Sources and Additional Links



"The Village Pharmacy"
Image from tutornext.com



References:-

1) Alexander, T., Knutson, A. and Harrington, M. (1999). The Best of Growing Edge. Retrieved from http://books.google.ca/books?id=spOi7N2slikC&pg=PA154&lpg=PA155&ots=kmc7pfTM0F&dq=cultures+that+use+neem#v=onepage&q=cultures%20that%20use%20neem&f=false

2) Board, N. (2008). Handbook on Neem and Allied products. Retrieved from http://books.google.com/books?id=dxOOnHxdJFwC&pg=PA201&lpg=PA202&dq=side+effects+of+neem#v=onepage&q=side%20effects%20of%20neem&f=false

3)Botelho, M.A., Araujo dos Santos, R., Martins, J.G., Carvalho, C.O., Paz, M.C., Azenha, C., Ruela, R.S., Queiroz, D. B., Ruela, W. S., Marinho, G. and Ruela, F.L. (2008). Efficacy of a mouthrinse based on leaves of the neem tree (Azadirachta indica) in the treatment of patients with chronic gingivitis: A double-blind, randomized, controlled trial. E-Journal from the Journal of Medicinal Plants Research. 2(11), 341-346. Retrieved from www.academicjournals.org/jmpr/PDF/pdf2008/.../Botelho%20et%20al.pdf

4) Carter, J.M. (2010). Evidence-based Medicine: An Overview of Key Concepts. E-Journal from the Journal of Ostomy Wound Management. 56(4), 68-85. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/204242944

5) Dr. Rahman. (n.d.). Neem: The Wonder Tree. Retrieved from http://www.neemfromindia.com/neem_articles.php#2

6)Ganguli, S. (2002). In this issue. E-Journal from the Current Science. 82 (11). Retrieved from http://www.ias.ac.in/currsci/jun102002/1303.pdf

7) Hanum, I.F. and Van der Maesen, L.J.G (Eds.). (1997). PROSEA: Plant Resources of South-East Asia 11, Auxillary Plants. Retrieved from http://books.google.com/books?ei=qZ_wTPzSAenfnQe3lsWrCw&ct=result&id=H-NdErdm0W4C&dq=neem%27s+active+components&q=neem+uses+today#v=onepage&q=neem%20uses%20today&f=false

8) Koh, H.L., Kian, C.T. and Tan, C.H. (2009). A guide to medicinal plants: an illustrated, scientific and medicinal approach. Retrieved from http://books.google.com/books?id=HFJWD9bwm9oC&printsec=frontcover#v=onepage&q&f=false

9) Kumar, G.H., Priyadarsini, R.V., Vinothini, G., Letchoumy, P.V. and Nagini, S. (2010). The neem limonoids azadirachtin and nimbolide inhibit cell proliferation and induce apoptosis in an animal model of oral oncogenesis. E-Journal from the Invest New Drugs. 28, 392–401. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/19458912

10) McIntyre, A. (2005). Herbal treatment of children: Western and Ayurvedic perspectives. Retrieved from http://books.google.com/books?id=QLin14nRVBsC&printsec=frontcover#v=onepage&q&f=false

11) Mehta, B. and Mehta, M. (2005). Organic Chemistry. Retrieved from http://books.google.com/books?id=QV6cwXA9XkEC&printsec=frontcover#v=onepage&q&f=false

12)Patel, J.P., Hemavathi, K.G. and Bhatt, J.D. (2005). Study of the antinociceptive effect of neem leaf extract and its interaction with morphine in mice. E-Journal from the Indian Journal of Pharmacology. 37(1), 37-38. Retrieved from http://www.ijp-online.com/article.asp?issn=0253-7613;year=2005;volume=37;issue=1;spage=37;epage=38;aulast=Patel

13) Singh, K.K., Phogat, S., Tomar, A., and Dhillon R.S. (Eds.). (2008). Neem: A Treatise. Retrieved from http://books.google.ca/books?id=PyYRUCoIDk4C&printsec=frontcover#v=onepage&q&f=false

14) Subapriya. R and Nagini, S. (2005). Medicinal Properties of Neem Leaves: A Review. E-Journal from the Current Medicinal Chemistry - Anti-Cancer Agents.  5 (2), 149-156. Retrieved from www.ncbi.nlm.nih.gov/pubmed/15777222

15) Wynn, S.G. and Fougère, B. (2007). Veterinary Herbal Medicine. Retrieved from http://books.google.com/books?id=iLbZDzumqt0C&printsec=frontcover#v=onepage&q&f=false

Image from ineedcoffee.com

Additional Links:-

http://neemfoundation.org/ 

Neem Worship:
Myths vs. Realities for the Usefulness of Neem Oil

http://www.paghat.com/neemworship.html 

Adverse Effects/Cautions/Cross Drug/Herb Interactions

  



