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Analgesic activity of Cryptostegia grandiflora (Roxb.)R.br. leaves methanol extract using mice

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Abstract

Objective To evaluate analgesic property of leaf methanol extract of Cryptostegia grandiflora (Roxb.) R.Br. using mice.Methods Analgesic activity was evaluated by abdominal writhing and tail flick methods using Swiss albino mice. Acetyl salicylic acid was used as standard drug.ResultThe leaf methanol extract did not show any signs of toxicity upto 5000 mg/kg b.w. The leaf methanol extract (LME) was tested at three different dosages viz., 250, 500 and 750 mg/kg b.w. orally. All the three doses of LME showed significant (P < 0.001) analgesic activity, among them dose at 750 mg/kg b.w. showed 62.93% inhibition, but less effective than standard acetyl salicylic acid (93.70%) as revealed by writhing test. In Tail-flick model, the LME at the dose of 500 mg/kg b.w. showed significant activity (P < 0.001) when compared to the other two doses as evidence by the increase in the latency of tail response to thermal stimulation.Conclusions This investigation revealed that the C. grandiflora LME demonstrated significant analgesic effect in both abdominal writhing and tail flick models. Among the three different doses tested, the 500 mg/kg b.w. was found to be more potent. The results of this investigation revealed that the LME of C. grandiflora possesses significant analgesic property and supported the traditional medicinal claims on C. grandiflora.
S494
Document heading
Analgesic activity of Cryptostegia grandiflora (Roxb.)R.br. leaves
methanol extract using mice
Santhosh Kondajji Hanumanthappa, Manjunatha Hanumanthappa*, Krishna Venkatarangaiah, Pradeepa Krishnappa,
Rajesh Kashi Prakash Gupta
Department of P.G. Studies and Research in Biotechnology and Bioinformatics, Kuvempu University, Shankaraghatta - 577451, Karnataka, India
Asian Pacific Journal of Tropical Disease (2012)S494-S498
Asian Pacific Journal of Tropical Disease
journal homepage:www.elsevier.com/locate/apjtd
*Corresponding author: Dr. Manjunatha H. Assistant professor, Dept. of P.G.
studies in Biotechnology and Bioinformatics, Kuvempu University, Jnana sahyadri,
Shankarghatta-577451 Shimoga Dist., Karnataka, India.
Mail id: manjunatha75@gmail.com
Cell No: +918105580506
Phone No: (Office) 08282-256235
Fax: +91(0) 08282-256255
1. Introduction
Pain is an unpleasant sensory and emotional experience [1]
occurred by blocking pain signals interfering with the brain
signals. Pain motivates the individual to withdraw from
damaging situations, to protect a damaged body part while
it heals, and to avoid similar experiences in the future [2] if
not, leads to many diseases such as tumor, physical trauma,
surgical procedures, noxious chemical stimulation etc [3].
Most of the pain relieving drugs produced pronounced side
effects on the physiology of the body such as sweating,
apprehension, nausea and palpitation [4]. Hence there is an
utmost need for an alternative effective treatment against
pain without side effects. Natural occurring bioactive
compounds in the plants are believed to be an important
source with potential therapy for pain. Many drugs are used
to relieve the pain. Morphine [5] and aspirin [6] are used pain
killer since time immemorial. Any pain caused primarily by
stimulation of the nociceptor can be said to be nociceptive
pain [7]. Pain is centrally modulated via a number of
complex processes including opiate, dopaminergic,
descending noradrenergic and serotonergic systems [8].
Several plants are reported to possess analgesic property
as many investigators screened the plant extracts and
their phytoconstituents for their analgesic property viz.,
Bowdichia virgilioides [9], Capparis ovate [10], Urtica
circularis [11], Phlomis umbrosa [12], Delonix elata [13].
