PHARMACOLOGICAL SCREENING OF EUPHORBIA NERIIFOLIA LEAF HYDROALCOHOLIC EXTRACT
Papiya Bigoniya1, A.C. Rana2
1. Radharaman College of Pharmacy, Radharaman Group of Institutes, Ratibad, Bhopal-02, M.P., India 2. Rayat College of Pharmacy, Rail Majra, Ropar-144553, Punjab, India
Keywords: Pharmacological screening of Euphorbia neriifolia Linn. (Euphorbiaceous) leaf hydro alcoholic extract were performed to explore the analgesic, anti-inflammatory, diuretic, antidiarrhoeal and antiulcer activities. All tests were conducted on rats using 100, 200 and 400 mg/kg dose as LD50 of extract was found to 2779.71 mg/kg. Study revealed strong analgesic effect of E. neriifolia against thermal (P<0.001), and in mechanical and chemical (p < 0.01) noxious stimuli and anti-inflammatory activity (P<0.001 to 0.01) at the 1000 mg/kg dose. In carrageenan-induced paw edema and cotton pellet induced granuloma model E. neriifolia extract showed significant (P<0.001 to 0.01) antiinflammatory activity. Extract considerably increases urine volume as an effective hypernatraemic and hyperchloraemic diuretic. E. neriifolia showed laxative property by increasing wet defecation along with castor oil. Extract showed very prominent protection against ethanol-induced ulceration as well as on pyloric ligated ulceration in dose dependent manner. Extract increases total hexoses (P<0.001), hexosamine (P<0.05), sialic acid and total carbohydrate content (P<0.001) with a decrease in total protein content (P<0.001) of gastric mucosa at 400 mg/kg dose. Presence of phytoconstituents like tannins, flavonoids, alkaloids and triterpenoidal saponins may be responsible for the found pharmacological activities.
Abstract

Euphorbia neriifolia, analgesic, anti-inflammatory, diuretic, laxative, antiulcer

Article Information

Identifiers and Pagination:
Year:2010
Volume:2
First Page:1
Last Page:17
Publisher Id:JAppPharm (2010 ). 2. 1-17
Article History:
Received:September 2009
Accepted:December 4, 2009
Collection year:2009
First Published:January 13, 2010

INTRODUCTION
From prehistoric times, various communities and civilizations throughout the world are using herbal
medicines. For the past several decades, people are increasingly consuming herbal medicines without
prescription. They are traditionally considered as harmless since they belong to natural sources. Herbal
formulations have reached widespread acceptability as therapeutic agents like anti-diabetics, anti-arthritics,
aphrodisiacs, hepatoprotective, cough remedies, memory enhancers and adaptogens. Euphorbia neriifolia
Linn. (Euphorbiaceous) was selected for the present study considering its use in traditional medicine
thorough literature search to find out scientific basis of the claimed therapeutic potentials.
There are over 1500 species of Euphorbias in the world ranging from annual weeds to trees. E. neriifolia
grows luxuriously around the dry, rocky, hilly areas of North, Central and South India. It is an herb full of
spine, popularly known as ‘sehund’ or ‘thohar’ in Hindi. Leaves are thick succulent, 6-12 inch long, ovular
in shape. In traditional system, leaves are used as aphrodisiac, diuretic, cough and cold, bleeding piles and
in ano-rectal fistula (1). The tribal population of Chhattisgarh region uses the milky latex as an ingredient
of aphrodisiac mixture. Latex is used to de-root skin warts, earache and in arthritis. Plant is bitter, laxative,
carminative, improves appetite, useful in abdominal troubles, bronchitis, tumors, leucoderma, piles,
inflammation, enlargement of spleen, anemia, ulcers, fever, and in chronic respiratory troubles (2). Natives
of Chhattisgarh use externally boiled ‘thohar’ milk in castor oil with salt to cure the deep cracks in soles of
legs. The milk of ‘thohar’ is also used commonly like aloe gel in case of burns. ‘thohar’ milk can be used
successfully for healing of wounds. Application of lukewarm ‘thohar’ leaves reduces itching pain and
swelling in piles (3).
Several triterpenoids like Glut-5-en-3ß-ol, Glut-5(10)-en-1-one, taraxerol and ß-amyrin has been isolated
from powdered plant, stem and leaves of E. neriifolia (4, 5). Antiquorin have been isolated from ethanol
extract of fresh root of E. neriifolia (6). Neriifolione, a triterpene and a new tetracyclic triterpene named as
nerifoliene along with euphol were isolated from the latex of E. neriifolia (7, 8).
E. neriifolia is easily available in large quantity in the dry hilly areas of North and Central India. This plant
can be used as a cheap source of active therapeutics as Propagation of these plants is easy and cheap which
can be grown in large number with very less expenses. E. neriifolia latex showed wound healing activity in
guinea pig by increasing epithelization, angiogenesis, tensile strength and DNA content in wounds (9). We
have already reported mild CNS depressant, wound healing and immunomodulatory activity of leaf hydroalcoholic
extract (10-13). Saponin separated from E. neriifolia leaf posses good hemolytic and in-vitro
antioxidant activity but it is devoid of antibacterial activity upto 10 mg/ml concentration containing euphol
as major constituent (14).
E. neriifolia have been widely used to treat a number of ailments in traditional system of medicine in north
and central India. Sufficient scientific data is not available to support these above said claims. Based on
literature information the present study was undertaken with the aim to confirm its uses in folklore
medicine as analgesic, anti-inflammatory, diuretic and ulcer protective.


