Content uploaded by Venkatachalam Karthikeyan
Author content
All content in this area was uploaded by Venkatachalam Karthikeyan on Jun 25, 2016
Content may be subject to copyright.
http://www.ijddhrjournal.com. (C)Int. J. of Drug Discovery & Herbal Research
766
INTERNATIONAL JOURNAL OF DRUG DISCOVERY AND HERBAL RESEARCH (IJDDHR)
4(4): Oct-Dec: (2014), 766-772
ISSN: 2231-6078
Abstract
Citrus aurantium L commonly called as bitter orange.
Economically, C.aurantium is of appreciable importance
as a source of edible fruit and is widely used in folk
medicines. The aim of the present review is to present
comprehensive information of the ethno medical
information, chemical constituents, biological and
pharmacological research on C. aurantium which will be
presented and critically evaluated. The close connection
between traditional and modern sources for ethno
pharmacological uses of C.aurantium is especially for
treatment against inflammation, malarial fever, diarrhoea,
digestive and fever. Essential oil from the whole plant,
flower and seeds has conclusively established their mode
of action in treatment of various diseases and other health
benefits. Strong interdisciplinary programmes that
incorporate conventional and new technologies will be
critical for the future development of C. aurantium as a
promising source of medicinal products. In the present
review, attempts on the important findings have been
made on whole plant, bark, flower, seed and root of C.
aurantium.
Key Words: Citrus aurantium, Rutaceae, Whole plant,
Root, Seed, Flower, Bark.
Introduction
Citrus aurantium commonly known as bitter orange is
widely and easily available plant belonging to the family
Rutaceae. The leaves, fruit, barks, flower and root are
used traditionally for the treatment of wide panel of
diseases. It is also known as sour orange, Seville orange,
bigarade orange [1]. Citrus aurantium (Khatta: Hindi,
Narangam, Narattai: Tamil) is a tree with greenish white,
glabrous shoots which cultivated in India for its fruit and
used for various medicinal purposes. Bitter orange is
regularly cultivated in Khasi hills and cacher. It is native
to southeastern Asia. It is 3rd most important fruit crop in
India. Its ethno-medicinal application has been well
known for a long time [2]. It is traditionally known to be
useful for the treatment of wide panel of diseases like
stomach ache, vomiting, blood pressure, cough, cold,
bronchitis, ear ache, dysentery, diarrhea, abdominal pain
and fever. Bark used for UTI ailments. Infusion of dried
flower is orally used for influenza, insomnia, as a
cardiovascular analeptic, anti spasmodic, for cold,
sedative, digestive. Root is used as treat boils and urinary
tract infections.
Flower is used as cardiovascular analeptic, sedative,
antispasmodic and digestive. This plant is much more
popular in India and widely cultivated. In India fruits used
for pickles. The economic aspect of this crop evidently
proved that as commercial crop. In fact the revenue
generated by this crop can be further magnified by many
folds, if its medicinal applications are scientifically
explored well. By a well coordinated effort, we can
exploit properly this plant. It may be further envisaged
that the revenue generated by this plant would easily
exceed that generated by any major crop of the country
even with a present level of traditional agro economic
practices. Though there is good level of traditional and
experimental evidences to support various claims and
advantages of this plant, still it needs proper evaluation
and exploitation.
The exceptional medicinal value of C.aurantium has long
been recognized and economically appreciable
importance as a source of edible fruit; the present review
assesses the potential of C.aurantium in relation to its
traditional uses and in terms of findings based on modern
bioscientific research. The link between conventional
remedies and recent research in various areas has been
well established in other plants [3, 4] which facilitate to
determine effective mode of action of plant derived
products. The present plant is known to contain several
pharmacological important biomolecules whose efficacy
is well established by several biochemical and
pharmacological studies. This review indents to compile
various studies on this plant and critically evaluates the
issues related to the ethno botanical, ethno medical and
ethno pharmacology of C.aurantium whole plant, seed,
root, bark and flower.
Taxonomy
Kingdom : Plantae
Division : Eudicots
Class : Rosids
Order : Sapindales
Family : Rutaceae
Genus : Citrus
Species : aurantium
Binomial name : Citrus aurantium L.
Botanical information [5]
Name of the plant : Citrus aurantium L.
Synonym : Bitter orange, Sour
.................orange, Seville orange, Bigarade orange
Citrus aurantium (Bitter Orange): A Review of its Traditional Uses, Phytochemistry
and Pharmacology
Karthikeyan V*1, Karthikeyan J 1
1,Department of Pharmacy, Cherraan’s Institute of Health Sciences, Coimbatore, Tamil Nadu.
