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Evaluation of analgesic and anti-inflammatory effects of fresh onion juice in experimental animals

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  • Payame Noor University, Tehran, Iran

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Onion is a well known traditional medicinal plant that has been consumed for its putative nutritional and health benefits for centuries. This study was carried out to determine the possible analgesic and anti-inflammatory effects of fresh onion juice in experimental animals. Hot plate and formalin tests were used to study the analgesic effect of fresh onion juice in mice during acute and chronic pain stages modeling, respectively. The anti-inflammatory effect of fresh onion juice was assessed by applying carrageenan sub plantar injection to Sprague-Dawley rats. The obtained results illustrated a significant analgesic property for fresh onion juice in both pain phases compared with positive control group (Pv≤0.05); the effects were similar to that of morphine (5 mg/kg) as the standard treatment. In inflammation assessment, fresh onion juice was able to decrease the hind paw thickness significantly in comparison with control group (Pv≤0.001). In the mean time, it also demonstrated better results than the standard treatment, diclofenac with a 10 mg/kg dosage, (Pv≤0.05). It can be concluded that fresh juice of onion is capable of inhibiting both acute and chronic pain as well as inflammation, with a more strong effect towards inflammation.
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African Journal of Pharmacy and Pharmacology Vol. 6(23), pp. 1679-1684, 22 June, 2012
Available online at http://www.academicjournals.org/AJPP
DOI: 10.5897/AJPP12.179
ISSN 1996-0816 ©2012 Academic Journals
Full Length Research Paper
Evaluation of analgesic and anti-inflammatory effects of
fresh onion juice in experimental animals
Sima Nasri1, Mahdieh Anoush2* and Narges Khatami1
1Department of Physiology, Payame Noor University of Tehran, Tehran, Iran.
2School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.
Accepted 16 May, 2012
Onion is a well known traditional medicinal plant that has been consumed for its putative nutritional
and health benefits for centuries. This study was carried out to determine the possible analgesic and
anti-inflammatory effects of fresh onion juice in experimental animals. Hot plate and formalin tests were
used to study the analgesic effect of fresh onion juice in mice during acute and chronic pain stages
modeling, respectively. The anti-inflammatory effect of fresh onion juice was assessed by applying
carrageenan sub plantar injection to Sprague-Dawley rats. The obtained results illustrated a significant
analgesic property for fresh onion juice in both pain phases compared with positive control group
(Pv≤0.05); the effects were similar to that of morphine (5 mg/kg) as the standard treatment. In
inflammation assessment, fresh onion juice was able to decrease the hind paw thickness significantly
in comparison with control group (Pv≤0.001). In the mean time, it also demonstrated better results than
the standard treatment, diclofenac with a 10 mg/kg dosage, (Pv≤0.05). It can be concluded that fresh
juice of onion is capable of inhibiting both acute and chronic pain as well as inflammation, with a more
strong effect towards inflammation.
Key words: Allium cepa, analgesic, anti-inflammatory, hot plate test, formalin test, carrageenan test.
INTRODUCTION
Onion (Allium cepa) is among the oldest cultivated plants,
and it is used both as a food and for medicinal application
(Lanzotti, 2006). A. cepa is a member of the family
Liliaceae, which consist of over 250 genera and 3700
species. The origin of A. cepa may be the region between
the rivers Euphrates and Tigris, which is the former
Mesopotamia and actually Iraq (Hegi, 1939). Nowadays
onion is cultivated all over the world, especially in
moderate climates (Muhlbauer et al., 2003).
Onion bulbs consist of water, carbohydrate, fibre,
protein, fat, vitamins (C, E) and minerals. This plant is a
rich source of several phytonutrients with interesting
*Corresponding author. E-mail: anoushm@zums.ac.ir. Tel: +98
241 4273637. Fax: +98 241 4273639.
Abbreviations: LT, Latency time; IP, intra-peritoneal; FOJ,
fresh onion juice.
pharmacological properties such as thiosulphinate,
volatile sulfur compounds and more polar compounds of
phenolic or steroidal origin like flavonoids (Lanzotti,
2006). Therefore, onion is among those useful plants for
treatment or prevention of a number of diseases,
including cancers (Shenoy and Choughuley, 1992;
Shutenko et al., 1999), coronary heart diseases (Lanzotti,
2006), diabetes (Sheela et al., 1995) and cataract
(Sanderson et al., 1999). Besides, many scientific
researchers showed that onion extract has significant
antioxidant activity because of its high amount of
flavonoids such as quercetin. (Nuutila et al., 2003; El-
Sayed and Rizk, 2009).
A study in the year 2003 showed that hydrophilic
ethanolic extract of onion inhibited osteoclast activity and
increased the bone formation process (Muhlbauer et al.,
2003(. In addition, it has been shown recently that the
oral intake of fresh onion juice had both spermatogenesis
and anti-protozoal effects in Toxoplasma gondii infected
rats (Khaki et al., 2011; Gharadaghi et al., 2012). Also,
1680 Afr. J. Pharm. Pharmacol.
there was an evidence of possible anti-inflammatory
effect for onion extract (Alpsoy et al., 2011). Inflammation
is as a result of increase in the number of leukocytes and
some other complex mediator molecules. One of the
most important ubiquitous substances that indicate and
modulate cell and tissue responses involved in
inflammation are prostaglandins (Gupta et al., 2006).
Among the most widely used medications for analgesia
and inflammation are the non-steroidal anti-inflammatory
drugs (NSAIDS) and their worldwide use demonstrated
their efficacy in reducing pain and inflammation (Laine,
2001). The NSAIDs consist of traditional non-selective
NSAIDs which inhibit both COX-1 and COX-2 and
selective COX-2 inhibitors (Ulrich et al., 2006). Although
they are effective at relieving pain and inflammation, both
types of NSAIDs are associated with serious adverse
events specially when used chronically (Herndon et al.,
2011). The traditional NSAIDs are associated with an
increased risk of gastrointestinal ulcers, including
gastrointestinal hemorrhage, perforation and obstruction
(Dhikav et al., 2003). The selective COX-2 inhibitors have
an improved gastrointestinal tolerability profile; however,
serious cardiovascular effects emerged from clinical
studies in recent years (Ong et al., 2007). Thus, many
researchers have dedicated their efforts to search for
safer drugs as well as natural products with less adverse
effects.
