymes, such as cytochrome P450s (CYPs). This increases the availability of the insecticide at its specific target site. The combination of both insecticides and synergists increases the toxicity of the mixture. Given the demonstrated resistance to the classical insecticides in numerous Anopheles spp., the use of synergists is becoming increasingly pertinent. Tropical plants synthesize diverse phytochemicals, presenting a repository of potential synergists. Methods Extracts prepared from medicinal plants found in Jamaica were screened against recombinant Anopheles gambiae CYP6M2 and CYP6P3, and Anopheles funestus CYP6P9a, CYPs associated with anopheline resistance to pyrethroids and several other insecticide classes. The toxicity of these extracts alone or as synergists, was evaluated using bottle bioassays with the insecticide permethrin. RNA sequencing and in silico modelling were used to determine the mode of action of the extracts. Results Aqueous extracts of Piper amalago var. amalago inhibited CYP6P9a, CYP6M2, and CYP6P3 with IC50s of 2.61 ± 0.17, 4.3 ± 0.42, and 5.84 ± 0.42 μg/ml, respectively, while extracts of Kalanchoe pinnata, inhibited CYP6M2 with an IC50 of 3.52 ± 0.68 μg/ml. Ethanol extracts of P. amalago var. amalago and K. pinnata displayed dose-dependent insecticidal activity against An. gambiae, with LD50s of 368.42 and 282.37 ng/mosquito, respectively. Additionally, An. gambiae pretreated with K. pinnata (dose: 1.43 μg/mosquito) demonstrated increased susceptibility (83.19 ± 6.14%) to permethrin in a bottle bioassay at 30 min compared to the permethrin only treatment (0% mortality). RNA sequencing demonstrated gene modulation for CYP genes in anopheline mosquitoes exposed to 715 ng of ethanolic plant extract at 24 h. In silico modelling showed good binding affinity between CYPs and the plants’ secondary metabolites. Conclusion This study demonstrates that extracts from P. amalago var. amalago and K. pinnata, with inhibitory properties, IC50 < 6.95 μg/ml, against recombinant anopheline CYPs may be developed as natural synergists against anopheline mosquitoes. Novel synergists can help to overcome metabolic resistance to insecticides, which is increasingly reported in malaria vectors. Graphical Abstract |
| format | Article |
| id | doaj-art-bd20da3b344e4a52b1eb60a018721b15 |
| institution | Kabale University |
| issn | 1475-2875 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj-art-bd20da3b344e4a52b1eb60a018721b152025-01-26T12:15:54ZengBMCMalaria Journal1475-28752025-01-0124112310.1186/s12936-025-05254-4Evaluating the potential of Kalanchoe pinnata, Piper amalago amalago, and other botanicals as economical insecticidal synergists against Anopheles gambiaeSheena Francis0William Irvine1Lucy Mackenzie-Impoinvil2Lucrecia Vizcaino3Rodolphe Poupardin4Audrey Lenhart5Mark J. I. Paine6Rupika Delgoda7Caribbean Centre for Research in Biosciences, Natural Products Institute, University of the West IndiesCaribbean Centre for Research in Biosciences, Natural Products Institute, University of the West IndiesEntomology Branch, Division of Parasitic Diseases and Malaria, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and PreventionEntomology Branch, Division of Parasitic Diseases and Malaria, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and PreventionCell Therapy Institute, Paracelsus Medical UniversityEntomology Branch, Division of Parasitic Diseases and Malaria, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and PreventionVector Group, Liverpool School of Tropical MedicineCaribbean Centre for Research in Biosciences, Natural Products Institute, University of the West IndiesAbstract Background Synergists reduce insecticide metabolism in mosquitoes by competing with insecticides for the active sites of metabolic enzymes, such as cytochrome P450s (CYPs). This increases the availability of the insecticide at its specific target site. The combination of both insecticides and synergists increases the toxicity of the mixture. Given the demonstrated resistance to the classical insecticides in numerous Anopheles spp., the use of synergists is becoming increasingly pertinent. Tropical plants synthesize diverse phytochemicals, presenting a repository of potential synergists. Methods Extracts prepared from medicinal plants found in Jamaica were screened against recombinant Anopheles gambiae CYP6M2 and CYP6P3, and Anopheles funestus CYP6P9a, CYPs associated with anopheline resistance to pyrethroids and several other insecticide classes. The toxicity