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Annals of Biological Research, 2010, 1 (2) :108-113
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ISSN 0976-1233
108
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Antifertility effects of Azadirachta indica (Neem) - A Review
Parveen Bansal
1
, Renu Bansal
1
, Vikas Gupta
2*
1
Baba Farid University of Health Sciences, Faridkot, India
2
National Institute of Ayurvedic Pharmaceutical Research, Patiala, India
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Abstract
Most population studies conclude that today's skyrocketing growth in human population is
creating a serious underlying threat to the well being of the world's natural and economic
resources. Whether neem, can help to reduce runaway population growth is' uncertain.
However, as noted earlier, exploratory research has indicated that certain neem, ingredients
have contraceptive properties. Thus it is possible that, given research attention, products from
this tree could come into widespread use for the reduction of unwanted pregnancies. This
review gives a bird's eye view mainly on the contraceptive therapeutic potential of neem tree so
as to promote the research on this magic tree.
Keywords: Azadirachta indica, Contraceptive, Spermicidal, Implantation, Male fertility
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INTRODUCTION
Neem, a native of Indian subcontinent is a highly esteemed tree for the people in the region. The
plant is considered sacred and is used by the Hindus in several ceremonies, rituals and in
worship of the New Year day [1]. It is associated with a rural festival "Ghatasthapana" to avert
diseases [2-4]. The Juice of fresh green leaves of Azadirachta indica was believed to suppress"
Kam vasna" (desire for sex) so saints and "sanyasees" in shrines and the pupils studying in
"Gurukul" consumed it for the same purpose. From an initial caution and scepticism neem, has
now been universally accepted as a miracle tree. During last three decades neem has attracted
the brains of The scientific community and has attained a place of pride in national and
international scenario. Neem has been found to contain a vast array of biologically active
compounds, which are chemically diverse and have got an enormous therapeutic potential. Not
only this many reviews have been already appeared from time to time on its constituents in
general [5-7]. Its chemistry dates back to 1880-1890 when influenced by its folk-lore medicinal
values the chemists took up the isolation of active principles and Siddiqui [8] was the first to
report the isolation of three products namely nimbin, nimbidin and nimbinin from its oil. The
National Research Council of USA has given an excellent account of this tree in their
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publication 'Neem' A tree for solving global problems'. The society of pesticide science in India
has also given an elaborative account regarding this tree in "Neem Research and Development'.
Two other comprehensive compilations on the multifaceted research involving diverse
disciplines of science were done by Jacobson and Tiwari [9, 10]. This review has been done to
provide an insight into pharmacological work done to substantiate traditional claims to establish
its contraceptive potential in modem medicine demonstrated as antimplantation effect,
spermicidal effect, oral contraceptive, abortifacient, antispermatogenic effect and antifertility
effect. Its contraceptive effect has been tried through oral, vaginal and subcutaneous routes of
application. Either oil as such, or oil or leaf extracts have been used.
Neem is being projected as a cheap and effective antifertility agent. In 1959 the antifertility
property of neem components in rats and human were published [11, 12]. In this study addition
of aqueous solution of sodium nimbidinate salt to semen of rat and human being resulted in
death of sperm in different percentage and in different time period. Similarly oil proved to be
spermicidal against rhesus monkey and human spermatozoa in vitro [13], when used intra
vaginally the oil prevented pregnancy in rats (20 µl), rhesus monkeys and women (10ml). The
oil did not reveal any side effects on repeated application as confirmed by histopathological
studies on reproductive organs or other tissues where as oral dose of as low as 25µl oil
demonstrated a complete anti implantation effect in rat [14]. In vitro testing of spermicidal
activity of neem oil posed a problem of mixing the oil with water phase i.e. semen. So
cyclohexane, which had no effect on spermatozoa motility at 2% concentration, was used to
dissolve most of the test neem products. After diluting the mixture with a solution oftween-80
(0.1 %), the spermatozoa movement could be observed under a microscope [15]. Both the
precoital and postcoital antifertility effects of vaginal application of neem oil have been
subsequently confirmed in rhesus monkeys [16]. According to a report from scientists of
Defence Institute of Physiology and Allied Sciences (DIPAS), a neem extract (Nim-76) is
believed to be refined to give birth control effect. This study showed that neem oil applied
intravaginally before sexual intercourse prevented pregnancy without any adverse effect on
vagina, cervix and uterus. Further radio lisotopic studies indicated that neem oil is not absorbed
from the vagina [14]. The active components of neem oil have been found to be absorbed
through the vaginal mucosa into circulation and exerted antifertility effects in addition to direct
spermicidal effect.
