Neem : A Natural Boon

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Neem (Azadirachta indica) is a member of the Meliaceae family.

Its extracts have a vast pharmacological activity and are used as raw materials for pesticide, medicine and other commodities. Each part of neem have its own therapeutic importance and use i.e. anthelmintic, antiemetic, antacid, antileprotic, antipyretic, analgesic, mosquito repellant, antifertility etc. There are many literature and articles on exploring various pharmacological activity of neem. Here we are presenting a review exploring different parts of neem plant along with its therapeutic significance and uses.

Introduction

Neem (Azadirachta indica) is a member of the Meliaceae family. It is a plant native to south Asia and Southeast Asia, which grows well in the hot river valley areas. Neem is regarded as “The Wonder Tree” and “Nature’s Drug Store”, because its extracts have a vast pharmacological activity and are used as raw materials for pesticide, medicine and other commodities. Neem is considered to be “one of the most promising of all plants and the fact that it may eventually benefit every person on this planet”. Probably no other plant yields as many strange and varied neem-products or has as many exploitable byproducts.[1, 2]. Taxanomical description is given in Table 1.

Habitat-Neem is a fast-growing tree that can reach a height of 15-20 m, rarely to 35-40 m., Leaves alternate, imparipinnate; leaflets subopposite serrate, very unequal at base; Flowers hermaphrodite, in axillary panicles; calyx 5-lobed; Petals 5,much exceeding the calyx, free, imbricate; Disk 0; Staminal tube a little shorter than the petals, cylindric, widening above, 9-10 lobed at the apex, the lobes truncate again slightly toothed; anthers within the tubes opposite to and shorter than the lobes. Ovary 3-celled; style elongate, slender; stigma shortly cylindric, 3 lobed; Ovules 2 in each cell, collateral; Fruit a 1-seeded drupe, endocarp woody; Seed ellipsoid; albumen 0; cotyledons thick, fleshy [3].

Therapeutic activity of different parts of Neem plant

Bark of Neem plant is bitter, astringent and give bad taste in the mouth. It acts as a refrigerant. Bark extract relieves from “kapha” and “pitta dosha including cough and ulcers. Bark extract acts as anthelmintic, antiemetic, antacid, antileprotic, antipyretic[4], analgesic and anti-inflammatory agent. Bark extract is also useful in blood purification, amenorrhoea, fatigue, thirst, and urinary tract infections. The young branches of neem plant are useful in asthma, piles, tumors and urinary discharges. The root bark is more active and speedy in its action than the bark. Extracts of Azadirachta indica seeds shows activity against multidrug resistant Salmonella enterica serovar Typhi isolates.[5] it is also effective against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans[6]. Whereas Neem extract is used for antibacterial finishing of polyester/cotton blend fabrics.[7] and effective against food borne pathogens and spoilage bacteria.[8]

Neem Leaves

The leaves of neem plants can be categorized as the tender young leaves which are astringent, cause “vata”, good for eye, skin diseases and in leprosy whereas the old leaves are anthelmintic, alexeteric, insecticidal, good in ophthalmic, biliousness and cure ulcers quickly. The leaves are carminative and expectorant, anti-inflammatory, anti-rheumatic, useful in syphilitic sores, earache, boils, in all blood impurities. A decoction of neem leaves relieves nose troubles; heal wounds, used as a gargle in stomatitis and bad gums. The juice of the leaves is useful in biliousness and cures snake-bite (Ayurveda). [9] Leaf extract of neem (Azadirachta indica. A. Juss) shows antiviral activity against group B coxsackieviruses.[10] Acetone–water neem leaf extract with antimalarial activity is antiretroviral[11]. Antisecretory and antihemorrhagic activity of Azadirachta indica is used to treat cholera and diarrhea [12]. The leaf and seed extracts of Azadirachta indica were tested for antifungal activity against dermatophytes and the minimum inhibitory concentration (MIC) of neem seed extract was found to be lower than that of neem leaf when tested against different species of Trichophyton and Epidermophyton floccosum.[13]

