INTRODUCTION:

Pesticides has become a major component in large scale food production¹. The increase in the world population has direct impact on food production as a result there is a more dependence on chemical pesticides. Overuse of chemical pesticides has hazardous effect on both biotic and abiotic factors². During the last few decades it has been observed that pesticides residues did spread in the environment and contaminate terrestrial ecosystem as well as aquatic ecosystem^3,4. According to a report presented by world health organization (WHO) and United Nation environment Programme (UNEP) around 200,000 deaths and about three million people pesticide poisoning has been reported in developing countries^5,6. The increase in the use of chemical pesticide has resulted in unpredicted environmental issues, pest insurgence and health hazards on soil and plant which are ecologically unacceptable activity⁷.

An alternative method is to shift our concern from chemical, synthetic pesticide to organic, safe, and non-toxic pesticides⁸. Biopesticides are naturally derived formulation for the control of pest in an eco-friendly manner⁹. There is no definite definition of biopesticides. They are generally produced through the bio-products of microbes and plants and thus are very much safe to the environment¹⁰. Biopesticides possess considerable benefits to the farmers as well as to the environment. World is producing about 3000 tons of biopesticides every year which is rapidly increasing in a significant rate. India has a vast diversity of biopesticides⁹. Among all the biopesticides, Neem (Azadirachta indica) has emerged as a reliable biopesticides¹¹.Neem is on the top list of botanicals used as biopesticides in the world¹².

NEEM (Azadirachta indica):

Neem tree (Azadirachta indica A.Juss) belongs to the family Meliaceae, is an evergreen tropical tree native to India and Burma¹³.It is also grown in most of the parts of South east Asia and West Africa. Neem has been used as an ayurvedic medicine since 4000 years ago due to its varied medicinal properties. Most of the plant parts of neem has been used as antiseptic, antiviral, antipyretic, antiulcer and as antifungal medicine. Neem has been recognized as “Life giving tree”, “Village pharmacy”, “Divine tree”, “sacred offering of nature”^14,15. It is also known as ‘Indian lilac’ or ‘Margosa’ and ‘Azad- Darakth- E- Hind’ which means‘ Free tree of India’ in Persia. Nima is the sanskrit name for neem which is derived from the term ‘nimbati swasthyamdadati’ which means ‘to give good health’. ‘Charak-Samhita’ and ‘Susruta-Samhita’, has enlisted the benefits of neem^16,17.Due to its enormous medicinal use, it has been recognized as the tree of 21^st century’ by the United Nations¹⁸.

The systematic position of Neem:

Kingdom: Plantae

Division: Magnoliophyta

Order: Sapindales

Family: Meliaceae

Genus: Azadirachta

Species: indica

Neem is a large growing tree and attains a height of upto 25-30 m with profuse branching often forming a broad crown. Neem tree becomes full productive after 10 years and produces about 50kg of fruits annually. It has a life span of about 200 years .It can withstand a wide range of climatic, topographic and edaphic factors. Neem tree grows well in less rainfall regions usually ranging between 450-1200mm, thus it requires very little water for its growth. Neem can be grown in dry, calcareous regions .It can grow upto an altitude of 1500m. Neem tree requires a pH range of 4-10 for its growth. It can grow mostly in all types of soil but not in black cotton soils and deep well drained soil^12,13. Neem has a unique ability of calcium mining thus it can neutralize acidic soils. Each part of the neem possess fungicidal, insecticidal, and nematicidal properties, among all the plant parts, leaves and seed have been most widely used as an insecticide^19,20.

