1. INTRODUCTION:

Neem (Azadirachta indica) is fast growing evergreen popular tree and has been used in Ayurvedic medicine for more than 4000 years due to its medicinal properties [1]. Neem is a large found wild and often cultivated in India. The plant product or natural products shows an important role in diseases prevention and treatment through the enhancement of antioxidant activity, inhibition of bacterial growth and modulation of genetic pathways [2]. Neem is called ‘Arishta’ in Sanskrit word that means “reliever of sickness” [3]. It is typically grown in tropical and semi-tropical regions. The height of the tree is about 12 meters to 15 meters and rarely 25-35 m.

It is a flowering plant and normally starts fruiting after 3-5 years. The tree becomes productive within 10 years [4]. The neem tree develops into a substantial shade tree with a thick, round canopy and can live for 150-200 years [5]. All the part of the tree is bitter in taste. The neem tree is an incredible plant that has been declared the “Tree of the 21st century” by the United Nations. The US National Academy of Science published a report in 1992 entitled “Neem: A tree for solving global problems” [3]. The therapeutics role of number of plants in disease management is still being enthusiastically researched due to their less side effect and affordable properties. It has been accepted that drugs based on allopathy are expensive and also exhibit toxic effect on normal tissues and on various biological activities [2]. Traditionally, the leaves and their paste are used for curing allergic skin reactions and antivirally treating smallpox and chicken pox. It is a largely accepted fact that numerous pharmacologically active drugs are derived from natural resources including medicinal plants. The earliest Sanskrit medical writings refer to the benefits of Neem’s fruits, seeds, oil, leaves, roots and barks. Each has been used in the Ayurvedic and Unani systems of medicines. Now, being used in the manufacture of modern-day medicines, cosmetics and toiletries [4]. The number of benefits of neem is listed in ancient documents like ‘Charak-Samhita’ and ‘Sushruta -Samhita’. It is commonly called ‘Indian Lilic’ or ‘Margosa’ belongs to family Meliaceae and tribe melieae [3]. Leaves are green in colour, bluntly serrate and alternate. The flowers are white, having a scented odour especially night. Its fruit is smooth, oblong and small in size and is called, Nimboli [6].

2. Botanical Description of Neem:

Two species of Azadirachta Indica have been reported viz. Azadirachta indica A. Juss is native to indian subcontinent and Azadirachta excels kack is native to Philipines and Indonesia. Neem is a member of Mahogany family [3]. Neem was described by De Jussieuin in 1830 and its taxonomic classification is as follows:

Table 1: Taxonomic position of Neem [3]

Kingdom	Plantae
Order	Rutales
Suborder	Rutinae
Family	Meliaceae
Subfamily	Melioideae
Tribe	Melieae
Genus	Azadirachta
Species	Indica

Neem is used in the treatment of inflammation, infections, fever, skin diseases and dental disorders. It is also used for its hypoglycemic, hypolipidemic, hepatoprotective and hypotensive activities and to control fever. The juice from the leaves is used as a tonic to increase appetite and to remove intestinal worms. Therapeutically, the leaf extract is used for its antimicrobial activity against dental pathogens. Neem oil is very useful in the preparation of mosquito-repellent tablets. Because of its unpleasant smell, it is best when it is added to a formula with other essential oils, such as citronella. Leaf and bark extracts have also been found to possess significant antioxidant property [4].

3. Biological Activities of some Neem Compounds:

Although a large number of compounds have been isolated from various parts of neem, a few of them have studied for biological activities, as shown in following [3] Table:

Table 2: Biological Activities of Neem compound [3]

COMPOUND NAME	SOURCE	BIOLOGICAL ACTIVITY
Nimbidin	Seed Oil	Anti-inflammatory Anti-arthritic Anti-pyretic Hypoglycaemic Anti-gastric ulcer Spermicidal Anti-fungal Anti-bacterial Diuretic
Sodium Nimbidate	Seed Oil	Anti-inflammatory
Azadirachtin	Seed Oil	Anti-malarial
Nimbin	Seed Oil	Spermicidal
Nimbolide	Seed Oil	Anti-malarial Anti-bacterial
Gedunin	Seed Oil	Anti-malarial Anti-fungal
Mahmoodin	Seed Oil	Anti-bacterial
Gallic acid, (-) epicatechin and catechin	Bark	Anti-inflammatory Immunomodulatory
Margolone, margolonone and isomargolonone	Bark	Anti-bacterial
Cyclic trisulphide and cyclic tetrasulphide	Leaves	Anti-fungal
Polysaccharide	Bark	Anti-inflammatory
Polysaccharide- G1A, G1B	Bark	Antitumor
Polysaccharide- G2A, G3A	Bark	Anti-inflammatory