of these extracts alone or as synergists, was evaluated using bottle bioassays with the insecticide permethrin. RNA sequencing and in silico modelling were used to determine the mode of action of the extracts. Results Aqueous extracts of Piper amalago var. amalago inhibited CYP6P9a, CYP6M2, and CYP6P3 with IC50s of 2.61 ± 0.17, 4.3 ± 0.42, and 5.84 ± 0.42 μg/ml, respectively, while extracts of Kalanchoe pinnata, inhibited CYP6M2 with an IC50 of 3.52 ± 0.68 μg/ml. Ethanol extracts of P. amalago var. amalago and K. pinnata displayed dose-dependent insecticidal activity against An. gambiae, with LD50s of 368.42 and 282.37 ng/mosquito, respectively. Additionally, An. gambiae pretreated with K. pinnata (dose: 1.43 μg/mosquito) demonstrated increased susceptibility (83.19 ± 6.14%) to permethrin in a bottle bioassay at 30 min compared to the permethrin only treatment (0% mortality). RNA sequencing demonstrated gene modulation for CYP genes in anopheline mosquitoes exposed to 715 ng of ethanolic plant extract at 24 h. In silico modelling showed good binding affinity between CYPs and the plants’ secondary metabolites. Conclusion This study demonstrates that extracts from P. amalago var. amalago and K. pinnata, with inhibitory properties, IC50 < 6.95 μg/ml, against recombinant anopheline CYPs may be developed as natural synergists against anopheline mosquitoes. Novel synergists can help to overcome metabolic resistance to insecticides, which is increasingly reported in malaria vectors. Graphical Abstracthttps://doi.org/10.1186/s12936-025-05254-4Jamaican plantsKalanchoe (Bryophyllum) pinnataPiper amalago var. amalagoCYPMosquitoesRNA-seq |
| spellingShingle | Sheena Francis William Irvine Lucy Mackenzie-Impoinvil Lucrecia Vizcaino Rodolphe Poupardin Audrey Lenhart Mark J. I. Paine Rupika Delgoda Evaluating the potential of Kalanchoe pinnata, Piper amalago amalago, and other botanicals as economical insecticidal synergists against Anopheles gambiae Malaria Journal Jamaican plants Kalanchoe (Bryophyllum) pinnata Piper amalago var. amalago CYP Mosquitoes RNA-seq |
| title | Evaluating the potential of Kalanchoe pinnata, Piper amalago amalago, and other botanicals as economical insecticidal synergists against Anopheles gambiae |
| title_full | Evaluating the potential of Kalanchoe pinnata, Piper amalago amalago, and other botanicals as economical insecticidal synergists against Anopheles gambiae |
| title_fullStr | Evaluating the potential of Kalanchoe pinnata, Piper amalago amalago, and other botanicals as economical insecticidal synergists against Anopheles gambiae |
| title_full_unstemmed | Evaluating the potential of Kalanchoe pinnata, Piper amalago amalago, and other botanicals as economical insecticidal synergists against Anopheles gambiae |
| title_short | Evaluating the potential of Kalanchoe pinnata, Piper amalago amalago, and other botanicals as economical insecticidal synergists against Anopheles gambiae |
| title_sort | evaluating the potential of kalanchoe pinnata piper amalago amalago and other botanicals as economical insecticidal synergists against anopheles gambiae |
| topic | Jamaican plants Kalanchoe (Bryophyllum) pinnata Piper amalago var. amalago CYP Mosquitoes RNA-seq |
| url | https://doi.org/10.1186/s12936-025-05254-4 |
| work_keys_str_mv | AT sheenafrancis evaluatingthepotentialofkalanchoepinnatapiperamalagoamalagoandotherbotanicalsaseconomicalinsecticidalsynergistsagainstanophelesgambiae AT williamirvine evaluatingthepotentialofkalanchoepinnatapiperamalagoamalagoandotherbotanicalsaseconomicalinsecticidalsynergistsagainstanophelesgambiae AT lucymackenzieimpoinvil evaluatingthepotentialofkalanchoepinnatapiperamalagoamalagoandotherbotanicalsaseconomicalinsecticidalsynergistsagainstanophelesgambiae AT lucreciavizcaino evaluatingthepotentialofkalanchoepinnatapiperamalagoamalagoandotherbotanicalsaseconomicalinsecticidalsynergistsagainstanophelesgambiae AT rodolphepoupardin evaluatingthepotentialofkalanchoepinnatapiperamalagoamalagoandotherbotanicalsaseconomicalinsecticidalsynergistsagainstanophelesgambiae AT audreylenhart evaluatingthepotentialofkalanchoepinnatapiperamalagoamalagoandotherbotanicalsaseconomicalinsecticidalsynergistsagainstanophelesgambiae AT markjipaine evaluatingthepotentialofkalanchoepinnatapiperamalagoamalagoandotherbotanicalsaseconomicalinsecticidalsynergistsagainstanophelesgambiae AT rupikadelgoda evaluatingthepotentialofkalanchoepinnatapiperamalagoamalagoandotherbotanicalsaseconomicalinsecticidalsynergistsagainstanophelesgambiae |