In this study, the analgesic effect of fresh onion juice in
both chronic and acute pain induction model with hot
plate and formalin test respectively in mice, as well as its
anti-inflammatory effect using carrageenan induced paw
edema in rats were investigated.
MATERIALS AND METHODS
Experimental animals
Male albino mice (25 to 30 g) and male Sprague-Dawley rats (220
to 250 g) were used in this study. Animals were obtained from
Tehran University of Medical Sciences and housed in the animal
holding unit of the School of Pharmacy at Zanjan University of
Medical Sciences with a 12 h light-darkness cycle, air-conditioning
(22 ± 2°C 45 to 55% humidity) in plexi-glass cages and free access
to food and water. All animals received human care according to
the guidelines published by the National Institutes of Health (NIH,
2000). The ethic regulations were followed in accordance with
national and institutional guidelines for the protection of animal
welfare during experiments. This study was approved by The Ethics
Committee of Payame Noor University. All animals were given three
days time to get acclimatized with laboratory conditions before
experiments begin.
Chemicals
Carrageenan lambda type I and formalin 35% solution were
purchased from Sigma-Aldrich Co. (Hamburge, Germany). Sodium
chloride solution 0.09% was obtained from Soha Helal
Pharmaceutical Hygienic (Tehran, Iran), while morphine and
diclofenac ampoules were bought from Darou Pakhsh
Pharmaceuticals Mfg. Co. (Tehran, Iran) and Tolid Darou Co.
(Tehran, Iran) respectively.
Preparation of fresh onion juice
Fresh white onions (A. cepa.) was purchased from a retail store
(Zanjan, Iran) and identified by botanists in the herbarium of School
of Pharmacy, Zanjan University of Medical Sciences. On the day of
experiments the onions were pealed, weighed and crushed well in
an electrical mill. Then the crushed product was filtered using sterile
filter papers with 40 micrometers mesh size. The transparent liquid
obtained was used freshly within 2 h after preparation to investigate
the possible analgesic and anti-inflammatory effects.
Carrageenan-induced paw edema in rats
Male Sprague-Dawley (S.D) rats (n=36) were divided into six
groups with six rats in each. Paw edema was induced by sub-
plantar injection of 50 µl 1% (w/v) solution of sterile carrageenan in
saline to the right hind paw (Zhang et al., 2011). Three groups of
animals received different doses of fresh onion juice (5, 7.5 and 10
ml/kg) intraperitoneally (I.P) half an hour before carrageenan
injection. Animals in the negative control group received normal
saline, while animals in the positive control group were
administered 10 mg/kg of diclofenac (Darou Pakhsh, Iran), the
standard anti-inflammatory drug and another group given 5 mg/kg
of morphine (Tolid Darou, Iran) intraperitoneally. Paw edema was
measured according to Olajide et al. (1999); before and at 1, 2, 3
and 4 h after induction of inflammation using a caliper vernier (scale
0.1 mm).
Hot plate method
The hot plate test described by Eddy and Leimback (1953) was
used to assess the analgesic effects of fresh onion juice (Kumar et
al., 2009). The animals were divided into six groups with eight mice
in each. Three groups were treated with different doses of fresh
onion juice (5, 7.5 and 10 ml/kg) via I.P injection; one group
received normal saline (7.5 ml/kg) as negative control group,
another group, received morphine (5 mg/kg) as positive control and
the final group of mice received naloxone (4 mg/kg) 10 min before
fresh onion juice. Moreover, 15 min after the administration of fresh
onion juice; the animals were placed on a hot plate with 50 ± 0.5°C.
A cut-off time period (40 s) was considered as maximal latency at
which the animal was picked up from the hot plate by the examiner
to avoid injury to mice tissues. Licking or picking up the hind paw
was recorded as the reaction time and measured at time points of
0, 15, 30, 45 and 60 min (Kumar et al., 2009). Morphine (5 mg/kg)
was used as a reference drug (Abbas et al., 2011).
Formalin test and the pain score
In order to perform this test, 32 male S.D rats were rendered in 4
groups with 8 rats in each as follows: Negative control group
received 7.5 ml/kg of normal saline, while positive control group
treated with 5 mg/kg morphine as the standard drug intra-
peritoneally 15 min before formalin injection. The test group
received 7.5 ml/kg fresh onion juice (as an optimum dose) and one
group received I.P injection of naloxone (4 mg/kg) 15 min before
formalin injection. Formalin test chamber includes a plexi glass box
with a 45° mirror at the bottom of the box in order to monitor the
position of the animal in the chamber for accurate observation. All
of the animals received formalin as the standard stimulant of both
acute and chronic phase of inflammatory pain (Kim et al., 2007).
Prior to formalin injection, the animals were placed in another cone
shaped chamber for 30 min. After injection of 50 µL formalin (2.5%)
into their right paw, they were transferred to the plexi glass box and
were observed by recording the reflexes every 15 s based on
Nasri at al. 1681
4
4.5
5
5.5
6
6.5
7
7.5
8
8.5
0
60
120
180
240
Time (min)
Hind paw thickness (mm)
(mm)
Morphine (5 mg/kg)
Diclofenac (10 mg/kg)
Control (normal saline 7.5
ml/kg)
***
***
***
***
**
***
***
***
Figure 1. The effects of fresh onion juice, morphine and diclofenac towards hind paw edema in carrageenan
induced acute inflammation. A vernier caliper was applied to measure the hind paws thickness right before and
at four time points with 60 min intervals. Each measurement was repeated three times and the average was
recorded for that animal. The diagram shoes that FOJ was even more effective than both diclofenac and
morphine. All values represent mean ±S.E.M and are at least from 8 independent animals. **Shows significant
difference (p≤0.01) with control group; ***Shows significant difference (p≤0.001) with control group.
original Dubuisson Dennis method with the score of 0, 1, 2, 3 as
follows (Abbott et al., 1995): zero (0) score mentions that animal
has a complete balance and is walking normally regardless to the
injected foot; score (1) applied for the time points that the animal
has a moderate imbalance while moving because of pushing the
body weight towards the injected foot; score (2) was correlated to
the time points when animal was not only walking with a high
imbalance but also raising the painful injected foot from the box
floor; score (3) is given to the animal licking the painful injected feet
intensely or shaking it. The quantitative data was counted per 5 min
and recorded based on the pain score on each time interval. The
data gathered within 60 min after formalin injection was calculated
as follows:
Pain score: [0T0 + 1T1 + 2T2 + 3T3] / 20
Where T0, T1, T2 and T3 refer to the frequency for 15 s that animals
expressed behaviors related to 0, 1, 2 and 3 scores, respectively.
