A REVIEW ON AZADIRACHTA INDICA

www.wjpps.com Vol 6, Issue 12, 2017.

249

Adithya et al. World Journal of Pharmacy and Pharmaceutical Sciences

A CURRENT REVIEW ON AZADIRACHTA INDICA (NEEM)

Tirupati Naga Adithya*, S. Jilani Basha, M. Koshma, S. Dada Khalandar, Y. Sudha

Rani and V. Jaya Sankar Reddy

Department of Pharmacology, Krishna Teja Pharmacy College, Chadalawadanagar, Tirupati,

Andhra Pradesh, India.

ABSTRACT

Azadirachta indica (The Neem) has been known as the wonder tree

for centuries in the Indian subcontinent. It has become important in

the global context today because it offers answers to the major

concerns facing mankind. It is a fast growing, evergreen tree

found commonly in India, Africa and America. Neem is one of the

most useful traditional medicinal plant in India. It is a highly

esteemed tree with several beneficial properties and applications,

especially known for its incredible therapeutic and ethnomedicinal

values for mankind. Neem also has shown antiviral, anti-fungal and

antibacterial properties. It helps support a strong immune system

and is used in cases of inflammatory skin conditions. It has been

used in different medicinal systems like; Ayurveda, unani, homeopathic medicine,

therefore considered as cynosure of modern medicine. Neem has been used as the traditional

medicine since a long time. Current review gives a depth analysis of the various

pharmacological activities like anti-bacterial, Antimalarial, Anti-ulcer activities etc. and

chemical constituents like Azadirachtin, Nimbin, Nimbidin, Quercetin, Gedunin etc.

KEYWORDS: Ayurveda, Anti-bacterial, Anti-malarial, Anti-ulcer, Azadirachtin.

INTRODUCTION

Azadirachta indica, commonly known as Neem, belongs to Family Meliaceae, is one of the

most versatile medicinal plants that has gained worldwide importance due to medicinal and

insecticide properties. There are several studies showing the effects of Azadirachta indica in

experimental and clinical models.[1]

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

SJIF Impact Factor 6.647

Volume 6, Issue 12, 249-269 Review Article ISSN 2278 – 4357

*Corresponding Author

Tirupati Naga Adithya

Department of

Pharmacology, Krishna Teja

Pharmacy College,

Chadalawadanagar, Tirupati,

Andhra Pradesh, India.

Article Received on

21 Sept. 2017,

Revised on 11 October 2017,

Accepted on 01 Nov. 2017

DOI: 10.20959/wjpps201712-10518


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Azadirachta indica is a fast growing evergreen popular tree found commonly in India, Africa

and America. It has been used in ayurvedic medicine for more than 4000 years due to its

medicinal properties. Neem is called „arista‟ in Sanskrit a word that means „perfect, complete

and imperishable‟.

Arishtha is the Sanskrit name of the neem tree meaning „reliver of sickness‟ and hence is

considered as „Sarbarogaribarini‟. The tree is regarded as „village dispensary‟ in India.[2]

The International Scientific Community has included Azadirachta indica tree into the top ten

lists of plants to be studied and used for the sustainable development of the planet and the

health of living beings. Azadirachta indica, identified by WHO/UNEP 1989 as an

environmentally powerful natural pesticide.

There are about 14 million Azadirachta indica trees growing only in India and the plant is

adapted to sub-arid and sub-humid areas of tropical and subtropical areas.[3]

The importance of the neem tree has been recognized by the US National Academy of

Sciences, which publish a report in 1992 entitled „Neem a tree for solving global problems‟.

The number of benefits of neem is listed in ancient documents like „Charak-Samhita‟ and

„Susruta-Samhita‟. It is commonly called „Indian Lilic‟ or „Margosa‟, belongs to the family

Meliaceae, subfamily Meloideae and tribe Melieae. Neem is the most versatile, multifarious

trees of tropics, with immense potential.[4]

Neem (Azadirachta indica) is considered harmless to humans, animals, birds, beneficial

insects and earthworms, and has been approved by the US Environmental Protection Agency

for use on food crops Neem (Azadirachta indica) of family meliaceae is evergreen tree of

potential medicinal value found in most tropical countries.[5, 6]

These compounds belong to natural products called triterpenoids (Limonoids). The active

principles are slightly hydrophilic, but freely lipophilic and highly soluble in organic solvents

like hydrophilic, alcohols, ketones and esters.[7]

HISTORY

The history of the Neem tree is inextricably linked to the history of the Indian civilization.