MATERIAL AND METHODS
Collection and extraction of plant material
E. neriifolia leaves were collected from cultivation field hedge plants of suburban areas of Bhopal (latitude
23.21°, longitude 77.84°, BHOP), Madhya Pradesh, India, in September 2005. The plant was identified
with the help of available literature and authenticated by Dr. AP Shrivastava, taxonomist and Principal,
P.K.S Govt. Ayurveda College, Bhopal, India. A voucher specimen was deposited in the herbarium of
department (No. 1085).
The leaves were air dried under shade and milled into coarse powder, extracted in Soxhlet extractor
successively with different organic solvents such as petroleum ether (60–80°C), chloroform, acetone and
95% ethanol in increasing order of polarity. The marc was dried in hot air oven below 50°C before
extracting with next solvent. The extracts obtained with each solvent was distilled to remove 1/4th of
solvent then the extracts were dried using a vacuum oven below 30°C and percentage weight calculated in
terms of w/w. 95% ethanolic extract was dark brown in color and extractive value was 4.85 % (w/w) of the
dry weight of starting material. Presence of triterpenoidal steroids was confirmed by the Salkowski test and
Noller’s test (15). Presence of saponin was confirmed by Froth test and Hemolysis test (16). Presence of
flavonoids was confirmed by Shinoda test and Alkaline reagent test (16).
Test animals
Laboratory bred Wistar albino rats of both sexes (150 – 200 g) maintained under standard laboratory
conditions at 22 ± 2°C, relative humidity 50±15% and photoperiod (12-h dark and light), were used for the
experiment. Commercial pellet diet (Hindustan Lever, India) and water were provided ad libitum. In order
to avoid diurnal variation all the experiments were carried out at same time of the day i.e. between 10 a.m.
to 5 p.m. Approval was obtained from Institutional Animal Ethical Committee (approved body of
Committee for the Purpose of Control and Supervision of Experiments on Animals, Chenni, India) of
Radharaman College of Pharmacy, Bhopal, before carrying out the experiments and care provided to the
animal was as per the WHO ‘guidelines for the care and use of animals in scientific research.
Determination of LD50
Ld50 was determined according to the guidelines of Organization for Economic Co-operation &
Development (OECD) following the Up & Down method (OECD guideline No. 425) and Fixed dose
method (OECD guideline No. 420). Based on these agreements a Limit test was performed to categorize the
toxicity class of the compound and then Main test was performed to estimate the exact LD50 (Anonymous,
1992). The limit test was started from 2000 mg/kg dose. LD50 was found greater then the test dose so the
test substance could be classified in the hazard classification as class 5, 2000 mg/kg<LD50<5000 mg/kg in
the Globally Harmonized System (GSH) (17).
The suspension of the extract was prepared freshly with 2% carboxyl methyl cellulose (CMC). Animals
were divided into five groups of 6 rats each. Group 1 (vehicle control) was treated only with 2% CMC (0.5
ml/100gm). Group 2 animals were treated with standard drug as per the protocol of study design and group
3-5 with different doses of E. neriifolia leaf extract.
Thermal stimulus (Eddy’s hot plate method): Analgesia test was carried out by placing a rat on Eddy’s
hot plate (Techno, India) at 55±0.5°C for a maximum period of 30 sec. and noting the basal reaction time
i.e. licking front paws or making an effort to jump out of the chamber (18). Increase in reaction time after
drug administration against basal reaction time was noted in sec. Cut-off time of 30 sec. was selected to
avoid tissue damage. The percentage of pain inhibition after 60 minutes of drug treatment was calculated
according to the following formula (19).
Pain inhibition percentage (PIP) = (T1 - T0) / T0 × 100. T1 = Post drug latency (reaction time after drug
treatment) and T0 = Pre drug latency (basal reaction time).
Thermal stimulus (Tail flick method): Analgesia test was carried out by placing the tail tip (last 1-2 cm)
of rat on radiant heat of the Tail Flick analgesiometer (Techno, India) heated at 55±0.5°C for a maximum
period of 15 sec and noting the basal reaction time (flicking of tail). Increase in tail flick response 45 min
after drug treatment was noted and percentage increase in reaction time calculated (18).
Mechanical stimulus: Application of an arterial clip (with jaws covered by a rubber tubing) to the tail base
of the rat induces physical pressure due to compression and act as a mechanical stimulus. Attempt to
dislodge the clip (biting or kicking etc.) in <15 sec were considered as positive response (20). Failure of
such response in treated animals was taken as criteria for analgesia. Basal reaction time and reaction time
45 min after drug administration was noted and percentage increase in reaction time calculated.
Chemical stimulus: Writhing is defined as a stretch, torson or constriction of abdomen and extension or
drawing up of a hind leg etc, given the writhing agent, 3% aqueous acetic acid (2 ml/kg i.p). The writhing
episodes produced for 10 minutes after 30 minutes of administration of extracts or standard drug (aspirin,
