Abstract
Mosquitoes (Diptera: Culicidae) represent an important threat to millions of people worldwide, since they act as vectors for important pathogens, such as malaria, yellow fever, dengue and West Nile. Control programmes mainly rely on chemical treatments against larvae, indoor residual spraying and insecticide-treated bed nets. In recent years, huge efforts have been carried out to propose new eco-friendly alternatives, with a special focus on the evaluation of plant-borne mosquitocidal compounds. Major examples are neem-based products (Azadirachta indica A. Juss, Meliaceae) that have been proven as really effective against a huge range of pests of medical and veterinary importance, including mosquitoes. Recent research highlighted that neem cake, a cheap by-product from neem oil extraction, is an important source of mosquitocidal metabolites. In this review, we examined (i) the latest achievements about neem cake metabolomics with special reference to nor-terpenoid and related content; (ii) the neem cake ovicidal, larvicidal and pupicidal toxicity against Aedes, Anopheles and Culex mosquito vectors; (iii) its non-target effects against vertebrates; and (iv) its oviposition deterrence effects on mosquito females. Overall, neem cake can be proposed as an eco-friendly and low-cost source of chemicals to build newer and safer control tools against mosquito vectors.
Similar content being viewed by others
References
Abdel-Ghaffar F, Al-Quraishy S, Sobhy H, Semmler M (2008) Neem seed extract shampoo, Wash Away Louse®, an effective plant agent against Sarcoptes scabiei mite infesting dogs in Egypt. Parasitol Res 104:145–148
Abdel-Ghaffar F, Semmler M, Al-Rasheid KAS, Mehlhorn H (2009) In vitro efficacy of ByeMite® and Mite-Stop® on developmental stages of the red chicken mite Dermanyssus gallinae. Parasitol Res 105:469–471
Abdel-Ghaffar F, Al-Quraishy S, Al-Rasheid KAS, Mehlhorn H (2012) Efficacy of a single treatment of head lice with a neem seed extract: an in vivo and in vitro study on nits and motile stages. Parasitol Res 110:277–280
Al-Quraishy S, Abdel-Ghaffar F, Al-Rasheid KAS, Mehlhorn J, Mehlhorn H (2011) Effects of a neem seed extract (MiteStop®) on mallophages (featherlings) of chicken: in-vivo and in-vitro studies. Parasitol Res 110:617–622
Al-Quraishy S, Abdel-Ghaffar F, Al-Rasheid KAS, Mehlhorn J, Mehlhorn H (2012) Observations on effects of a neem seed extract (MiteStop®) on biting lice (mallophages) and bloodsucking insects parasitizing horses. Parasitol Res 110:335–339
Amer A, Mehlhorn H (2006a) Larvicidal effects of various essential oils against Aedes, Anopheles, and Culex larvae (Diptera, Culicidae). Parasitol Res 99:466–472
Amer A, Mehlhorn H (2006b) Repellency effect of forty-one essential oils against Aedes, Anopheles and Culex mosquitoes. Parasitol Res 99:478–490
Anjali CH, Sharma Y, Mukherjee A, Chandrasekaran N (2012) Neem oil (Azadirachta indica) nanoemulsion—a potent larvicidal agent against Culex quinquefasciatus. Pest Manag Sci 68:158–163
Balandrin MF, Lee SM, Klocke JA (1988) Biologically active volatile organosulfur compounds from seeds of the neem tree, Azadirachta indica (Meliaceae). J Agric Food Chem 36:1048–1054
Baumer M (1983) Notes on trees and shrubs in arid and semi-arid regions. In: FAO/UNEP programme “Ecological Management of Arid and Semi-Arid Rangelands in Africa, Near and Middle East”, EMASAR Phase II
Benedict MQ, Levine RS, Hawley WA, Lounibos LP (2007) Spread of the tiger: global risk of invasion by the mosquito Aedes albopictus. Vect Bor Zoon Dis 7:76–85