The spermicidal property in post coital stages is rather undesirable because if used in pregnant
women, it may lead to defects in embryonic development. Nim-76 a potent volatile fraction
however inhibited spermatozoa motility in vitro in rat and human beings [17, 18]. It was found
superior than raw neem oil in that it acts mainly by its spermicidal effect and no alterations in
hormone values were observed. Several other studies have also shown that the mechanism 'of
action of neem is not hormonal but probably direct spermicidal" [19, 20]. These findings were
based on an analysis of the histoarchitecture of the uterus of treated rats and were subsequently
confirmed by other workers [21]. Since the effect seems to be non hormonal it would be
expected to elicit fewer side effects than the steroidal contraceptives.
According to another report [22] neem oil in graded doses of 2, 4, 6 ml per kg. body weight did
not inhibit ovulation activity in rabbits. According to other study neem oil constituents based
formulation is 100% active to prevent pregnancy and does not produce any side effects [23].
Subcutaneous application of neem oil components like nimbi din or nimbidiol did not show any
estrogenic activity [24,25]. In another report neem oil up to 0.3 ml/rat subcutaneously did not
possess any estrogenic, antiestrogenic, progestrational or antiprogestational activity [26].
Subcutaneous administration of neem oil has been reported to inhibit pregnancy [27]. Study
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indicates that the administration of neem oil may kill the blastocysts kin in the uterus of
pregnant rats.
Another group of scientists have shown that feeding of neem extracts for shorter duration
caused no significant changes in the ovarian or uterine histology however longer treatment did
cause arrest of follicular growth and thickening and scattering of stromal and glandular cells
[28].
Male rats when tested for fertility after feeding neem oil had been found to result in a significant
loss of reproductive function [22]. There were no inhibitions of spermatogenesis in any of the
groups demonstrating that probably the drug induced functional sterility without interfering
with structural integrity of the testis or the process of spermatogenesis. Another report has given
contrast results in which administration of neem bark extract (50% EtOH) or neem seed oil
(petroleum ether extract at a dose of 0.5g/kg body weight for 2 months caused arrest of
spermatogenesis [29]. An active principle in water extracts of crushed green leaves caused
reversible antifertility action without inhibition of spermatogenesis. This active principle was
thermo stable [30, 31]. This extract was also found active in mice, rats, rabbits and guinea pigs
[32]. When 100 mg of dried leaf powder suspended in 1ml of distilled water per day, was given
for a period of 24 days, it was suggestive of reversible antiandrogenic effect on the histological
and biochemical parameters of testis of adult albino rats [33, 34].
Upadhyay et al. [35] observed a long-term contraceptive effect of single intra-vas administration
of neem oil in male rats. The antifertility effect was observed for 8 months and was found to be
an alternative approach to vasectomy. No inflammatory/obstructive changes in epididymis and
vas deferens were observed. There was no change in blood testosterone levels. Purified neem
seed extract called praneem was reported to cause termination of pregnancy by bleeding and a
decrease in progesterone levels in rats, baboons and monkeys [36]. It was also reported to
abrogate pregnancy in primates [37].
Indigenously available neem oil in its natural form as tested for its spermicidal activity (in vitro
and in vivo). Undiluted neem oil was found to possess strong spermicidal action (within 30s.)
against rhesus monkey and human spermatozoa in vitro, whereas 3 mg. of neem leaf extract,
when treated with human spermatozoa, kills 100% of sperm within 20 s. The time taken by
sperm to travel to the oviduct from the cervix in women is 5-68 min, when all conditions are
favorable in the fertile period [38]. Therefore, neem leaf extract is more advantageous than the
undiluted neem oil, which takes 30 s to kill the sperm.
Praneem polyherbal cream has been developed by garg et al. [39], which has synergistic
spermicidal concentration for praneen (25%) reetha saponins (0.05%) and quinine
hydrochloride (0.34%) and was found at this concentration to result in 100% immobilization of
sperm within 20s [40]. Until now, neem seed extract or oil or oil components were studied as an
effective contraceptive that .is hydrophobic in nature. The neem leaf extract, which is
hydrophilic in nature, mixes immediately with water as well as body fluids and kills sperm
within 20 s, with its use, a more potent vaginal contraceptive may be developed.
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 by Upadhyay et
al. [41]. Female Wistar rats of proven fertility were given a single dose (100 µl) of neem oil by
intrauterine route; control animal received the same volume of peanut oil. Whereas all control
animals became pregnant and delivered normal litters, the rats treated with neem oil remained
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infertile for variable periods ranging form 107 to 180 days even after repeated mating with
males of proven fertility. The block in fertility was, however, reversible as half of the animal's
regained fertility and delivered normal litters by five months after treatment, without any
apparent teratogenic effects. Unilateral administration of neem oil in the uterus blocked
pregnancy only on the side of application, whereas the contra lateral uterine horn treated with
peanut oil had normally developing foetuses; no sign of implantation or foetal resorption was
noted in the neem-oil-treated horn. The ovaries on both side had 4-6 coropora lutea, indicating
no effect of treatment on ovarian function. The animal treated with neem oil showed a
significant leukocytic infiltration in the uterine epithelium between days 3 and 5 post coitum
i.e., during the preimplantation period. Intrauterine application of neem oil appears to induce a
preimplantation block in fertility.