Major Neem products:

Neem plant parts has been used since time immemorial because of their wide importance. Major neem products such as neem oil, leaf extract, seed extract, root extracts as well as the by-product of neem i.e., neem cake contain pesticidal properties and are used as bio-pesticide, fungicide and organic manure⁸. Other than fungicidal and pesticidal activity, they can also be used as biofertilisers in the form of neem cake to kill the pathogens present in the soil. Neem plant parts possess analgesics, Anticholinergic, Antihelminthic, Antihistaminic, Antiprotozoal, Antipyretic, Antiviral, Bactericidal, Contraceptives, Fungicides, Insecticides, Insect repellents, Veterinary medicines. Cosmetics, Hair oils, Lubricants, Propellants, Shampoos, Soaps,Tooth pastes etc¹⁷. Apart from the plant parts used in the form of medicines, more than 135 bioactive compounds has been isolated from neem which possess very promising activities such as antimalarial, antiiflammatory, antiarthritic, antipyretic, hypoglycaemic, antigastric ulcer, spermicidal, antifungal and antibacterial etc. Nimbin was the first bioactive compound studied.^21-25.

Neem as biopesticides and biofertilisers:

Neems as pesticides are widely used in the agriculture as it possess insecticidal properties and thus can control pests. Due to the toxicity spread by the synthetic pesticides, in most of the regions, farmers are shifting to the use of organic pesticides²⁶. Due to the growing popularity of herbal pesticides, neem pesticides manufacturers are in a verge of making profit. To test the efficiency of neem to be used as pesticides, neem pesticides once prepared are exported to the developed countries to set up the clinical trails¹³. Neem oil and seed cake possess anti-germicidal and anti bacterial properties thus can protect from many insect and bacterial pathogens. The main advantage of using neem as a pesticide is that it doesn’t leave any residues on plant. Table 1 represents the use of neem formulations in various crops to protect against the insect pests.

The main ingredient in the manufacturing of neem pesticides is Azadirachtin (C₃₅H₄₄O₁₆). Azadirachtin is a most active compound which is found in several isoforms (Azadirachtin A to Azadirachtin K ^41. AZ (A, B, C, D, E, F, G, I, J and K) are the different isomers of Azadirachtin, out of which AZ A is the most profusely occurring bioactive compound which shows repellent, antifeedent and insecticidal activity against a number of pests, thus it is mostly used for manufacturing commercial pesticides^42. The chemical structure of Azadirachtin has been represented in Fig 1. Azadirachtin is the main highlight of research due to its insecticidal potential. It is known to influence the feeding habit of insects, affects their growth and reproduction, however the mode of action of azadirachtin is still unknown. Apart of being greatly known as insecticide, it also has an adverse effect on fungi, nematodes, virus, protozoans⁴³. Azadirachtin also reduces larval growth such as in Tinea dubiella (Stainton) and Tineola bisselliella (Humel). It acts on endocrine and neuroendocrine systems of insects and thus disturbs the growth and development of insects. Azadirachtin only acts on the pests and pathogens, however it does not act on pollinators and also non toxic to invertebrates ^44-46.

Fig-1 Chemical structure of Azadirachtin⁴⁷

The amount of azadirachtin can be increased if treated with Arbuscular Mycorrhizae⁴⁸. It was David Morgan who isolated active ingredient Azadirachtin from the seeds of Azadirachta indica⁴⁹. However the full structural determination of azadirachtin was completed about 17 years later after its discovery in the laboratoraties of Steven Ley, W Kraus and K Nakanishi^50-52. Tetran or triterpenoids in azadirachtin is similar to an insect hormone ecdysomes that plays an important role as insect growth regulator which disturbs the feeding habit of insects and also inhibits the ability of molting from pupa to larval cycle and thus eventually disrupts the life cycle of insects⁴¹.It is used as bioinsectide repellant against thrips, whiteflies, aphids, leaf miners, bugs and many insect pests. The direct effect of azadirachtin has been represented in Fig 2.

Fig 2-Direct effects of Azadirachtin¹⁹

Antifeedant:

Neem possess antifeedent property which is an ability to degrade the numerous pests and thus protect plants¹³. The presence of compounds such as azadirachtin, salanin and melandriol in the neem treated plants if ingested creates an antiperistalitic wave in the alimentary canal of the insects and causes nausea, because of this the feeding ability of insects is disturbed^53,54. In Spodoptera litura also, an economically important pests, antifeedant activity of neem was observed⁵⁴.