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Neem during prehistoric times

In the annals of the ancient Siddha system of medicine, the first medicinal plant mentioned as

well as found a place, in ancient Tamil literature is neem or margosa. The earliest mention

about the uses of medicinal plants were found in Thirumular Thirumantiram-Ennayiram,

Tholkappiam and the ancient Tamil works of Sangam literature, which were believed to have

been written thousands of years ago.

Siddha mission to china and transmigration

Kalangi Nathar decided to enter into Samadhi in seclusion for 3000 years. In China, Bhogar

was instructed by Kalangi Nathar in all aspects of the Siddha sciences. These included the

preparation and use of the kaya kalpa herbal formulae to promote longevity.

Neem in Indus valley civilization

The first recorded indication that neem was being used in the medical treatment was about

4500 years ago. There is evidence found from excavations at Harappa and Mohenjo-Daro

cultures.[8]

PLANT PROFILE

Common name: Neem.

Biological Source

Neem consists of the fresh or dried leaves and seed oil of Azadirachta indica J. Juss (Melia

Indica or M. Azadirachta Linn).

Family

Meliaceae.

Synonyms

English: Indian lilac.

Sanskrit: Nimba.

Hindi: Neem.

Telugu: Vepa.

Tamil: Vaypum.

Malaysia: Pokok semambu.

Burmese: Tamar.


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Persian: Azadirakhta.

Taxonomical Classification:

Kingdom: Plantae.

Order: Rutales.

Suborder: Rutinae.

Family: Meliaceae.

Subfamily: Melioideae.

Tribe: Melieae.

Genus: Azadirachta.

Species: indica.

Natural Habitat

It is found in India, Pakistan, Sri Lanka, Malaya, Indonesia, Japan, Tropical region of

Australia and Africa. In India, it is found in Uttar Pradesh, Maharashtra, Tamil Nadu,

Rajasthan, and M.P.[9]

India stands first in neem seed production and about 4,42,300 tons of seeds are produced

annually yielding 88,400 tons of neem oil and 3,53,800 tons of neem cake.[10]

Cultivation Collection of Neem

Neem is a large tree growing about 25 m in height with semi-straight to straight trunk, 3 m in

girth and spreading branches forming a broad crown. A neem tree normally starts fruiting

after 3-5 years.

Neem tree requires little water and plenty of sunlight. The tree grows naturally in areas where

the rainfall is in the range of 450 to 1200 mm. Neem grows on altitudes up to 1500m.

It can grow well in wide temperature range of 0oC to 49

oC. It cannot survive water-logged

areas and poorly drained soils. The pH range for the growth of neem tree lies in between 4 to

10. It grows on almost all types of soil. Neem trees have the ability to neutralize acidic soils

by a unique property of calcium mining. [11]

MACROSCOPIC DESCRIPTION

Tree

The neem tree (Azadirachta indica) is a fast growing tropical evergreen related to mahogany.


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Leaves

Compound, alternate, rachis 15-25 cm long, 0.1 cm thick; leaflets with oblique base,

opposite, exstipulate, lanceolate, acute, serrate, 7-8.5 cm long and 1.0-1.7 cm wide, slightly

yellowish-green; odour, indistinct; taste, bitter.[12]

Stem bark

Bark varies much in thickness according to age and parts of tree from where it is taken;

external surface rough, fissured and rusty-grey; laminated inner surface yellowish and

foliaceous, fracture, fibrous, characteristic odour and bitter taste.

Constituents

Tetranortriterpenoids, margocin, nimbidiol, nimbolicin, azadirinin.

Identity, Purity and Strength

Foreign matter : Not more than 02%.

Total Ash : Not more than 15%.

Acid-insoluble ash : Not more than 03%.

Alcohol-soluble extractive : Not less than 06%.

Water-soluble extractive : Not less than 07%.

Important Formulations: Amrtastaka, Astangadasanga Lanha.

Therapeutic Uses

Sotha, Aruci, Chardi, Daha, Hrllasa, Jvara, Kasa, Krmi, Kandu, Kustha, Netraroga, Phiranga,

Prameha, Raktavikara, Trsna¸¡, Visamajvara, Vrana, Kaphapittaja Vikara, Srama,

Hrudayavidaha.