*Corresponding Author
Email : karthikseera27@gmail.com
Mob. 918608001243
Review Article
http://www.ijddhrjournal.com. (C)Int. J. of Drug Discovery & Herbal Research
767
Karthikeyan et al.
INTERNATIONAL JOURNAL OF DRUG DISCOVERY AND HERBAL RESEARCH (IJDDHR)
4(4): Oct-Dec: (2014), 766-772
ISSN: 2231-6078
Vernacular names
Sanskrit : Brihatjambhira
Hindi : Khatta
Urudu : Nagorongo
Telugu : Mallikanarangi
Tamil : Narangam, Narattai
Kannada : Heralay
Malayalam : Karna
Plant description [6, 7]
A tree or rarely a shrub; young shoots glabrous, greenish
white. Leaves foliate; Leaflets 7.5-15cm. Long, elliptic or
ovate, obtuse, acute or acuminate; petioles naked or
winged, the wing often obovate and nearly as large as the
blade. Flower bisexual, pure white. Stamens 20-30. Fruit
is globose, generally oblate, not mamillate, usually
orange-coloured; rind loose or adherent; Pulp sweet,
yellow, rarely red.
History and Geographical distribution
Widely cultivated in India - said to be indigenous in the
Mothronwala Swamp Dehradun, Garhwal, Kumaon,
Sikkim, Khasia hills, Manipur mountain forests of the
Peninsula. It is growing in semi-wild state particularly in
the Naga and Khasi hills.
The sour orange is native of south eastern Asia. Natives
of the South Sea Islands, especially Fiji, Samoa, and
Guam, believe the tree to have been brought to their
shores in the prehistoric period. Arabs are thought to have
been carried it to Arabia in the 9th Century. It was
reported that to be growing in the Sicily in 1002 A.D and
it was cultivated around Seville, Spain, in the end of 12th
Century. For 500 years, it was the only orange in Europe,
and it was the first orange to reach to the New World. It
was naturalized in Mexico by 1568 and in the Brazil by
1587, and not long after it was running wild in Cape
Verde Islands, Bermuda, Jamaica, Puerto Rico and
Barbados. Sir Walter Raleigh has taken sour orange seeds
to England; they were planted in the Surrey and the trees
began bearing regular crops in 1595, but were killed by
cold in 1739.
Spaniards were introduced the sour orange into St.
Augustine, Florida. It was quickly accepted by the early
settlers and local Indians in the 1763, sour oranges were
being exported from the St. Augustine to England.
Cultivation
Area and production
Citrus is the 3rd most important fruit crop in India and the
area under its cultivation is estimated at 2.4 lakhs hectares
with a production of 19 lakhs tones. It occupies about 9%
of the area under fruit cultivation. With regard to
production of citrus fruits, India occupies a significant
position in the world productivity. India’s orange (sweet,
mandarin and sour) production amounts to15% of the
orange production in Asia, next only to China. The major
citrus producing states, viz. Andhra Pradesh, Bihar,
Gujarat, Maharashtra, Punjab, Tamil Nadu and Madhya
Pradesh contribute 82 % of the total citrus production in
India with Andhra Pradesh leading with a contribution of
39%.
Climate
Citrus crop thrives well in frost-free sub-tropical to semi-
tropical climate. However, most of the species tolerate
light frost. Being evergreen, it has no specific requirement
of winter chilling but cessation of growth during winter
helps in flower bud induction resulting in spring
flowering. Best growth occurs within 29-35°C. An annual
rainfall of 700 mm is sufficient if it is well-distributed.
Unevenly distributed rainfall can be supplemented by
irrigation and best quality fruits are obtained in semi-arid,
sub-tropical regions.
Soil
Citrus thrives well in deep, loose, well-aerated soils
devoid of any hard pan of calcium carbonate in the
rooting zone. The ideal soil pH is 5.5 to 7.5 but with
proper management it can grow with success even in
highly acidic soils up to 4.5 and those containing free
lime with pH 8. The crop is highly sensitive to water-
logging in the root zone and is susceptible to salt injury;
hence it does not thrive in saline and alkaline soils.
Loamy soils with comparatively heavier sub-soils or even
heavy soils with good drainage are ideal for the crop.
Propagation
Citrus trees are propagated both by seed and vegetative
means. Vegetative propagation is preferred because it
ensures true to type plants, uniform quality, regular
bearing, etc. Notwithstanding the merits of vegetative
propagation, seed propagation is still in vogue in the case
of certain citrus species. Many citrus species can be raised
from cutting when they are desired to be clonally
propagated on their own roots. A large number of graft
compatible species and varieties are available in India.
Seed Propagation
It requires collection of seed from fruits of healthy, virus-
free old trees which have a good pedigree performance.