4. Biological Activities of Neem:

The most important active constituent is azadirachtin and the others are nimbolinin, nimbin, nimbidin, nimbidol, sodium nimbinate, gedunin and salannin [2]. Nimbidin, a major crude bitter principle extracted from the oil of seed kernels of Azadirachta Indica demonstrated several biological activities. From this crude principle some tetranortriterpenes, including nimbin, nimbinin, nimbidinin, nimbolide and nimbidic acid have been isolated [7]. Nimbidin and sodium nimbidate possess significant dose dependent anti-inflammatory activity against carrageenan induced acute oedema in rats and formalin- induced arthritis [8,9].

A significant antiulcer effect was observed with nimbidin in preventing acetylsalicyclic acid, indomethacin, stress or histamine [10]. Oral administration of nimbidin demonstrated significant hypoglycemic effect in fasting rabbits [3]. Nimbidin can also supress basal as well as histamine and carbachol-stimulated gastric acid output and may act as antihistamine by blocking H2 receptors, thereby helping as an antiulcer agent. The spermicidal activity of nimbidin and nimbin was found in rats and human as early as 1959 [3]. Nimbidin also demonstrated antifungal activity by inhibiting the growth of Tinea rubrum [11]. Diuretic activity was found in dogs as sodium nimbidinate [3].

Nimbolide show antimalarial activity by inhibiting the growth of Plasmodium falciparum. Nimbolide also shows antibacterial activity against S. aureus and S. coagulase [12]. Gedunin isolated from neem seed oil has been reported to possess both antifungal and antimalarial activities [3].

Azadirachtin, a tetranortriterpenoid plant limonoid which can be isolated from the seeds of the neem tree. Azadirachtin is a common example of a natural plant defence chemical affecting feeding, through chemoreception (primary antifeedancy), that consist in the blockage of input from receptors that normally respond to phagostimulants and through a reduction in food intake due to toxic effects if consumed (secondary antifeedancy), where food intake is reduced after application of azadirachtin in ways which bypass the mouth part chemoreceptors [13]. Antifeedancy can be accessed from crude to refined neem extracts to neem enriched to pure azadirachtin. Lepidoptera (insect) show effective sensitivity to azardirachtin with antifeedant effects at concentrations ranging between 1 and 50 ppm. Azadirachtin has also growth regulatory effects on larval insects like disruption of moulting, growth inhibition [3].

Mahmoodin, a deoxygedunin isolated from seed oil, has been shown to possess moderate antibacterial action against some strains of human pathogenic bacteria. Condensed tannins from the bark contain gallic acid, (-) epicatechin, catechin, they’re responsible for inhibiting the generation of chemiluminescence by activated human polymorphonuclear neutrophil (PMN), includes these compounds inhibit burst of PMN during inflammation [14]. Margolone, margolonone and isomargolonone isolated from neem stem bark are active against staphylococcus and Serratia species. Sulphur containing compounds such as cyclic trisulphide and tetrasulphide isolated from the steam distillate of fresh, matured neem leaves have antifungal activity [15].

Polysaccharides from neem exhibit various biological effects. Two water soluble polysaccharide GIA and GIB isolated from the bark of melia azadirachta, demonstrated strong antitumor effect. Some active ingredients isolated from the lipid part of neem fruits, exhibit antiulcer activity in stresss induced gastric lesions [13].

5. Mechanism of Action of Active Compounds:

Neem has therapeutics implication in the disease’s prevention and treatment. But, the exact molecular mechanism in the prevention of pathogenesis is not understood entirely. It is considered that Azadirachta indica shows therapeutic role due to the rich source of antioxidant and other valuable active compounds such as azadirachtin, nimbolinin, nimbin, imbidin, nimbidol, salannin, and quercetin [16].