Dose

3-6 g[13]

Flower, fruits and seeds

The tree is often covered in delicate flowers in the early summer. The flowers (white and

fragrant) are arranged axillary, normally more-or-less drooping panicles which are up to 25

cm long. It has a semi-sweet, olive-sized fruit. The seed inside is rich in oil with tremendous

medicinal and botanical properties.[14]


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Constituents

15-Acetoxy-7-deacetoxydihydroazadirone (neeflone), nonacosane (saturated hydrocarbon)

Identity, Purity and Strength

Foreign matter : Not more than 02%.

Total Ash : Not more than 14%.

Acid-insoluble ash : Not more than 05%.

Alcohol-soluble extractive : Not less than 05%.

Water-soluble extractive : Not less than 12%.

Important Formulations

Kusthakalmala Rasa, Kustha Sailendra Rasa, Krm ivinasanana Rasa.

Therapeutic Uses

Sotha, Aruci, Chardi, Daha, Hrllasa, Jvara, Kasa, Krmi, Kandu, Kustha, Netraroga, Phiranga,

Prameha, Raktavikara, Trsna¸¡, Visamajvara, Vrana, Kaphapittaja Vikara, Srama,

Hrudayavidaha.

Dose

2 - 4 g puspa curna.

10 - 20 ml puspa svarasa.[13]

MICROSCOPIC DESCRIPTION

Leaf-midrib

Leaflet through midrib shows a biconvex outline, epidermis on either side covered externally

with thick cuticle, below epidermis 4-5 layered collenchyma present. Stele composed of one

crescent-shaped vascular bundle towards lower and 2-3 smaller bundle towards upper

surface, rest of tissues composed of thin-walled, parenchymatous cells having secretory cells

and rosette crystals of calcium oxalate. Phloem surrounded by non-lignified fibre strand,

crystals also present in phloem region.[15]

Lamina

It shows dorsa-ventral structure; epidermis on either surface, composed of thin walled,

tangentially elongated cells, covered externally with thick cuticle; anomocytic stomata

present only on lower surface.


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Palisade single layered; spongy parenchyma composed of 5-6 layered, thin-walled cells,

traversed by a number of veins; rosette crystals of calcium oxalate present in a few cells;

palisade ratio 3.0-4.5; stomatal index 13.0-14.5 on lower surface and 8.0-11.5 on upper

surface.[12]

Stem bark

It shows outer exfoliating pieces hard, woody, and considerably thick in older barks, almost

entirely dead elements of secondary phloem, alternating with discontinuous tangential bands

of compressed cork tissue.

It composed of several layers of stone cells occurring in regularly arranged groups together

with collapsed phloem elements filled with brown contents; in between the successive zones

of cork tissue 3-5 layers of fibre groups with intervening thin-walled and often collapsed

phloem elements present.

Each zone of cork tissue consists of several layers of regular, thin-walled cells occasionally

with a few compressed rows of thick-walled cells towards.[14]

CHEMICAL CONSTITUENTS

Limonoids like nimocinolide and iso-nimocinolide affect fecundity in house flies (Musca

domestica) at a dose ranging between 100 and 500 ppm. They also show mutagenic

properties in mosquitoes (Aedes aegypti) producing intermediates.[14]

The essential oil consisting of sesquiterpene derivatives, the flowers contain nimbosterol and

flavonoids like kaempferol, melicitrin etc. Flowers also yield a waxy material consisting of

several fatty acids like arachidic (0.7%), stearic (8.2%), palmitic (13.6%), oleic (6.5%) and

linoleic (8.0%). The pollen of neem contains several amino acids like glumatic acid, tyrosine,

arginine, methionine, phenylalanine, histidine, arminocaprylic acid and isoleucine.[16,17]


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Sr. No. Neem compound Source Pharmacogical activity

1. Nimbidin Seed oil

Anti-inflammatory, Anti-arthritic,

Antipyretic

Hypoglycaemic ,Anti-gastric ulcer

Spermicidal, Anti-fungal, Anti-

bacterial, Diuretic

2. Nimbin Spermicidal Seed oil Spermicidal

3. Nimbolide Seed oil Anti-bacterial

4. Gedunin Seed oil Anti-fungal, Anti-malarial

5. Azadirachtin Seed oil Anti-malarial

6. Mahmoodin Seed oil Antibacterial

7. Gallic acid ,epicatechin and

catechin Bark

Anti-inflammatory and immuno-

modulatory

8. Margalone, margolonone &

isomargolonone Bark Anti-bacterial

9. Polysaccharides GIa

Bark Anti-tumour

10. Polysaccharides GIIa

GIIIa Bark Anti-inflammatory

11. NB-II peptidoglycan Bark Immuno-modulatory

12. Cyclic trisulphide and cyclic

tetrasulphide Leaf

Antifungal

Polysaccharides Anti-inflammatory

Chemical Constituent & Uses of Neem Plant[4]