Cryptostegia grandiflora (Roxb.) R. Br. (Family:
Asclepiadaceae) is widely distributed throughout tropical
Africa, Madagascar and some parts of India [14, 15]. The
juice of aerial parts of C. grandiflora are reported to,
produce caoutchoue when exposed to sunshine [16]. It is
also reported that this plant decoction is consumed to treat
nervous disorders [17]. This plant species is also reported to
possesses various biological activities like antioxidant [18],
antitumour [19] antiviral [20] and control the schistosomiasis
[21]. The aqueous solution of ethanol extract of aerial parts
exerted significant hypoglycemic action in normal rabbits
ART ICLE INFO ABSTRAC T
Article history:
Received 19 June 2012
Received in revised from 5 July 2012
Accepted 7 Octoberr 2012
Available online 28 October 2012
Keywords:
Cryptostegia grandiflora
Acute toxicity
LME
Analgesic activity
Objective: To evaluate analgesic property of leaf methanol extract of Cryptostegia grandiflora
(Roxb.) R.Br. using mice. Methods: Analgesic activity was evaluated by abdominal writhing
and tail flick methods using Swiss albino mice. Acetyl salicylic acid was used as standard drug.
Result: The leaf methanol extract did not show any signs of toxicity upto 5000 mg/kg b.w. The
leaf methanol extract (LME) was tested at three different dosages viz., 250, 500 and 750 mg/kg b.w.
orally. All the three doses of LME showed significant (P<0.001) analgesic activity, among them
dose at 750 mg/kg b.w. showed 62.93% inhibition, but less effective than standard acetyl salicylic
acid (93.70%) as revealed by writhing test. In Tail-flick model, the LME at the dose of 500 mg/kg b.w.
showed significant activity (P<0.001) when compared to the other two doses as evidence by the
increase in the latency of tail response to thermal stimulation. Conclusions: This investigation
revealed that the C. grandiflora LME demonstrated significant analgesic effect in both abdominal
writhing and tail flick models. Among the three different doses tested, the 500 mg/kg b.w. was
found to be more potent. The results of this investigation revealed that the LME of C. grandiflora
possesses significant analgesic property and supported the traditional medicinal claims on C.
grandiflora.
Contents lists available at ScienceDirect
Santhosh Kondajji Hanumanthappa et al./Asian Pacific Journal of Tropical Disease (2012)S494-S498 S495
[22, 23] and the latex derived from this plant have proteolytic,
bacteriolytic activity and possess relevant enzymatic
activities against pathogenic related proteins [24, 25]. Rigorous
literature survey revealed that there are no reports available
regarding analgesic property of C. grandiflora, hence the
present study was undertaken to evaluate the analgesic
activity of the leaf methanol extract (LME) of C. grandiflora
to substantiate its traditional claims as decoction to treat
nervous disorders through scientific evaluations.
2. Materials and methods
2.1. Plant material and extraction
The leaves of C. grandiflora were collected in December
2009 from the villages near by Davanagere district,
Karnataka, India. The plant material was identified and
authenticated by Prof.Y.L. Krishnamurthy and plant
herbarium has been deposited (No: KU/SD/SP229) in the,
Department of Botany, Kuvempu University.
The leaves were cleaned with deionized water and were
shade dried, grounded porously by using mechanical
blender and passes through 40-mesh sieve. About 1 kg of
powdered material was loaded into four Soxhlet timbles
of 250 g each and extracted using methanol for about 48 h.
The extracts were filtered (Whatman No.1 filter paper) and
concentrated in vacuum under reduced pressure using
rotary flash evaporator (Buchi, Flawil, Switzerland) and then
the extract was kept on water bath for complete evaporation
of solvent. Finally the dried extract was preserved in air tight
container until use.
2.2. Animals
Healthy Swiss albino mice weighing 20-25 g were procured
from Central Animal House, National College of Pharmacy,
Shimoga, Karnataka, India and were housed at 232
, humidity 55-60% and were fed with standard commercial
pellet diet (Durga Feeds and Foods, Bangalore) and water
ad libitum. All the animals were acclimatized for one week
before the experiments, and all experiments were carried
out according to the institutional animal ethics committee
guidelines (Re: NCP/IAEC/CL/07/12/2010-11).