Neem oil in vitro proved to be a strong spermicidal agent. Rhesus monkey and human
spermatozoa became totally immotile within 30 seconds of contact with the undiluted oil. In
vivo studies in rats (20) rabbits (8), rhesus monkeys (14), and human volunteers (10) proved
that neem oil has also been found to have anti-implantation/ abortifacient effect in rats and
rabbits if applied intravaginally on day 2 to day 7 of expected pregnancy [42]. The minimum
effective dose is 25 µl for rats. One month after the stoppage of neem oil application there was
complete reversibility in fertility in these animals. It has no deleterious effect on the subsequent
pregnancies and the offspring. Histopathological studies on rat's vagina, cervix and uterus
showed no ill effects of neem oil in these tissues. In contrast, nonyl-phenoxy polyethoxy
ethanol, a polyethoxy ethanol, a popular vaginal contraceptive cream, showed signs of severs
irritant reaction in these tissues. Radioisotope studies indicated that neem oil was not absorbed
from the vagina, it thus out its possible systemic effects. Results of the present study indicated
that neem oil is an "ideal" female contraceptive, being easily available, cheap and non-toxic.
Another study was carried out to evaluate the effective concentration of aqueous extract of old
and tender Azadirachta indica (neem) leaves to immobilize and kill 100% human spermatozoa
within 20 s [43]. The results of the 'study revealed that the aqueous extract of old and tender
neem leaves is a potent spermicidal, which is demonstrated through docs-dependent study on
the effect of motility of spermatozoa and then confirmed by viability test. No morphological
changes were found in the sperm head, mid- piece and tail when compared with untreated
sperm. Therefore, 100% killing of sperm may by due to blockage of some biochemical pathway
like energy utilization, which would require' further investigation. The potency of lyophilized
aqueous extract of old and tender leaves remains the same and the effectiveness does not change
with storage time to 4 year.
According to Dhawan et al. [44] Ethanol/water (1:1) extract of the dried seed, administered
orally to female rats at a dose of 100 mg/kg, did not demonstrate any antiimplantation effect. A
similar type of study has shown inactivity of the seed oil administered by gastric incubation at a
dose of 5.0ml/ animal [45]. Lal et al. [46, 47] has shown just contradictory results by
demonstrating activity of essential oil administered orally to the rat a, the dose of 4.0 ml kg on
days 1-3. In two different studies antispermatogenic effect of dried leaf extract was screened.
Ethanol (80%) extract of the dried leaf, administered intragastrically to male rats at a dose of
100 mg/kg daily for 21 days was inactive for antispermatogenic activity however there was loss
of libido in 100% males [48] whereas the dried leaf administered intra gastrically to male rats at
a dose of 20-60 mg/animal daily for 24 days was active [49]. The seed oil has also been shown
to effect the sperm/egg interaction at a concentration of 10-25% and thus inhibit fertilization
and development of fertilized ova [50]. The dried seed administered intravaginally was active as
spermicidal in baboon, monkey and rabbit [51].
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CONCLUSION
Keeping in view the importance of neem tree in national regional land international perspective
there is an urgent need to locate collect and study its diversity and develop effect measures to
store it for current and future use. At the same time it is also essential to undertake ethno
botanical studies to link its various therapeutic uses with ethnic/ folklore remedies to evaluate
how different tribes use neem in different areas of its occurrence. There is a dire need to
document this folklore traditional knowledge, which is vanishing rapidly due to lack of
awareness in these people, also effective measures are required to document available diversity
and bring out systematic information for wider dissemination and utilization of world's genetic
diversity in neem for exploring its therapeutic potential further.
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... Azadirachta indica A. Juss.(Meliaceae) (common name "neem"), is native to the Indian subcontinent and was introduced first to Africa and then to the rest of the world through Middle East and Caribbean (Kumar and Navaratnam, 2013). A. indica possesses contraceptive properties and this activity has been the object of several studies in the past years (Bansal et al. 2010;Chattopadhyay, 1993;Chaube et al., 2006Chaube et al., , 2014Sitasiwi et al. 2018). ...