TRADITIONAL USES

Neem has been used as traditional medicine for the treatment of tetanus, urticaria, eczema,

scrofula and erysipelas. It is also used as an anthelmintic, antifeedant, antiseptic, diuretic,

contraceptive, febrifuge, parasiticide, pediculocide and insecticide.[18]

Ayurvedic Pharmacopoeial Products

Some of the important polyherbal neem preparations of the Ayurvedic Pharmacopoeia and

their main uses are:

Aparjith Dhttp - Fumigant for purification of air (air sterilizer).

Dhattur tailam - Oil for skin diseases and muscular pain.

Jatyadi tailam - Oil for ulcer.

Jeevanti adi Kashyam- For smallpox.

Kandavadu Lepah - poultice for itching.

Nimbadi Kashyam - For skin diseases.

Nimbadijatailam palit- For baldness.

Panch nimba churnam- Powder for skin diseases.


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Thiktakam ghritam- Butter fat for skin diseases.

Yograjaguggulu - For rheumatoid arthritis.

THERAPEUTIC SCREENING STUDIES OF NEEM

Neem bark

Neem stem bark extract shows lethal effect in three common snail species Biomphalaria

pfeifferi, Bulinus trunca- tus and Lymnaea natalensis and against fish, Aphyosemon

giardneri.

Methanolic extract of neem bark demonstrated oral LD50 at about 13 g/kg in acute toxicity

studies on mice. Detailed toxicity studies have recently been conducted in rats with the neem

bark aqueous extract showing antacid secretory– antiulcer activity of the bark extract and also

show no lethal effect with the bark extract.

Neem Seed

Various neem seed preparations such as aqueous neem seed kernel extract demonstrated

toxicity to Oreochromisniloticus (tilapia) and Cyprinus carpio (carp).

An aqueous extract of neem seed kernel (1 ml/100g body weight daily of a 50 g/l solution)

produces trypsin inhibitory activity in weanling rats.

Retardation of spermatogenesis was observed by feeding neem seed cake to rats. Calves fed

with neem seed cake showed reduced haemoglobin content in the blood, along with

depression.

Neem Oil

Neem seed oil showed acute toxicity in rats and rabbits with LD50 of 14 ml/kg and 24 ml/kg

respectively, the possible target organs for toxic effects being the CNS and the lungs.

These toxic effects might be due to presence Afaflatoxin and other toxic compounds present

in neem oil. Mechanistic investigations indicate that neem oil uncouples mitochondrial

oxidative phosphorylation, thus inhibiting the respiratory chain. It also decreases intra-

mitochondrial levels of acetyl CoA and acid-soluble CoA esters and reduces the

mitochondrial ATP.


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Neem Leaves

Methanolic extract of neem leaf exhibits oral toxicity in mice, showing signs of ill health and

discomfort, gastrointestinal spasms, apathy, hypothermia and terminal convulsions, leading to

death.

Crude neem leaf extracts causes genotoxicity in male mice germ cell at a dose of 0.5– 2 g/kg

body weight for 6 weeks.

Some structural change in meiotic chromosomes along with chromosome strand breakage or

spindle disturbances and abnormal regulation of genes controlling sperm shape were

observed.

Neem leaf extract when administered for 48 days in albino rat‟s cause‟s decrease in sperm

count, sperm motility and forward velocity, probably due to androgen deficiency.

Oral administration of 20–60 mg dry leaf powder for 24 days in rats causes decrease in the

weight of seminal vesicle and ventral prostrate and regressive changes of the histological

parameters through its anti-androgenic property.

Therapeutic Uses

Treating scalp conditions, including dandruff, itchiness and head.

Providing relief for skin disorders such as eczema and psoriasis.

Treating and healing fungal infections, ringworm, infected sores and burns.

Treating acne, nail fungus and restoring brittle nails.