The first 5 min after injection for all groups was taken as acute
phase 0 to 5 min and 16 to 60 min as chronic phase.
Statistical analysis
In order to perform comparative statistical analysis of the results
between different groups, SPSS 17.0 software was applied. All the
results were expressed as (mean ± SEM) and P values equal or
less than 0.05 (Pv≤0.05) were determined as significant levels of
difference.
RESULTS
Effects of morphine and fresh onion juice on
carrageenan-induced inflammation
As shown in Figure 1, the thickness of hind paw was
measured after a sub-plantar injection of carrageenan
while rats were received diclofenac, morphine, fresh
onion juice and normal saline as positive control,
morphine test, fresh juice test and negative control
groups, respectively. Interestingly, fresh onion juice
illustrated the best response in this test and showed a
significant difference not only with negative control group
(PV ≤0.001), but also with the group which received both
morphine and diclofenac (PV ≤0.05); the later one was
selected as our standard treatment for anti inflammatory
assessments.
Effects of morphine and fresh onion juice on hot
plate acute pain model
Using this method, the sensitivity of mice towards pain
stimulates received via a standard hot plate, was
measured. In order to access the least bias with control
group, the ratio of latency time changes were measured
applying the formula below for each mouse:
(L.Tt - L.T0) / L.T0
L.Tt expresses the latency time for each mouse in the
specific time intervals after receiving treatments, while
L.T0 shows the latency time at the zero point just prior to
receiving any treatment.
According to the dose-response curve results, the 7.5
ml/kg dosage had the best latency time responses.
Therefore, this dose has been used later on, in other
protocols and tests. It can be deducted from Figure 2
1682 Afr. J. Pharm. Pharmacol.
Time (min)
15 30 45 60
Control (7.5 ml/kg)
Naloxone (4 mg/kg) + OFJ (7.5 ml/kg)
Morphine (5 mg/kg)
OFJ (7.5 ml/kg)
Figure 2. The analgesic effects of fresh onion juice in comparison with that of morphine on hot plate test. The
latency time for animals’ response to hot plate stimulus was measured within 15 min intervals during 60 min. The
FOJ’s injection moment was equal to 0 time point. The results were calculated as (L.Tt- L.T0)/ L.T0. naloxone was
used as an antagonist for opioid receptors in order to determine if the extract show its effect via opioid receptors. All
values represent Mean ±S.E.M and are at least from 8 independent animals. **Shows significant difference (p≤0.01)
with control group; ***Shows significant difference (p≤0.001) with control group.
thatmorphine has the best analgesic effect with a
noticeable significant difference (PV≤0.001) which was
almost the same for the fresh juice especially in first 30
min. This result expresses that the fresh juice plays its
best role as an analgesic agent in first 30 min with a high
significant difference according to control group
(PV≤0.05). Although the diagram for morphine illustrates a
sharp increase in the first 30 min followed by a plateau
phase; adding naloxone to the morphine treated ones,
changed the shape of the diagram and makes it similar to
the one for fresh juice.
Effects of morphine and fresh onion juice on
formalin-induced pain
During this method, the pain score was calculated
according to original Dubuisson Dennis method which
has been lately modified (Mokhtari, 2011) during 60 min.
The results obtained from this method indicate that our
treatments were useful in the first 45 min in depriving the
pain score significantly (PV≤ 0.05). According to Figure 3,
no significant difference was observed between morphine
and fresh juice (Pv≥0.05) in controlling both acute and
chronic pain phase which were determined at 0 to 5 min
for acute pain phase, and 16 to 60 for chronic one.
On the other hand, Figure 3 indicates the possible
relationship between the effects of morphine and fresh
juice while we used naloxone together with the fresh
onion juice; as it can be seen there were observed no
significant differences between two groups in all time
intervals. Adding naloxone to morphine received animals
made the diagram more similar to control group, hence
the results for that group was not illustrated in Figure 3.
DISCUSSION
In this study, three different methods have been applied
in order to identify the possible analgesic as well as anti
inflammatory effects of fresh onion juice in mice and rats.
According to the well known models for both hot plate
and carrageenan test, it has been suggested in current
protocols in pharmacology as well as some articles to
apply mice for hot-plate test investigations and rats for
carrageenan induced inflammation (Buadonpri et al.,
2009; Bannon and Malmberg, 2007) Results obtained
from carrageenan test indicates a strong anti-
inflammatory effect with a significant difference not only
with the negative control group (Pv≤0.001), but also with
the positive control one (Pv≤0.05). This finding illustrates
a possible potent COX inhibitory effect of onion juice in its
therapeutic dosage because it was as effective as the
standard treatment (diclofenac) towards inflammation.
The odd finding of this step was the similar anti
inflammatory response for both morphine and diclofenac.
This finding is a subsidiary for the very recent finding of a
research group in Denmark proving a noticeable anti-
inflammatory characteristic for opioids in general, as well
as morphine in particular (Lindegaard et al., 2010) with
an unknown mechanism.
According to some studies, fresh onion juice is capable
Nasri at al. 1683
-0.5
0
0.5
1
1.5
2
2.5
0
1
2
3
4
5
6
7
8
9
10
11
12
Time intervals (every 5 min)
Control (normal salin 7.5ml/kg)
Naloxone (4mg/kg)+OFJ (7.5ml/kg)
OFJ (7.5ml/kg)
Morphine (5 mg/kg)
**
***
*
***
***
***
**
*
*
Pain score
Figure 3. The effects of fresh onion juice, morphine and naloxone plus FOJ on both acute and chronic pain phases
induced by formalin in male mice. Right after formalin injection, the pain scores were calculated during one hour and
because of the biphasic nature of pain, the acute phase was allocated the first 5 min after formalin injection, while
chronic pain arose between 20 to 25 min and lasted for 10 min. This figure illustrates the significant differences
between treated groups and control group which received normal saline. All values represent Mean ±S.E.M and are at
least from 8 independent animals. * Shows significant difference (p≤0.05) with control group; **shows significant
difference (p≤0.01 with control group; ***shows significant difference (p≤0.001) with control group.
