A overview: non-steroidal anti-inflammatory drugs and mechanisms

Abstract

The inflammatory response represents a generalized response to infection or tissue damage and is designed to remove cellular debris, to localize invading organisms and arrest the spread of infection. NSAIDS are metabolized primarily in the liver. They vary in their half-lives and bioavailability. Given the multitude of available NSAIDs, the variability of their half-lives allows for different dosing regimens. The fluid in the inflamed area is known as inflammatory exudates, commonly called as pus. These exudates contain dead cells and debris in addition to body fluids. The inflammatory response is characterized by the following symptoms: Reddening of the localized area, swelling, pain and elevated temperature. Reddening results from capillary dialation that allows more blood to flow to the damaged tissue. Elevated temperature results from capillary dialation which permits increased blood flow through these vessels, with associated high metabolic activities of neutrophils and macrophages. The release of histamine from mast cells during antigen antibody reactions is well known, as is its involvement in the inflammatory response to skin injury. The present review focused on list and precautions of NSAID with its typed and classification, Analgesic activity study, histamine.

Full text

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Corresponding Author: Sachin S Mali, Lecturer, Department of Pharmaceutics, Adarsh institute of Pharmacy, Vita, Maharashtra,
India. E-Mail: sachinmali143@gmail.com 94
Indian J. Pharm. Biol. Res. 2014; 2(4):94-103
Review Article
A overview: non-steroidal anti-inflammatory drugs and mechanisms
Prasad V. Patrekar
1
, Sachin S. Mali
1
, Komal Kashid
1
, Snehal More
1
, Savita S. Mali
1
, Sujata D. Dongare
1
1
Department of Pharmaceutics, Adarsh Institute of Pharmacy, Vita, Maharashtra, India
ARTICLE INFO:
Article history:
Received: 29 October 2014
Received in revised form:
15 November 2014
Accepted: 20 November 2014
Available online: 31 December
2014
Keywords:
Inflammation,
NSAID,
Histamine,
Analgesic activity.
ABSTRACT
The inflammatory response represents a generalized response to infection or tissue damage
and is designed to remove cellular debris, to localize invading organisms and arrest the spread
of infection. NSAIDS are metabolized primarily in the liver. They vary in their half-lives and
bioavailability. Given the multitude of available NSAIDs, the variability of their half-lives
allows for different dosing regimens. The fluid in the inflamed area is known as inflammatory
exudates, commonly called as pus. These exudates contain dead cells and debris in addition to
body fluids. The inflammatory response is characterized by the following symptoms:
Reddening of the localized area, swelling, pain and elevated temperature. Reddening results
from capillary dialation that allows more blood to flow to the damaged tissue. Elevated
temperature results from capillary dialation which permits increased blood flow through these
vessels, with associated high metabolic activities of neutrophils and macrophages. The release
of histamine from mast cells during antigen antibody reactions is well known, as is its
involvement in the inflammatory response to skin injury. The present review focused on list
and precautions of NSAID with its typed and classification, Analgesic activity study,
histamine.
Introduction
The inflammatory response represents a generalized response
to infection or tissue damage and is designed to remove
cellular debris, to localize invading organisms and arrest the
spread of infection. The inflammatory response is
characterized by the following symptoms: Reddening of the
localized area, swelling, pain and elevated temperature.