AGRICULTURAL APPLICATIONS OF NEEM

Neem used as Manure

Neem cake is used to manufacture high quality organic or natural manure, which does not

have any aftermaths on plants, soil and other living organisms. It can be obtained by using

high technology extraction methods like cold pressing or other solvent extraction. It can be

used directly by mixing with the soil or it can be blended with urea and other organic manure

like farm yard manure and sea weed for best results.


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Benefits

It is bio degradable and eco-friendly, nourishes the soil and plants by providing all the macro

and micro-nutrients, helps to eliminate bacteria responsible for denitrifying the soil, ideal for

cash crops and food crops.

Neem used as Urea Coating Agent

Neem and its parts are being used to manufacture urea coating agent to improve and maintain

the fertility of soil. The fertility of the soil can be measured by the amount of Nitrogen,

Potassium and Phosphorous present in it. There are certain bacteria found in soil, which

denitrify it. Urea coating is generally available either in liquid form or powdered form.

Properties of Neem Urea Coating are Anti feedant, anti-fertility and pest growth regulator.

Benefits

Neem Urea Coatings are excellent soil conditioners, natural or bio pesticides, environmental

friendly, non-toxic, reduces urea consumption, convenient and easy to apply, high soil

fertility and increases the yield of crops.[19]

Neem as Soil Conditioner

The process of Neem seed granules sprinkling should be followed by proper irrigation so that

the product reaches the roots. It is a natural soil conditioner that helps improve the quality of

soil, thereby enhancing the growth of plants and fruits.

Benefits

Neem is a natural soil conditioner that helps improve the quality of soil, thereby enhancing

the growth of plants and fruits. It not only helps the plants grow, but also prevents them from

being destroyed by certain pests and insects.

Neem as fumigant

Neem tree has been used against household, storage pests and crop pests. Neem pest fumigant

is available in gaseous state and is used as a pesticide and disinfectant. This natural fumigant

not only kills pests but also affects them negatively by acting as feeding, mating disruption,

inhibition of growth etc.

Benefits

Neem fumigants are eco-friendly, do not harm other microorganisms, are nontoxic, and do

not contaminate terrestrial and aquatic environment. Pests do not develop resistance to it,


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there are no negative after effects, are relatively less expensive, are pest repellent and nourish

the soil and function as pest reproduction controller.

Neem Oil Cake as Fertilizer

Neem Cake is an organic by product of Neem Seed Oil production. It is used as a natural

fertiliser. The quality of the neem cake is determined by the amount of oil left in it, and also

the process by which the extraction was done. The Physical form of the Neem Oil Cake is in

Powder or Flakes Form.

Mode of Action

1. Neem Cake is active in increasing the growth, leafage, results in rich blossoming,

strengthening the roots.

2. It accelerates root development and overall plant growth and protects the plant from

Nematodes and white ants.

3. It has antifungal properties and highly suitable for application in Greenhouses.

Benefits

Neem cake mixed with soil on and around the roots of the plants, Vegetables, bushes and

trees, will have a remarkable result in the improvement of the plant immunity.[20]

PHARMACOLOGICAL SCREENING & PROPERTIES OF NEEM

Azadirachta indica (Neem) is one of the most promising medicinal plant, having a wide

range of various pharmacological properties, especially as antibacterial, antifungal, antiulcer,

anti-tubercular and Antioxidant activities etc. Water soluble extract of neem leaves was found

to possess significant neuroprotective, anti-fertility and hypotensive activities etc.[21]

1. Anti-Bacterial Activity

The petroleum ether, methanol and aqueous extracts of the leaves of Azadirachta indica

(Meliaceae), was screened for their anti-microbial activity using the cup plate agar diffusion

method.[22]

They were tested against six bacteria; two Gram- positive bacteria (Bacillus subtilis and

Staphylococcus aureus) and four Gram-negative bacteria (Escherichia coli, Proteus

vulgaris).[23]


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The susceptibility of the microorganisms to the extracts of these plants was compared with

each other and with selected antibiotics. The methanol extract of A. indica exhibited

pronounced activity against Bacillus subtilis (28 mm).[24]

2. Anti-Fertility Activity

Neem leaves have shown reversible male anti-fertility activity. Neem oil appears to be a safe

and very effective contraceptive, pre and post coital. The way it was applied in the studies it

was 100% effective in preventing pregnancies. Population is the main problem worldwide

today it is necessary to control it on time.[25]