Possible mechanism of action of Azadirachta indica is presented as follows:

1. Neem plays role as free radical scavenging properties due to rich source of antioxidant. Azadirachtin and nimbolide showed concentration dependent anti-radical scavenging activity and reductive potential in the following order: nimbolide > azadirachtin > ascorbate.

2. Neem ingredient shows effective role in the management of cancer through the regulation of cell signaling pathways. Neem modulates the activity of various tumour suppressor genes (e.g. p53, pTEN), angiogenesis (VEGF), transcription factors (e.g.NF-𝜅B), and apoptosis (e.g. bcl2, bax).

3. Neem also plays role as anti-inflammatory via regulation of pro-inflammatory enzyme activities including cyclooxygenase (COX), and lipoxygenase (LOX) enzyme [2].

6. Therapeutic Benefits of Neem and Its Various Ingredients in Health Management:

Active constitutes play role in the diseases cure via activation of antioxidative enzyme, rupture the cell wall of bacteria and play role as chemopreventive through the regulation of cellular pathways. Pharmacological activities of neem are discussed in detail Fig- (e).

a) Anti-oxidant Activity:

The process through which free radicals are created, is a normal function of the body but the resulting molecules are unstable and can damage other cells [3]. Free radical or reactive oxygen species are one of the main culprits in the genesis of various diseases. However, neutralization of free radical activity is one of the important steps in the disease prevention. Antioxidants stabilize/deactivate free radicals, often before they attack targets in biological cells and also play role in the activation of antioxidative enzyme that plays role in the control of damage caused by free radicals/reactive oxygen species [17]. Plants natural products, seeds, oil, leaves, bark, and roots show an essential job in disease prevention because of the rich source of antioxidant [2].

Leaf and bark extracts of A. indica have been studied for their antioxidant activity and results of the study clearly indicated that all the tested leaf and bark extracts of neem have significant antioxidant properties [18]. Another important study was performed based on all parts of Siamese neem tree to assess the antioxidant activity and results suggest that extracts have strong antioxidant potential. A series of disorders, including cardiovascular disease, eye health, cataracts and age-related neurodegeneration (decline of the brain cells and nervous system) and even cancer occurs due to high levels of free radicals. Neem protects against chemically induced carcinogens and liver damage by boosting antioxidant levels [19].

Another study was carried out to evaluate in antioxidant activity in different crude extracts of the leaves of Azadirachta indica (neem) and antioxidant capacity of different crude extracts was as follows: chloroform > butanol > ethyl acetate extract > hexane extract > methanol extract [20]. Result of the study suggested that the chloroform crude extracts of neem could be used as a natural antioxidant [2].

b) Anti-Cancer Activity:

Cancer is multifactorial disease and major health problem around the world. The alteration of molecular/genetic pathways plays role in the development and progression of malignant growth. The treatment module based on allopathic is effective on one side but also shows adverse effect on the normal cell [21]. Neem contains flavanoids and various other ingredients that play an important role in inhibition of cancer development. Large number of epidemiological studies proposes that high flavonoid admission might be related with a diminished danger of malignancy [22]. The anticancer activity of aqueous and ethanolic extract of neem leaves has been tested on a number of cell lines viz. breast, lung, cervical. Neem oil holds various neem limonoids which prevents mutagenic effects. A study was performed to investigate the cytotoxic effects of nimbolide found in leaves and flowers on human choriocarcinoma (BeWo) cells and results showed that treatment with nimbolide resulted in dose and time-dependent inhibition of growth of BeWo cells [23]. A study was made to assess the chemopreventive potential of the limonoids, azadirachtin, and nimbolide and results showed that azadirachtin and nimbolide inhibited the development of DMBA-induced HBP carcinomas through influencing multiple mechanisms such as prevention of procarcinogen activation and oxidative DNA damage, upregulation of antioxidant and carcinogen detoxification enzymes, and inhibition of tumour invasion [24].

Fig. (e): Pharmacological activities of Azadirachta indica L. neem in diseases management through the modulation of various activities.