Reddening results from capillary dialation that allows more
blood to flow to the damaged tissue. Elevated temperature
results from capillary dialation which permits increased blood
flow through these vessels, with associated high metabolic
activities of neutrophils and macrophages. The dialation of
blood vessels is accompanied by increased capillary
permeability causing swelling as fluid accumulates in the
spaces surrounding tissue and cells. Pain in the case of
inflammation is due to the lysis of blood cells that trigger the
production of bradykinin and prostaglandins. The area of
inflammation also becomes walled off as a result of the
development of fibrinous clots. The deposition of fibrin
isolates the inflamed area, cutting off normal circulation. The
fluid in the inflamed area is known as inflammatory exudates,
commonly called as pus. These exudates contain dead cells
and debris in addition to body fluids. After the expulsion of
the exudates, the inflammation may terminate and tissues may
return to their normal state (Atlas, 1995). Pain belongs to a
basic sensory abnormality associated with inflammation. Pain
develops when nerve fiber terminals of polynodal nociceptors
become sensitized by mediators of inflammation. The pain
producing inflammatory mediators are bradykinin,
prostaglandins (PGE1 and PGE2) and leukotrienes,
especially LTB4. Pain becomes evoked by the synergistic
action of bradykinin and prostaglandins (Antoni, 1991). Based
on visual observation, the ancients characterised inflammation
by five cardinal signs, namely redness (rubor), swelling
(tumour), heat (calor; only applicable to thebody'extremities),
pain (dolor) and loss of function (functio laesa). The first four
of thesesigns were named by Celsus in ancient Rome (30–38
B.C.) and the last by Galen (A.D 130–200). Inflammation is a
complicated and not fully understood communication between
cellular and humoral elements. More recently, inflammation
was described as "the succession of changes which occurs in a
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Mali et al. / Indian J. Pharm. Biol. Res., 2014; 2(4):94-103
Review Article 95
living tissue when it is injured provided that the injury is not
of such a degree as to at once destroy its structure and
vitality". Inflammation is a normal, protective response to
tissue injury caused by physical trauma, noxious chemicals or
microbiological agents. The inflammatory response is
characterized by the following symptoms: Reddening of the
localized area, swelling, pain and elevated temperature.
Reddening results from capillary dialation that allows more
blood to flow to the damaged tissue. Elevated temperature
results from capillary dialation which permits increased blood
flow through these vessels, with associated high metabolic
activities of neutrophils and macrophages. The dialation of
blood vessels is accompanied by increased capillary
permeability causing swelling as fluid accumulates in the
spaces surrounding tissue and cells. Pain in the case of
inflammation is due to the lysis of blood cells that trigger the
production of bradykinin and prostaglandins. The area of
inflammation also becomes walled off as a result of the
development of fibrinous clots. The deposition of fibrin
isolates the inflamed area, cutting off normal circulation. The
fluid in the inflamed area is known as inflammatory exudates,
commonly called as pus. These exudates contain dead cells
and debris in addition to body fluids. After the expulsion of
the exudates, the inflammation may terminate and tissues may
return to their normal state (Atlas, 1995). Pain develops when
nerve fiber terminals of polynodal nociceptors become
sensitized by mediators of inflammation. The pain producing
inflammatory mediators are bradykinin, prostaglandins (PGE1
and PGE2) and leukotrienes,especially LTB[1-9]. Pain
becomes evoked by the synergistic action of bradykinin and
prostaglandins.
Causes of inflammation
The numerous causes of inflammation may be classified as
follows:
• Microbes-e.g. bacteria, viruses, protozoa, fungi,
• Physical agents- e.g. heat, cold, mechanical injury,
ultraviolet and ionising radiation.
• Chemical agent-
-organic: e.g: microbial toxins, organic posion
-inorganic: e.g: acids, alkalis[Ross n Wilson
P.N.371]
Types of inflammation
Figure 1: Types of inflammation
Acute Inflammation
These inflammation having short duration process E.g: days to
a few weeks, and may range from mild to a very severe. The
cardial signs of inflammation are, redness, heat, pain,
swelling, loss of function. The acute inflammatory response is
described as a collection of overlapping events, increased
blood flow, accumulation of tissue fluid, migration of
leucocytes, increased core temperature, pain and suppuration.