Benelli G (2015) The best time to have sex: mating behaviour and effect of daylight time on male sexual competitiveness in the Asian tiger mosquito, Aedes albopictus (Diptera: Culicidae). Parasitol Res doi:10.1007/s00436-014-4252-7
Benelli G, Flamini G, Fiore G, Cioni PL, Conti B (2013a) Larvicidal and repellent activity of the essential oil of Coriandrum sativum L. (Apiaceae) fruits against the filariasis vector Aedes albopictus Skuse (Diptera: Culicidae). Parasitol Res 112:1155–1161
Benelli G, Canale A, Conti B (2013b) Eco-friendly control strategies against the Asian tiger mosquito, Aedes albopictus (Diptera: Culicidae): repellency and toxic activity of plant essential oils and extracts. Pharmacol Online 47:44–51
Benelli G, Conti B, Garreffa R, Nicoletti M (2014) Shedding light on bioactivity of botanical by-products: neem cake compounds deter oviposition of the arbovirus vector Aedes albopictus (Diptera: Culicidae) in the field. Parasitol Res 113:933–940
Benelli G, Bedini S, Cosci F, Toniolo C, Conti B, Nicoletti M (2015) Larvicidal and ovideterrent properties of neem oil and fractions against the filariasis vector Aedes albopictus (Diptera: Culicidae): a bioactivity survey across production sites. Parasitol Res. doi:10.1007/s00436-014-4183-3
Boeke SJ, Boersma MG, Alink GM, van Loon JJA, van Huis A, Dicke M, Rietjens IMCM (2004) Safety evaluation of neem (Azadirachta indica) derived pesticides. J Ethnopharmacol 94:25–41
Bowatte G, Perera P, Senevirathne G, Meegaskumbura S, Meegaskumbura M (2013) Tadpoles as dengue mosquito (Aedes aegypti) egg predators. Biol Control 67:469–474
Bhownik D, Yadav CJ, Tripathi KK, Sampath Kumar KP (2010) Herbal remedies of Azadirachta indica and its medicinal applications. J Chem Pharm Res 2:62–72
Conti B, Flamini G, Cioni PL, Ceccarini L, Macchia M, Benelli G (2014) Mosquitocidal essential oils: are they safe against non-target aquatic organisms? Parasitol Res 113:251–259
Coria C, Almiron W, Valladares G, Carpinella C, Luduena F, Defago M, Palacios S (2008) Larvicide and oviposition deterrent effects of fruit and leaf extracts from Melia azedarach L. on Aedes aegypti (L.) (Diptera: Culicidae). Bioresour Technol 99:3066–3070
Dua VK, Pandey AC, Raghavendra K, Gupta A, Sharma T, Dash A (2009) Larvicidal activity of neem oil (Azadirachta indica) formulation against mosquitoes. Malar J 8:124
Egho EO (2012) Seeds of neem tree (Azadirachta indica A. Juss). Promising biopesticide in the management of cowpea insect pests and grain yield in the early cropping season at Asaba and Abraka, Delta State, Nigeria. J Agric Sci 4:181–189
Gallo FR, Multari G, Federici E, Palazzino G, Giambenedetti M, Petitto V, Poli F, Nicoletti M (2011) Chemical fingerprinting of Equisetum arvense L. using HPTLC densitometry and HPLC. Nat Prod Res 25:1261–1270
Gallo FR, Multari G, Federici E, Palazzino G, Nicoletti M, Petitto V (2012) The modern analytical determination of botanicals and similar novel natural products by the HPTLC fingerprint approach. In: Studies in natural products chemistry. Atta-Ur-Rahman (Ed.). Elsevier, Paris, 37:217–258
Gallo FR, Multari G, Federici E, Palazzino G, Nicoletti M, Petitto V (2013) Bearberry identification by a multidisciplinary study on commercial raw material. Nat Prod Res 27:735–742
Hemingway J, Ranson H (2000) Insecticide resistance in insect vectors of human disease. Annu Rev Entomol 45:371–391