The extracted seeds are mixed with ash and dried in the
shade. The nursery is located away from old existing
orchards to reduce the hazards of pests. Soil which is free
of soil-borne pathogens and nematodes is selected and
properly fertilized with adequate organic manures and
laid out into beds of convenient size. Bold seeds collected
from desired trees are treated with fungicides before
sowing to prevent seed-borne infections. The seeds have
no dormancy and are sown immediately after extraction;
treating them with IAA (100ppm) improves germination.
Sowing is done in May-June or September-October in
Southern and Western India, in spring or rainy season in
Northern India and in July-August in Assam. The seeds
are sown 2-3cm deep in lines 8-25 cm apart.
http://www.ijddhrjournal.com. (C)Int. J. of Drug Discovery & Herbal Research
768
Karthikeyan et al.
INTERNATIONAL JOURNAL OF DRUG DISCOVERY AND HERBAL RESEARCH (IJDDHR)
4(4): Oct-Dec: (2014), 766-772
ISSN: 2231-6078
Planting
Planting of seedlings or budding in orchards is usually
done after the initial rains. Pits of 50-75 cm are dug in a
square system 5-8 m apart in summer. The soil is replaced
after adding to it about 40kg of farmyard manure.
Irrigation
Citrus requires irrigation in places where the annual
rainfall is below 890 mm. The trees are sensitive to
excessive moisture and water-logging, and moisture stress
is avoided during growth period and in flowering and
fruiting as it reduces the fruit size. The soil is allowed to
dry out only during spring and summer months but
wilting is avoided. Irrigations absolutely essential tlll the
fruits attain 2 cm diameter.
Manures and Fertilizers
Nutrients
Quantity/hectare
Nitrogen
21Kg
Phosphorus
5 Kg
Potassium
41 Kg
Calcium
19 Kg
Magnesium
3.6 Kg
Sulphur
3 Kg
Copper
9 g
Iron
50 g
Manganese and Zinc
13 g
Interculture
Interculture is chiefly done to remove weeds which
compete with the trees for moisture and nutrients, and for
incorporating manure.
Harvesting and yield
Harvesting is done in most of the citrus species the fruits
remain fresh for several weeks in the tree without any
deterioration after attaining fruit maturity. They do not
improve their quality after harvest, and are, therefore,
harvested when fully riped citrus fruits are considered
fully mature for harvesting when they turn from green to
golden yellow even tough colour break is not reliable
index of fruit maturity.
Storage
Citrus fruits can be stored well for a few days at room
temperature and in cold storage for several months
without any appreciable depreciation in quality.
Ethno medical Information
Plant orally used for fever, epilepsy, emotional shock,
cold, rheumatism, digestive and gall bladder problems,
hepatic disorder, in food preparation and externally used
for skin blemishes, externally and internally for bruising
in Haiti [8]. Hot aqueous extract of dried plants orally used
for malaria in Sudan [9]. Hot aqueous extract of entire
plants orally used for menorrhagia in India [10]. Juice of
branches orally used to treat convulsions in children in
Cook Island, the scraped branches of the Citrus and
Psidium guajava are squeezed through cloth in to water to
treat convulsion in children, the medicine is considered
best prepared at the time of a full or new moon, but not
between a breast feeding baby and mother drink a
sweetened solution once. Other fits and convulsions use
the scraped bark of new shoots with the Guava bark. The
solution is given daily for three days and repeated in a
month. Effects described are from a multi-component
remedy. Decoction of fresh branches used orally to treat
Gonorrhea in Cook Island. Gonorrhea may be treated with
the following medicine scraped bark with two ripe and
unripe Morinda citrifolia fruits are pounded a tablespoon
measure of powdered Piper methysticum are mixed,
squeezed through a cloth into half a gallon of water and
boiled. The cooled solution is drunk daily for two days.
Effects described are from a multi-component remedy [11].
Branches used for vomiting by oral route in Mexico.
Branches used for stomach ache by oral route in Mexico
[12].
Phytochemical studies
Dried whole plant contains Isoquinoline alkaloid-
Synephrine, 5-methyl tyramine was reported in China [13].
Alkaloid- Diphenylamine confirmed in whole plant
extract by chromatographic method [14] and Triterpene -
Limonin, Nomilin was isolated in Sudan [9].
Essential oil review
Monoterpene- Limonene was found to be main
constituents of essential oil of C.aurantium whole plant
[15, 16] and Sesquiterpene- α-Bergamotene, β-Bisabolene,
β-Caryophyllene were reported as constituents of EO [17].
Monoterpene- Linalool, Linalool acetate [18] and Alkaloid-
3-(but-cis-1-enyl) pyridine is present in commercial
sample of essential oil [19] were reported.
Pharmacological studies
Laxative
Decoction of mixture of rheum species, Mangolia
officinalis and Citrus aurantium screened for laxative
effect in China [20]. It is active. Effects described are from
a multi-component prescription.