Oviposition deterrents:

One of the most important property of neem is its oviposition deterrent property that deters the economic value of plants^8. Neem formulation works in a specific way to control the pests and also stops to increase in their number. It has been observed that neem formulation disrupts and kills female insects in depositing eggs¹³. Egg formation is disrupted due to inhibition by azadirachtin or sometimes by the formation of ecdysteroid which also stops the females in egg formation⁵⁵.Similarly in case of male insects ecdysteroid acts as an suspension for undergoing the meiotic process responsible for production of sperm^56,57. The oviposition deterrent activity has been found in many insect pests such as Callosobruchus chinensis (Pulse beetle)^58, cabbage moth, Mamestra brassicae^59, peach fruit-fly (B. Zonata)⁶⁰and potato tuber moth, Phthorimaea opercullela⁶¹. The oviposition of insect pests causing disease in cauliflower has also been observed by adding neem formulation and neem seed extract^62.

Growth regulation:

Application of neem formulation as pesticides reduces the growth of many insects’ pests. Neem extracts controls the growth, increases mortality rate of insects and also cause a decrease in their fertility. It has been reported that neem formulation disrupts the growth of more than 400 insects of different orders⁶³. Azadirachtin presence in the neem formulation resulted in the inhibition of the formation of ecdysone, which is responsible for molting in insects which is a vital stage in the growth and development of insects .Neem oil consists of some compounds that inhibits the formation of enzyme ecdysone 20-monoxygenase responsible for converting ecdysone to active hormone⁶⁴. When an insect larva ingest neem formulated plant product, azadirachtin presence in it will deteriorates the ecdysome enzyme which is responsible for causing larval moulting, and thus larva could not transformed into pupal stage and even if transformed will get died soon. In case of lower concentration of azadirachtin, the adult emerging out from the pupae will be completely malformed and sterile⁵³. Neem oil is also known to influence the growth of Aspergillus sp⁶⁵.

There is no proper finding whether only azadirachtin can be used as fungicide. However, some research focus on the effect of azadirachtin as fungicide. To test the efficiency of azadirachtin as a fungicide, a comparative study was done against Macrophomina phaseolina causing charcoal disease with some synthetic chemicals like mancozeb and bavistin. The results indicated that radial growth of M.phaseolina can be controlled with the application of azadirachtin at 25% concentration by 84.2%, while mancozeb and bavistin inhibited the growth by 86.3% and 86.4% respectively if incubated for 96 hours at 30±1℃. If azadirachtin and bavistin is used in a concentration of 30ppm or above, the growth of the pathogen is completely inhibited,while mancozeb can control the growth by only 87.3%⁶⁶. Neem oil at a concentration of 0.15 inhibits M.phaseolina at a much greater rate than that of benomyl⁶⁷. Thus neem also possess antimicrobial activity^68-77. Neem formulation can be used as biofertilisers, because of its ability to increase the fertility of the soil and also can inhibit the pathogenic microorganisms present in the soil. Neem seed cake can be used as biofertilisers which is prepared from the material left after oil is squeezed out from seeds. It helps in providing nutrients to the plant. Neem can be used as biofertilisers to both cash crops and food crops, mainly sugarcane and rice¹³. Neem seed cake provide macronutrients to the plant which is essential for plant growth, helps to increase the yield of the crop yield and also are ecofriendly and biodegradable. There are many reports which highlighted the use of neem in the form of neem cake as biofertilisers. In a comparative study conducted to understand the efficiency of neem to be used as biofertilisers to grow guava cultivar Sardar in west Bengal, it has been observed that fruits from the plants receiving neem cake at 9kg/plant/year caused the maximum fruit weight of 230.5g⁷⁸. In Indian citrus industry, Rangpur lime has a major role in production of export quality Nagpur mandarin. As it is fairly resistant to Phytophthora infections, it is highly recommended and popular rootstock in Indian conditions. It has been observed that growth of Rangpur lime seedling in nursery stage is very slow and need much time to attain biddable size. In a study combined effect of biofertilisers affecting the growth of Rangpur lime was studied in which 11 combinations of inoculums were prepared in which Glomus fasciculatum (Gf) (50g and 100g), Glomus mosseae (Gm) (50g and 100g), Phosphate Solubilizing Bacteria (PSB) 3 g and neem cake 20g per seedling were given at the time of transplanting of Rangpur lime seedling in polythene bags ^79,
80. Table 2 represents the requirements of neem cake for manuring .