Article
Background Azadirachta indica A. Juss. is an Indian medicinal plant with innumerable pharmacological properties. Studies have proven that the phytochemicals from neem possess remarkable contraceptive abilities with limited knowledge on its mechanism of action. Purpose The present review aims to summarize the efficiency of A. indica treatment as a contraceptive. Methods The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were used. Published scientific articles on antifertility, antispermatogenic, antiovulation, hormone altering, contraceptive, and abortifacient activities of A. indica were collected from reputed Journals from 1980 to 2020 using electronic databases. Specific keywords search was completed to collect numerous articles with unique experiment design and significant results. This was followed by the selection of the requisite articles based on the criteria designed by the authors. Data extraction was based on the common research elements included in the articles. Results A total of 27 studies were considered for reviewing, which included key pharmacological investigations. In the beginning, authors evaluated a number of publications on the contraceptive properties of A. indica, in which it was revealed that most of the publications were made between 1995 and 1999. All the collected articles were categorised and reviewed as antifertility, antispermatogenic, antiovulation, hormone altering, contraceptive, and abortifacient. Authors also assessed studies based on the plant parts used for pharmacological evaluations including leaves, seeds, stem-bark, and flowers. The article was primarily divided into different sections based on the previous works of authors on phytochemistry and pharmacological review articles. Conclusion Although A. indica is not reported with the complete alleviation of reproductive system in both male and female animal models, studies have proven its efficacy as a contraceptive. Extracts and phytochemicals from neem neither reduced the libido nor retarded the growth of secondary sexual characters, thus indicating only a temporary and reversible contraceptive activity. However, there is a dearth for clinical studies to prove the efficacy of A. indica as a herbal contraceptive.
... Penelitian ini menggunakan Mus musculus L. strain Swiss Webster yang diduga bersifat lebih sensitif terhadap bahan uji yang diberikan sehingga menyebabkan penurunan bobot badan hewan uji di kelompok perlakuan. Bansal et al. (2010) menyatakan bahwa faktor lain yang dapat mempengaruhi adalah lama pajanan bahan uji. Hasil penelitian ini menunjukkan bahwa paparan bahan uji selama 2 minggu belum mempengaruhi bobot badan, tetapi paparan bahan uji melebihi hari tersebut sudah mampu mempengaruhi bobot badan. ...
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Penggunaan Nimba sebagai tanaman obat perlu dikaji dengan lebih teliti karena memiliki beberapa senyawa yang bersifat toksik. Penelitian ini bertujuan untuk menguji pengaruh penggunaan ekstrak ethanol daun A. indica sebagai bahan obat herbal terhadap perubahan bobot badan mencit jantan. Ekstraksi daun Nimba dilakukan dengan teknik maserasi menggunakan ethanol 70%. Dua puluh empat mencit Swiss Webster jantan dewasa dengan usia 2.5 bulan digunakan sebagai hewan uji. Penelitian dilakukan menggunakan Rancangan Acak Lengkap, dengan empat perlakuan dan 6 ulangan. Perlakuan yang diberikan yaitu P0 (akuades), P1, P2, dan P3 berupa ekstrak ethanol daun Mimba dengan dosis 8, 11.2 dan 14 mg/kgBB/hari. Perlakuan diberikan secara oral selama 21 hari. Pengamatan bobot badan dilakukan pada awal perlakuan, dilanjutkan setiap tujuh hari. Konsumsi pakan diukur setiap tiga hari. Konsumsi minum diukur setiap hari. Data dianalisa dengan ANOVA dilanjutkan dengan uji DMRT. Hasil penelitian menunjukkan bahwa rerata bobot badan hewan uji pada akhir perlakuan adalah 36.62±3.52 untuk P0, 33.02±1.69 untuk P1, 32.40±2.89 untuk P2 dan 32.93±1.79 untuk P3. Bobot badan hewan uji kelompok kontrol menunjukkan perbedaan bermakna (p<0.05) dengan kelompok perlakuan P1, P2 dan P3. Konsumsi minum hewan uji kelompok kontrol menunjukkan perbedaan bermakna (p<0.05) dengan kelompok perlakuan P2 dan P3 tetapi konsumsi pakan menunjukkan perbedaan tidak bermakna (p>0.05). Dapat disimpulkan bahwa paparan ekstrak ethanol daun Nimba menyebabkan penurunan bobot badan hewan uji. Kata kunci: nimba, bobot badan, mencit
... Suryawanshi [17] states that Neem contains anti-fertility compounds which potentially active in male and female animals. The results of Bansal et al. [3] proves that the Neem oil dosage of 0.2mL/kg BW can be applied to adults. Neem has been used as plants that affect human fertility and proven to induce temporary sterility [18]. ...
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... With its extremely bitter properties, A. indica has been a corner stone of Ayurvedic therapy for pitas, or disorders caused by over eating sweets and in the treatment of diabetes [20]. According to Bansal et al. [21], the addition of sodium nimbidinate salt in aqueous form to semen of rat and human resulted in death of sperm in different percentages. Neem oil claimed spermicidal activity against rhesus monkey and human spermatozoa in in-vitro condition, and when the oil is used intra vaginally it prevented implantation and pregnancy in rats with concentration of 20 microlitre. ...
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