of inhibiting arachidonic acid metabolism (Dorsch et al.,
1988) and so it can prevent formation of leukotrienes and
thromboxanes, via inhibiting COX and LOX
(lipoxygenase) pathways responsible for its anti apoptotic
effect (Alpsoy et al., 2011). On the other hand, it was
proven that flavonoids express anti-inflammatory
properties by which they inhibit the proliferation and
activity of lymphocytes (Recio et al., 1995). According to
high content of flavonoids such as quercetin (Lanzotti,
2006) in onion juice and extract, it can be claimed that
this potent anti-inflammatory effect might be because of
quercetin as would need to be investigated in further
studied. Moreover, one paper suggested that onion can
cause analgesia as well as local anesthesia via
mitochondria (Nouette-Gaulain et al., 2011); which
encouraged us towards assessment of the analgesic
capability for fresh onion juice.
The analgesic effect of fresh onion juice was studied
via two different processes. The hot plate test results
indicated that the fresh juice was helpful in reducing
acute pain in comparison with the negative control group
that received mere normal saline (Pv≤0.05). This effect
was not as potent as morphine (the standard treatment),
with a high significant difference (Pv≤0.001) compared
with negative control group. Moreover, in order to
examine if fresh onion juice penetrates the CNS system
and affect the same receptors as for morphine, naloxone
was injected to one group simultaneously with fresh
onion juice. The results indicated that there might not be
any interactions between these two treatments (morphine
and fresh onion juice). Hence, more studies are needed
to determine the possible analgesic pathway by which
fresh onion juice attenuates pain; which led us to set up
another test using formalin in order to compare the acute
and chronic pain and the effects of both treatments on
these two phases of pain.
Formalin test results showed that fresh juice illustrated
significant analgesic effect both in acute and chronic pain
phases which were assumed as the first 5 min after
formalin sub-plantar injection and the time period
between 16 to 50 min, respectively. It has been assumed
that these two stages represent two different type of pain
related to direct nerve stimulation (acute pain) followed
by an inflammatory process (chronic stage). Diverse
studies proved that opioids such as morphine affect both
stages with the highest inhibitory response presumably
via mu receptors in the central nervous system (Abbas et
al., 2011); on the other hand, there are NSAIDs such as
indomethacine with the most inhibition towards the
chronic stage via COX inhibition (Randolph and Peters,
1997).
According to the literature, reduction in pain,
inflammation and the signal transduction pathway(s)
responsible for both phenomena mentioned above,
results in a decline in plasticity at dorsal root of spinal
cord via deprivation in P substance and/or stimulant
amino acids such as glycine and glutamate from nerve
endings (Willis, 2001; Hunter and Singh, 1994; Terayama
1684 Afr. J. Pharm. Pharmacol.
et al., 2000). In addition, there is a substance called
ajoene found both in garlic and onion which has been
proposed to inhibit the pain receptors at dorsal root of
spinal cord, thus resulting in an inhibition of pain signal
transduction (Yassaka et al., 2010).
Conclusion
It can be concluded that the fresh onion juice is capable
of inhibiting pain and inflammation, the later most
especially, and both the exact mechanism(s) for this
effect via receptor purification as well as the main fraction
responsible for, should be studied in the near future.
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... Allium cepa L. (Liliaceae) is commonly known as onion. The Liliaceae family includes over 250 genera and 3700 species (Nasri et al. 2012;Akash et al. 2014;Bisen and Emerald 2016). Onion, one of the oldest cultivated plants (Lanzotti 2006), originated from central Asia (Benkeblia 2004;Albishi et al. 2013) and is currently cultivated all over the world, particularly in zones with moderate climates (Nasri et al. 2012;Bisen and Emerald 2016). ...
... The Liliaceae family includes over 250 genera and 3700 species (Nasri et al. 2012;Akash et al. 2014;Bisen and Emerald 2016). Onion, one of the oldest cultivated plants (Lanzotti 2006), originated from central Asia (Benkeblia 2004;Albishi et al. 2013) and is currently cultivated all over the world, particularly in zones with moderate climates (Nasri et al. 2012;Bisen and Emerald 2016). A. cepa is characterised by its colour (yellow, red, or white), and taste (sweet or non-sweet) (Benkeblia 2004;Albishi et al. 2013). ...
... In Chinese medicine, A. cepa tea is used against fever, headache, cholera, dysentery, common cold, and arthritis (Corzo-Mart ınez et al. 2007). This plant was also used as an antifungal (Lanzotti 2006), anticancer, anti-inflammatory (Elberry et al. 2014), antioxidant, antispasmodic (Albishi et al. 2013;Benmalek et al. 2013), antimicrobial, antimutagenic (Shri and Bora 2008), antidiabetic (Ali et al. 2000;El-Aasr et al. 2010;Nasri et al. 2012), antiplatelet (Galmarini et al. 2001), and anti-asthmatic agent (Takahashi and Shibamoto 2008). Moreover, A. cepa showed antimicrobial, antithrombotic, antitumor, anti-hyperlipidaemic, anti-arthritic, anti-hyperglycemic anticarcinogenic properties (Upadhyay 2017). ...
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Context Allium cepa L. (Liliaceae), known as onion, is consumed throughout the world. Onion and its derivatives including saponins, aglycones, quercetin, cepaenes, flavonoids, organosulfurs, and phenolic compounds, showed various pharmacological properties and therapeutic effects. Objective Anti-inflammatory, antioxidant, and immunomodulatory effects of A. cepa and its main constituents, along with the underlying molecular mechanisms are presented. Methods Databases including, Web of Knowledge, Medline/PubMed, Scopus, and Google Scholar were checked for articles published between 1996 and the end of July 2020, using the key-words Allium cepa, quercetin, anti-inflammatory, antioxidant and immunomodulatory. Results A. cepa and its constituents mainly quercetin showed anti-inflammatory effects mediated via reduction of total and differential WBC counts, inhibition of chemotaxis of polymorphonuclear leukocytes, COX, and LOX pathways and prevented formation of leukotrienes and thromboxanes, prostaglandin E2 (PGE2) as onVCAM-1, NF-κB, MARK,d STAT-1, JNK, p38 and osteoclastogenesis. A. cepa and its derivatives showed antioxidant effect by decreasing lipid peroxidation, NAD(P)H, MDA, NO, LPO and eNOS but enhancing antioxidants such as SOD, CAT, GSH, GPx, GSPO, TrxR, SDH, GST and GR activities and thiol level. Immunomodulatory effects of the plant and quercetin was also shown by reduction of Th2 cytokines, IL-4, IL-5, and IL-13 as well as IL-6, IL-8, IL-10, IL-1β and TNF-α and IgE levels, but increased CD4 cells, IFN-γ level and IFN-γ/IL4 ratio (Th1/Th2 balance). Conclusions The effect of onion and its constituents on oxidative stress, inflammatory and immune system were shown indicating their therapeutic value in treatment of various diseases associated with oxidative stress, inflammation, and immune-dysregulation.
