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Cancer Biology & Therapy 12:6, 467-476; September 15, 2011; 2011 Landes Bioscience
Keywords: neem, Azadirachta indica, herbal medicine, nimbolide, azadirachtin, anticancer drug
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Introduction
Neem (Azadirachta indica) is a tropical evergreen, profusely
branched tree with oblique leaves and stout trunk of timber values with insect-repellant properties. Earlier this plant was also
known as Melia azadirachta (L) and Antelaea azadirachta (L).
It is a native of Myanmar (Burma) and India. But, it may be
found in Bangladesh, Sri Lanka and African countries, as well. It
is about 20 ft tall and belongs to Meliaceae family (Fig. 1AD).
The neem tree is known by a variety of names, such as,
Indian lilac (English), Azadirakhta (Persian), Margosa and
neeb (Arabic), Tamar (Burmese), Kohomba (Sinhala), Pokok
semambu (Malaysia), Dogon yaro (some Nigerian languages),
neem (Hindi and Bangla), nimba (Sanskrit and Marathi),
*Correspondence to: Rajkumar Paul; Email: rajkumarpaul81@gmail.com
Submitted: 05/20/11; Accepted: 06/09/11
DOI: 10.4161/cbt.12.6.16850
www.landesbioscience.com
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Figure 1. (A) A neem tree,52 (B) an inflorescence of neem,53 (C) fruits of neem54 and (D) seeds of neem.55
468
consequent decrease in the level of 3H-B--P-DNA adduct formation. These molecular and biochemical modulations observed
at the initiation phase of carcinogenesis highlight the chemopreventive significance of A. indica extracts. In another interesting
study, Chaimuangraj et al. observed that dietary feeding of the
neem leaf extract (20, 100, 250 mg/Kg body weight) significantly
inhibited the azoxymethane-induced aberrant crypt foci (ACF)
and also significantly decreased the proliferating cell nuclear
antigen (PCNA) labeling indices (p < 0.0006) in the colon epithelium in rats. The preventive action of neem flowers has been
demonstrated by several research groups against the neoplastic
developments due to chemicals including DMBA and BP.8-10
These results indicate that dietary use of extracts from various
parts of A. indica may play a promising role in future drug discovery and development programs as far as chemoprevention
of cancer is concerned. Most of the ethnomedicinal and early
studies on neem with respect to its anticancer properties suffered
from lack of credible mechanistic principles. Serious attempts at
unraveling the possible scientific interpretations of the chemopreventive/anticancer effects of neem extracts have been made
in recent years. O6-alkylguanines are potently mutagenic and
Ethnomedicinal/Ritualistic uses
Scientific significance
Remarks
Powdered neem leaves are used externally for healing wounds. Earlier, neem leaves were burnt into
powdered form, mixed with mustard oil and applied
on open wounds to speed healing.
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Parts of
neem tree
Treatable ailments
Bark
Twig
Leaf
Flower
Fruit
Seed
Oil
Gum
Therapeutic uses
Types of preparations
Immunostimulant activity
45
Hypoglycaemic activity
46, 56
Antiulcer effect
57
Antifertility effect
Seed oil
4749, 58, 59
Antimalarial activity
6062
Antifungal activity
6364
Antibacterial activity
6365
Antiviral activity
Anticancer activity
10