There is significant reversal of biochemical, histological and functional changes induced by carbontetrachloride in rats by ethanol extract treatment of Azadirachta indica leaf.[14] Aqueous leaf extract significantly prevents and reverses the hepatotoxic damage induced by antitubercular drugs in rats.[15] Azadirachta indica leaf extract shows Hepatoprotective activity against paracetamol induced hepatic damage in rat.[16] Azadirachta indica (Neem) leaf extract shows chemopreventive potential in murine carcinogenesis model systems.[17] The antioxidant properties of neem leaf fractions may be responsible for modulating key hallmark capabilities of cancer cells such as cell proliferation, angiogenesis and apoptosis in the HBP carcinogenesis model.[18] Neem leaf glycoprotein restores the impaired chemotactic activity of peripheral blood mononuclear cells from head and neck squamous cell carcinoma patients by maintaining CXCR3/CXCL10 balance.[19]

Neem Seeds

Seeds are good for the treatment of leprosy (Yunani). The oil from the seed is bitter, anthelmintic, alterative and good for skin diseases. The oil is a useful local remedy in some chronic forms of skin diseases and ulcers, by stimulating and exciting a healthy action. Applied to foul and sloughing ulcers, it retards the sloughing process to some extent, prevents the production of maggots and dislodges them if already produced. The oil is universal external application for rheumatism and is taken internally by women in pregnancy. Dental gel containing neem extract significantly reduces the plaque index and bacterial count[20] Neem extract acts on four organisms causing dental caries i.e. Streptococcus mutans, Streptococcus salivavius, Streptococcus mitis, and Streptococcus sanguis.[21] It is also antiseptic and commonly used for animals both internally and externally. Major D.B.Spencer in his “Record of Indian Fever, 1899” states that “The oil I think is the most active medicinal part of the plant. Externally it has stimulant, antiseptic and alternative properties and is very useful in chronic syphilitic sores and indolent ulcers. The oil is also extremely useful as a parasiticide in various cutaneous affections such as ring worm, scabies and others. When the parasite is in the deeper layer of skin, it will be necessary to rub the oil well in for perhaps 10 minutes or more at a time. Internally, the oil in 5-10 minim doses, once or twice a day is useful in chronic malarial fevers. Neem oil has good larvicidal properties for Anopheles gambiae[22] Application of neem, Azadirachta indica to rice-fields are positively evaluated with the dual objective of controlling the culicine mosquito vectors of Japanese encephalitis virus and enhancing the grain yield.[23] A crude acetone/water (50/50) extract of neem leaves was evaluated for activity against the asexual (trophozoites/schizonts) and the sexual (gametocytes) forms of the malarial parasite, Plasmodium falciparum, in vitro and was found that neem leaf extract has both schizonticidal and gametocytocidal activities.[24] The neem seed extract at 15µg/mL concentration (below MIC) is observed to be sufficient for distorting the growth pattern of the dermatophytes. (Trichophyton rubrum, Trichophyton mentagrophytes and Microsporum nanum).[25] Effect of aqueous extract from Neem (Azadirachta indica A. Juss) on hydrophobicity, biofilm formation and adhesion in composite resin by Candida albicans is proposed[26]. The hexane and alcoholic extracts of neem seed seem to be promising anticandidal agents.[27]. A novel use of neem (Azadirachta indica) oil, a traditional plant product, for long term and reversible blocking of fertility after a single intrauterine application is described.[28]. Extracts of Azadirachta indica and Melia azedarach seeds inhibit folliculogenesis in albino rats may have been due to disruption of the process of follicle selection due to atresia.[29] There is provided a means for reversible fertility control for prevention of pregnancy in female mammals for several months through the use of neem oil or its components, applied locally to the uterus. There is also provided a spermicidal composition containing neem oil or its components in combination with reetha extract as a vaginal cream.[30] Ultrastructural changes in leydig cells and cauda epididymal spermatozoa induced by Azadirachta indica leaves in albino rats proves that antiandrogenic and antispermatogenic properties of Azadirachta indica leaves appear to lead to a reduced fertilizing ability of the sperm.[31, 32]  An alternate approach to vasectomy for long-term male contraception following a single intra-vas application of a traditional plant (Azadirachta indica) product having immunomodulatory properties is also evaluated.[33]