3. Neuroprotective Activity

When blood flow to brain region that has undergone critical period of ischemia is re-

established, additional injury is to be expected from the reperfusion. In the present study,

bilateral common carotid artery (BCCA) occlusion for 30 min followed by 45 min

reperfusion resulted in increase in lipid peroxidation, superoxide dismutase (SOD) activity

and fall in total tissue sulfhydryl (T-SH) groups.[26]

4. Anti-Tubercular Activity

Neem oil inhibited growth of mycobacterium strains in concentration of 12.5 mg/ml. Neem

oil and Nimbidol in higher concentration exhibited partial inhibitory influence whereas

Nimbidin prolong the survival period of mice affected with tuberculosis.[27]

5. Analgesic Activity

Neem seed oil (NSO) of 2ml/kg body weight is comparable to morphine with a dose of

1mg/kg body weight, NSO produces a better analgesic effect than morphine with 45 minute

of interval and it resembles indomethacine.[28,29]

6. Anti-Diabetic Activity

The pharmacological hypoglycemic action of Azadirachta indica has examined in diabetic

rats. After treatment for 24 hrs, Azadirachta indica 250mg/kg (single dose study) reduced

glucose (18%), cholesterol (15%), triglycerides (32%), urea (13%), creatinine (23%), and

lipids (15%). Multiple dose study for 15 days also reduced creatinine, urea, lipids,

triglycerides and glucose.[30]


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7. Anti-Oxidant

Extracts from young flowers and leaves have strong antioxidant potential. An indicator of

oxidative stress, malondialdehyde (MDA), was reduced by 46.0% and 50.6% for flower- and

leaf-based extracts[31]

, respectively, prompting the recommendation to use neem as a

vegetable bitter tonic to promote good health.[32]

8. Anti-Dermatitis

Neem can treat many skin disorders, including scabies and lice; in a paste combination with

Curcuma longa (turmeric), neem was used to treat scabies, 97% shows cure and no adverse

reactions were shown.[6]

9. Anti HIV-AIDS

In HIV/AIDS patients, a 12-week oral administration of acetone water neem leaf extract

(IRAB) had a significant influence in vivo on CD4 cells (which HIV reduces) without any

adverse effects in the patients.[33]

10. Anti-Ulcer Activity

Neem bark extract reduced human gastric acid hyper secretion, and gastro-oesophageal and

gastro-duodenal ulcers. After 10 weeks, the duodenal ulcers were nearly fully healed; after 6

weeks one case of oesophageal ulcer and gastric ulcer were fully healed. [34]

11. Anti-Malarial Activity

The antimalarial activities of the tablet suspension of the bark and leaf of Azadirachta indica

were evaluated on Plasmodium yoelli nigeriensis infected mice.

The tablet suspensions exhibited high prophylactic, mode-rate suppressive and a very

minimal curative schizonticidal effect.[35]

12. Anti-Viral Activity

The in-vitro antiviral property of Azadirachta indica polysaccharides for poliovirus. The

water extracted polysaccharides from A. indica leaves with anti-bovine herpes virus type-1

(BoHV-1) activity.[36]


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13. Larvicidal Activity

Aqueous extracts of four plants were tested for larvicidal properties laboratory reared larvae

were exposed to 1-5 ppm. It shows that the A. indica elicited 70-99% mortality to larvae. The

extracts of A. indica were found to be significantly effective in controlling Culex larvae. [37]

14. Anti-Inflammatory activity

The anti-inflammatory activity of epoxyazadiradione against macrophage migration

inhibitory factor.[38]

Azadirachta indica interacts with retinoic acid receptors and inhibits

retinoic acid-mediated biological responses.[39 27]

15. Anti-snake venom Activity

A snake venom phospholipase A2 (PLA2) inhibitor (AIPLAI) was isolated from leaves of A.

indica (neem) and the mechanism of PLA2 inhibition by AIPLAI in vitro condition was also

studied.[40]

16. Anti- Carcinogenic Activity

The identification of a sulfono-quinovosyl-diacyglyceride from A. indica and studies on its

cytotoxic activity and DNA binding properties.[41]

Ethanolic neem (A. indica) leaf extract

induced apoptosis and inhibits the IGF signalling pathway in breast cancer cell lines[42]

It

showed that molecular basis of „hypoxic‟ breast cancer cell radio-sensitization with

phytochemicals.[43,44]

Induction of apoptosis in human breast cancer cells by nimbolide.[45]

The neem oil limonoids

induces p53-independent apoptosis and autophagy.[46]

The anticancer biology of Azadirachta

indica was carried.[47]