Antiulcer Activity
Aqueous extract of plant screened for antiulcer activity in
rat and found inactive against Hcl/Ethanol induced gastric
ulcers at 500mg/kg dose [21].
Neuraminidase Inhibition Activity
Methanol extract of whole plant screened for
neuraminidase inhibition activity and found active at
1ppm concentration [22].
Whole plant Essential oil
Antifungal Activity
Essential oil screened in Paraguay for antifungal activity
(plant pathogens) by agar plate method. It is active against
Polyporus versicolor, Lentinus lepideus and Lenzites
trabea [23]. Essential oil screened in Egypt for antifungal
activity in agar plate method and found inactive against
Trichoderma viride, P.cyclopium [24].
http://www.ijddhrjournal.com. (C)Int. J. of Drug Discovery & Herbal Research
769
Karthikeyan et al.
INTERNATIONAL JOURNAL OF DRUG DISCOVERY AND HERBAL RESEARCH (IJDDHR)
4(4): Oct-Dec: (2014), 766-772
ISSN: 2231-6078
Antibacterial Activity
Essential oil screened for antibacterial activity in Egypt
by agar plate method and found active against S. aureus,
P.aeruginosa and inactive against E.coli, B.areus [24].
Essential oil screened in Thailand for antibacterial activity
in agar plate method and found that active against S.
pyogenes and S. aureus [25].
Antiyeast activity
Commercial sample of essential oil screened in Australia
for antiyeast activity in agar plate method 0.25% found
active against C. albicans [26].
Smooth Muscle Relaxant activity
Essential oil of plant screened for smooth muscle relaxant
activity and found active in guinea pig trachea at ED50
64mg/liter dose and also found inactive in guinea pig
ileum at 100mg/liter [27].
Insect Repellent Activity
Essential oil screened in India for insect repellent activity
in Apis florae. It is active in 0.0125% by Olfactometer
test [28].
Antiulcer Activity
Essential oil screened for glutathione-S-transferase
induction in mouse liver. Dose of 30mg/animal given by
intragastric route every 2 days for total of 3 doses is
inactive in ulcer in liver, stomach and small intestine [29].
Anti tumor Activity
Essential oil screened for tumor promotion inhibition in
rat. Dose 1% of diet is active in CA-mammary-DMBA [8].
Essential oil of plant screened for Glutathione-S-
transferase induction activity in mouse stomach, small
intestine, liver by intragastric route at dose 30mg/animal
and find inactive. Dose was given every 2 days for a total
of 3 doses [29].
Action on CNS
Essential oil of plant screened for tranquilizing effect in
mouse by inhibition (1.897mg/L) and found active.
Greatest activity was seen within 30 minutes of dosing.
Air concentration of compound at end of exposure of
1hour was given [30]. Essential oil screened in Yugoslavia
for CNS depressant activity by using gold fish externally
used and found that it is inactive [31].
STEM PITH
Immunosuppressant Activity
Aqueous extract of dried stem pith screened for
immunosuppressant activity in mouse by intra gastric
route (500mg/kg) and found active against con-A induced
proliferation in thymocytes, also active against LPS
induced proliferation in splenocytes [32]. Statistical data in
report indicate significant results.
Nitric Oxide Synthesis activity
Aqueous extract of dried stem pith screened for nitric
oxide synthesis stimulation activity and found inactive in
macrophages and inactive against LPS induced
proliferation in macrophages with gamma interferon [32].
Statistical data in report indicate significant results.
BARK REVIEW
Ethno medical information
Dried bark is boiled and used for urinary tract ailments by
oral route in Cook Islands [33].
Phytochemical studies
Fungus infected bark contains coumarin- Scoporane in
Israel were reported [34, 35].
Pharmacological studies
Cytotoxic Activity
Aqueous and methanolic extract of dried bark screened in
Japan for cytotoxic activity (5%) by cylinder plate method
and found equivocal against CA-Ehrlich-Ascites and
inhibition is found to be 28 mm and 27 mm for respective
extracts [36]. Methanolic and Acetone extract of dried bark
screened in Japan for cytotoxic activity by cylinder plate
method and found equivocal in CA-Ehrlich-Ascites and
inhibition is found to be 27 mm and 30 mm for respective
extracts [36].
FLOWER REVIEW
Ethno medical information
Infusion of dried flower of C.aurantium var amara orally
used for influenza, insomnia and as a tranquilizer in
Canary Islands [37]. Extract of dried flowers of
C.aurantium var amara orally used as a cardiovascular
analeptic in Tunisia [38]. Infusion of dried flower orally
used for cold and antispasmodic in Brazil [39]. Infusion of
flower and leaf were used orally as a sedative and
digestive in Italy [40]. Infusion of dried flowers orally used
as a digestive in Spain [41].