Image from banadirtimes.com





Lesions on the liver cause by Neem oil.
Image from essentialoils.co.za



    Although Neem is a natural remedy to many ailments, certain side effects have been observed (Board, 2008). Toxicity studies of Neem oil on rats reported by Board have shown that intra-vaginal application of Neem oil prevents pregnancy by entering the circulation and manifesting its anti-fertility effects (2008). It is also observed to cause a significant alteration in testicular cell numbers resulting in androgen production inhibition (Board, 2008). Decreased serum protein concentration and protein levels in the liver and kidney have been observed (Board, 2008). Additionally at high dosages, these organs revealed mild lesions and suffered dysfunction. (Board, 2008).  Other revealed adverse effects include Reye’s syndrome in children, nausea, vomiting, diarrhoea, drowsiness, acidosis, anorexia, hypersensitivity and encephalopathy (Koh et al., 2009). In Botelho’s clinical study, Neem based mouthwash was noticed to have caused mild side effects which included burning sensation, epithelium desquamation, and altered tongue sensitivity (2008). Pregnant, lactating women and emancipated people are advised against the consumption of Neem. (Koh et al., 2009).

   Although not enough research has been done on cross drug-herb interactions, it has been advised that people on any medication, especially diabetic patients on insulin, others on oral hypoglycaemic agents, glyburide/glibenclamide and thyroid replacement therapy, should seek their doctor’s advice before consuming Neem. (Koh et al., 2009; Wynn and Fougère, 2007). However Patel et al. showed that combination of Neem with morphine can relieve pain with fewer side effects than when these drugs are used alone (2005).

Indian Government's approval letter for Neem based products.
Image from wspharmacy.com






Current Use and What the Science Says?

A Neem product for every ailment: You name it!
Image from tulipabeauty.co.uk

   

   Due to its antibacterial, anti-fungal and anti-parasitic properties, Neem is used to treat a myriad of illnesses ranging from lice, skin disorders to diabetes, ulcers and gastritis (McIntyre, 2005).

   Mouthwashes containing compounds such as chlorhexidine are used to treat gingivitis and periodontitis (Botelho et al., 2008). However due to their side-effects, Neem is now being used increasingly in herbal mouthwashes (Botelho et al., 2008).                            


Neem mouthwash.
Image from neemtreefarms.com



  To evaluate Neem’s anti-plaque and anti-gingivitis properties, Botelho et al. conducted a clinical trial on 55 patients who had not used antibacterial mouthwash for the last month (2008). For seven days, the experimental group used Neem leaf based mouthwash and the control group used chlorhexidine for 30 seconds twice a day (Botelho et al., 2008). Streptococcus mutans in saliva, plaque and gingival indexes were measured at 7 days and 1 month (Botelho et al., 2008). Results showed that the gingival index decreased from 1.52 to 0.45 in the Neem group and from 1.63 to 0.42 in the control group (P<0.001) (Botelho et al., 2008). Plaque index values decreased from 1.62 to 0.71 and 1.75 to 0.45 (P<0.001) in the respective groups (Botelho et al., 2008). No statistically significant differences were observed between the two groups (Botelho et al., 2008). However since long term use of chlorhexidine is limited by altering taste and staining of teeth, Neem could be used as a substitute (Botelho et al., 2008).

   This study is a level 1 study being a double blind, randomized study where subjects and investigators were masked during treatment (Carter, 2010).  Baseline parameters such as teeth number/condition, diet, smoking habits, and living conditions were similar, thus eliminating biases. Additionally sufficient background knowledge and information about excluded subjects was provided. Although the neem treatment produced mild side effects, the results prove it to be an efficient substitute (Botelho et al., 2008).

    Neem extracts are also being tested as anticancer drugs (Kumar et al., 2010). Its limonoid components are known to possess cytotoxicity against cancer cell lines (Kumar et al., 2010). Thus its antiproliferative and apoptosis properties were evaluated by Kumar et al. in male hamsters which were divided into 8 groups (2010). Thrice a day for 14 days, group 1’s right buccal was painted with dimethylbenz[a]anthracene (DMBA), groups 2–5 with DMBA in addition to intra-gastric administration of azadirachtin and nimbolide at a concentration of 10 and 100 μg/kg respectively, groups 6 and 7 were administered only azadirachtin and nimbolide at a concentration of 100 μg/kg while group 8 was the control (Kumar et al., 2010). Group 1 showed a 100% incidence of squamous cell carcinoma (SCC) while group 3 showed 33% incidence (Kumar et al., 2010). Others exhibited severe dysplasia although no tumours were observed (Kumar et al., 2010). Azadirachtin and nimbolide in groups 2-4 decreased tumour incidence and groups 6 to 8 possessed normal epithelium (Kumar et al., 2010). Immuno-histochemical and Western blot analyses also proved that these compounds inhibited (DMBA) induced carcinomas by influencing the expression of molecules involved in proliferation and apoptosis (Kumar et al., 2010).