some of the most important substances released in
inflammation as shown in table:
Table 1: Acute Inflammation
Substance
Made by
Trigger for release
Main pro inflammatory action
Histamine mast cells (in most
tissue),basophils(blood),store
d in cytoplasmic granules
Binding of antibody to
mast cell and basophils Vasodilation,itching,increase vascular
permeability,degranulation,smoothmuscle
contraction(e.g.bronchocostriction)
Serotonin
(5-HT) Platelet mast cell and
basophils(stored in
granules)also in CNS(acts as
When platelets are
activated,and when
mast cells/basophils
Vasoconstrictions,increases permeability

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Review Article 96
Figure 2: Acute Inflammation
Chronic Inflammation
Figure 3: Chronic Inflammation
neurotransmitter) degranulate
Prostaglandi
ns
(PGs)
Nearly all cells not stored but
made feom cell membrane as
required
Many differnt stmuli
e.g drugs,toxins,other
inflammatory
mediators,hormones
Diverse,sometimes
opposing,e.g.fever,pain,vasodilation or
vasoconstriction,increases vascular
permeability
Heparin Liver,mast
cell,basophilis,(stored in
cytoplasmic granules)
Released when cells
degranulte Anticoagulant(prevents blood clotting),which
maintains blood supply(nutients O2)to injuried
tissue and washes away microbes and wastes
Bradykinin Tissue and blood When blood clots,in
trauma and
inflammation
Pain
vasodilation

Mali et al. / Indian J. Pharm. Biol. Res., 2014; 2(4):94-103
Review Article 97
This process having a longer duration of action ,considerably
more tissue is likely to be destroyed.The process involved is
same as the acute inflammation.The inflammatroy cells are
mainly lymphocytes instead of neutrophilis and fibroblasts are
activated,leading to the laying down of collagen,and fibrosis.If
the body defences are unable to clear the infection,they may
try to wall it off instead,forming nodules called as
granulomas,within which are collection of defensive
cells.Tuberculosis is an example of an infection that frequently
becomes chronic,leading to grnuloma formation.The causative
agent is mycobacterium tuberculosis,is resistant to body
defence and so pockets of organism are sealed up in
granulomas within the lungs.
Classification of NSAIDs
A. Non selective COX inhibitors (traditional NSAIDs)
1. Salicylates:Aspirin
2. Propionic acid derivatives:Ibuprofen
3. Anthranilic acid derivatives:Mephenamic acid
4. Aryl-acetic acid
derivatives:Diclofenac,Acelofenac
5. Oxicam derivatives:Piroxicam,Tenoxicam
6. Pyrrolo-pyrrole derivatives:Ketorolac
7. Indole derivatives:Indomethacian
8. Pyrazolone derivatives:Phenyl
butazone,Oxyphenbutazone
B. Preferential COX-2 inhibitors
1. Nimesulid, Meloxicam, Nabumetone
C. Selective Cox-2 inhibitors
1. Celecoxib, Etoricoxib, Parecoxib
D. Analgesic Antipyretic with poor inflammatory action
2. Paraaminophenol derivatives:paracetamol
3. Pyrazolone derivatives:Metamizol,propiphenazone
4. Benzoxazocine derivatives:Nefopam [k d tripathi
P.N.184]
Marketed preparations and dose[2-5]
A. Nonselective COX-2 inhibitors
1. Salicylates
• Aspirin-
• Ecospirin 75,150,325,mg tablets
• Disprin 350 mg tablets
• Aspirin 350 mg tablets
• An injectable preparation has been made available
recently:
• Biospirin:Lysine acetylsalicylate 900 mg+ glycine
100mg/vial for dissolving 5 mlwater and i.v. injection
[k d tripathi P.N.191]
2. Propionic acid derivatives
• Ibuprofen:
Ibugesic plus tablets
Combination of aspirin(650mg) and codeine(60mg)
in reliving dental surgery pain
• Naproxen:
In acute gout dose 750 mg stat followed by 250 mg 8
hourly till attack subsides
• Ketoprofen:
Ketorol DT tablet
• Flurbiprofen:
Ocuflur,flur,flurbin,0.03% eyedrops,1 drop of 6
hourly [k d tripathi P.N.193]
3. Anthranilic acid derivatives
• Mephanamic acid:
Dose:250-500 mg, Medol 250-500 mg capsule,
Meftal 250,500 mg tablet,100mg/5 ml
suspension,Ponstan 125,250,500 mg tablet,50 mg/ml
syrup [k d tripathi P.N.193,194]
4. Aryl acetic acid derivatives
• Diclofenac sodium:
Dose:50 mg TDS,then BD oral,75 mg deep i.m.