... Onion is a bulbous herb which belongs to the family Liliaceae and is cultivated all over the world and used as an ingredient in food and also consumed for medicinal purposes [16]. Nasri and colleagues [17] investigated the anti-inflammatory effects of onion in animals and attributed its anti-inflammatory properties to cyclooxygenase inhibition. According to Marefati and colleagues [18], onion extract significantly reduces IL-4 levels while increasing IFN-γ and IFN-γ/IL-4 ratio in Broncho alveolar lavage fluids of ovalbuminsensitized rats. ...
... Quercetin  Anti-inflammatory: by suppressing cyclooxygenase, IL-4 and IL-5, IL-6, IL-1β and TNF-α activities [17][18][19][20]. ...
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COVID-19 is a global pandemic that has claimed over 6,000,000 deaths since its appearance in late 2019. It is caused by the virus SARS-CoV2. In severe COVID-19 patients, the transition to ARDS is primarily due to cytokine storm, which is characterised by excessive inflammatory response and elevated levels of ferritin and pro-inflammatory cytokines in the serum, infiltration of neutrophils and monocytes into the lung; and reduced viral inhibiting cytokines, all of which contribute to the severity of the disease leading to death. The focus of this review is on the collation of medicinal plants with strong anti-inflammatory activities, which could be used alone or synergistically for enhanced therapeutic effect to cushion cytokine storm damaging effects. The plants collated evidently show by in vitro and in vivo analysis strong anti-inflammatory effects via suppression of Interleukin-8, Interleukin-6, Interleukin-1α, Interleukin-1β, Tumor Necrosis Factor-α, Interferon-γ, monocyte chemo-attractant protein-1, and nuclear factor kappa B (NF-κB) expression, in addition to inhibiting cyclooxygenase I and II (COX I and II), and inducible nitric oxide synthase (iNOS) activity. The medicinal plants collated in this review could be used alone or synergistically in the future in clinics for enhanced therapeutic effects to cushion cytokine storm damaging effects. Isolation of the active principle and studies of the specific mechanism of action of the plants could be the objectives of future research.
... Allium cepa (Liliaceae) Bulbs Organic sulfur compounds, including trans-S-(1propenyl) cysteine sulfoxide, S-methyl-cysteine sulfoxide, S-propylcysteine sulfoxide and cycloalliin; flavonoids; phenolic acids; sterols including cholesterol, stigma sterol, β-sitosterol; saponins; sugars and a trace of volatile oil composed mainly of sulfur compounds, including dipropyl disulfide, fructans Antimicrobial, anti-inflammatory Petroleum ether, methanol and aqueous extracts [40][41][42] ...
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Rheumatoid Arthritis (RA) is a chronic autoimmune disease of unknown aetiology that affects 0.5% of the population and can result in disability owing to joint destruction, characterized by joint synovial inflammation and progressive cartilage and bone destruction resulting in gradual immobility. The greatest disadvantage in the presently available potent synthetic drugs lies in their toxicity and reappearance of symptoms after discontinuation. With limitations of existing drug molecules herbal drugs are gaining interest among RA patients. Medicinal plants are plants containing inherent active ingredients used to cure disease or relieve symptoms of arthritis. The aim of this review is to update information on RA including causes, epidemiology, prevalence, symptoms and diagnosis, classification, medications, toxicities of allopathic anti-rheumatic drugs and importance of herbal drugs for the management of RA. The present review also focuses on the medicinal plants that interact with the mediators of inflammation and are used in the treatment of rheumatoid arthritis (RA).
... In antiinflammation study, fresh onion juice was able to decrease the hind paw thickness significantly in comparison with control group and standard diclofenac group with a 10 mg/kg dosage. It can be concluded that fresh juice of onion is capable of inhibiting both acute and chronic pain as well as inflammation, with a stronger effect towards inflammation [27]. These results suggest that the leaves of the plant might be used as a potential source to treat gout and other inflammatory disorders [28] . ...
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Hyperuricemia is a clinical condition characterized with excess of uric acid in the blood. It develops either by overproduction of uric acid caused by a metabolic disorder or due to under excretion of blood uric acid due to abnormal renal urate transport activity. Gout is a chronic progressive rheumatic disease in which elevated serum urate levels lead to the precipitation of monosodium urate crystals within the joints and other tissues. Medicinal plants have been used to treat various ailments since ancient times; hence, ethnobotanical investigations play an important role in pharmacological studies. This article provide a comprehensive review ofsome Evidence based In-silico, In-vitro, In-vivo and Clinical studies to support the scientific use of Ayurveda herbal medicine for hyperuricemia and and Gout. Ayurvedic Medicinal plants with Anti-inflammatory, Analgesic, Anti-hyperuricemic, Anti-oxidant property along with Mūtrarōgahara, Śōthahara, Vātahara, Āmavātahara properties are expected to have effect in Hyperuricemia and Gout. The purpose of this review is to collect and document information of the Ayurveda herbal medicine with anti-hyperuricemic and anti-gout potential.
... Allium cepa L. (A. cepa) or onion species are used as vegetables and employed in traditional medicine as therapeutic agents [1][2][3]. Onion is a perennial plant that is cultivated in almost all countries, mainly in moderate climate regions such as Iran [4][5][6]. ...