100 mg/kg, p.o) were counted and percentage protection was calculated as shown below (20).
Percentage protection = (100 - no. of wriths in test / no. of wriths in control) × 100
Anti-inflammatory activity study
Carrageenan-induced rat hind paw edema: Inflammatory edema was produced by injecting 0.1 ml of
1% w/v carrageenan solution in normal saline beneath the sub-plantar surface of right hind paw of all the
animals. The volume of the paw before and three hr after carrageenan treatment was measured by mercury
displacement technique using plethysmometer and percentage inhibition calculated (21).
Cotton pellet induced granuloma: Sterilized pre weighed cotton pellets were implanted in both axillae
and groin regions through a single midline incision on the dorsal surface according to the method of
D’Arcy et al. (22) on rats anaesthetized with pentobarbitone sodium (30 mg/kg). Drugs were administered
3 h after implantation and continued for seven days. On the 8th day the pellets were dissected out, dried at
60°C the dry weights were determined. The difference between the initial and final weight of cotton pellet
was considered the weight of granulomatous tissue produced.
Diuretic activity
Urine output along with electrolyte concentration: Animals were deprived of food and water for 16
hours. All the rats received priming dose of normal saline 25 ml/kg orally. Immediately after administration
of vehicle, different doses of extract and standard drug frusemide (5 mg/kg, p.o) all the rats were placed in
metabolic cages (group wise) specially designed to separate urine and faeces at room temperature of
25±0.5°C (23). The urine was collected in measuring cylinder up to 5 h after drug administration. During
this period no food and water was made available to animals. Concentration of Na+ and K+ in urine was
measured by Flame photometer (Elico, India). Chloride ion concentration was estimated by titration with
silver nitrate solution (N/50) using 3 drops of potassium chromate solution as indicator (24).
Experimental Models for antidiarrheal study
Castor oil-induced diarrhea on rats: The method of Awouters et al. (25) was followed with minor
modification. 24 h fasted animals were treated with vehicle, standard drug (loperamide 0.5 mg/kg) and
different doses of extract. After 1 h, each animal received 1 ml of castor oil orally and was then observed
for defecation placing them in separate cages up to 6 h. The consistency and frequency of faecal matter,
and the number of respondents were noted on filter papers placed beneath the perforated metal cages.
Purging index (PI) was calculated as follows.
Purging index (PI) = % respondent x average no of stools/average latent period
Experimental Models for antiulcer study
Pyloric ligation-induced gastric ulceration: Under light ether anaesthesia, the abdomen was opened by a
small midline incision of 1 cm below the xiphoid process. Stomach was exposed and a tight knot was
applied around the pyloric sphincter. The stomach was placed carefully and abdomen wall closed by
interrupted sutures. Vehicle, ranitidine (20mg/kg) and test extract were administered orally 15 min before
pyloric ligation. After 4 hours animals were killed by decapitation, abdomen was opened and the stomach
was isolated after suturing the lowed esophageal end. The stomach was then cut open along the greater
curvature and ulcer index was determined using a hand lens. Gastric contents were collected in a graduated
centrifuge tube, volume measured, pH determined, centrifuged at 1000 RPM for 10 min and subjected to
biochemical analysis. Ulcer grading was determined following the scoring system suggested by (26).
Ulcer index = 10/X where, X = Total area of stomach mucosa / Total ulcerated area. (27).
Gastric contents (1ml diluted with 9 ml of D.W.) titrated against 0.01N NaOH using Toper’s reagent till
orange color, corresponds to free acidity and further titrated to pink color with phenolphthalein, total
volume of NaOH corresponds to total acidity (28).
Acidity expressed as Vol. of NaOH × Normality × 100 / 0.1 mEq/L/100g
Total hexose’s, fructose of the gastric juice was determined as per the method of Zachariah and Landrum
(29), hexosamine following Dische and Borenfreund (30), sialic acid by Warren (31). Total carbohydrate
(TC) measured as sum of hexose, fucose, hexosamine and sialic acid. The total protein content (PR) of the
gastric juice was also measured following method of Lowry et al. (32). The mucin activity measured as
total carbohydrate to protein ratio (TC/TP).
Ethanol-induced gastric ulceration: Animals were administered with test extract 45 min before oral dose
of absolute alcohol (1ml) (33). One hour after ethanol administration, animals were sacrificed by giving
overdose of ether. The stomach was removed, opened along the greater curvature, rinsed with normal saline
and scored for the severity of ulceration as mentioned earlier.
Statistical Analysis
Experimental data were analyzed using one way ANOVA followed by Turkey-Kramer multiple
comparison test. P value less than 0.05 were considered statistically significant. Graph Pad Prism Version
3.02 was used for statistical calculations.