Phytochemical studies
Dried flower contains Steroid- Desmosterol, Ergosterol,
β-Sitosterol, Stigmasterol and ‘O’ Saponins (unspecified
type or hemolytic absent) [42]. Alkaloid- caffeine was
reported in dried flower extract [43]. Flower essential oil
contains Monoterpene- -limonene, Linalool, Linalool
acetate [44].
Pharmacological studies
Anti amoebic Activity
Essential oil of flower screened (1.0µl/ml) for anti
amoebic activity in Broth culture method and found active
against Entamoeba histolytica [45].
SEED REVIEW
Pharmacological studies
Cytotoxic Activity
Aqueous extract of dried seed screened in China for
cytotoxic activity by cell culture method (500mcg/ml) and
found inactive in human embryonic cells HE-1 and weak
activity in CA-mammary micro alveolar [46].
Antigen Activation Activity
Hexane and 95% ethanolic extract of dried seed screened
in Japan for Epstein-Barr virus early antigen activation
inhibition activity (10µg/ml) by cell culture method and
found inactive against 12-O-tetradecanoylphorbol-13-
acetate (TPA) induced carcinogenesis in lymphoblasts
human [47].
http://www.ijddhrjournal.com. (C)Int. J. of Drug Discovery & Herbal Research
770
Karthikeyan et al.
INTERNATIONAL JOURNAL OF DRUG DISCOVERY AND HERBAL RESEARCH (IJDDHR)
4(4): Oct-Dec: (2014), 766-772
ISSN: 2231-6078
Antimicrobial Activity
Oil of dried seed screened for antibacterial, antifungal,
antiyeast activity by agar plate method (10mg/ml) and
found inactive against S. viridans, Diplococcus
pneumoniae, C. diphtheriae, S. aureus, Streptococcus
pyogenes, Piedraia hortae, Microsporum canis,
Microsporus gypseum, Trichophyton mentagrophytes,
Phialophora jeanselmei, Candida albicans, Candida
tropicalis and also screened for anthelmintic activity and
found inactive against Anthelmintic parasite [48].
Phytochemical studies
Triterpene - Limonin, Nomilin, Deacetyl nomilin,
Obacunone was reported in seed extract [49], Triterpene –
Ichangin-17- β-D-glucoside, Isolimonic acid, β-D-
Glucoside, Limonin-17-o- β- D-glucoside, Deacetyl
nomilin-17-o-β-D-glucoside, Nomilin-17- β-D-glucoside,
Deacetyl nomilinic acid-17- β-D-glucoside, Deacetyl
nomilinic acid-19-(OH)-17-β-D-glucoside, Nomilinic acid
-17- β-D-glucoside, Obacunone-17- β-D-glucoside was
reported earlier [50]. Triterpene- Ichangin, Isolimonic
acid, Limonin, Nomilin, Nomilin glycoside, Deacetyl
nomilin, Nomilinic acid, 19-(OH) deacetyl nomilinic acid
aglycone, Deacetyl nomilinic acid, Obacunone Nomilinic
acid was present in seed extract [51]. Triterpene- Ichangin,
Isolimonic acid, Nomilinic acid, Deacetyl nomilinic acid
was found to be important constituents in other study [52].
Seed extract contains Triterpene- Limonin, Deacetyl
nomilin [53].
ROOT REVIEW
Ethno medical information
Extract of dried root and fruit of C aurantium aff are
orally used for polio in Tanzania. Aqueous extract of
dried root of C.aurantium aff orally used for stomach
upset in Tanzania [54]. Decoction of dried root, fruit and
leaf are orally used for fever, hypertension, diarrhea,
ulcers and digestive for stomach ache in Nicaragua [55].
Pharmacological studies
Protein Binding Activity
Dichloromethane extract of dried root screened in France
for P-glycoprotein binding activity and found active in
erythroleukemia (K562) [56].
Mutagenesis
Dried root screened in France for multi drug resistance
efflux pump inhibition by cell culture method
(017.5µg/ml) and found active in erythroleukemia (K562)
against DMBA induced mutagenesis [56].
Phytochemical studies
Fresh root contains Coumarin- Seselin was reported [57].
Dried fruit + leaf + root contain ‘O’alkaloid [58].
Coumarin- Braylin, Geranyl-oxy pyranocoumarin,
Seselin, Suberosin, Xanthoxyletin, Xanthyletin was
isolated from root extract [59].
Conclusion
The present review discusses the significance of
C.aurantium as a valuable source for medicinally
important compounds besides its edible fruit which is a
store house of minerals, vitamins, antioxidants and other
nutrients. Correlation between the ethno medical
employment and the pharmacological activities has been
duly observed and described in the present review.