2.3. Acute toxicity study
Acute oral toxicity [26] study was performed as per OECD-
423 guidelines (acute oral toxic class method). Albino mice
(n = 6) of either sex selected by random sampling technique
were used for the study. The animals were kept fasting for
overnight providing only water, after which the methanol
extract was administered orally at the dose level of 50 mg/
kg body weight by intragastric tube and observed for 72 hrs.
This dosage was gradually increased up to 5000 mg/kg until
any behavioral changes or mortality was observed.
2.4. Preparation of extract
The three different concentrations of LME and the standard
drug were prepared for oral administration in the form of
suspension in 1% DMSO as suspending agent.
2.5. Analgesic activity
2.5.1. Abdominal writhing method
The abdominal writhing method described by [27] was
carried out to measure the analgesic action. Analgesic
activity of the crude LME was carried out using adult Swiss
albino mice of either sex weighing 20-25 g, five groups with
6 animals per group were selected for abdominal writhing
method [28]. Group I animals were treated with 0.6% acetic
acid (dose 10 ml/kg) intraperitoneally. After 5 min of acetic
acid administration, numbers of writhes were counted for
20 min. This reading was taken as control. Group II, III and
IV were administered orally with the 1% DMSO dissolved
LME at the dose of 250, 500 and 750 mg/kg body weight
respectively. Group V was administered with standard drug
acetyl salicylic acid (100 mg/kg b.w.) and was used for the
comparison of analgesic activity. After one hour incubation
all the groups except group I animals were administered
with acetic acid. After 5 min, each group mice were observed
for the number of writhes for the duration of 20 min. The
mean value for each group was calculated. A reduction
in the writhing number compared to the control group
was considered as evidence of analgesia. The percentage
inhibition of writhing was calculated as: % Inhibition = A-B
/ A X 100. Where, A = mean number of writhes produced by
the control group and B = mean number of writhes produced
by the test groups.
2.5.2. Tail flick method
Analgesic effect of the LME was determined by the tail-
flick method as described by Sewell and Spencer (1976) [29].
Swiss albino mice of either sex weighing between 20-25 g
were divided into 4 groups of six mice in each group. Group
I mice were treated with normal saline (10 m1/kg b.w.).
Group II, III and IV were administered orally with the 1%
DMSO dissolved LME at the dose of 250, 500 and 750 mg/kg
b.w. respectively. One to two centimeter of the experimental
mice tail was immersed in warm water kept constant at 50
. The pain reaction time was the time taken by the mice
to deflect their tails. The first reading is discarded and the
reaction time was taken as a mean of the next two readings.
The latent period of the tail-flick response was taken as
the index of analgesic activity and was determined before
and at 0.5, 1.0, 1.5, 2.0, 2.5 and 3.0 h after the administration
of drugs. The maximum reaction time was fixed at 0.5 h (30
min). The maximum possible analgesia (MPA) was calculated
according to the method of Idid et al., (1992) [30].
2.6. Statistical analysis
The data of analgesic activity was expressed as mean
S.E.M of six animals in each group. The statistical analysis
was carried out using one way ANOVA followed by Tukeys
t-test. The difference in values at P 0.01 was considered
as statistically significant.
Santhosh Kondajji Hanumanthappa et al./Asian Pacific Journal of Tropical Disease (2012)S494-S498
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3. Results
3.1. Acute toxicity study
Acute toxicity (LD50, p. o.) of leaf methanol extract of C.
grandiflora (LD50) for oral administration was evaluated using
mice. It is inferred that up to 50 to 5000 mg/kg b. w. did not
show any observable behavioral changes or mortality. It is
found to be a safer dose for administration and the LD50 was
taken at 1/10th of the examined concentration of the extract.