RESULTS
E. neriifolia hydroalcoholic extract was found to contain sugar, tannins, flavonoids, alkaloids, triterpenoidal
saponin on preliminary phytochemical analysis. LD50 of E. neriifolia leaf extract was found to 2779.71
mg/kg from main test. A dose range of 100, 200 and 400 mg/kg was selected for pharmacological
screening.

rats
n = 6 per group. **P<0.01, ***P<0.001 and ns = not significant as compared to control values.
Aspirin and E. neriifolia (400 mg/kg) treatment showed 75.78% and 69.47% inhibition of edema
volume compared to vehicle control group.
E. neriifolia extract in 400 mg/kg dose showed 432.22% pain inhibition (P<0.001) in Eddy’s hot plate
method after 60 minutes of drug treatment. Increase in tail flick and tail clip response 45 min after drug
treatment was noted to be 416.36% (P<0.001) and 165.94% (P<0.01) respectively in 400 mg/kg dose. In
this same dose acetic acid induced writhing episodes protection was found to be 53.83% (P<0.01).

Figure III. Effect of E. neriifolia extract treatment on cotton pellet induced granuloma tissue
development in rats
n = 6 per group. *P<0.05, **P<0.01, ***P<0.001 and ns = not significant as compared to control
values. Diclofenac and E. neriifolia (400 mg/kg) treatment showed respectively 66.14% and 60.61%
inhibition in granulomatous tissue mass development compared to vehicle control group.
E. neriifolia extract produced dose dependent diuretic activity, onset of diuresis was extremely significant
at 400 mg/kg dose whereas increase in total volume of urine formed was extremely significant at both 200
and 400 mg/kg dose. Fifth hour urine volume for 400 mg/kg dose was 17.45 ml as compared to 6.65 ml of
control shown in Table 1. The electrolyte changes induced by the standard drug, vehicle and different doses
of extract are shown in Table 2.

E. neriifolia leaf extracts increased frequency of defecation also the number of wet and deformed feaces.
Extract increased purging index to 286.22 as compared to 201.63 of vehicle control and showed increase in
wet defecation. Although the tested doses of E. neriifolia leaf extract did not produce diarrhoea alone but
with castor oil, it produced diarrhoea, which was 20.29 % more than the castor oil alone (Table 3). E.
neriifolia leaf extract has not been tested for other parameters of antidiarrhoeal activity as it itself shows
laxative properties.

Purging index (PI) = % respondents × average no of stools / average latent period. % protection = C – T / C
× 100 (Mean no. of wet faeces). **P<0.01, ***P<0.001 and ns = not significant when compared to control
values.
E. neriifolia showed anti ulcer activity at 200 and 400 mg/kg dose. E. neriifolia reduced pH of gastric
content significantly both at 200 (P<0.05) and 400 (P<0.001) mg/kg dose. Volume of gastric content was
significantly (P<0.05) reduced only at 400 mg/kg dose. Reduction in free acidity, ulcer index and ulcer
grading was extremely significant (P<0.001) at 200 and 400 mg/kg dose although reduction in total acidity
was significant (P<0.01) only at 400 mg/kg dose. All the results were recorded in Table 4.
Table – 4 Effect of E. neriifolia extract treatment on secretory parameters and ulcer index in pyloric
ligated rats