There is a need to minimize the gap between the studies
conducted so far and to exploit fully medicinal properties
of C.aurantium. However, there is a need to study the
acute toxicity, sub acute toxicity, chronic toxicity and
pharmacological safety profiling of plants. Detailed
animal acute and chronic toxicity studies of compounds
are required prior to clinical testing.
Two goals seem to be largely open for future exploitation.
First, once the accurate and precise chemical composition
of these compounds is known, will lead further studies to
understand metabolic pathways of these useful products,
and second, understanding metabolic engineering will
enhance the synthesis and accumulation of these
compounds considerably.
C.aurantium is a very important part of biodiversity and
it’s sustainably use for future generations. The bitter
orange plant still is a rather an untapped source for
isolation and characterization of novel useful products;
however, at the same time it also opens up new avenues
for novel therapeutics for fighting against dreadful
disease.
References
1. Periyanayagam K., Dhanalakshmi S. and Karthikeyan
V. (2013). Pharmacognostical, SEM and EDAX profile
of the leaves of Citrus aurantium L. (Rutaceae).
Innovare Journal of Health sciences, 1(2): 1-5.
2. Periyanayagam K., Dhanalakshmi S., Karthikeyan V.
and Jegadeesan S. (2013) Phytochemical studies and
GC/MS analysis on the isolated essential oil from the
leaves of Citrus aurantium Linn. Journal of Natural
products Plant Resources, 3(6): 19-23.
3. Gutierrez R.M.P., Mitchell S. and Solis R.V. (2008).
Psidium guajava: a review of its traditional uses,
phytochemistry and pharmacology. J Ethnopharmacol,
117: 1-27.
4. Jagtap U.B. and Bapat V.A. (2010). Artocarpus: A
review of its traditional uses, phytochemistry and
pharmacology. J Ethnopharmacol, 129:142-166.
5. Anonymous. (2005). Wealth of India Raw materials.
Ca-Ci, Vol III, New Delhi: National Institute of Science
Communication and Information Resources
(NISCAIR), CSIR.
6. Anonymous. (2001). The Ayurvedic Pharmacopoeia of
India. Part I, Ist edn, Vol 1, Government of India;
Ministry of Health and Family Welfare, Indian Systems
of Medicine and Homeopathy: 140-145.
7. Kirtikar K.R. and Basu B.D. (1998). Indian Medicinal
Plants. 2nd ed, Vol. I: Bishen Singh Mahendra Pal Singh,
Dehradun.
http://www.ijddhrjournal.com. (C)Int. J. of Drug Discovery & Herbal Research
771
Karthikeyan et al.
INTERNATIONAL JOURNAL OF DRUG DISCOVERY AND HERBAL RESEARCH (IJDDHR)
4(4): Oct-Dec: (2014), 766-772
ISSN: 2231-6078
8. Paul A., and Cox P.A. (1995). An ethno botanical survey
of the uses for Citrus aurantiun (Rutaceae) in Haiti. Econ
Bot, 49(3): 249-256.
9. Khalid S.D., Farouk A., Geary T.G. and Jensen J.B.
(1986). Potential antimalarial candidates from African
plant an in vitro approach using Plasmodium Falciparum.
J Ethnopharmacol, 15(2): 201-209.
10. Jain S.K. and Tarafder C.R. (1970). Medicinal plant-lore
of the santals. Econ Bot, 24: 241-278.
11. Holdsworth D.K. (1990). Traditional medicinal plants of
Rarotonga, Cook Islands part I. Int Crude Drug Res,
28(3): 209-218.
12. Dimayuga R.E., Urgen M. and Ochoa N. (1998).
Antimicrobial activity of medicinal plants from Baja
California sur (Mexico). Journal of Pharmaceutical
Biology, 36(1): 33-43.
13. Guo Z. (1983). Effect of Zhi-shi (Citrus aurantium) and
its active principles on the contractility and automaticity
of CAT papillary muscle in endotoxin shock. Hu-nan I
Hsueh Yuan Hsueh Pao 8(3): 267-271.
14. Karawva M.S., Khayyal S.E., Farrag N.M. and Ayad
M.M. (1986). Screening of diphenylamine as an
antihyperglycemic in certain edible plant organs. Egypt J
Pharm Sci, 25(1/2/3): 21-25.
15. Russin W.A. and Gould M.N. (1988). Cancer chemo
preventive effects of terpene components of orange oil.
Amer J Bot, 75(6): 133.
16. Pino J.A. and Rosado A. (2000). Composition of cold-
pressed bitter orange oil from Cuba. J Essent Oil Res,
12(6): 675-676.