Article
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The health benefits of Allium cepa (A. cepa) have been proclaimed for centuries. Various pharmacological and therapeutic effects on respiratory, allergic, and immunologic disorders are shown by A. cepa and its constituents. Flavonoids such as quercetin and kaempferol, alk(en)yl cysteine sulfoxides including S-methyl cysteine sulfoxide and S-propyl cysteine sulfoxide, cycloalliin, thiosulfinates, and sulfides are the main compounds of the plant. A. cepa displays broad-spectrum pharmacological activities including antioxidant, anti-inflammatory, antihypertensive, and antidiabetic effects. Our objective in this review is to present the effects of A. cepa and its constituents on respiratory, allergic, and immunologic disorders. Different online databases were searched to find articles related to the effect of A. cepa extracts and its constituents on respiratory, allergic, and immunologic disorders until the end of December 2020 using keywords such as onion, A. cepa, constituents of A. cepa, therapeutic effects and pharmacological effects, and respiratory, allergic, and immunologic disorders. Extracts and constituents of A. cepa showed tracheal smooth muscle relaxant effects, indicating possible bronchodilator activities or relieving effects on obstructive respiratory diseases. In experimental animal models of different respiratory diseases, the preventive effect of various extracts and constituents of A. cepa was induced by their antioxidant, immunomodulatory, and anti-inflammatory effects. The preventive effects of the plant and its components on lung disorders induced by exposure to noxious agents as well as lung cancer, lung infection, and allergic and immunologic disorders were also indicated in the experimental and clinical studies. Therefore, this review may be considered a scientific basis for development of therapies using this plant, to improve respiratory, allergic, and immunologic disorders.
... Onion (Allium cepa L.), a member of Amaryllidaceae family, is one of the most economically important vegetables in all parts of the world due to its nutritional and medicinal values, including anticancer, anti-cholesterol, anti-inflammatory and antioxidant properties (Nasri et al., 2012). At the same time, onion contains important amounts of mineral salts, sulphur and potassium salts, and various trace elements, vitamins (B1, B2, C, E, K), carotene (provitamin A), glycosides, etheric oils and plant hormones like insulin (Slimestad et al., 2007). ...
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In this study 269 phosphate solubilizing bacteria (PSB) strains were isolated from onions rhizosphere. The 15 most efficient PSB were selected. Based on BIOLOG profiling and the LOPAT test system, the strains were identified as Enterobacter cloacae (7), Yersinia intermedia, Pantoea agglomerans, Bacillus subtilis(2),Bacillus pumilius, Lysinibacillus sphaericus and Bacillus atrophaeus(2). The PSB effect on onion growth was investigated under greenhouse conditions. These PSB increased plant height (11.7 to 38.8%), the number of leaves (3 to 70%), the bulb diameter (6.4 to 64.5%), the average root length (2.6 to 44.7%),the fresh weight of the bulb (2.9 to 34.1%) and the dry weight of the bulb (1.5 to 40.6%) when compared to the negative control. Among these strains the most effective inoculants were the highest P solubizing E.cloacae EB-14 and E. cloacae OB-169 strains, which significantly increased all parameters compared to the commercial plant activator ISR 2000. These results demonstrated the potential use of these PSB as inoculants for onion growth.
... (Nationalhorticulture database 2018). Onions are a good source of dietary fiber, protein and also provide potential health benefits such as reducing cancer, lowering blood sugar, improving bone health, and also acting as an anti-inflammatory (Nasri et al. 2012). Many fungal, bacterial, and nematode diseases decrease the productivity of the onion. ...
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Chitinase-producing Trichoderma species have been recognized long ago against the phytopathogenic fungi. In this study, we evaluated the production of chitinase enzyme for seventeen isolates of Trichoderma isolated from onion growing districts of Punjab and assessed their bio-efficacy against damping-off in onion. In vitro, these Trichoderma isolates were screened for their antagonistic activity against the damping-off pathogen Fusarium oxysporum f.sp. cepae by dual culture assay. These isolates were also screened for their chitinase enzyme activity; it was found that isolates T5 and T8 are showing higher antagonistic activity on Fusarium oxysporum f.sp. cepae and also produced large amounts of chitinase enzymes in the presence of commercial colloidal chitin. The selected chitinolytic isolates were used in field studies to confirm the feasibility of their biological control efficacy against onion damping-off. In the field experiment, the seed+soil treatment of chitinolytic isolate (T8) showed a critical decrease of damping-off in onion by 88.75% over control.
... In this vein, it was proven that flavonoids express anti-inflammatory properties by which they inhibit the proliferation and activity of lymphocytes [24]. Acetic acid induced writhing test is a model of visceral pain which is a very sensitive test for analgesic drugs [25]. It clearly indicated that aqueous extract of Violet of galmi exhibited more degree of anti-inflammatory activity than Goudami extract. ...
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Background oxidative stress and inflammation remain the main health problems often linked to degenerative diseases. The aim of this study was to evaluate antioxidant, analgesic and anti-inflammatory properties of onion growth in Cameroon. Methods Aqueous extracts were produced from two varieties of onion (Violet of galmi; Goudami) and were quantified for their polyphenols content. Concentrations of extracts (0.1, 0.5, 1, 1.5 mg/mL) were also prepared, their in vitro antioxidant properties evaluated by using standard methods. Anti-inflammatory effect of onion extracts was assessed by applying carrageenan sub plantar test to Wistar rats, but acetic acid test was used to study analgesic effect. Results The polyphenols content and antioxidant activities of onion extracts changed significantly ( p < 0.05) with variety and increased ( p < 0.05) with concentration. Total phenolic (range 58.03–67.43%), Total Reducing power (range 0.27–0.94%), DPPH radical scavenging (range 37.33–202.08%) were higher in Violet of galmi extracts, while Ferrous ion chelating power (range 23.15–97.42%) was higher in Goudami extract. The two varieties of onion extracts reduce ( p < 0.05) rat paw edema in a dose dependent manner compared with negative control group. Violet of Galmi variety (1.5 mg/kg) reaches 100% of inhibition after 2 h whereas the Goudami variety (1.5 mg/kg) reaches 100% of inhibition after 3 h. In terms of analgesic activity, aqueous extract of the two varieties of onion exhibited analgesic effect characterized by reduction in writhes. Analgesic activity increased significantly ( p < 0.05) with concentration of onion but Violet of galmi extracts has also shown more efficacy than Goudami extracts. Conclusion The present findings suggest that aqueous extract of violet of galmi and Goudami bulb onions have antioxidant activity and protective effects against inflammation and pain.