Isman MB (2006) Botanical insecticides, deterrents and repellents in modern agriculture and an increasingly regulated world. Annu Rev Entomol 51:45–66
Jensen M, Mehlhorn H (2009) Seventy-five years of Resochin® in the fight against malaria. Parasitol Res 105:609–627
Kondo S, Konishi T, Murugan K (2004) Larvicidal effects of neem (Azadirachta indica) seed kernel extracts against Paratanytarsus grimmii (Diptera: Chironomidae) and Aedes albopictus (Diptera: Culicidae). Med Entomol Zool 55:247–250
Lees RS, Knols B, Bellini R, Benedict MQ, Bheecarry A, Bossin HC et al (2014) Review: improving our knowledge of male mosquito biology in relation to genetic control programmes. Acta Trop 132S:S2–S11
Locher N, Al-Rasheid KAS, Abdel-Ghaffar F, Mehlhorn H (2010) In vitro and field studies on the contact and fumigant toxicity of a neem-product (Mite-Stop®) against the developmental stages of the poultry red mite Dermanyssus gallinae. Parasitol Res 107:417–423
Mariani S, Nicoletti M (2013) Antilarval activity of neem cake extracts against Aedes albopictus. Pharmacol Online 3:137–140
Mehlhorn H, Walldorf V, Abdel-Ghaffar F, Al-Quraishy S, Al-Rasheid KAS, Mehlhorn J (2012) Biting and bloodsucking lice of dogs—treatment by means of a neem seed extract (MiteStop®, Wash Away Dog). Parasitol Res 110:769–773
Mulla MS, Su T (1999) Activity and biological effects of neem products against arthropods of medical and veterinary importance. J Am Mosq Control Assoc 15:133–152
Murugan K, Babu R, Jeyabalan D, Senthil Kumar N, Sivaramakrishnan S (1996) Antipupational effect of neem oil and neem seed kernel extract against mosquito larvae of Anopheles stephensi (Liston). J Entomol Res 20:137–139
Murugan K, Hwang JS, Kovendan K, Prasanna KK, Vasugi C, Naresh KA (2011) Use of plant products and copepod for the control of dengue vector, Aedes aegypti. Hydrobiologia 666:331–338
National Research Council (1992) Neem: a tree for solving global problems. In: Report of an ad hoc panel of the Board on Science and Technology for International Development. National Academy Press, Washington
Nicoletti M, Toniolo C (2012) HPTLC Fingerprint analysis of plant staminal cell products. J Chem Separ Tech 3:7–11
Nicoletti M, Murugan K (2013) Neem the tree of XXI century. Pharmacol Online 3:115–121
Nicoletti M, Serafini M, Aliboni A, D’Andrea A, Mariani S (2010) Toxic effects of neem cake extracts on Aedes albopictus larvae. Parasitol Res 107:89–84
Nicoletti M, Mariani S, Maccioni O, Coccioletti T, Murugan K (2012a) Neem cake: chemical composition and larvicidal activity on Asian tiger mosquito. Parasitol Res 111:205–2013
Nicoletti M, Maccioni O, Coccioletti T, Mariani S, Vitali F (2012b) Neem tree (Azadiractha indica A. Juss) as source of bioinsecticides. In: Perveen (Ed.) Insecticides—advances in integrated pest management, InTech, Rijeka, Croatia, pp. 411–428
Nicoletti M, Toniolo C, Gallo FR, Multari G, Palazzino G (2013) Traceability in multi-ingredient botanicals by HPTLC fingerprint approach. J Plan Chromatogr 26:243–247
Nicoletti M, Murugan K, Del Serrone P (2014) Current mosquito-borne disease emergencies in Italy and climate changes. The neem opportunity. Tr Vect Res Parasitol 1:2
Oliva CF, Damiens D, Benedict MQ (2014) Male reproductive biology of Aedes mosquitoes. Acta Trop 132S:S512–S519
Paupy C, Delatte H, Bagny L, Corbel V, Fontenille D (2009) Aedes albopictus, an arbovirus vector: from the darkness to light. Microb Infect 11:1177–1185