17. Burk L.A. and Chung L.Y. (1992). The stereo structure of
Bisabolene tri hydro chloride. J Nat Prod, 55(9): 1336-
1338.
18. Hanneguelle S., Thibault J.N., Naulet N. and Martin G.J.
(1992). Authentication of essential oils containing linalool
and linalyl acetate by isotopic methods. J Agr Food
Chem, 40(1): 81-87.
19. Maurcer B. and Hauser A. (1992). New pyridine
derivatives from essential oils. Chimia, 46(4): 93-95.
20. Gu W., Bai Y., Li Z., Zhang Y., Tian L.I. and Tian F et
al. (1985). Effect of different decocting methods on the
extract contents of Rhubarb Anthraquinone in DA cheng
QI Tang and its pharmacological effect. Chung Tsao Yao,
16(1): 8-11.
21. Jeong C.S., Kyun J.E., Kang M.H., Kim H.P., Park J.M.
and Lee S.Y. (2002). Anti gastric and anti-ulcerative
effect of P020701. Korean J Pharmacog, 33(4): 389-394.
22. Lee C.H., Kim S.I., Lee K.B., Yoo Y.C., Ryu S.Y. and
Song K.S. (2003). Neuraminidase inhibitors from
Reynoutria elliptica. Arch Pharma Res, 26(5): 367-374.
23. Maruzzella J.C., Scrandis D., Scrandis J.B. and Grabon G.
(1960). Action of odoriferous organic chemicals and essential
oils on wood-destroying fungi. Plant Dis Rept, 44:789-792.
24. Ross S.A., El-keltawi N.E. and Megalla S.E. (1980).
Antimicrobial activity of some egyptian aromatic plants.
Fitoterapia, 51: 201-205.
25. Roengsumran S., Petsom A., Thanivanvarn S.,
Pornpakakul S. and Khantahiran S. (1997).
Antibacterial activity of some essential oils. J Sci Res
Chulalongkorn Univ, 22(1): 13-19.
26. Hammer K.A., Carson C.F. and Riley T.V. (1998). In-
vitro activity of essential oils, in particular Nelaleuca
alternifolia (Tea-tree) oil and tea tree oil products
against Candida SPP. J Antimicrob Chem Ther, 42(5):
591-595.
27. Reiter M. and Branat W. (1985). Relaxant effects on
tracheal and illeal smooth muscles of the guinea pig.
Arzneim-Forsch, 35(1): 408-414.
28. Gupta M. (1987). Essential oils: A new source of bee
repellents. Chem & Indust, 6: 161-163.
29. Lam L.K.T. and Zheng B.L. (1991). Effects of essential
oils on Glutathione S-tranferase activity in mice. J Agr
Food Chem, 39(4): 660-662.
30. Jager W., Buchbarer G., Jirovetz l., Dietrich H. and
Plank C. (1992). Evidence of the sedative effect of
neroli oil, citronellal and phenyethyl acetate on mice. J
Essent Oil Res, 4(4): 387-394.
31. Wesley-Hadzija B. and Bohing P. (1956). Influence of
some essential oils on the central nervous system of
fish. Ann Pharm Fr, 14: 283.
32. Yul J.Y. and Eun J.S. (1998). Effect of Aurantii nobilis
Pericarpium and Aurantii immaturi Pericarpium on
Immunocytes in Mice. Korean J Pharmacy, 29(3): 173-
178.
33. Whistler W.A. (1985). Traditional and herbal medicine
in the Cook Islands. J Ethnopharmacol, 13(3): 239-280.
34. Afek U., Sztejnberg A. and Crmely S. (1986). 6, 7-
Dimethoxy coumarin, a citrus phytoalexin conferring
resistance against phytophthora gummosis.
Phytochemistry, 25(8): 1855-1856.
35. Afek U. and Sztejnberg A. (1988). Accumulation OS
Scoparone, a phytoalexin associated with resistance of
citrus to phytophthora citrophthora. Phytopathology,
78(12): 1678-1682.
36. Veki H., Kaibara M., Sakagawa M. and Hayashi S.
(1961). Anti-tumor activity of plant constituents I.
Yakugaku zasshi, 81: 1641-1644.
37. Darias V., Bravo L., Barquin E., Herrera D.M. and
Fraile C. (1986). Contribution to the ethno
pharmacological study of the Canary Islands. J
Ethnopharmacol, 15(2): 169-193.
38. Boukef K., Souissi H.R., and Balansard G. (1982).
Contribution to the study of plants used in traditional
medicine in Tunisia. Plant Med Phytother, 16(4): 260-
279.
39. Elisabetsky E. and Eastilhos Z.C. (1990). Plants used as
Analgesics by Amazonian carboclos as a basis for
selecting plants for investigation. Int J Crude Drug Res,
28(4): 309-320.