3.2. Analgesic activity
3.2.1. Writhing method
The number of abdominal writhes observed during 20 min.
period after 0.6% acetic acid administration through i.p. in
control group was 85.80 0.86. The treatment of methanol
extract at the dose of 250, 500 and 750 mg/kg b.w. reduced
the number of writhes to 36.800.58 (57.10 % analgesia), 36.80
0.58 (75.05% analgesia) and 31.800.86 (62.93 % analgesia)
respectively. But the effect of LME was slightly less potent
than the standard drug acetyl salicylic acid with 05.400.51
writhes, eliciting 93.70% analgesia, Although the effect was
found to be significant (P<0.01) and the data is depicted in
the Table 1.
3.2.2. Tail flick method
During the tail flick experiment, the effect of LME in
mice was observed over a period of 3h, while 1% DMSO
administered to animals as control group remained
non-toxic on the latent period of tail-flick response.
Before the administration of LME, the initial reading was
documented. Following oral administration at three different
concentrations (250, 500 and 750 mg/kg b.w.) of LME using
gavage, the effect of LME was significant (P<0.01) over
3h observation period. Analgesic effect after the LME
administration was recorded at every 30 min. time intervals
and was found to be evident within 0.5h of experiment. At 250
mg/kg dosage, the analgesia was observed to be increased
from 4.40 0.24 to 9.20 0.37%. Similarly, at 500 mg/kg
dosage, the analgesia increased to 10.80 0.37%. While at
750 mg/kg b.w. dosage the calculated analgesia (MPA) value
was (P< 0.01) significantly decreased to 9.600.68% against
the control group. The effect of LME on analgesic response
induced by noxious heat (50 ) as shown in Table 2.
4. Discussion
Medicinal plants formulations are widely used in several
therapies including pain killing and nervous disorders.
Leaves of medicinal plants are common substance of many
folk and traditional herbal medicines. C. grandiflora is a
toxic vine, and though it is a toxic plant, the leaf decoction
of this plant is consumed to treat various nervous disorders
and wound healing [31].
Acute toxicity study of LME of C. grandiflora revealed
that up to 5000 mg/kg b. w. did not show any observable
changes in the behavior or mortality of animals. Hence, one
tenth of this dose was considered to be the safer dose for
administration.
The preliminary phytochemical screening revealed the
presence of alkaloids, glycosides, flavonoids, steroids,
saponins, tannin and phenolic compounds. Many
investigators have reported the actions of secondary
metabolites such as flavonoids and alkaloids played a
major role in analgesic activity [32, 33]. The presence of
secondary metabolites like saponins, flavonoids, tannins,
and terpenoides may be attributed for analgesic activity
[34]. However, alkaloids are well known for their ability
to inhibit pain perception [35, 36], whereas flavonoids are
primarily targeting prostaglandin synthesis involved in pain
perception, indicating that flavonoid components of the
plant extract might be responsible for analgesic property of
the extract [37,38,39].
In the present study, analgesic activity of LME of C.
Table 1
Analgesic activity of C. grandiflora leaf methanol extract by writhing method.
Drug treatment Dose Number of writhes % inhibition of
writhings
Control(acetic acid)10 ml/kg (i.p.)85.800.86 -
Acetyl salicylic acid 100 mg/kg (p.o.)05.400.51 93.70**
Leaf methanol extract 250 mg/kg (p.o.)36.800.58 57.10**
500 mg/kg (p.o.)21.401.03 75.05**
750 mg/kg (p.o.)31.800.86 62.93**
Values are the mean 依S.E.M. of six mice. Symbols represent statistical significance.*P < 0.05, ** P < 0.01, ns - not significant, as compared to
control group.