Rao DR, Reuben R, Venugopal MS, Nagasampagi BA, Schmutterer H (1992) Evaluation of neem, Azadirachta indica, with and without water management, for the control of culicine mosquito larvae in rice-fields. Med Vet Entomol 6:318–324
Rao DR, Reuben R, Nagasampagi BA (1995) Development of combined use of neem (Azadirachta indica) and water management for the control of Culicinae mosquito in rice fields. Med Vet Entomol 9:25–33
Schmahl G, Al-Rasheid KAS, Abdel-Ghaffar F, Klimpel S, Mehlhorn H (2010) The efficacy of neem seed extracts (Tresan®, MiteStop®) on a broad spectrum of pests and parasites. Parasitol Res 107:261–269
Semmler M, Abdel-Ghaffar F, Al-Rasheid KAS, Mehlhorn H (2010) Nature helps: from research to products against blood sucking parasites. Parasitol Res 105:1483–1487
Semmler M, Abdel-Ghaffar F, Schmidt J, Mehlhorn H (2014) Evaluation of biological and chemical insect repellents and their potential adverse effects. Parasitol Res 113:185–188
Shanmugasundaram, Jeyalakshmi T, Sunil Dutt M, Balakrishna Murthy P (2008) Larvicidal activity of neem and karanja oil cakes against mosquito vectors, Culex quinquefasciatus (Say), Aedes aegypti (L.) and Anopheles stephensi (L.). J Environ Biol 29:43–45
Sharma VP, Dhiman RC (1993) Neem oil as a sand fly (Diptera: Psychodidae) repellent. J Am Mosq Control Assoc 9:364–366
Senthil Nathan S, Kalaivani K, Murugan K (2005) Effects of neem limonoids on the malaria vector Anopheles stephensi Liston (Diptera: Culicidae). Acta Trop 96:47–55
Su T, Mulla MS (1998a) Antifeedancy of neem products containing Azadirachtin against Culex tarsalis and Culex quinquefasciatus (Diptera: Culicidae). J Vector Ecol 23:114–122
Su T, Mulla MS (1998b) Ovicidal activity of neem products (azadirachtin) against Culex tarsalis and Culex quinquefasciatus (Diptera; Culicidae). J Am Mosq Control Assoc 14:204–209
Su T, Mulla MS (1999) Oviposition bioassay responses of Culex tarsalis and Culex quinquefasciatus to neem products containing azadirachtin. Entomol Exp Appl 91:337–345
Walldorf V, Mehlhorn H, Al-Quraishy S, Al-Rasheid KAS, Abdel-Ghaffar F, Mehlhorn J (2012) Treatment with a neem seed extract (MiteStop®) of beetle larvae parasitizing the plumage of poultry. Parasitol Res 110:623–627
Wan MT, Watts RG, Isman MB, Strub R (1996) Evaluation of the acute toxicity to juvenile Pacific Northwest salmon of azadirachtin, neem extract and neem-based products. Bull Environ Contam Toxicol 56:432–439
Wang H-W, Liu Y-X, Li Z-R, Chen Y-X, Yang Y-F, Yang Y-X, Li Z-R, Qiu M-H (2013) New triterpenoids from the kernel of Azadirachta indica. Nat Prod Bioprospect 3:33–37
WHO (2013) World Malaria Report 2013. Geneva, Switzerland, 282 pp
Xue RD, Barnard DR, Ali A (2001) Laboratory and field evaluation of insect repellents as oviposition deterrents against the mosquito Aedes albopictus. Med Vet Entomol 15:126–131
Acknowledgments
We would like to thank Professor Heinz Mehlhorn and the anonymous reviewers for their comments on an earlier version of this review. We gratefully acknowledge the contributions of our co-authors to the original work. Giovanni Benelli is supported by a MIS. 124 MODOLIVI Grant. Funds were also provided by the Italian Ministry of Education, University and Research (MIUR). Funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Benelli, G., Murugan, K., Panneerselvam, C. et al. Old ingredients for a new recipe? Neem cake, a low-cost botanical by-product in the fight against mosquito-borne diseases. Parasitol Res 114, 391–397 (2015). https://doi.org/10.1007/s00436-014-4286-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00436-014-4286-x