40. De-feo V. and Senatore F. (1993). Medicinal plants and
phytotheraphy in the Amalfitan coast, Salerno province,
Campania, Southern Italy. J Ethnopharmacol, 39(1): 39-51.
http://www.ijddhrjournal.com. (C)Int. J. of Drug Discovery & Herbal Research
772
Karthikeyan et al.
INTERNATIONAL JOURNAL OF DRUG DISCOVERY AND HERBAL RESEARCH (IJDDHR)
4(4): Oct-Dec: (2014), 766-772
ISSN: 2231-6078
41. Vazquez F.M., Sauarez M.A and Perez A. (1997).
Medicinal plants used in the Barros area, Badajoz
province (Spain). J Ethnopharmacol, 44(2): 81-85.
42. Moursi S.A.H., Al-Khatib M.H. and Al-Shabibi M.M.
(1980). Phytochemical investigation of the flowers of
Citrus aurantium. Fitoterapia, 51: 207-209.
43. Stewart I. (1985). Identification of Caffeine in Citrus
flowers and leaves. J Agr food Chem, 33(6): 1163-1165.
44. Ma L.A., Zheng Y.Q., Sun Y., Liu M.X. and Wu. Z.P.
(1988). Aroma volatile constituents of Citrus aurantium
var anara Engl. Beijing Daxue Xuebao Ziran Kexueban,
24(6): 687-694.
45. De blasi V., Debrot S., Menoud P.A., Gendre L. and
Schowing J. (1990). Amoebicidal effect of essential oils
in vitro. J Toxicol Clin Exp, 10(6): 361-373.
46. Sato A. (1989). Studies on anti-tumor activity of crude
drugs 1. The effects of aqueous extracts of some crude
drugs in shorterm screening test. Yakugaku Zasshi,
109(6): 407-423.
47. Iwase Y., Takemura Y., Ju-ichi M., Kawaii S., Yano M.
and Okuda Y. et al. (1999). Inhibitory effect of Epstein-
Barr virus activation by Citrus fruits, a cancer
chemopreventor. Cancer Lett, 139(2): 227-236.
48. Naovi S.A.H., Khan M.S.Y. and Vohora S.B. (1991).
Anti-bacterial, Anti-fungal and Anthelmintic
investigations on Indian medicinal plants. Fitoterapia,
62(3): 221-228.
49. Rouseff R.L. and Nagy S. (1982). Distribution of
limonoids in Citrus seeds. Phytochemistry, 21: 85-90.
50. Benneh R.D., Miyake M., Ozaki Y. and Hasegawa S.
(1991). Limonoid Glucosides in Citrus aurantium.
Phytochemistry, 30(11): 3803-3805.
51. Miyake M., Ayano S., Ozaki Y., Herman Z. and
Hasegawa S. (1992). Limonoids in seeds of sour orange
(Citrus aurantium). Nippon Nogei Kagatu Kaishi, 66(1):
31-34.
52. Benneh R.D. and Hasegawa S. (1980). Isolimonic acid, a
new citrus limonoid. Phytochemistry, 19; 2417-2419.
53. Dreyer D.L. (1966). Citrus bitter principles V. Botanical
distribution and chemotaxonomy in the rutaceae.
Phytochemistry, 5: 367-378.
54. Hedberg I., Hedberg O., Madati P.J., Mshigeni K.E.,
Mshiu E.N. and Samuwlssom G. (1983). Inventory of
plants used in traditional medicine in Tanzania. Part III.
Plants of the families Papilionaceae-Vitaceae. J
Ethnopharmacol, 9(2/3): 237-260.
55. Coee F.G. and Anderson G.J. (1996). Ethno botany of the
garifuna of Eastern Vicaragua. Econ Bot, 50(1): 71-107.
56. Simon P.W., Chaboud A., Darbour N., Dipletro A.,
Dumonter C., Raynaud J. and Barron D. (2003). The two-
complementary method assay for screening new reversal
agents of cancer cell multidrug resistance. Pharmaceutical
Biol, 41(1): 72-77.
57. Tomer E., Goren R. and Monselise S.P. (1969). Isolation
and Identification of Seselin in Citrus roots.
Phytochemistry, 8: 1315-1316.
58. Coe F.G. and Amderson G.J. (1996). Screening of
medicinal plants used by the Garifuna of Eastern
Nicaragua for Bioactive compounds. J Ethnopharmacol,
53: 29-50.
59. Nordbyhe. And Nagy S. (1981). Chemotaxonomic study
of neutral coumarins in roots of Citrus and poncirus by
Thin-layer, Gas-liquid and High performance liquid
chromatographic analysis. J Chromatogr A, 207: 21-28.