Effect of E. neriifolia leaf extract on increase of total hexoses (P<0.001) and hexosamine (P<0.05) was
significant at 400 mg/kg dose but had no effect on fucose (P>0.05) content. Leaf extract increased sialic
acid at all the tested doses which was extremely significant (P<0.001) at 200 and 400 mg/kg dose and
increase in total carbohydrate content was extremely significant (P<0.001) at 400 mg/kg dose. Decrease in
total protein content was extremely significant (P<0.001) at 400 mg/kg dose as shown in Table 5.
E. neriifolia leaf extract decreased ulcer index, ulcer grading and free acidity on ethanol induced ulceration
which was extremely significant (P<0.001) at all the tested doses. Decrease in total acidity and volume of
gastric content was significant at 200 (P<0.05) and 400 (P<0.01 & 0.001) mg/kg dose respectively which is
reported in Table 6.
DISCUSSION
E. neriifolia showed excellent analgesic activity against thermal stimuli, moderate activity against
mechanical stimulus and less against chemical noxious stimuli. The hot plate model is commonly used to
assess analgesic activity of narcotic analgesics and other drugs such as sedative, hypnotics or
psychomimetic drugs, which act centrally (34). The abdominal writhing elicited by acetic acid has been
reported to be a very sensitive but less selective model that enables the detection of antinociceptive activity
of compounds in laboratory animals. Collier et al. (35) proposed that acetic acid acts indirectly by releasing
endogenous mediators, which stimulate neurons that are sensitive to other drugs such as narcotics and
centrally acting agents. The abdominal constriction response is thought to involve local peritoneal
responses. Several studies demonstrated that steroids produce antinociception when assessed in several
chemical models of nociception in animals, which might be true with extract due to presence of steroids
and alkaloids (36).
The psychopharmacological profile suggested that E. neriifolia leaf extract exhibited an anxiolytic and
antipsychotic action without effecting motor coordination and spontaneous activity. This may be due to the
generalized central depressant activity of the extract that also correlates with anxiolytic activity observed
on elevated plus-maze (10). E. neriifolia behaved like other central nervous system depressants by elevating pain threshold when tested against different noxious stimulus. E. neriifolia produced analgesia
against thermal as well as on mechanical and chemical noxious stimuli. This indicated that E. neriifolia was
effective on acute as well as on chronic pain and the antinociceptive effect was mediated centrally.
Carrageenan induced paw edema model is prototype of exudative phase inflammation. The edema
development method is biphasic; the initial phase is due to release of histamine, serotonin and kinins in the
first few hours after injection of carrageenan (37). The more pronounced second phase occurs in 2-3 hrs
due to release of prostaglandin like substances. The significant anti-inflammatory activity of E. neriifolia
may be due to the presence of steroidal saponins or flavonoids by exerting predominant inhibition of
inflammatory mediators from phlogogenic stimuli (38). The association of both analgesic and antiinflammatory
effects is well documented for various non-steroidal anti-inflammatory agents.
E. neriifolia leaf extract produced potent diuresis, increasing the urine volume three times than the control
by increasing urine sodium and chloride concentration along with water. Though extract appeared to cause
good diuresis, the actual mode of action is not clear from the test. E. hirta, another Euphorbiaceae plant is
used as diuretic agent by the Swahilis and Sukumas of East Africa. The diuretic effect of extract is
mediated by increasing Na+, K+ and HCO3
- concentration in urine (39). The delay in onset of diuresis
induced by the extracts may be attributed to poor absorption of the active principles present in the crude
preparations. From the above observations, it can be suggested that E. neriifolia extract is an effective
hypernatraemic and hyperchloraemic diuretic.
Digestive effect of the accumulated gastric juice is believed to be responsible for producing ulcers in the
pyloric ligated rats. Reflex or neurogenic effect in addition to acid secretion has also been suggested to play
an important role in the formation of gastric ulcer in this mode (40). E. neriifolia leaf extract decreased
gastric lesions and pH of gastric content as well as total and free acidity. Effect on volume of gastric
content was evident only at high dose. The extract was more effective for reduction of gastric acidity than
the volume of gastric content. The effect of extract on soluble mucosubstances showed that increase in total
hexose and sialic acid was extremely significant, it also increased hexosamine but had no effect on fucose
content. The extract increased total carbohydrate and decreased total protein of gastric content suggesting
stimulation of gastric mucosal growth and protection against high acidity.
E. neriifolia leaf extract offered extremely significant protection against ethanol induced ulceration on all
tested doses. The extract reduced gastric lesions, volume and acidity of gastric fluid. It is well known that