Table 2-Requirements of neem cake for manuring

Characteristics	Requirements
Maximum moisture (% by mass)	10.0
Minimum water soluble organic N% by mass on moisture free basis	2.5
Maximum total ash (% by mass)	13.0
Maximum acid insoluble ash (% by mass on moisture-free basis	5.0

Source- Indian Standards Institution specification 8558 ⁸¹.

CONCLUSION AND FUTURE PROSPECT:

Neem (Azadirachta indica A.Juss) is the most important plant in the world which is very useful to the humankind. Neem the ‘divine tree’ is a gift to the nature. All parts of the plant can be either used as biopesticides or biofertilisers. The presence of compound azadirachtin, the predominant pesticidal active ingredient makes the neem of utmost importance. Neem extracts and neem formulation are ecofriendly, biodegradable and thus are less toxic to the environment. Neem products are also suitable for integrated pest management because of the non-toxic behaviour to the non-targeted organisms, easy preparation. Since the world is facing lot of health problems due to the surplus use of chemical pesticides, there should be a growing concerns on the use of biopesticides and biofertilisers, in which neem stands to be the most important one. The continuous use of chemical pesticides often leads to the deterioration of the soil quality which in turn will be quite wasted land in the near future. There will be one time when there will be no food not grown from chemicals, and future generations will be unhealthy, will be highly prone to deadly diseases. Thus there is a need to educate people for its judicious use as biopesticide and biofertilisers.

CONFLICT OF INTEREST:

The authors declare no conflict of interest.

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Received on 11.11.2021 Modified on 02.04.2022

Research J. Pharm. and Tech 2023; 16(4):2029-2034.

DOI: 10.52711/0974-360X.2023.00334

Crops	Neem formulation used	Target pests	References
Maize	Extract from Neem and GLIRICIDIA treatment (Gliricidia sepium)	Spodoptera frugiperda, Macrodactylus spp., Franklieniella	27
	Neem oil and seed cake	Spodoptera fungiperda	28
	Neem seed kerel extract	Raphalosi phumphadi	29
	Local neem	Setophilus zearinis	30
Rice	Oil extracts of seeds of Neem	Pyricularia oryzae	31
	Sweet flag rhizome, Kut root of curry leaf, kinow peel, turmeric rhizome and commercial neem formulation (nimbicidin and repellin) and one synthetic pesticides cypermethrin	Tribolium castaneum	32
	Multineem 300ppm@2.5Lper hectare	Brown plant hopper,stem borer	33
	Nimbecidine@5mL per litre weight,5 mL per litre of neem oil	Brown plant hopper	34
Citrus (Kagzilime)	10% suspension of neem and naffatia(I.fistulosa)	Phyllocnistis Citrella, Diaporthe citri	35
Potato and egg plant	Neem oil and neem kernel water extract	Jacobiasca lybica, Bemissia tabaci, Aphis gossypii	36
Potato	Neem oil and karanja oil(1:1)	Colorado potato beetle	37
	Neem oil 300ppm	Green peach aphid	38
Tomato	Neem cake,leaves,refined product “aza’0.1%	Root knot nematode	39
	Nursery bed treatment 3kg/m²	Root knot nematode	40