Table 2
Analgesic activity of C. grandiflora leaf methanol extract by tail flick method
Group(N)Dose (p.o.)0.5h1.0h1.5h2.0h2.5h3.0h
Contro(1% DMSO)10 ml/kg 3.030.05** 2.80.06** 2.9 0.04** 3.20.08** 3.10.02** 3.40.05**
Leaf Methanol extract 250mg/kg 9.200.37** 7.200.37** 7.00.45** 5.600.40** 5.800.20** 4.400.24**
500 mg/kg 10.800.37** 9.600.24** 9.200.20** 8.800.49** 9.200.37** 8.200.20**
750 mg/kg 9.600.68** 9.600.40** 8.600.40** 8.400.57** 8.200.58** 7.600.40**
Values are the mean S.E.M. of six mice. Symbols represent statistical significance.*P < 0.05, ** P< 0.01, ns - not significant, as compared to
control group.
Santhosh Kondajji Hanumanthappa et al./Asian Pacific Journal of Tropical Disease (2012)S494-S498 S497
grandiflora was evaluated by using acetic acid induced
abdominal writhing and tail flick method in mice. In acetic
acid induced experiment, animal models react with unique
abdominal stretching behavior which is called writhing. The
reduction in abdominal writhing indicates the percentage
levels of analgesia in the acetic acid writhing reflex model
[40] in which the pain is due to the release of free arachidonic
acid from phospholipid tissue [41] via, cyclooxygenase
(COX) and prostaglandin biosynthesis [42]. The acetic acid
induced writhing response is a sensitive procedure to
evaluate peripherally acting analgesics and the response
is thought to be mediated by peritoneal mast cells [43], acid
sensing ion channels [44] and the prostaglandin pathways [45].
Prostaglandins E2 and F2α are reported to be increased in
the peritoneal fluid of mice due to administration of acetic
acid, this could be produced by neutrophil polynuclear cells
but also by destruction of macrophages [46, 47]. The significant
pain reduction of LME might be due to the presence of
alkaloids and flavonoids analgesic principles acting against
the prostaglandin pathways.
The centrally acting analgesics generally raise the pain
threshold of mice towards heat [48]. The thermal induced
nociceptive tests are more sensitive to opioid receptors and
non-thermal tests are sensitive to κ-opioid receptors as
they are G-protein-coupled receptors (GPCRs) [49, 50, 51].
The narcotic analgesics inhibit both peripheral and central
mechanism of pain, while nonsteroidal anti-inflammatory /
analgesics agents (NSAIAs) inhibit only peripheral pain [52,
53]. The inhibition of pain could take place not only from
the presence of opioids and/or opiodiomimetics but also
from bio-active compounds and secondary metabolites
like phenolic and steroidal constituents [54, 55]. Significant
analgesic response was observed at the dose of 250 and 500
mg/kg b.w. However, steady state response was not observed
to be maintained at higher concentration of 750 mg/kg b.w.
Among the three doses, 500 mg/kg b.w. showed significant
(P< 0.01) analgesic response against acetic acid induced
writhing. The significant effect of these extracts is due to the
presence of a biological active constituent in higher levels
or due to the effect of more than one phytoconstituents. The
LME of C. grandiflora at three different doses showed good
peripheral analgesic activity by decreasing the number of
writhes and exhibited central analgesic activity by showing
significant (P<0.001) effect on the latent period of tail-flick
response at the dose of 500 mg/kg b.w. The present study
revealed that the leaf methanol extract of C. grandiflora
exhibited significant analgesic property but less effective
than the standard reference.
Conflict of interest statement
We declare that we have no conflict of interest.
Acknowledgement
The first author wishes to thank the University Grants
Commission implemented Rajiv Gandhi National Fellowship
(RGNF) India. UGC letter No. : F. 14-2(SC)/2010 (SA-III)
Dated: May 2011.