   This experiment was a randomized study where baseline characteristics of the hamsters were the same, thus reducing bias. Extensive background knowledge was provided and many different tests including statistical tests were carried out to prove Neem’s efficacy. Thus the study can be ranked as a high evidence level study whose results demonstrate that Neem extracts can be used as an agent for cancer prevention and therapy once further studies are performed in human cancer cell lines (Carter, 2010; Kumar et al., 2010).



The herb that could cure diseases like cancer as well!!
Image from

http://www.beforeandafterdiet.net/wraps_neem.html

 


Neem flowers.
Image from cookatease.com

 


Active Components and Preparation

Image from blogs.dolcera.com



Components of Neem. Image from nzdl.org



  More than 300 active components have been isolated from the Neem tree with 21 bioactive compounds possessing potential therapeutic value (Ganguli, 2002; Kumar et al., 2010). Neem extracts contain many active tetranortriterpenoid compounds especially limonoids out of which azadiractin, meliacarpin, nimbin, nimbolinin and salannin are the five important ones. (Hanum and Van der Maesen, 1997; Mehta and Mehta, 2005). Azadiractin is the most active component with various isolated distinguishable forms (A to K) out of which the most abundant is Azadirachtin A (Dr. Rahman, n.d.). Other compounds found in Neem include ‘glycerides, polysaccharides, sulphurous compounds, flavonoids and their glycerides, amino acids and aliphatic compounds’ (Hanum and Van der Maesen, 1997).

Image from valleynaturals.com

Image from goodnessdirect.uk.co

    Scientific research has proved Neem’s efficacy in treating numerous ailments and thus it has become a principal ingredient in many products such as toothpastes and mouthwash (Singh et al., 2008).  Neem seed oil is used in soaps, shampoos and is used to treat Athlete’s foot, dandruff, acne, leprosy while leaf extracts are used in face creams and anti-fertility drugs (Singh et al., 2008). Additionally powdered Neem leaves are increasingly being used in capsule form to treat many disorders simultaneously (Singh et al., 2008).






Neem capsules for acne.
Image from astronutrition.com

                                   



Neem Capsule Dosage.
Image from nitawriter.wordpress.com







Neem Contraceptive Pills.
Image from archives.nic.in



History/Traditional Use

    Azadirachta indica (Neem) is a tree that belongs to the mahogany family Meliaceae (Singh et al., 2008). It is one of two species in the genus Azadirachta that originated in Asia and Burma (Singh et al., 2008). It is native to India, although it is also found in other parts of South Asia such as Sri Lanka and Pakistan (Singh et al., 2008).



The magnificient Neem tree. Image from the-hemp-center.com


   Since the sixth century BC, Sanskrit texts have recorded the ‘microbicidal and prophylactic’ effects of Neem and for approximately the last 2500 years, Neem extracts have been used as a multipurpose treatment (Dr. Rahman, n.d.). Its use is also mentioned in Persian and Urdu scriptures (Singh et al., 2008).

 



Image from infinityfoundation.com



 



Man using neem twig as a toothbrush. Image from life.com



    Neem forms an integral part of the Indian culture (Alexander et al., 1999). Thus it has and is still being extensively used as the principal herb of Ayurvedic and Unani medicine (Alexander et al., 1999). Neem, being a versatile plant, has wide-ranging medicinal properties that are used to address several health concerns such as malarial fevers, diabetes, warts, burns, ulcers, stomach problems, hypertension and cancer (Subapriya and Nagini, 2005). It boosts the immune system, has antibacterial, antiviral, antifungal, antiparasitic properties as well as moisturizing, contraceptive and anti-aging effects (Subapriya and Nagini, 2005). Additionally, it was used as a fertilizer and natural pesticide to protect stored grains (Alexander et al., 1999). In Africa as well, Neem twigs were used as toothbrushes to maintain healthy teeth because of their antiseptic properties (Alexander et al., 1999).



Neem seeds. Image from organicindia.com



  Traditional healers have treated chicken pox with a paste of Neem leaves that was rubbed on infected patches while a mixture of a teaspoon of dried Neem leaf powder, clarified butter and honey was used for skin allergies (Alexander et al., 1999; Singh et al., 2008). To stop bleeding in piles, Neem powdered seeds with warm water was ingested on an empty stomach (Singh et al., 2008).



Woman crushing Neem seeds to make oil.
Image from ecotippingpoints.org





Image from nzdl.org