Voveran,Diclonac, monovac 50 mg enteric coated
tablet,100 mg S.R.tablet,25mg/ml in 3 amp.for
i.m.inj. Diclomax 25,50mg tablet,
• Diclofenac potassium:
Voltaflam 25,50 mg tablets, Ultra-k 50 mg tablets,
Voveran 1% topical gel, Diclonac 0.1% eye
drops.[k.d tripathi 193,194]
5. Oxicam Derivatives
• Piroxicam:
Dose:20 mg BD for two days followed by 20 mg
OD;Dolonex,pirox 10,20 mg capsule,20 mg
dispersible tablets,20 mg/ml injection in 1 and 2 ml
amps,Piricam 10,20 mg Capsule
• Tenoxicam:
Tobitil 20 mg tablets, dose 20 mg OD
[k.d.tripathi.194]
6. Pyrrolo-pyrrole derivatives
• Ketorolac:
Ketorol, zorovon, ketanov, torolac 10 mg tablets,30
mg in 1 ml amp.
Ketlur,acular 0.5% eye drops ,1-2 drops 2-4 times a
day for noninfective ocular inflammatory
conditions.[k.d.tripathi.194,195]
7. Indole derivatives
• Indomethacin:
Dose:25-50 mg BD-QID.those not tolerating the drug
orally may be given nightly suppository.
Idicin, Indocap 25 mg capsule,75 mg SR capsule,
Indoflam 25,75 mg capsules,1% eye drops. Recticin
50 mg suppository [k.d.tripathi 195]
8. Pyrazolones derivatives
• Phenyalbutazone
Esgipyrin tablets
B. Preferential COX-2 inhibitors
• Nimesulide
Dose:100 mg BD; nimulid,nimgesic,nimodol 100 mg
tablet,50mg/5ml suspension
• Meloxicam
Dose:7.5-15 mg OD;melflam,mel OD,muvik,mcam
7.5 mg,15 mg tablets
• Nabumetone
Nabuflam 500 mg tablets;1 tablet OD
C. Selective COX-2 inhibitors
• Celecoxib

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Review Article 98
Celact,revibra,colcibra 100,200 mg capsule
• Etoricoxib
Dose:60-120 mg OD;Etody,torocoxia,etoxib,nucoxia
60,90,120 mg tablets
• Parecoxib
Dose:40 mg oral/i.m /i.v.repeated after 6-12
hours.Revaldo,valto-p 40 mg/vial inj.,paroxib 40 mg
tablet
D. Analgesic Anti pyretics with poor anti inflammatory
action
• Paraaminophenol derivatives
a.Paracetamol
Metacin,paracin 500 mg tablets,125mg/5 ml syrup,
Crocin pain relief 650 mg + caffeine 50 mg tablets
• Pyrazolone Derivatives
a.Propiphenazone
Pyrlfil tablet
• Benzoxazocine derivatives
Nefopam
Dose: 30-60 mg TDS oral,20 mg i.m. 6 hourly.
Nefomax 30 mg tablets,20 mg in 1 ml ampule.
Mechanism of action of NSAIDs
Anti inflammatory
The most important mechanism of anti inflammatory action of
NSAIDs is considered to be inhibition of PG synthesis at the
site of injury.The antiinflammatory potency of different
compounds roughly corresponds with their potency to inhibit
COX. However, nimesulide is a potent anti-inflammatroy but
relatively weak COX inhibitor. PGs are only one of the
mediators of inflammation; inhibition of COX does not
depress the production of other mediators like LTs, PAF,
cytokines etc. Inflammation is the result of concerted
participation of large number of vasoactive, chemotactic and
proliferative factors at different stage, and there are many
targets for inflammatory action[8-11].
Features of non selective COX inhibitors and selective COX-2
inhibitors:
Table 2: COX inhibitors and selective COX-2 inhibitors
Action COX-1/COX-2inhibitors COX-2 inhibitors
1.Analgesic + +
2.Antipyretic + +
3.Antiinflammatory + +
4.Antiplatelet aggregatory + -
5.Gastric mucosal damage + -
6.Renal salt/water retantion + +
7.Delay/prolongation of labour + +
8.Ductus arteeriosus closure + ?
9.Aspirin sensitive asthma
precipitation + -
Antipyretic effect
NSAIDs exert their antipyretic effect by inhibition of
prostaglandin E2 (PGE2) synthesis, which is responsible for
triggering the hypothalamus toincrease body temperature
during inflammation.
