Neem (Azadirachta indica): larvicidal properties – a review

Introduction: Disease vector mosquitoes are a public health problems worldwide. However, controlling these insects is a challenge, so natural insecticides are a promising strategy due to their potential and low toxicity. Neem (Azadiractha indica A. Juss, Meliaceae) is a tree that has several bioactive compounds and a wide spectrum of action, including repellency and larvicide. Objective: This review aims to show the use of Neembased products used against disease vectors. Several articles were analyzed and showed that different derived compounds are being evaluated, such as extracts, oils, neem cake (extraction by-product), in addition to synthesized nanoparticles. Results: Based on the results, we provide a list of compounds evaluated that have shown to be variable in relation to the LC50 values in relation to the three species of mosquitoes (Culex quinquefasciatus, Anopheles stephensi and Aedes aegypti). Conclusion: Prove the medical relevance of this tree in combating these disease vectors.


Introduction
The Brazil is one of the largest consumers of pesticides in the world 1  Thus, glimpsing the combat of these insects and especially their larvae, without the use of chemical pesticides today, is still an attitude that human beings cannot overlook. However, the use of botanical insecticides has gained prominence, especially with the use of substances derived from the Neem tree (Azadiractha indica A. Juss, Meliaceae). From this tree, it is possible to generate products with a broad spectrum of activity against pests, and has been shown to be an

Methodology
Literature on the Neem tree and its insecticidal action was taken from indexed scientific journals and

Results and discussion
Literature overview Neem is a tree, widely cultivated in the Indian subcontinent, but rapidly expanding worldwide, including in subtropical regions of America 29 . Its use has, among other advantages, a broad spectrum of activity, including medicinal, antibacterial, antifungal and insecticidal properties, of medical relevance, low resistance induction and low mammalian toxicity 29,30 .
Today, the United Nations recognizes the tree as the "21 st Century Tree" 31,32 . Among its features is its fast and easy growth, reaching up to 40 meters in height. In addition, its bioactive potential and low toxicity make it a frequent target for medical and environmental studies, such as insertion in insect control programs 33 . Plant cultivation is already described in different countries in Asia, Africa and America, but India is still the main producer 31 .
All parts of neem have phytochemicals with different action potentials, but commercial use is limited to removable parts such as leaves, fruits and especially seeds, which are one of the main materials used in the production of bioactive compounds 31 . More than 100 of these compounds have been described, being alkaloids, flavonoids, saponins, tannins, phenols, cardiac glycosides and terpenoids. Among terpenoids the main constituents are azadiractin, nimbine, nimbidine and nimbolides 34-36 .
Azaractin is found in neem leaves and bark, but a greater amount of this biologically active substance is found in seeds and is considered to be the richest plant part of this molecule 36 Being the basis of many insecticides, it has hormonal regulatory properties, acting in various physiological processes in larvae and adults of disease vectors 38 .
One product whose research has reported insecticidal action is nanoparticles based on Neem seed extract. This has gained prominence with studies on green nanoparticles with insecticidal properties, bioactivity synthesis, large scale production and the lowest environmental impact 39 .
Recently, neem cake has also been researched, a The study also indicated that protective activity time was directly proportional to concentration 41 . Benelli et al.
(2014) 11 also reported that several neem cake fractions were able to exert good mosquito repellency (above 70%) at a concentration of 100 ppm.
Insecticidal activity however is still the main search for Neem based products. In this sense, several researchers have evaluated the potential, larvicide of A.
indica in different formulations against mosquitoes of medical importance 31,42 . Given this, it can be seen in  There was no mortality in the control containers. One of the advantages of the emulsifier is biocompatibility, better dispersion in water and consequently, causing the larvae to be exposed to higher concentrations of this substance.  66 . In this study, after 12h and 48h of exposure, it was observed the formation of apoptotic bodies, as well as a significant increase in the reactive species of intracellular oxygen (ROS) after exposure to the active principle of Neem.

Conclusion
From this review, we can conclude that different by-products derived from the Neem tree have been studied and shown potential and effective effects in combating insect vectors of diseases. In addition, its importance is still high, since phytochemicals are promising because of their relative safety and low toxicity to the environment.
The vast activity of this plant makes it a great control tool. Its multiple modes of action, coupled with its different metabolites, means that a substantial number of studies are and are being conducted each year. Their goal is unique, it is common, to seek more and more information to complement the findings and enhance the effects on reducing mosquito vectors and diseases caused or not, with less damage to human health, animals and the environment.

Conflicts of interest
The authors declare no conflicts of interest.