Azadirachta indica and their active compounds play pivotal role in the prevention of cancer development and progression. Azadirachta indica hold various ingredients and theses constituents activate the tumour suppressor genes and inactivate the activity of several genes involved in the cancer development and progression such as vascular endothelial growth factor (VEGF), nuclear factor kappa light chain enhancer of activated B cells shortly known as NF-𝜅B and phosphoinositide-3-kinase (PI3K/Akt). Neem has been reported to be a good activator of tumour suppressor gene and inhibitor of VEGF and phosphoinositol PI3K/Akt pathways. It also activates apoptosis, suppression of NF-𝜅B signaling, and cyclo-oxygenase pathway. Nimbolide, a phytoconstituent of neem has been found to promote apoptosis via modulation of the phosphoinositide-3-kinase (PI3K)/Protein Kinase B(Akt)/Glycogen synthase kinase 3 (GSK-3β) signaling pathway in oral cancer [2].

c) Anti-bacterial Activity:

Activity of the bark, leaf, seed and fruit extracts of neem has been evaluated against bacteria isolated from oral cavity. Results have revealed that bark and leaf extracts possess activity against all the tested bacteria. Seed and fruit extracts have shown activity at higher concentrations only. Neem bark extract (NBE) has also been found to significantly block HSV-1 entry into cells at concentrations ranging from 50-100mg/Ml [25]. Neem has also shown potential to be used in wound dressings [1].

The antibacterial activity of neem extracts against 21 strains of foodborne pathogens was evaluated and result of the study suggested that neem extracts possess compounds containing antibacterial properties that can potentially be useful to control foodborne pathogens and spoilage organisms [26]. Another experiment was made to evaluate the antibacterial activity of the bark, leaf, seed, and fruit extracts of Azadirachta indica (neem) on bacteria isolated from adult mouth and results revealed that bark and leaf extracts showed antibacterial activity against all the test bacteria used [27].

d) Anti-viral Activity:

Neem inhibits the growth of Dengue virus, a hemorrhagic fever related to Ebola, and interferes with the reproduction of the coxsackie B virus [28]. Methanolic extract of neem leaves has shown virucidal activity against coxsackievirus virus B-4. The antiviral activity of neem leaves has been found to be due to the presence of flavonoids, triterpenoids and their glycosides. The minimal inhibitory concentrations (8000μg/mL) of the leaves extract has been found to have no toxicity against Vero (African green monkey kidney) cells [29].

e) Antimalarial activity:

Antimalarial activity of neem leaf and stem bark extracts has been evaluated against Plasmodium berghei infected albino mice. The leaf and stem bark extracts have shown efficacy in reducing the level of parasitemia in infected mice to about 51-80% and 56-87%, respectively [30]. The effect of methanolic extracts of seed kernels of ripe and unripe fruits of neem have also been studied on early erythrocytic schizogony of P. berghei infected inbreed mice [31].

f) Antifungal activity:

The antifungal activity of neem leaves and seed kernel have been evaluated against Monilinia fructicola, Penicillium expansum, Trichothecium roseum and Alternaria [32]. The aqueous, ethanolic and ethyl acetate extracts of neem leaves have also shown significant activity against Aspergillus flavus, A. fumigatus, A. niger, A. terreus, Candida albicans and Microsporum gypseum. Ethyl acetate extract has shown the strongest antifungal activity and its HPLC analysis revealed the presence of nimonol [1]. A recent study has shown that addition of neem powder to acrylic resin denture base materials reduces the adhesion of C. albicans which prevents denture stomatitis [33].

The current research proved its antifungal properties which control fungi that can cause athlete’s foot, ringworm and Candida, the organism that causes yeast infections and thrush [28]. Different concentrates of neem leaf on seed borne parasites Aspergillus and Rhizopus and results affirmed that development of both the contagious species was fundamentally repressed and controlled with both alcoholic and water extract. Moreover, alcoholic concentrate of neem leaf was best [5].

g) Anti-ulcerative Activity:

Utilizing Neem bark diminishes 77% gastric acid secretion as well as gastric secretion volume 63% and pepsin movement 50%, because of its anti-inflammatory compounds [28]. Neem has also been used in the treatment of peptic ulcers. Aqueous extract of neem leaves has been found to display a significant