Analgesic effect
Although they are classified as mild analgesics, NSAIDs have
a more significant effect on pain resulting from the increased
peripheral sensitization that occurs during inflammation and
leads no receptors to respond to stimuli that are normally
painless. In particular, it is believed that inflammation leads to
a lowering of the response threshold of poly modal no
receptors.
Pharmacokinetic
NSAIDS are metabolized primarily in the liver. They vary in
their half-lives and bioavailability. Given the multitude of
available NSAIDs, the variability of their half-lives allows for
different dosing regimens. Although decreased frequency of
dosing improves compliance as a general rule, consideration
must be given to the increase in renal dysfunction associated
with longer-acting NSAIDs. It has also been speculated that
use of daily dosed medications, by improving compliance,
may increase the risk for GI bleeding. Variability in
susceptibility to adverse effects of various NSAIDs does not
seem to be due to difference in pharmacokinetics. Hepatic
function, renal function, and age must be considered before
prescribing and dosing.

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Review Article 99
Catabolic pathway of AA
Figure 4: Catabolic pathway of AA
Mediators
Figure 5: Mediators
Figure 6: Mediators

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Review Article 100
Figure 7: Mediators
Histamine
The release of histamine from mast cells during antigen
antibody reactions is well known, as is its involvement in the
inflammatory response to skin injury. Also, increased numbers
of mast cells are present in the rheumatoid synovium and in
the asthmatic lung, correlated with raised levels of histamine.
The advent of non sedating H1 antihistamines has allowed
them to be tested in much higher doses than ever before, and
some evidence suggests that histamine may play a role in
allergic asthma[11-15].
Bradykinin
Small amounts of bradykinin cause pain, vasodilatation, and
edema, all contributing to inflammation. Bradykinin-like
immunoreactivity has been detected in rat pleural
inflammatory exudates. Kinins are also present in nasal
secretions after immunological challenge, and a kininogenase
is released from human lung mast cells. Inhaled bradykinin
causes bronchoconstriction in normal and asthmatic
individuals, but not through release of PGs.
Thromboxane A2 and prostacyclin
The anti platelet effects of aspirin could not be explained by
inhibition of the synthesis of PGE2 or PGF2a because these
PGs do not affect platelet aggregation to any great extent.
Prostacyclin, as it was later termed, relaxes blood vessels and
inhibits aggregation of platelets. Its synthesis in endothelial
cells of blood vessel walls is of special importance.
Interleukin-l
IL-i is a polypeptide produced by activated macrophages that
mimics the symptoms of chronic inflammation. It has had
other names, including endogenous pyrogen. IL-i-like activity
(equivalent to 1.69 U/mi) has been detected in synovial fluids
from patients with rheumatoid arthritis. Its actions include
activation of lymphocytes and production of fever, the latter
being mediated by release of PGE2.
The prostaglandins
Apart from non nucleated erythrocytes, all cells are capable of
synthesizing PGs, which are released in response to many
kinds of trauma or any disturbance of the cell membrane. In
other words, the pathological release of PGs that contributes to
inflammation, fever, and pain is inhibited by aspirin and other
NSAIDs. The aspirin like drugs also share, to a greater or
lesser extent, certain side effects, such as a propensity to
irritate the stomach, nephrotoxicity in high concentrations, and
interference with the birth process. It was suggested that these
side effects resulted from the inhibition of the physiological
release of a protective PG.
Platelet-activating factor (PAF)
The phospholipid PAF-ac ether is released by the action of
phosphor lipase A2 from most pro inflammatory cells, as well
as by vascular endothelial cells and platelets .It induces
inflammatory reactions in various animal species and in
human skin. PAF also mimics themain clinical features of
asthma and is particularly effective in producing hyper
reactivity and accumulation of eosinophils in lung tissue.
Asthmatic patients have high levels of circulating PAF and
their eosinophils make more PAF than those of normal
controls. The anti asthmatic glucocorticoids, by suppressing
phospholipase A2, will thus reduce the formation of PAF.
Furthermore, PAF antagonists, such as the ginkgolides, are
currently being investigated for the treatment of asthma.