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... 1,2,3 It has proven helpful in medicine for its narcotic, analgesic, anti-oxidant, anti-asthmatic, spasmolytic, and anesthetic qualities. 4 6 Steroids, alkaloids, anthraquinone tannins, glycosides, flavonoids, triterpenes, saponins, and phenolic substances were detected in the initial phytochemical screening. 7 Numerous researchers have documented the secondary metabolite's analgesic properties. ...
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The plant Brugmansia suaveolens (Bercht. & Presl) belongs to the family Solanaceae and is endemic to the Malnad region (Shimoga) of the Western Ghats. Traditionally leaf extract has been applied externally to treat cut wounds, pain-killer swellings, scalds, inflammations, skin rashes, and hemorrhoids. The objective is to synthesize silver nanoparticles (AgNPs) conjugated Leaf methanol extract of B. suaveolens analyzed and characterized based on multiple (X-ray diffraction (XRD); Scanning electron microscopy (SEM); Fourier transform infrared (FTIR) spectroscopy and ultraviolet–visible (UV–Vis) spectroscopy) analytical methods. After characterization, the analgesic activity of extract bio-synthesized with silver nanoparticles was evaluated and compared with different concentrations of leaf methanol extract alone. Analgesic activity was examined by writhing and tail-flick testing. Reduction in the writhing and tail withdrawal time after administration of 250 mg/kg b.w./d of leaf methanol extract bio-synthesized with silver nanoparticle is more significant than 250, 500, and 750 mg/kg b.w./d extracts alone and is slightly less significant when compared to the standard drug. This has proved that the bio-synthesized silver nanoparticles may have played a fundamental role as drug delivery vehicles to target tissues more conveniently and efficiently compared to nascent extract.
... There are various reports in the literature of the anti-tumour and anti-microbial potential of bioactive extracts of C. grandiflora, as well as analgaesic properties (Doskotch et al. 1972;Mukherjee et al. 1999;El Zalabani et al. 2003;Singh et al. 2011;Hanumanthappa et al. 2012;Morais et al. 2021). Castro et al. (2014) reported that C. grandiflora was widely used in folk medicine on the Caribbean coast of Colombia -particularly, as an anti-inflammatory -and identified metabolites in the leaves that proved to have anti-inflammatory properties in both in vitro and in vivo experiments. ...
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Cryptostegia grandiflora and C. madagascariensis (Apocynaceae) are the only two species of this Madagascan plant genus. Both have been transported around the world as ornamentals due to their attractive flowers and based on a perceived potential as sources of rubber – hence, the common name rubber vine – because of their copious latex, which also contains toxic cardiac glycosides. As a result of their vigorous growth and ability to climb over and smother vegetation, both species have become invasive, posing an actual or potential threat to native ecosystems in many tropical and sub-tropical countries, as well as to human and animal health. Classical biological control (CBC), or the introduction of co-evolved natural enemies to control an invasive alien species in its exotic range, has successfully been used to tackle C. grandiflora in northern Queensland, Australia. This strategy is currently being evaluated for its suitability to manage C. madagascariensis in north-eastern Brazil using the same Madagascan rust fungus, Maravalia cryptostegiae , released as a CBC agent in Australia. For CBC to be successful, it is critical to understand the taxonomy of the invader as well as the origin(s) of its weedy biotype(s) in order to select the best-matched co-evolved natural enemies. Based on an exhaustive search in published and unpublished sources, we summarise the taxonomy and uses of these rubber vines, follow their historical movements and track their earliest records and current weed status in more than 80 countries and territories around the world.
... The genus Solanum is found to be one of the largest and most complex genera among the Angiosperms and the most characteristic and principal genus of the family Solanaceae (Yokose et al., 2004). Plants of this genus represent a wide variety of secondary metabolites with various biological activities, which from an economic, agricultural and pharmaceutical perspective, make them very valuable (Hanumanthappa et al., 2012;Bhakta, 2004). It is known that several of these species have numerous medicinal uses. ...