in ethanol induced ulceration leucotrienes cause gastric damage while prostaglandin E2 protects gastric
mucosa against various ulcerogens. Ranitidine does not decrease severity of ulceration in ethanol induced
injury to the gastric mucosa as its activity is independent of luminal acid (41). Prostaglandins form a vital
component of gastric mucosal defense locally throughout the gut in high concentrations and the major
stimulant for their synthesis is cell trauma by acid or alkali, and is known to have an antisecretory effect on
gastric acid production. It has been proposed that non-prostanoids protects gastric mucosa through the
mobilization of endogenous prostaglandins. As reported earlier sucralfate inhibit alcohol induced ulceration
via stimulation of endogenous prostaglandins release from the gastric mucosa implicating cytoprotection as
a possible mechanism (42). The antiulcerogenic effect of the extract may be due to increase in
microcirculation, mobilization of prostaglandins in gastric mucosa in addition to its ability to reduce total
acidity and to increase TC/TP ratio.
E. neriifolia leaf extract showed very prominent protection against ethanol induced ulceration as well as on
pyloric ligated ulceration but the effects were more pronounced on protection of gastric lesions and acidity.
The phytochemical analysis of the extract reveled prominent presence of tannins and flavonoids, these
substances are known to affect the integrity of mucous membrane. Tannins being astringent may precipitate
microproteins in the site of ulcer thus preventing absorption of toxic substances forming a protective layer
and resisting the mucous layer against the attack of proteolytic enzymes. Tannins could prevent ulcer
development with their protein precipitating and vesoconstrictory effects (43). Flavonoids also protect ulcer
development by improving microcirculation and increasing capillary resistance in turn increasing gastric
defensive factors (44)
In conclusion, these experimental studies showed potent analgesic, anti-inflammatory, mild diuretic and
anti-ulcer activity of E. neriifolia, which gives scientific basis to its uses in traditional medicine. The results
indicated that E. neriifolia extract exerts the cytoprotective effect in addition to their gastric antisecretory
activity that could be due to, partly at least, to the presence of flavonoids (41). Presence of tannins may also
be responsible for its protective effect by maintaining an efficient gastric mucosal microvascular supply.
Further studies are required to establish and elaborate the mechanism of antiulcer activity of E. neriifolia
leaf extract. Detailed pharmacological studies should be carried out to establish the mode of action and
bioactive components responsible for the therapeutic usefulness.
Acknowledgements
The authors are grateful to All India Council of Technical Education, New Delhi for the financial assistance
by awarding National Doctoral Fellowship to one of the authors (Dr. P. Bigoniya, grant no.
FD/NDFS/2003-04). The authors are also thankful to Ranbaxy Laboratories Ltd., Dewas, Reckitt &
Colman, UK and Lupin Lab., India, for providing the gift sample of Ranitidine, Loperamide and Frusemide
respectively used for the study.
REFERENCES
1. Kirtikar K.R. and Basu B.D., (1996), Indian Medicinal Plants. 2nd Ed., International Book Distributors,
Dehradun,: 1581.
2. Anonymous., (1976), The Wealth of India: Raw Materials. Vol X., Council of Science and Industrial
Research (CSIR) Publications, New Delhi,: 588-590.
3. Oudhia P., (2003), Medicinal herbs of Chhattisgarh. India having less known traditional uses, VII.
Thura (Euphorbia neriilofia, family: Euphorbiaceae), Research note, [on line], Available on:
www.botanical.com, Accessed on: 9th May 2008.
4. Chatterjee A., Saha S.K. and Mukhopadhyay S., (1978), Lewis acid-catalysed rearrangement of glut-
5-en-3ß-y1 acetate and glut-5(10)-en-3ß-y1 acetate. Ind J Chem 16B: 1038-39.
5. Anjaneyulu V. and Ramachandra R., (1965), Crystallization principles of Euphorbiaceae. Part IV:
Triterpenes from the stems and leaves of E. neriilfolia. Curr Sci 34: 606-09.
6. Ng A.S., (1990), Diterpenes from Euphorbia neriifolia. Phytochemistry 29: 662-64.
7. Ilyas M., Praveen M. and Amin K.M.Y., (1998), Neriifolione, a triterpene from Euphorbia neriifolia.
Phytochemistry 48: 561-3.
8. Mallavadhani U.V., Satyanarayana K.V., Mahapatra A. and Sudhakar A.V., (2004), A new
tetracyclic triterpene from the latex of Euphorbia neriifolia. Nat Product Res 18(1): 33-7.
9. Rashik A.M., Shukla A., Patnaik G.K., Dhawan B.N. and Kulshrestha D.K., (1996), Wound healing
activity of latex of Euphorbia neriifolia Linn. Ind J Pharmacol 28(2): 107-09.
10. Bigoniya P. and Rana A.C., (2005), Psychopharmacological profile of hydro-alcoholic extract of
Euphorbia neriifolia leaves in mice and rats. Ind J Exp Biol 43: 859-62.
11. Bigoniya P. and Rana A.C., (2007), Wound healing activity of Euphorbia neriifolia leaf extract. J Nat
Remedies 7(1): 94-101.
12. Bigoniya P. and Rana A.C., (2008a), A Comprehensive Phyto-pharmacological Review of Euphorbia
neriifolia Linn. Phcog Rev 2(4): 57-66.
13. Bigoniya P. and Rana A.C., (2008b), Immunomodulatory activity of Euphorbia neriifolia leaf hydroalcoholic
extract in rats. Ind Drugs 45(2): 90-97.
14. Bigoniya P. and Rana A.C., (2006), Hemolytic and In-vitro Antioxidant Activity of Saponin Isolated