Antioxidant activity
1213, 15, 16
11
Leaf extract
68
References
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470
S. no
Name of constituents
Chemical formula
Isolated from
Nimbin
C30H36O9
205
Nimbinin
C28H34O6
202
C26H34O7
228
Oil
Salannin
C34H44O9
167
Oil
Deacetyl Nimbin
C28H34O8
208
Nimbolide
C27H30O7
245
Leaves
Meliantriol
C30H50O5
176
Oil
Azadirone
C28H36O4
192
Oil
Epoxyazadiradione
C28H34O6
202
Oil
10
Azadiradione
C28H34O5
205
Oil
11
Gedunin
C28H34O7
218
Oil
12
7-Deacetyl Gedunin
C26H34O6
259
Oil
13
Meldenin
C28H38O5
240
Oil
14
Salannin-lactone
C34H44O10
244
Oil
15
Nimbin-lactone
C30H36O10
184
Oil
16
Azadirachtin
C35H44O16
155
Seeds
17
Vepinin
C28H36O5
Oil
18
Nimbolin A
C39H46O8
180
Trunk wood
19
Nimbolin B
C39H46O10
243
Trunk wood
Nimbidinin
C26H34O6
282
Oil
Vilasinin
C26H36O5
255
Leaves
20
21
22
23
24
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Nomolin
C28H34O6
205
Fruits
Nimolicin
C28H34O5
166
Fruits
17-Hydroxy-azadiradione
C28H34O6
Fruits
17-Hydroxy-azadiradione
C28H34O6
177
Fruits
26
17-Epi-azadiradione
C28H34O5
205
Fruits
27
1-Methoxy-1,2-dihydroepoxy-azadiradione
C29H38O7
235
Seeds
28
1, 2-Diepoxy-azadiradione
C28H34O7
110
Seeds
25
29
7-Acetylneotrichilenone
C28H36O5
208
Seeds
30
7-Deacetyl-7-benzoylazadiradione
C33H36O5
Amorphous
Seeds
31
7-Deacetyl-7-benzoylepoxy-azadiradione
C33H36O6
Amorphous
Seeds
32
7-Deacetyl-7-benzoylgedunin
C33H36O7
278
Seeds
33
Nimbinene
C28H34O7
134
34
6-Deacetyl nimbinene
C26H32O6
141
35
Nimbandiol
C26H32O7
121
36
6-o-Acetyl-nimbandiol
C28H34O8
178
Oil
37
3-Deacetylsalannin
C32H42O8
214
Oil
38
Salannol
C32H44O8
208
Oil
39
1,3-Diacetyl-vilasinin
C30H40O7
157
Oil
40
Nimocinol (6-Hydroxy-azadirone)
C28H36O5
130
Leaves
41
-Sitosterol
C29H50O
140
42
-Sitosterol--D-glucoside
C35H60O6
283
Blossom, leaves
and heart wood
43
Cycloeucalenol
C30H50O
138
Wood oil
44
24-Methylene-cycloartanol
C31H52O
122
Wood oil
45
C30H50O
Heart wood
46
4-Methyl-5-ergosta-8,24 (28)-dien-3-ol
C29H48O
Heart wood
47
Leaf
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Name of constituents
Chemical formula
Isolated from
Kaemferol
C15H10O6
276
Blossoms
Quercetin
C15H10O7
313
Myricetin
C15H10O8
357
Blossoms
Sugiol
C20H28O2
292
Trunk bark
Nimbiol
C18H24O2
250
Trunk bark
Glucoside of Quercetin
C21H20O12
Leaves
Glucoside of Kaemferol
C21H20O11
Leaves
Melicitrin
C20H18O12
Blossoms
Quercetin-3-galactoside (Hyperin)
C21H20O12
237
10
Kaemferol-3-glucoside (Astragalin)
C21H20O11
178
Blossoms
11
Quercitrin
C21H20O11
250
Leaves
12
Rutin
C27H30O16
214
Leaves
13
Isorhamnetin
C16H12O7
305
Leaves
14
Rhamnoside of Quercetin
C21H20O11
245
Leaves
15
5-Hydroxy-methyl furfural
C6H6O3
Fruit
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and internal stimuli, etc. However, a large body of modern literature on cancer shows that TNF is a strong survival factor for
cancer, because it activates NFB (a strong transcription factor)
that may induce innumerous genes that support survival of cancer.37 Using BALB/-c mice as an experimental model it has been
observed that there was a significant enhancement in the peritoneal macrophage activity and expression of activation marker
CD44 following regular subcutaneous administration of aqueous neem extract. This extract was also observed to enhance the
CD4, CD8 and CD25 positive sub-population of lymphocytes.