The effect of neem leaf extract on rel protein-regulated cell death/ radio-sensitization in

pancreatic cancer cells.[48]

Novel molecular targets of Azadirachta indica associated with

inhibition of tumour growth in prostate cancer.[49]

17. Dental Diseases

Nimbidin gargal & dentifrices have been found effective in bleeding gums & pyorrhoea,

„Silvose T & Silvo TRS‟. Which are patented extracts of the bark neem. It is active ingredient

in tooth paste & other oral hygiene preparation. Neem extract when added to a tooth paste in

preventing & healing the inflammation of gums.[50]


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18. Anti-Fungal Activity

The ethanolic extract of A. indica leaves is more effective against Rhizopus and Aspergillus

compared to aqueous leaf extract.[51]

Aqueous and ethanolic extract of neem leaves were

found effective against Candida albicans by which these organism shows sensitivity at the

concentration of 15% and 7.5% on aqueous extract and the Minimum Inhibitory

Concentration (MIC) was 7.5%.[52,53]

19. Anti-Allergic Activity

Nimbin inhibited the stimulation produce by histamine in guinea pig ileum in a dose of

1mg/litre. In doses of 2mg/ml Nimbidin block the stimulant action of acetylcholine in frog

rectus abdominal muscles.[54]

20. Anti-Pyretic Activity

Methanol extract of Neem leaves shows antipyretic effects when administrated orally in

rabbits and rats.[55]

NEEM PATENTS & CONFERENCES

Patents

Sixty-five patents for products derived from the Neem tree have been filed with the EPO till

2013 of which 22 have been granted, 28 are “dead” for various reasons, and 15 are currently

being examined. These include claims for insecticides, fungicidal effects, methods of

extraction, and storage stable formulations of one of the active ingredients, azadirachtin,

contraceptives, and medical uses. It is important to note that the Neem patents do not involve

a genetically engineered product; neither has the tree itself been patented, nor any of its

parts.[56]

Conferences

During the past five decades intensive investigations on the diverse properties of neem have

been carried out. As a result large numbers of research publications and books have been

published. Many conferences have been conducted at national and international level.

1. First International Neem Conference, Rottach- Egern, Germany, 1980.

2. Second International Neem Conference, Rauis- chholzhausen, Germany, 1983.

3. Third International Neem Conference, Nairobi, Kenya, 1986.

4. First World Neem Conference, Bangalore, India, 1993.

5. Second World Neem Conference, Queensland, Australia, 1996.


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6. Third World Neem Conference, Vancouver, Can- ada, 1999.

7. Fourth World Neem Conference, Mumbai, India, 2002.

8. Fifth World Neem Conference, Maritius, 2006.

9. Sixth World Neem Conference, 2012. Nagpur, India.

Neem, correctly stated as “Tree for Solving Global Problems” is one of the most precious gift

by nature to us. It is indeed a „Green Gold‟, which we should nourish and cherish for

centuries to come.[1]

FUTURE PERSPECTIVES

The global market for herbal medicine alone is pegged at $5 trillion with an annual growth

rate of about 11 percent. The rapidly growing market of the herbal/alternative medicine

shows its world-wide popularity and acceptance.

There is no doubt that the products of the Neem plant enshrine bright prospects as a reliable

cure for cancer, but its protocol needs fine tuning for use in the clinical trials. One of the

important reasons is its nominal side effects.

A multi-institutional trial may be set up to spruce up chances for its speedy acceptance in the

clinics, particularly where cancer medicines are scarcely afford- able. However, this

suggestion may not find warm favour from companies that invest sumptuously to produce

costly cancer medicines.

The world market for alternative medicine has increased to about 10.895 billion USD as per a

recent report by the World Health Organisation (WHO).

CONCLUSION

Neem (Azadirachta indica) has been an ancient source of herbal activity against a variety of

human health problems. Researchers have been trying to purify the active ingredients from

this plant and to work out their mechanistic, therapeutic and clinical aspects on the reliable

systems.

Neem leaf and its constituents have been demonstrated to exhibit various pharmacological

properties. Neem products may cause some unpleasant side effects, particularly if taken in

overdoses.


266


It comes out of my own personal experiences and study of the effects and properties of

Neem. It is also my conviction that Neem is a wonderful cure for diseases and gives much to

humans including shade, good air, health and overall well-being.

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A REVIEW ON AZADIRACHTA INDICA