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Review Article 101
Figure 8: Histamine
NSAID (List of non steroidal anti-inflammatories)
• Aspirin (Anacin, Ascriptin, Bayer, Bufferin, Ecotrin,
Excedrin)
• Choline and magnesium salicylates (CMT, Tricosal,
Trilisate)
• Choline salicylate (Arthropan)
• Celecoxib (Celebrex)
• Diclofenac potassium (Cataflam)
• Diclofenac sodium (Voltaren, Voltaren XR)
• Diclofenac sodium with misoprostol (Arthrotec)
• Diflunisal (Dolobid)
• Etodolac (Lodine, Lodine XL)
• Fenoprofen calcium (Nalfon)
• Flurbiprofen (Ansaid)
• Ibuprofen (Advil, Motrin, Motrin IB, Nuprin)
• Indomethacin (Indocin, Indocin SR)
• Ketoprofen (Actron, Orudis, Orudis KT, Oruvail)
• Magnesium salicylate (Arthritab, Bayer Select, Doan's
Pills, Magan, Mobidin, Mobogesic)
• Meclofenamate sodium (Meclomen)
• Mefenamic acid (Ponstel)
• Meloxicam (Mobic)
• Nabumetone (Relafen)
• Naproxen (Naprosyn, Naprelan*)
• Naproxen sodium (Aleve, Anaprox)
• Oxaprozin (Daypro)
• Piroxicam (Feldene)
• Rofecoxib (Vioxx)
• Salsalate (Amigesic, Anaflex 750, Disalcid, Marthritic,
Mono-Gesic, Salflex, Salsitab)
• Sodium salicylate (various generics)
• Sulindac (Clinoril)
• Tolmetin sodium (Tolectin)
• Valdecoxib (Bextra)
Note: Some products, such as Excedrin, are combination drugs
(Excedrin is acetaminophen, aspirin, and caffeine). Note that
acetaminophen (Paracetamol; Tylenol) is not on this list.
Acetaminophen belongs to a class of drugs called analgesics
(pain relievers) and antipyretics (fever reducers). The exact
mechanism of action of acetaminophen is not known.
Acetaminophen relieves pain by elevating the pain threshold,
that is, by requiring a greater amount of pain to develop before
it is felt by a person. It reduces fever through its action on the
heat-regulating center of the brain. Specifically, it tells the
center to lower the body's temperature when the temperature is
elevated. Acetaminophen relieves pain in mild arthritis but has
no effect on the underlying inflammation, redness and
swelling of the joint Paracetamol, unlike other common
analgesics such as aspirin and ibuprofen, has no anti-
inflammatory properties, and so it is not a member of the class
of drugs known as non-steroidal anti-inflammatory drugs or
NSAIDs.

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Review Article 102
Latest anti-inflammatory drugs Table 3: Latest anti-inflammatory drugs
Recent drug Dosage form Drug content
Acecloflam Tablet Acelofenac 100 mg
Paracetamol 325 mg
Serratiopeptidase 10mg
Etocoxiv Tablet Etoricoxib30, 60,120 mg
Fleura D Soft gel.capsule Diclofinac 50 mg
Metaxalone 400mg
Muvera Tablet Meloxicam 15,30mg
NSAIDs should never be combined
Preferentialy inhibitors of cyclo-oxygenase-2[cox 2] such as
meloxicam and the specific cox 2 inhibitor celecoxib are
approved for pain relief in osteoarthritis(OA).Although their
analgesic efficacy has been established their ability to
significantly reduce gastrointestinal(GI) side effects has not
been convincingly proven. They should also be used with
caution in patients with renal or heart failure. Recent
evidences on the relative safety of oral NSAIDs have indicated
differences in the risk of serious upper gastro intenstinal side
effects as per following scale[5-21]:
Lowest Risk
Ibuprofen
Intermediate Risk
Diclofenac, Indomethacin, Ketoprofen, Naproxen,
Nimesulide, Piroxicam, Celecoxib. Higher in the case of
nimesulid And possibly higher in the case of piroxicam
Highest Risk
Azapropazone It is suggested that NSAIDs should generally
be preferred to start at lowest recommended dose not to use
more than one oral NSAIDs at a time and to remember that all
NSAIDs are contraindicated in patients with peptic ulceration.
Opioids
Weak opioids such as codeine or dihydrocodiene,used alone ir
in combination with paracetamol may be effective option if
paracetamol does not relive pain or NSAIDs are unsuitable.
constipation is common, especially in the elderly but it may
be minimised by encouraging a high fibre diet and plenty of
fluids prescribing prophylactic laxatives.