At the same time, metastatic activity of sarcoma L-1 and lymphosarcoma RAW cells was attenuated by this extract.38 Nitric
oxide (NO), a key tumoricidal agent is known to regulate T-cell
proliferation, cytokine production, cell signaling and apoptosis.39
Several laboratories have demonstrated that the T-cell derived
cytokines IFN, along with IL-2 and/or TNF, are macrophage
activators and serve as a potent inducer of NO.40 NLGP along
with tumor antigen vaccination showed NO production and
upregulation of IL-12 and excess IFN.41 Neem leaf preparation
enhances tumor antigen presentation of the macrophages42 and
dendritic cells to the T and B cells for induction of antitumor
immunity by allowing generation of immune effector/memory
response.43 That NLGP can enable maturation of the myeloid
derived DCs and can optimize the antitumor T-cell functions is
also known. Thus, it can be used as a candidate vaccine tool for
antigen specific cancer immunotherapy.44
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References
1.
www.landesbioscience.com
53. http://en.wikipedia.org
54. http://www.neemproduct.com
55. http://bhptemp.mypcat.com
56. Waheed A, Miana GA, Ahmad SI. Clinical investigation of hypoglycemic effect of seeds of Azadirachtaindica in type-2 (NIDDM) diabetes mellitus. Pak J
Pharm Sci 2006; 19:322-5; PMID: 17105712.
57. Bandyopadhyay U, Biswas K, Sengupta A. Clinical
studies on the effect of Neem (Azadirachta indica) bark
extract on gastric secretion and gastroduodenal ulcer.
Life Sci 2004; 75:2867-78; PMID: 15454339; DOI:
10.1016/j.lfs.2004.04.050.
58. Gbotolorun SC, Osinubi AA, Noronha CC,
Okanlawon AO. Antifertility potential of neem flower
extract on Sprague-dawley rats. Afr Health Sci 2008;
8:168-73; PMID: 19357745.
59. Prakash AO, Tewari RK, Mathur R. Non-hormonal
post-coital contraceptive action of neem oil in rats.
J Ethnopharmacol 1988; 23:53-9; PMID: 3419204;
DOI: 10.1016/0378-8741(88)90114-6.
60. Brahmachari G. Neem-an omnipotent plant: a retrospection. ChemBioChem 2004; 5:408-21; PMID:
15185362; DOI: 10.1002/cbic.200300749.
61. Joshi SN, Katti U, Godbole S. Phase I safety study of
Praneem polyherbal vaginal tablet use among HIVuninfected women in Pune, India. Trans R Soc Trop
Med Hyg 2005; 99:769-74; PMID: 16084547; DOI:
10.1016/j.trstmh.2005.01.007.
62. Khalid SA, Duddeck H, Gonzalez-Sierra M. Isolation
and characterization of an antimalarial agent of the
neem tree Azadirachta indica. J Nat Prod 1989; 52:9226; PMID: 2607354; DOI: 10.1021/np50065a002.
63. Subapriya R, Nagini S. Medicinal properties of
neem leaves: a review. Curr Med Chem Anticancer
Agents 2005; 5:149-56; PMID: 15777222; DOI:
10.2174/1568011053174828.
64. Rao DV, Singh I, Chopra P, Chhabra PC, Ramanujalu
G. In vitro antibacterial activity of Neem oil. Indian J
Med Res 1986; 84:314-6; PMID: 3102364.
65. 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 J
Dent Res 2007; 18:148-51; PMID: 17938488; DOI:
10.4103/0970-9290.35822.
66. Udeinya IJ, Mbah AU, Chijioke CP, Shu EN. An
antimalarial extract from neem leaves is antiretroviral.
Trans R Soc Trop Med Hyg 2004; 98:435-7; PMID:
15138081; DOI: 10.1016/j.trstmh.2003.10.016.
67. Joshi SN, Katti U, Godbole S. Phase I safety study of
Praneem polyherbal vaginal tablet use among HIVuninfected women in Pune, India. Trans R Soc Trop
Med Hyg 2005; 99:769-74; PMID: 16084547; DOI:
10.1016/j.trstmh.2005.01.007.
68. Gandhi M, Lal R, Sankaranarayanan A, Banerjee
CK, Sharma PL. Acute toxicity study of the oil
from Azadirachta indica seed (neem oil). J
Ethnopharmacol 1988; 23:39-51; PMID: 3419203;
DOI: 10.1016/0378-8741(88)90113-4.
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