Neem Fruit

The unripe fruit is oily and bitter. It acts as a purgative, anthelmintic and cures urinary discharges, skin diseases, tumors, piles and toothache. The ripe fruit has the same properties as the unripe one; it is also useful in consumption and eye diseases.[34,35]

Neem Flowers

The flowers are bitter and stimulant. It acts as anthelmintic, remove “kapha” and biliousness. The flowers are useful in some cases of atonic dyspepsia, stomachache and general debility.[36]

Other Parts of Neem

The bark, gum, leaf and seeds are prescribed in combination with other drugs for the treatment of snake bite (Charaka, Sushruta, Vaidyavinoda, Yogaratnakara, Rasaratnakara, Vrindamadhava) and scorpion sting (Charaka, Haritasamhita, Subodhavaidyaka). The gum is demulcent tonic useful in catarrhal and other affections accompanied by great debility. The sap is considered a refrigerant, nutrient and alterative tonic. Isolation of a snake venom phospholipase A(2) (PLA(2) inhibitor (AIPLAI) from leaves of Azadirachta indica (Neem) holds good promise for the development of novel anti-snake venom drug in future.[35

Conclusion:

Neem has been an ancient source of therapeutic miracles exhibiting numerous potential medicinal activities. Still researches are exploiting the therapeutic usefulness of this plant through various ongoing research projects. Certain new pharmacological activities found in Neem viz larvicidal, antitumor, antifertility activity etc may open new vistas of drug discovery and development enriching the therapeutic wealth of Azadirachta indica.

References:

  1. Retrieved from URL http://www.azadirachtaindica.co.in/ on 21.8.08
  2. Retrieved from URL http://en.wikipedia.org/wiki/Azadirachta on 21.8.08
  3. Kirtikar K.R., Basu B.D. (eds Blatter,E., Cains, J. F., Mhaskar, K. S.) IN  Indian medicinal plants, Text vol. I, page 536-546
  4. Materia Medika Indonesia,V, 1989, page 67-71
  5. Shyamapada Mandal, Manisha Deb Mandal, Nishith Kumar Pal. Antibacterial potential of Azadirachta indica seed and Bacopa monniera leaf extracts against multidrug resistant Salmonella enterica serovar Typhi isolates. Archives of Medical Science 2007; 3(1):14-18.
  6. W.E. Mwatha,a S.C. Chhabrab and W. Fabryc. African Journal of Science and Technology 2001; 2(2): 113-118.
  7. M. Joshi, S. Wazed Ali, S. Rajendran. Antibacterial finishing of polyester/cotton blend fabrics using neem (Azadirachta indica): A natural bioactive agent. Journal of Applied Polymer Science; 106 (2): 793 – 800.
  8. Mahfuzul Hoque MD, Bari ML, Inatsu Y, Juneja VK, Kawamoto S. Antibacterial Activity of Guava (Psidium guajava L.) and Neem (Azadirachta indica A. Juss.) Extracts Against Foodborne Pathogens and Spoilage Bacteria. Foodborne Pathogens & Disease 2007; 4(4): 481-8.
  9. Kirtikar K.R., Basu B.D. (eds Blatter,E., Cains, J. F., Mhaskar, K. S.) IN Indian medicinal plants, Text vol. I : 536-546.
  10. Badam L, Joshi SP, Bedekar SS. 'In vitro' antiviral activity of neem (Azadirachta indica. A. Juss) leaf extract against group B coxsackieviruses. J Commun Dis. 1999;31(2): 79-90.
  11. I. J. Udeinya, A. U. Mbah, C. P. Chijioke and E. N. Shu. An antimalarial extract from neem leaves is antiretroviral. Transactions of the Royal Society of Tropical Medicine and Hygiene 2004; 98(7): 435-437.
  12. Thakurta, P., Bhowmik, P., Mukherjee, S., Hajra, T.K., Patra, A., Bag, P.K. Antibacterial, antisecretory and antihemorrhagic activity of Azadirachta indica used to treat cholera and diarrhea in India. Journal of Ethnopharmacology 2007; 111 (3): 607-612.
  13. Ranganathan S, Menon Thangam, Balajee s AM, Raja SM. Antidermatophytic activities of Azadirachta indica : an in vitro and in vivo studies. Indian Journal of Dermatology 1996; 41(4): 113-117.
  14. Mujumdar AM, Upadhye AS , Pradhan AM. Effect of Azadirachta indica leaf extract on carbontetrachloride-induced hepatic damage in albino rats. Indian journal of Pharmaceutical Sciences 1998; 60(6): 363-367.
  15. B.P. Kale, M.A. Kothekar, H.P. Tayade, J.B. Jaju,M. Mateenuddin. Effect of aqueous extract of Azadirachta Indica leaves on hepatotoxicity induced by antitubercular drugs in rats. Indian Journal of Pharmacology 2003; 35(3): 177-180.
  16. R. R. Chattopadhyay, M. Bandyopadhyay. Possible mechanism of hepatoprotective activity of Azadirachta indica leaf extract against paracetamol-induced hepatic damage in rats: Part III. Indian J Pharmacol. 2005; 37(3): 184-185.
  17. Trisha Dasgupta, S. Banerjee, P. K. Yadava and A. R. Rao. Chemopreventive potential of Azadirachta indica (Neem) leaf extract in murine carcinogenesis model systems. Journal of Ethnopharmacology 2004; 92(1): 23-36.
  18. Manikandan P, Letchoumy PV, Gopalakrishnan M, Nagini S. Evaluation of Azadirachta indica leaf fractions for in vitro antioxidant potential and in vivo modulation of biomarkers of chemoprevention in the hamster buccal pouch carcinogenesis model. Food And Chemical Toxicology 2008; 46(7): 2332-43.
  19. Chakraborty K, Bose A, Pal S, Sarkar K, Goswami S, Ghosh D, Laskar S, Chattopadhyay U, Baral R. Neem leaf glycoprotein restores the impaired chemotactic activity of peripheral blood mononuclear cells from head and neck squamous cell carcinoma patients by maintaining CXCR3/CXCL10 balance. International Immunopharmacology 2008; 8(2): 330-40.
  20. M. Raveendra Pai, Leelavathi D. Acharya and N. Udupa. Evaluation of antiplaque activity of Azadirachta indica leaf extract gel—a 6-week clinical study. Journal of Ethnopharmacology 2004; 90(1): 99-103.
  21. Prashant GM, Chandu GN, Murulikrishna KS , Shafiulla MD. The effect of mango and neem extract on four organisms causing dental caries: Streptococcus mutans, Streptococcus salivavius, Streptococcus mitis, and Streptococcus sanguis: An in vitro study. Indian Journal of Dental Research 2007;18(4): 148-51.
  22. Fredros O Okumu, Bart GJ Knols, and Ulrike Fillinger. Larvicidal effects of a neem (Azadirachta indica) oil formulation on the malaria vector Anopheles gambiae. Malar J. 2007; 6:63.
  23. D. R. Rao, R. Reuben, M. S. Venugopal, B. A. Nagasampagi, H. schmutterer. Evaluation of neem, Azadirachta indica, with and without water management, for the control of culicine mosquito larvae in rice-fields. Medical and Veterinary Entomology 1992; 6 (4): 318-324.
  24. Udeinya JI, Shu EN, Quakyi I, Ajayi FO. An Antimalarial Neem Leaf Extract has Both Schizonticidal and Gametocytocidal Activities. American Journal of Therapeutics 2008; 15(2): 108-10.
  25. Natarajan V, Venugopal PV, Menon T. Effect of azadirachta indica (neem) on the growth pattern of dermatophytes. Indian Journal of Medical Microbiology 2003; 21(2): 98-101.
  26. Sheila R.B. Polaquini, Terezinha I.E. Svidzinski, Carlos Kemmelmeier and André Gasparetto. Effect of aqueous extract from Neem (Azadirachta indica A. Juss) on hydrophobicity, biofilm formation and adhesion in composite resin by Candida albicans. Archives of Oral Biology 2006;51(6):482-490.
  27. Charmaine Lloyd AC, Menon T, Umamaheshwari K. Anticandidal activity of Azadirachta indica. Indian Journal of Pharmacology 2005; 37(6): 386-389.
  28. Upadhyay SN, Kaushic C, Talwar GP. Antifertility effects of neem (Azadirachta indica) oil by single intrauterine administration: a novel method for contraception. Proc Biol Sci. 1990; 22, 242(1305): 175-9.
  29. J.K. Roop, P.K. Dhaliwal and S.S. Guraya. Extracts of Azadirachta indica and Melia azedarach seeds inhibit folliculogenesis in albino rats. Brazilian Journal of Medical and Biological Research 2005; 38(6): 943-947.
  30. Talwar, Gursaran P., Upadhyay, Shakti , Kaushic, Charu , Singh, Amarjeet Sharma, Madan G. Reversible fertility control for prevention of pregnancy in females. United States Patent 5196197 published on 03/23/1993
  31. Omkar Parshad, M. T. Gardner, T. L., L. A. D. Williams, C. K. Fletcher. Antifertility Effects of Aqueous and Steroidal Extracts of Neem Leaf (Azadirachta indica) in Male Wistar Rats. Phytotherapy Research 1997;11(2): 168-170.
  32. Raka Kamal, R. S. Gupta, N. K. Lohiya. Plants for male fertility regulation. Phytotherapy Research 2003; 17(6): 579-590.
  33. Upadhyay SN, Dhawan S, Talwar GP. Antifertility effects of neem (Azadirachta indica) oil in male rats by single intra-vas administration: an alternate approach to vasectomy. .J Androl. 1993;14(4): 275-81.
  34. Kokate C.K., Purohit A.P., Gokhale S.B., NeemvIN Pharmacognosy, Nirali Prakashan, New Delhi.
  35. Iffat Ara, Bina Shaheen Siddiqui, Shaheen Faizi and Salimuzzaman Siddiqui. Structurally novel diterpenoid constituents from the stem bark of Azadirachta indica(meliaceae). J. Chem. Soc., Perkin Trans. 1 1989: 343-345.
  36. Mukherjee AK, Doley R, Saikia D. Isolation of a snake venom phospholipase A2 (PLA2) inhibitor (AIPLAI) from leaves of Azadirachta indica (Neem): Mechanism of PLA2 inhibition by AIPLAI in vitro condition. Toxicon. 2008; 51(8): 1548-53.