Other Drugs:
Topical analgesic such as NSAIDs, capsaicin, or rubefacients
may also provides some degree of pain relief in OA.
[P.N.147,148. MIMS volume 34 number 4.April 2004]
Analgesic activity study[8-19]
Hot-plate method (Thermal stimulus)
The mice selected were weighted (25-30g) and groups into
eight of six in each and the normal basal reaction time were
taken by repeating for 5 times. Group-3 to Group-5 received
chloroform extract and Group-6 to Group-8 received methanol
extracts respectively at a dose of 50mg/kg, 100 mg/kg and
200mg/kg body weight (p.o.). Group- 2 received Morphine
sulphate 5mg/kg body weight (s.c.) and served as standard.
Group- 1 administrated 1% DMSO in the dose of 10ml/kg
body weight (p.o.) served as control. All animals were
lowered onto the surface of a hot plate (50±1.00C) enclosed
with cylindrical glass and the time for the animal to jump or
lick the fore limb was noted as the reaction time (RT). Cut off
time in the absence of a response was 15 sec to prevent the
animals from being burnt. The observations were made before
and after administration of respective drugs at 30 min, 60 min,
120 min, and at the end of 180 min.
Tail immersion Test (Thermal stimulus)
The Swiss albino mice were selected by immersing the tail in
hot water at temperature 55
0
C ±5
0
C and the basal reaction
time was noted. The mice which showed a positive response
within a span of 5 seconds for withdrawal of the tail clearly
out of water were selected for further studies. The mice
selected were weighted (25-30g) and groups into eight of six
in each and the normal basal reaction time were taken by
repeating for 5 times. Group 3 to Group 5 received chloroform
extract and Group 6 to Group 8 received methanol extract
respectively at a dose of 50mg/kg, 100 mg/kg and 200mg/kg
body weight. Group 2 received Morphine sulphate 5mg/kg
body weight (s.c.) and served as a positive control. Group 1
served as solvent control (1% DMSO) and received the dose
of 10ml/kg body weight. The observations were made before
and after administration of respective drugs at 30 min, 60 min,
120 min, and at the end of 180 min.
Writhing Test (Chemical stimulus)
Aspirin like non-narcotic analgesic activity of the test extracts
was investigated by the ability to protect a painful writhing
syndrome in mice. The syndrome is characterized by
abdominal torsion, drawing up of hind limbs to the abdominal
wall, marked contraction of the abdominal area and periodical
arching of the back to rub the abdominal wall on the glazed
surface on which the mouse is kept. Writhing was consistently
produced in mouse by an intra peritoneal injection of 0.6%
aqueous acetic acid. Overnight fasted, healthy adult male
albino Swiss mice weighing between 18 to 25gm in groups of

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Review Article 103
six each were taken for present investigation. DMSO 1%
solution of the test extracts were administered orally in a dose
of 50mg/kg, 100mg/kg and 200mg/kg body weight
respectively to the test groups animal. The control group of
animals were given only DMSO 1% solution in the dose of
10ml/kg body weight. One group of animal was administered
with Diclofenac sodium as standard, orally in a dose of
5mg/kg (b.w). After a gap of 30 minutes of the administration
of the test extracts, all the groups of mice were given the
writhing agent, 0.6% aqueous acetic acid, in a dose of
1ml/100gm (b.w) intra peritoneally. Five minutes after
administration of acetic acid the number of writhing produced
in these animals were counted for next 10 minutes and the
number of writhing produce in the treated groups were
compared with those in the control group and the percentage
protection was calculated as show below,
Percentage protection = [(No.of writhes in control - No. of
writhes in test)/ No. of writhes in control] x 100
Conclusion
These suggestions are very helpful for most people with
inflammatory conditions such as sprains, strains, bursitis,
tendonitis, arthritis, etc. and can be used in conjunction with
supplementation. Most people find that eating this way also
often lowers blood lipids, smoothes out blood sugar variations,
helps with weight management, reduces digestive problems,
increases energy, and more.
Conflict of interest statement
We declare that we have no conflict of interest.
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