Fig. (f): Different Benefits of Neem.

antiulcerative activity on Wistar rats [34]. It acts mainly by inhibiting acid secretion and blocking oxidative damage of the gastric mucosa. The effect of neem has also been evaluated against peptic ulcers in albino mice. The mechanism of antiulcer activity of neem leaves extract has also been determined [1].

h) Hepatoprotective Effect:

Medicinal plants and their ingredients play a pivotal role as hepatoprotective without any adverse effects. A study was performed to investigate the hepatoprotective role of azadirachtin-A in carbon tetrachloride induced hepatotoxicity in rats and results confirmed that pretreatment with azadirachtin-A dose dependently reduced hepatocellular necrosis [35].

A study was performed to evaluate the protective effect of active constituent of neem such as nimbolide against carbon tetrachloride induced liver toxicity in rats and results suggest that nimbolide possesses hepatoprotective effect against carbon tetrachloride induced liver damage with efficiency and another study finding revealed that leaf extract was found to have protection against paracetamol-induced liver necrosis in rats [36]. Hepatoprotective effect of methanolic and aqueous extracts of Azadirachta indica (Neem) leaves was evaluated in rats and study result established that the plant has good potential to act as hepatoprotective agent [37].

i) Wound Healing Effect:

Different plants/their constituents play an important role in the wound healing effect. A study was made to evaluate the wound healing activity of the extracts of leaves of A. indica and T. cordifolia using extraction and cut injury models in Sprague Dawley rats and results revealed that extract of both plants significantly promoted the wound healing activity in both extraction and incision wound models [38]. Furthermore, in incision wound, tensile strength of the healing tissue of both plants treated groups was found to be significantly higher as compared to the control group [39]. Other results showed that leave extracts of Azadirachta indica promote wound healing activity through increased inflammatory response and neovascularization [40].

j) Immuno stimulatory Compound:

Immuno stimulating properties of neem is most important benefit. It boosts both the lymphocytic and cell-mediated systems, including “Killer T” cells which are able to destroy microbes, viruses and cancer cells by injecting toxic chemicals into the invaders [28].

k) Antinephrotoxicity Effect:

An experiment was made to investigate the effects of methanolic leaves extract of Azadirachta indica on cisplatin (CP)- induced nephrotoxicity and oxidative stress in rats and results confirmed that extract effectively rescues the kidney from CP-mediated oxidative damage [41].

l) Hypoglycemic activity:

The seed oil possesses active constituents capable of lowering blood glucose in both normal and hyperglycemic animals [42]. The aqueous extract of the leaves produced some hypoglycemia in normal and diabetic rats [43]. Effect of water-soluble alcoholic extract of A. Indica leaves on isolated tissue preparation were studied with a view to find out the possible mechanism of its reported anti-hyperglycemic effect [44]. Neem oil produced a significant blood glucose lowering activity in normal as well as alloxan induced diabetic rats after 3h and 6h. The decrease in blood glucose level was more pronounced in hyperglycemic rats [6].

The ethanolic extract of neem root bark has also been evaluated for antidiabetic activity. The neem root bark extract (NRE) showed statistically significant results at high dose in an oral glucose tolerance test (OGTT). Neem extract at a low dose (single dose study) significantly reduced glucose level. Multiple doses administered over a 15-day period have also been shown to significantly lower the above blood parameters in the treated group [45]. Azadirachtin, the active component of neem has also been found to display a protective action against pancreatic β-cells [46].

m) Antifertility activity:

Neem seed oil has been found to possess a powerful spermicidal as well as spermatogenesis inhibitory property. It has also been found to reduce sperm motility and count. Neem seed oil which is used as a powerful spermicidal and significantly inhibit spermatogenesis. It inhibits sperm motility and count and cessation of fertility. Neem also has anti implantation and abortifacients properties [47]. It has been found that spermatozoa of human and Rhesus monkeys die within 30 min of contact with neem seed oil using an intravaginal dose of 1 Ml [1].

Some other medicinal benefits of Neem are as follows.,

· Sexually Transmitted Diseases:

Neem shows great potential to control sexually transmitted diseases. Neem provided 75% protection from the HIV infection [28].