from Euphorbia neriifolia Leaf. Recent Progress in Medicinal Plants. Natural Products – II, Vol 2.,
Cap-20: 359-76.
15. Hawk P.B., Oster B.L. and Summerson W.H., (1954), The Practical Physiological Chemistry. 13th
Ed., McGraw Hill Book Co., New York,: 111.
16. Shellard E.J., (1957), Practical Plant Chemistry for Pharmacy Students. Pitman Medical Publishing
Co. Ltd., London,: 34-80.
17. Diener W., Mischke U., Kayser D. and Schlede, E., (1995), The evaluation of the OECD modified
version of acute toxicity class method (oral). Arch Toxicol 69: 729-34.
18. Wu Y., Tian-Sang W., Fang-Zhou Y. and Bao-Chang C., (2003), Analgesic and anti-inflammatory
properties of brucine and brucine N-oxide extracted from seeds of Strychnos nux-vomica. J
Ethnopharmacol 88(2-3): 205-14.
19. Rumana S. and Vorora S.B., (2000), Analgesic activity of arsenic preparations used in unani-tibb. Ind
Drugs 37: 274-79.
20. Witkin L.B., Husbner C.F., Galdi F., O’Keefe E., Spitaletta P. and Pulmmery A.J., (1961),
Pharmacology of 2 amino-indane hydrochloride (SU8629): a potent non-narcotic analgesic. J
Pharmacol Exp Ther 133: 400-08.
21. Winter C.A., Risley E.A. and Nuss G.W., (1962), Carrageenan induced edema in hind paw of the rat
as an assay for antiinflammatiory drugs. Proc Soc Exp Biol Med 111: 544-47.
22. D’Arcy P.F., Howard E.M., Muggleton P.W. and Jowsend S.B., (1960), The anti-inflammatory
action of griseofulvin in experimental animals. J Pharm Pharmacol 12: 659-65.
23. Leander J.D., (1983), A kappa opioid effect: increased urination in the rat. J Pharmacol Exp Ther
224: 89-94.
24. Jeffery G.H., Bassett J., Mendham J. and Denney R.C., (1989), Vogel’s Textbook of Quantities
Chemical Analysis. 5th Ed., Addison Wesley Longman Inc., London,: 582-83.
25. Awouters F., Niemeegers C.J.E., Lenaerts F.M. and Janssen P.A.J., (1978), Delay of castor oil
diarrhoea in rats: a new way to evaluate inhibitors of prostaglandin biosynthesis. J Pharm Pharmacol
30: 41-45.
26. Puurunen J., (1980), Effect of prostaglandin E2, cimitidine and atropine on ethanol induced gastric
mucosal damage in the rat. Scand J Gastroenterol 15: 485-88.
27. Ganguli A.K. and Bhatnagar O.P., (1973), Effect of bilateral adrenalectomy on production of restraint
ulcers in the stomach of albino rats. Canadian J Physiol Pharmacol 51: 748-55.
28. Hawk P.B., (1965), Hawk’s Physiological Chemistry. In: B.L. Oster (Eds.), 14th Ed., McGraw-Hill
Book Co., New York,: 483.
29. Zacharias D. and Landrum B.S., (1948), A specific color reaction of methylpentoses and a
spectrophotometric micromethod for their determination. J Biol Chem 175: 595-603.
30. Dische Z. and Borenfreund E. A., (1950), Spectrophotometric method for microdetermination of
hexosamine. J Biol Chem 184: 517-22.
31. Warren L., (1965), The thiobarbituric acid assay of Sialic acids. J Biol Chem 234(8): 1971-75.
32. Lowry O.H., Rosenbrough N.J., Farr A.L. and Randall R.J., (1951), Protein measurement with folin
phenol reagent. J Biol Chem 193: 265-75.
33. Goswami S., Jain S. and Santani D., (1997), Antiulcer activity of cromakalim, against
experimentally induced gastric and duodenal ulcers in rats and guinea pigs. J Pharm Pharmacol 49:
195-99.
34. Vaz Z.R., Cechinel-Filho V., Yunes R.A. and Calixto J.B., (1996), Antinociceptive action of 2-(4-
bromobenzoyl)-3 methyl-4,6-dimethoxy benzofuran a novel xanthoxyline derivative on chemical and
thermal models of nociception in mice. J Pharmacol Exp Ther 278: 304-12.
35. Collier H.O.J., Dinneen L.C., Johnson C.A. and Schneide C., (1968), The abdominal constriction
response and its suppression by analgesic drugs in the mouse. British J Pharmacol 32: 265-68.
36. Yin W., Wang T., Yin F. and Cai B., (2003), Analgesic and anti-inflammatory properties of brucine
and brucine N-oxide extracted from seeds of Strychnos nux-vomica. J Ethnopharmacol 88(2-3): 205-
14.
37. Mujumdar A.M., Naik D.G., Dandge C.N. and Puntambekar H.M., (2000), Antiinflammatory activity
of Curcuma amada Roxb. In albino rats. Ind J Pharmacol 32: 375-77.
38. Gupta M.B., Nath R. and Srivastava N., (1979), Anti-inflammatory and antipyretic effect of ß-
sitosterol. Planta Med 3: 157-63.
39. Johnson P.B., Abdurahman E.M., Tiam E.A., Abdu-Aguye I. and Hussaini I.M., (1999), Euphorbia
hirta leaf extracts increase urine output and electrolytes in rats. J Ethnopharmacol 65: 63-69.
40. Goswami S., Jain S. and Santani D.D., (1997), Antiulcer activity of cromakalim, against
experimentally induced gastric and duodenal ulcers in rats and guinea pigs. J Pharm Pharmacol 49:
195-199.
41. Alvarez A., Pomar F., Sevilla., Montero M.J., (1999), Gastric antisecretory and antiulcer activities of
an ethanolic extract of Bidens pilosa L. var. radiate Schult. Bip. J Ethnopharmacol 67(3): 333-40.
42. Konturek S.J., Redechi T., Piastuchi L., Brozowski T. and Drozdowicz D., (1987),
Gastrocytoprotection by colloidal bismuth subcitrate (De-Nol) and sucralfate: Role of endogenous
prostaglandins. Gut 28: 201-05.
43. John T.A. and Onabanjo, A.O., (1990), Gastroprotective effects of an aqueous extract of
Entandrophragma utile bark in experimental ethanol-induced peptic ulceration in mice and rats. J
Ethnopharmacol 29(1): 87-93.
44. Gonzaler F.G. and Di Stasi L.C., (2002), Anti-ulcerogenic and analgesic activities of the leaves of
Wilbrandia ebracteata in mice. Phytomedicine 9(2): 125-34.