Table 1: Taxanomical description of NEEM

Kingdom

Plantae

Division

Magnoliophyta

Order

Sapindales

Family

Meliaceae

Genus

Azadirachta

Species

indica

Table: 2 Some bioactive compounds from Azadirachta indica4

Compound

Source

Activity

Azadirachtin

Seed oil

Insect repellant

Nimbidin

Seed oil

Antiviral

Nimbin

Seed oil

Antiviral

Azadirachtin

Leaves

Insect repellant

Meliantriol

Leaves

Antifeedant

Salanin

Leaves

Sponsored Links

Antifeedant

Nimbosterol

Flowers

Insecticidal

Myricitin

Flowers

Insecticidal

Kaempferol

Flowers

Insecticidal

Deacetyl azadirachtinol

Fruits

Paralyzes insects swallowing mechanisms

Nimbin

Bark

Antiviral

Nimbinin

Bark

Antiviral

Nimbidin

Bark

Antiviral

Margolone

Bark

Antibacterial

Margolonone

Bark

Antibacterial

Isomargolone5

Stem bark

Antibacterial

Figure 1: Different uses of Neem

Different uses of Neem

About Authors:

Himanshu Gupta

Himanshu Gupta, completed his D.Pharm, B.Pharm, M.Pharm (Pharmaceutics) and now pursuing his PhD from Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi, India. He worked as Lecturer in UPTU and Research Associate in Department of Science & Technology, Min. of Science & Tech. sponsored project. He had research experience working with INMAS (DRDO), AIIMS, CIPL etc. He had many articles in reputed peer reviewed journals. He has great interest in natural products, ocular and novel drug delivery systems, Pharmacoscintigraphy, Nuclear medicine etc.