· Arthritis:

Neem has a long history of relieving inflamed joints. Neem not only helps in reducing inflammation but also suppress the pain. It is also useful in Rheumatism.

· Heart Disease:

Major causes of a heart attack include blood clots, high cholesterol, arrhythmic heart action and high blood pressure. Its leaf extracts have reduced clotting, lowered blood pressure and bad cholesterol, slowed rapid or abnormally high heartbeat and inhibited irregular heart rhythms.

· Dental Care:

People used Neem twigs as tooth brushes for centuries. Neem twigs contain antiseptic ingredients necessary for dental hygiene and prevents tooth decay, periodontal diseases, Infections, tooth decay, bleeding gums and sore gums.

· Skin Diseases:

Neem has been highly successfully against harmful fungi, parasites, and viruses. It has been most helpful in treating a variety of skin problems and diseases including psoriasis, eczema and other persistent conditions. Psoriasis is successfully treated with Neem oil [28].

· Insect repellent:

Early research demonstrates that applying concentrate of neem root or leaf to the skin repulses black flies. Likewise, applying neem oil cream to the skin appears to secure against certain kinds of mosquitos [2].

· Stress:

Low doses of Neem leaf extricates have sedative impacts. The impact vanishes at high doses. It reduces anxiety and stress [28].

· Neuroprotective Effect:

Antioxidant compounds in neem help to prevent brain damages, who had suffered a stroke by enhancing lipid peroxidation and increasing ascorbic acid (Vitamin C) in the brain.

· Vitiligo:

Vitiligo is believed to be an autoimmune disorder that causes patches of skin to lose its color. The dosage is of four grams of Neem leaves three times a day, ideally taken before each meal. Neem oil applied to the affected areas could aid in the reversal of discoloration.

· Liver functions:

It helps to protect the liver from damage, which in turn helps to cleanse the blood. Neem leaf minimize, chemically induced liver damage by stabilizing levels of serum marker enzymes and boosting levels of antioxidants, like those found in vitamin C and E and in natural carotenoids, which neutralize free radicals and prevent damage [28].

7. Commercial Uses of Neem:

Almost every part of the Neem tree viz. roots, leaves, flowers, seeds, trunks and branches has multiple uses. Neem is not only an excellent source of pesticides, it also provides good fodder, fuel and timber. This makes Neem tree a very potentially profitable [28].

a) Neem oil as a diesel fuel in i.e. engine:

An enormous increase in the number of automobiles in recent years has resulted in greater demand for petroleum products. With crude oil reserves estimated to last only for a few decades, therefore, effort are on way to research now alternatives to diesel. Depletion of crude oil would cause a major impact on the transportation sector. Of the various alternate fuels under consideration, biodiesel, derived from esterified vegetable oils, appears to be the most promising alternative fuel to diesel due to the following reasons [3].

Biodiesel can be used in the existing engines without any modifications.

· Biodiesel obtained from vegetable sources does not contain any sulfur, aromatic hydrocarbons, metals or crude oil residues.

· Biodiesel is an oxygenated fuel; emissions of carbon monoxide and soot tend to reduce.

· Unlike fossil fuels, use of Biodiesel does not contribute to global warming as the CO2 so produced absorbed by the plants. Thus, in nature CO2 is balanced.

· The Occupational Safety and Health Administration classify biodiesel as a non-flammable liquid.

· The use of biodiesel can extend the life span of diesel engines because it is more lubricating than petroleum diesel fuel.

· Biodiesel is mostly obtained from renewable vegetable oils/animal/fats and hence it may improve the fuel or energy security and thus leading to economy [48].

b) Neem (Azadirachta Indica) Bark:

Neem bark contains tannins which are used in tanning, dyeing etc. Compounds extracted from Neem bark are used in production of some dental-care products like toothpaste etc. [49]

c) Timber:

The sapwood of Neem tree is grayish white, while the heartwood is reddish brown. The wood is aromatic; it is easily sawn. It can be worked both by hand and by machines, but it does not take polish well. Neem timber is durable even in extended exposed conditions. In addition, it is resistant to termites and woodworms [49,50].

d) Neem Leaves:

Neem leaves possess excellent medicinal properties. In addition to it's usefulness in Pest management and Disease control they can also be fed to livestock when mixed with other fodder. In some countries, Neem leaves are used as mulch in tobacco and tomato fields. They can be very effectively used to kill weeds by spreading them over plant roots to retain moisture. Neem leaves can also be used to protect stored woolen and silk clothes from insects [50].

e) Neem Cake:

Neem cake is versatile and has many uses. It can be used as livestock feed, fertilizer and natural pesticide. It not only provides organic nitrogen but also inhibits the nitrification process, when mixed with urea, before applying in the fields. Such use of the neem coated urea in 90:10 proportion can save upto 30% of the total chemical nitrogen requirement of the crops which otherwise would go waste. This results in cost reductions of agricultural production. Neem cake is widely used in India as fertilizer for sugarcane and vegetable [28].

f) Fruits:

Neem fruits are bitter, purgative, antihemorrhodial and anthelmintic (vermifuge) in nature.

g) Flowers:

The flowers are used in vitiated conditions of pitta (balancing of the body heat) and kapha (cough formation). They are astringent, anthelmintic and non toxic [49].

h) Neem Seeds:

Neem seeds are also described as anthelmintic, antileprotic (cures or prevents leprosy) and antipoisonous. Seeds, along with leaves and dry Neem cake, are an active ingredient in mosquitocoils [50].

i) Neem Oil:

Neem oil, derived from crushing the seeds, is antidermatonic, a powerful vermifuge and is bitter in taste. It has a wide spectrum of action and is highly medicinal in nature. As an oil used in aromatherapy [28].

8. Neem in Ayurveda:

Neem is very unpleasant in taste, which gives it a ground-breaking cooling vitality (virya). This cooling principle, joined with its ability to help healthy blood, balances pitta—especially when there is heat in rakta dhatu (the blood). Excess pitta can show in various ways; one unmistakable area is the skin. Neem glues and oils have been connected to the skin as a method for mitigating and greasing up it, quieting aggravated and warmed sensations, keeping up agreeable body temperature, and supporting healthy skin and nails. Neem's light and dry characteristics enable it to counter kapha also. Neem supports healthy assimilation and arouses

Fig. (g): Neem used in ayurveda

meda dhatu agni (the metabolic/stomach related rule inside fat tissue), empowering appropriate digestion, and supporting glucose levels that are now in the typical range. Usually taken inside to encourage a condition of parity in the liver, pancreas, and stomach related tract. Neem's bitterness likewise improves taste, which is at the foundation of sound digestion. Neem has a comparable adjusting impact on pitta and kapha in prana vaha srotas (the respiratory sections). On a more extensive scale, neem bolsters normal purifying of the directs in the body just as the revival of solid tissues. Because neem is vata irritating without anyone else, it is joined with different herbs relying upon the ideal impact [5].

9. The Future Aspects of Neem:

a) Neem in Agricultural:

It is in agriculture where most of the scientists focused their research for exploring the benefits of Neem for crop production. Because of those findings, Neem oil, Neem cake, leaves and other parts of Neem tree are being used quite extensively in the agriculture sector in different parts of world. Its main uses in the agriculture sector include being an insecticide in food storage, as soil amendment, fertilizer efficiency enhancer, and very effective foliar pesticide [28]. Using neem derivatives for managing pests is a non-violant approach to controlling pests. Neem products work by intervening at several stages of the insect’s life. They may not kill the pest instant but incapacitate it in several ways. Neem emplys effects such as rellence, feeding and growth inhibition, mating disruption, chemo-sterilization, etc [51].

b) Neem Medicines:

Neem is widely used for treating fevers. It has anti-pyretic (fever reducing) property. In addition, neem products also have analgesic (pain relieving) and anti-inflammatory effects, i.e. for most common ailment’s neem can provide cheap, easily available and local entrepreneurship medicines. A wide multitude of diseases or conditions can be successfully treated with various elements of neem [5]. Herbal medicines are used for treatment of different types of diseases in all parts of world. Neem tree is an important part of these herbal

Fig. (h): Different Neem medicine products.