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Synthetic analgesic drugs have prominent side effects like gastritis, gastric ulcer, kidney disorder and cardiac arrhythmias. The genus Solanum has been primarily used for various therapeutic effects, mainly analgesics, in the indigenous system of medicine. The current research aimed to investigate and compare the analgesic activities of methanolic extracts of leaves of Solanum indicum, Solanum surattense and Solanum torvum. Using acetic acid induced writhing method and hot plate method, the analgesic activity was evaluated. Significant anti-nociceptive effects were observed on both animal models after the application of different doses of the extracts of Solanum species. The results exhibited that MESI, MESS and MEST at a dose of 200 and 400 mg/kg produced analgesic effects equivalent to diclofenac (10 mg/kg). However the extracts at 400 mg/ kg exhibited more pronounced analgesic activity. The results of this study demonstrated that the analgesic effects of all the three species were significant to each other and validate the traditional use of the plants of this Genus for the treatment of pain.
... Considering that inflammatory processes, especially those which are presented chronically, are associated with an overproduction of free radicals that induce oxidative stress and cause the onset of various degenerative diseases [9, 26], and the potent scavenging effect of DPPH and ABTS free radicals exerted by ether and dichloromethane fractions of Cryptostegia grandiflora, we consider that the important antioxidant activity of this plant might be a key contributing factor to the reduction of edema in animals treated with TPA. Analgesic activity of a methanolic extract of leaves of Cryptostegia grandiflora was recently described, attributing the significant pain reduction to the presence of flavonoids, alkaloids, tannins, saponins, terpenoids and phenolic compounds, especially to flavonoids and alkaloids analgesic principles acting against PG pathway and oxidative stress [27]. Considering that flavonoids has been described as anti-inflammatory compounds with several mechanism explaining their effect, including antioxidant and radical scavenging activities and modulation of the activities of arachidonic acid metabolism enzymes (phospholipase A2, cyclooxygenase and lipooxygenase) and nitric oxide synthase, their presence in leaves extracts of Cryptostegia grandiflora can be directly related to the anti-inflammatory activity demonstrated by us [28]. ...
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... The plant extract selection for anti-proliferative activity is based on basic research findings on ethnomedicinal knowledge (anti-viral, antitumor, anti-bacterial and antioxidant assay). However, CGLME has shown significant analgesic activity [8] and it has helped us to further explore its in vitro and in vivo antioxidant activity. ...
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Introduction Pain is a sensory and emotional experience. The emotional component is variable from person to person and in the same person from time to time. Management of pain has to take this fact into consideration. The patient must be believed about the pain. It is the physician's duty to relieve suffering. In addition, unrelieved pain can cause physical damage too. For one thing, it would worsen the pain experience by muscle spasm, peripheral and central sensitization and recruitment and by muscle spasm. Unrelieved acute pain can cause chronic pain, and long standing pain can cause anatomical and even genetic changes in the nervous system. Pain can be classified in several ways, but the most relevant in terms of therapeutic application is into nociceptive and neuropathic. In addition to such identification of the type of pain, it is also necessary to quantitate pain. Several scoring systems are available like the numerical scale, but it needs to be remembered that the patient is the only person who can quantitate his pain. The objective of this paper is to enable the reader to understand some basic facts about pain that have importance in actual management of people with pain. It is not a comprehensive review of pain mechanisms. Much of the known basic science on the subject, which may have future implications on management, is not included here.
Chapter
The in vitro and in vivo genetic toxicity tests currently in use for chemical screening and for regulatory approval of chemical substances evolved from a larger series of tests that were found useful for identifying germ cell mutagens and clastogens, and carcinogens. This chapter provides a brief history of genetic toxicity testing, the philosophy behind the selection of the tests currently in use and their recommended combinations, and brief descriptions of the various in vitro and in vivo tests for identifying presumptive carcinogens and germ cell mutagens. Also presented are general procedures and precautions that need to be followed for performing the tests and submitting the tests to regulatory authorities.