Dinesh Bhandari

Dinesh Bhandari, completed his D.Pharm and is now a final year B.Pharm student of DJ college of Pharmacy, Modinagar, UP.

Kamal Dua

Kamal Dua, Workign as a Lecturer, Department of Pharmaceutics, DJCOP,Niwari Road Modinagar and having more than three years of professional experience.

Vijay Kumar Sharma

Vijay Kumar Sharma Workign as a Asst.Professor, Department of Pharmaceutical Chemistry, DJCOP,Niwari Road Modinagar and having more than ten years of professional experience.

U.V.Singh Sara

Dr.U.V.Singh Sara, Workign as a Director and Head, Department of Pharmaceutics, DJCOP,Niwari Road Modinagar and having more than thirteen years of professional experience.

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Comments

Himanshu Gupta's picture

Please comment on it.

Sailaja Byrisetty's picture

Good job Himanshu Gupta. Refreshing information. What are the commercially successful neem products availble in India ? any idea ..

Himanshu Gupta's picture

Thanks for the appreciation.

http://www.springerprotocols.com/Abstract/doi/10.1385/0-89603-515-8:155

Please see this for commercial peoducts etc

Sailaja Byrisetty's picture

I think the link you posted only for subscribers. I am just interested in famous brand names . Just give me name if possible...

A.R.Khan's picture

Good information. Nice information presented in simple way. Neem has antifertility activity too...i just came to know.

Himanshu Gupta's picture

Thanks for appraisal of our work.

Eswar GsnkRao's picture

GooD Collection of info about neem....
I gone through your article and came to know so many new properties of our friendly everywhere available neem tree....
Eventoday in villages the villagers like to use neem stem bark as their brush, may be the basic reason is these many benefits...
I have small doubt !!!
I seen some diabetic patients who highly prefer neem leaves paste and karela paste as a remedy for their diabetes and say that their condition is controlled by using those items. What is your comment on this? B'coz I didn't found any property related to diabetes in your article, hence I am interested to know the fact! Will you plz have a discussion on this....

Expecting more articles like the present article with wide coverage...
eswar :-)

Regards

ESWAR :-) 

Himanshu Gupta's picture

Dear eswar,
Thanks for the promoting words. Actually natural herbs and trees are many more properties then we even expected. Natural herbal plants are multi disciplinary in action, one can not categorized 1 or 2 therapeutic propeties out of them.

We have presented a compilation of work already have done on neem. There is much more to explore. If there is no data available then this can be a next topic to work on. Neem as antidiabetic agent. The studies can be done on rats/rabbits to prove.

Karela helps, I have read about it..Neem is also bitter and I read that bitter plants have efficacy in controlling diabetes, may be there is some property..that need to be xplored...

thanks for your comments..

Eswar GsnkRao's picture

Thanks for your clarification....
Go on keeping such an informative blogs.
eswar :-)

Regards

ESWAR :-) 

Lakshya's picture

Dear Himanshu, A nice effort & good information representation. Neem indeed has been long known in our tradition & is treated with respect for its infinite gifts. As the discussion between you & Eswar, Neem & Karela are those components which are widely used by the practitioners in treating diabetes. It is so said that each & every part of the Neem tree is useful, it’s one of those trees which are termed under the category of "Kalpvriksha".
I will be very happy to see your contributions in blogs & also in PharmIndia group/forum.

Himanshu Gupta's picture

Thanks for appreciation. You are right Neem is one of the plants kept in category of 'Kalpvriksha'. There are manu such plants which need to be explored and to be commercialised. Hope to see some good work on them from India.