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The importance of traditional and indigenous knowledge is acknowledged on a worldwide scale for its coexistence principles and sustainable use techniques. In view of this, the present study is an attempt to document the ethno-veterinary plants used by the tribal communities of Western Himalaya. This study also provides the scientific validation of herbal medicines used in ethno-veterinary practices through a reverse pharmacological approach. A total of 59 informants were selected through a non-probability sampling method. Detailed information on the medicinal plants used in ethno-veterinary practices along with their habits and habitats, part/s used, remedy preparation methods, additives/ingredients used during preparation and administration, dosages administered, and route of administration was collected. Data was analyzed for the Relative Frequency of Citations (RFC), Use Values (UV), Informant Consensus Factor (ICF), and Jaccard Index (JI). Further, a reverse pharmacological approach was used for scientific validations of the documented herbal knowledge of plant species. During the study, 56 plant species belonging to 54 genera and 39 families were documented. Asteraceae was the dominant family followed by Lamiaceae, Amaranthaceae and Fabaceae. Life forms were dominated by herbaceous species and leaves were the most common plant parts used. The highest Relative Frequency of Citations (RFC) and Use Values (UV) were recorded for Brassica rapa L. (Brassicaceae). The Pearson correlation coefficient between RFC and UV shows a strong positive correlation between the proportion of uses of a plant species within a sample of informants and the number of times that a particular use of a plant species was mentioned by the informant. Studies of the biological activity of ethno-veterinary plants can provide clues of promising leads for the isolation and identification of useful compounds that may be developed into pharmaceuticals for human welfare.
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The possible protective potentials of quercetin (50 mg/kg, p.o.), green tea extract (1 mg/kg, p.o.) malt extract (625 mg/kg, p.o.) and deprenyl (10 mg/kg, i.p.) against paraquat (PQ)-induced lung injury in rats were examined. PQ was administered twice a week (20 mg/kg, i.p.) with or without daily pretreatment with any of the chosen agents for 3 successive weeks. Changes in the enzymatic activities of myeloperoxidase (MPO), superoxide dismutase (SOD) and lactate dehydrogenase (LDH) as well as reduced glutathione (GSH), protein thiols (Pr-SHs) and nitric oxide (NO) contents of the lungs were determined. In addition, estimation of lung content of thiobarbituric acid reactive substances (TBARS) measured as malondialdehyde. Moreover, histopathological examination of the lung tissue was performed. On the biochemical level, PQ provoked remarkable lung damage noted by elevation of neutrophils MPO activity accompanied by decreased activities of cytosolic SOD and LDH, depletion of GSH and Pr-SHs contents as well as increased production of NO and TBARS. Furthermore, histopathological examination revealed marked edema, subpleural hemorrhage, acute inflammation and lymphocytic infiltration. Treatment significantly protected against most of PQ-induced lung biochemical and histopathological changes. It could be concluded that quercetin, green tea, malt extract and deprenyl offered remarkable protection against PQ-induced lung injury.
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Non-steroidal anti-inflammatory drugs are among the most frequently prescribed drugs worldwide. Because of their 'over-the-counter' (OTC) availability, they are also consumed on non-prescription basis as well. Though reasonably safe in most cases in prescribed dosages and for short durations, these drugs cause gastrointestinal toxicity in a large number of cases. They can affect all segments of the gastrointestinal tract. In the mouth, they cause oral ulceration, in oesophagus, they can cause ulceration and stricture formation. In stomach and duodenum, they can cause ulcers, severe bleeding, perforation, and obstruction. Most cases of NSAID-induced gastrointestinal ulcers can heal spontaneously, even when the drug is continued. However, in some they can cause serious toxicity requiring hospital admission and aggressive management. Considering the large number of people using these drugs on a daily basis, even if these side effects occur in a small percentage of cases, this translates into a large figure. It is therefore imperative for physicians to be aware about the serious adverse effects associated with them, and use these drugs only when genuinely indicated. Self-medication or indiscriminate use of these drugs as analgesics should be discouraged. Lowest dose of the safe NSAIDs like ibuprofen and diclofenac should be used for shortest possible duration. Once the ulcers develop, they should be treated with proton pump inhibitors such as omeprazole. Prophylactic use of H2 blockers, or antacids is without benefit and is not recommended. However, proton pump inhibitors can also be used prophylactically, especially those at risk of serious toxicity. In such cases, and in those who can afford, cyclooxygenase-2 selective drugs such as celecoxib and rofecoxib can be used. Newer agents like licofelone represent an attractive option.
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Curcumin is the main active ingredient in Curcuma longa L. (Turmeric) and exhibits potent antioxidative and anti-inflammatory activities. In this study, the anti- inflammatory activity of curcumin was evaluated in a carrageenan-induced rat paw edema test and compared with that of indomethacin. Rats treated with indomethacin (10 mg/kg, p.o.) and curcumin (25, 50, 100, 200 and 400 mg/kg, p.o.) showed a significant reduction in carrageenan-induced paw edema (p
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Five alk(en)ylsulfinothioic acid alk(en)yl-esters isolated from onions and four synthetic thiosulfinates inhibited 5-lipoxygenase of porcine leucocytes, histamine release and leukotriene B4 and C4 biosynthesis of human polymorphonuclear leucocytes, thromboxane B2 biosynthesis by human platelets and allergen- and PAF-induced bronchial obstruction of guinea-pigs. The anti-asthmatic and anti-inflammatory effects of onions depend in part on the thiosulfinate moiety: (Formula: see text).
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The aim of this study was to investigate the antioxidant and anti-apoptotic effects of onion (Allium cepa) extracts (ACE) on doxorubicin (DOX)-induced cardiotoxicity. The rats in the ACE-pretreated group were given a daily dose of 1 ml ACE for 14 days. To induce cardiotoxicity, DOX (30 mg kg−1 body weight) was injected intraperitoneally by a single dose and the rats were sacrificed after 48 h. To date, no such studies have been performed on the cardioprotective and anti-apoptotic potential of ACE on DOX-induced cardiotoxicity. Our data indicate a significant reduction in the activity of in situ identification of apoptosis using terminal dUTP nick end-labeling in cardiomyocytes of the DOX-treated group with ACE therapy. The DOX-treated with ACE groups showed a significant decrease in malondialdehyde levels, and increased activities of superoxide dismutase, glutathione and glutathione peroxidase in comparison with the DOX-treated group. Creatine kinase, creatine kinase MB, lactate dehydrogenase activities and cardiac troponin I levels were significantly decreased in the DOX + ACE group in comparison with the DOX group. These biochemical and histological disturbances were effectively attenuated on pretreatment with ACE. The present study showed that ACE may be a suitable cardioprotector against toxic effects of DOX. Copyright © 2011 John Wiley & Sons, Ltd.