Herbal medicines and is mentioned in many ancient texts dealing with medicines. Traditional Indian medical authorities place it at the pinnacle of their pharmacopeia. Due to extraordinary properties of Neem, its bark, leaves, flowers, seed and fruit pulp were and are now used to treat a wide range of diseases and complaints ranging from leprosy, diabetes, ulcers to skin disorders and constipation etc. Different brands like Himalaya producing neem medicines. Scientists from the developed world are working extensively in exploring Neem tree and its properties to formulate new antibiotics [52].

c) Neem Cosmetics:

Different parts of Neem tree are being used extensively in manufacturing of soaps, skin creams/lotions, shampoos, toothpastes, beauty aids and toiletries. The Neem twigs are more commonly being used as antiseptic tooth brushes. In most cases Neem oil/extract is being used for making these cosmetics like soaps and tooth pastes etc. [28]. Neem and its parts are used extensively to manufacture high quality herbal cosmetics and beauty products. These natural cosmetics are in great demand, the world over because of their efficacy and zero side effects. Leading herbal products manufacturers are manufacturing fairness creams, body lotions, hand creams that are in great demand in US, UK etc. Neem oil and extracts can be used by

Fig. (i): Neem cosmetics products of different brands

adding it to creams and lotions and be applied on body. It is also used as skin cleanser, beauty enhancer and for a glowing complexion. Neem bark is extensively used to manufacture and export quality herbal and cosmetics and personal hygiene products. Leaves in powdered form are used to manufacture face and body lotions and creams. It is essential for maintaining a healthy and radiant skin. Neem leaf extracts added to shampoo to control dandruff. Leaf granules are used in herbal face packs due to its anti-fungal and anti-bacterial properties [53].

d) Food Storage:

In all areas of tropics, much of the harvested food is lost during storage because of worms, beetles and other infestations. People do not prefer to utilize synthetics bug sprays or any chemical insecticides on stored grains in general and more specifically for food stored for their own consumption. For centuries, Neem oil has provided farmers with an effective remedy against such insects. A very light coating of Neem oil protects stored food crops for up to 20 months from all types of infestations with no deterioration or loss of palatability. Storing food grains along with neem leaves repels the insects attacking the food grains. Neem leaves act as insecticide during storage. Dried neem leaves are used for storing food grains because they absorb moisture from them. Neem fresh leaves are also used on small scale for storage of food grain at home quite effectively, but this is being done on a small scale [28,50].

e) Soil Amendment:

Neem cake., After the Oil is extracted from the seed kernels, the left-over material is called Neem Cake. Neem cake has been used for many centuries throughout Indian sub-continent as an effective soil amendment. Farmers of this region have learned through experience that utilizing Neem cake in soil produces beneficial and healthier plants that have few or no insect/disease problem. A few examinations were additionally led by various researchers to discover why plants developed better in soil mixed with Neem cake. Their results showed that Neem cake is richer in plant available nutrients than manures; it killed damaging nematodes, promoted large population of earth worms, helped keep nitrogen in the soil available for plants and provide significant protection from insects. Nematodes suck juice from roots of plants to the point where they are unable to supply sufficient nutrients to the plant. Then the plants look unhealthy, fail to grow and may eventually die despite sufficient food, water and care. Neem cake allows plants to develop a strong defense system against these pest attacks by initially protecting plants from insect/pest. Secondly, Neem compounds absorbed through soil enhance these natural defense systems with proven nutritive, antifungal and insect repellent properties of Neem [54].

10. CONCLUSION:

The all parts of Azadirachta indica (Neem) have been in used since long times to treat the wide range of disease. Popularity of natural products or their derivatives role in diseases cure and prevention is increasing worldwide due to less side effect properties. Neem has been extensively used in Ayurveda, Unani and Homoeopathic medicine and has become a cynosure of modern medicine. The scientific studies have proved most of the claims of traditional medicines. However, further, detailed clinical research appears valuable to explore the full therapeutic potential of this plant in order to establish it as a standard drug. Looking upon wide prospects and potential of Neem for various purposes, it is worthwhile to cultivate the plant at large scale.

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Received on 06.09.2020 Modified on 26.09.2020

Res. J. Pharmacognosy and Phytochem. 2020; 12(4):245-255.

DOI: 10.5958/0975-4385.2020.00041.2