© 2016 The Author(s). This open access article is distributed under a Creative Commons Attribution (CC-BY) 4.0 license. You are free to: Share — copy and redistribute the material in any medium or format Adapt — remix, transform, and build upon the material for any purpose, even commercially. The licensor cannot revoke these freedoms as long as you follow the license terms. Under the following terms: Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. No additional restrictions You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits
Editor in Chief
Prof. Dr. Cornelia M. Keck (Philipps-Universität Marburg)
Marburg, Germany

Bibliography

Welcome to the research group of Prof. Dr. Cornelia M. Keck in Marburg. Cornelia M. Keck is a pharmacist and obtained her PhD in 2006 from the Freie Universität (FU) in Berlin. In 2009 she was appointed as Adjunct Professor for Pharmaceutical and Nutritional Nanotechnology at the University Putra Malaysia (UPM) and in 2011 she obtained her Venia legendi (Habilitation) at the Freie Universität Berlin and was appointed as a Professor for Pharmacology and Pharmaceutics at the University of Applied Sciences Kaiserslautern. Since 2016 she is Professor of Pharmaceutics and Biopharmaceutics at the Philipps-Universität Marburg. Her field of research is the development and characterization of innovative nanocarriers for improved delivery of poorly soluble actives for healthcare and cosmetics. Prof. Keck is executive board member of the German Association of Nanotechnology (Deutscher Verband Nanotechnologie), Vize-chairman of the unit „Dermocosmetics“ at the German Society of Dermopharmacy, active member in many pharmaceutical societies and member of the BfR Committee for Cosmetics at the Federal Institute for Risk Assessment (BfR).

Journal Highlights
Abbreviation: J App Pharm
doi: http://dx.doi.org/10.21065/19204159
Frequency: Annual 
Current Volume: 9 (2017)
Next scheduled volume: December, 2018 (Volume 10)
Back volumes: 1-9
Starting year: 2009
Nature: Online 
Submission: Online  
Language: English

Subject & Scope
  • Pharmaceutics
  • Physical Pharmacy 
  • Dosage Forms Science 
  • Pharmaceutical Microbiology & Immunology 
  • Industrial Pharmacy 
  • Bio-Pharmaceutics 
  • Pharmaceutical Chemistry 
  • Pharmaceutical Instrumentation 
  • Medicinal Chemistry 
  • Pharmacognosy 
  • Physiology &Histology 
  • Anatomy & Pathology 
  • Pharmacology & Therapeutics 
  • Pharmacy Practice 
  • Pharmaceutical Mathematics   
  • Biostatistics 
  • Dispensing 
  • Community Social & Administrative Pharmacy 
  • Hospital Pharmacy 
  • Clinical Pharmacy 
  • Pharmaceutical Quality Management 
  • Forensic Pharmacy 
  • Pharmaceutical Technology 
  • Pharmaceutical Management & Marketing

Consortium Publisher is an online publisher that enjoys global presence with International Journals

Follow Us

©2009 - 2019 Consortium Publisher Canada

Contact Info

6252 Lisgar Dr Mississauga Ontario L5N7V2 Canada
+1 (647) 526-0885
office@consortiumpublisher.ca
http://www.consortiumpublisher.ca/