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The expanding utilization of local anesthesia and analgesia revealed the occurrence of myopathies induced by local anesthetics. Such iatrogenic effect encouraged anesthesiologists to study the toxicity of local anesthetics and to reevaluate their protocols in order to reduce muscle pain and dysfunction. Studies performed in rats and human cells showed that bupivacaine induces muscle histological damages with sarcomers disruption along with structural alteration of mitochondria, the powerplant of the cell. Bupivacaine-induced myopathies (BIM) are underestimated as patients are not examined by the anesthesiologist after the surgery. Biochemical analyses indicate that BIM could be explained both by the alteration of mitochondrial energetics with consecutive oxidative stress and mitophagy, and the modification of sarcoplasmic reticulum activity with perturbations of calcium homeostasis. BIM is time-dependent, local anesthetic concentration-dependent, enhanced by preexisting metabolism alteration or young age, and could be prevented in part by antioxidant agents and rhEPO. These observations suggest that adapted changes in postoperative analgesia protocols, including the adjustment of LA concentration and volume, a more precise delivery of the drug and an adapted duration of analgesia, may prevent myopathies consecutive to local anesthesia.
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The relative contribution of the NMDA/glycine allosteric site and non-NMDA (AMPA) types of glutamate receptor to the acute and tonic phases of the behavioural nociceptive response to formalin has been studied in the rat. The AMPA receptor selective antagonist NBQX preferentially inhibited the acute phase indicating that AMPA receptors may be involved in mediating fast acute nociceptive transmission in the dorsal horn. In contrast, the strychnine-insensitive glycine site partial agonist (+)-HA-966 and the NMDA competitive antagonist CGS 19755 preferentially attenuated the tonic nociceptive phase. However, none of these compounds exhibited anti-inflammatory properties. Thus, both NMDA and non-NMDA antagonists can selectively block changes in neuronal excitability while tissue injury in the receptive field continues to evolve.
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We characterized the changes in nitric oxide (NO) levels in the brain during global forebrain ischemia and reperfusion and tested the ability of the natural flavonoid, quercetin, and a synthetic flavonoid, FB277, to increase the amount of available NO by elimination of the superoxide radicals produced during reperfusion. In Sprague-Dawley rats, we used a four-vessel occlusion model of forebrain ischemia (15 min) and reperfusion (30 min). Brain NO was measured on samples of cerebral cortex and cerebellum ex vivo by electron paramagnetic resonance (EPR) spectroscopy. The spin trap used was diethyldithiocarbamate sodium salt (DETC) associated with ferrous citrate. The complex Fe(DETC)2NO was detected at 77 K as a triplet signal at g = 2.035. Groups of animals were treated with quercetin or FB277 (3-morpholinomethyl-3',4',5,7tetramethoxyflavone) or polyethylene glycol-conjugated superoxide dismutase (PEG-SOD). In control (intact anesthetized animals), the signal was about 3 times greater in the cortex than in the cerebellum. During ischemia, the signal rose to 110% in cortex (NS) and 283% in cerebellum (P < 0.05). In reperfusion, it fell again to 91% of control in cerebellum (NS) and 35% in cortex (P < 0.05). Treatment by quercetin (5 mg/kg i.v.) of intact and ischemia-reperfusion groups did not significantly change the signal amplitude in the cerebellum, but did double it in the cortex (to 76% of control) for the ischemia-reperfusion group (P < 0.05). In contrast, FB277 (3.75 mg/kg i.v.) did not increase the signal in the cortex during ischemia-reperfusion, but did do so in the cerebellum (to 152% of control, P < 0.05). The results obtained for PEG-SOD (10,000 U/kg i.v.) were similar to those for FB277. In separate in vitro measurements, we found that quercetin but not FB277 efficiently scavenged superoxide. We hypothesize that quercetin but not FB277 scavenged superoxide anions released in the cortex during reperfusion, thus diminishing the amount of NO removed by the formation of peroxynitrite. The lack of effect of PEG-SOD may be related to the need for chronic treatment to obtain protection.
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Cataract results from oxidative damage to the lens. The mechanism involves disruption of the redox system, membrane damage, proteolysis, protein aggregation and a loss of lens transparency. Diet has a significant impact on cataract development, but the individual dietary components responsible for this effect are not known. We show that low micromolar concentrations of the naturally-occurring flavonoid, quercetin, inhibit cataractogenesis in a rat lens organ cultured model exposed to the endogenous oxidant hydrogen peroxide. Other phenolic antioxidants, (+)epicatechin and chlorogenic acid, are much less effective. Quercetin was active both when incubated in the culture medium together with hydrogen peroxide, and was also active when the lenses were pre-treated with quercetin prior to oxidative insult. Quercetin protected the lens from calcium and sodium influx, which are early events leading to lens opacity, and this implies that the non-selective cation channel is protected by this phenolic. It did not, however, protect against formation of oxidized glutathione resulting from H2O2 treatment. The results demonstrate that quercetin helps to maintain lens transparency after an oxidative insult. The lens organ culture/hydrogen peroxide (LOCH) model is also suitable for examining the effect of other dietary antioxidants.
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Brain stem descending pathways modulate spinal nociceptive transmission. In a lightly anesthetized rat preparation, we present evidence that such descending modulation undergoes time-dependent changes following persistent hindpaw inflammation. There was an initial decrease and a subsequent increase in the excitability of neurons in the rostral ventromedial medulla (RVM) involving facilitation and inhibition. These changes were most robust after stimulation of the inflamed paw although similar findings were seen on the non-inflamed paw and tail. The enhanced descending modulation appeared to be mediated by changes in the activation of the NMDA excitatory amino acid receptor. These findings demonstrate the dynamic plasticity of the pain modulating pathways in response to persistent tissue injury.