|
 |
| RESEARCH ARTICLE |
|
|
|
| Year : 2015 | Volume
: 47
| Issue : 3 | Page : 292-298 |
| |
A study of the mechanisms underlying the anti-inflammatory effect of ellagic acid in carrageenan-induced paw edema in rats
Mohammad Taghi Mansouri1, Ali Asghar Hemmati2, Bahareh Naghizadeh3, Seyyed Ali Mard4, Anahita Rezaie5, Behnam Ghorbanzadeh2
1 Deptartment of Pharmacology, Physiology and Atherosclerosis Research Centers, School of Medicine, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran
2 Deptartment of Toxicology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran
3 Pain and Physiology Research Centers, School of Medicine, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran
4 Deptartment of Physiology, Physiology Research Center, School of Medicine, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran
5 Deptartment of Physiology, School of Veterinary Medicine, University of Shahid Chamran, Ahvaz, Iran
| Date of Web Publication | 18-May-2015 |
Correspondence Address:
Dr. Behnam Ghorbanzadeh
Deptartment of Toxicology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz
Iran
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0253-7613.157127
Objectives: Ellagic acid (EA) has shown antinociceptive and anti-inflammatory effects. Inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2) enzymes and also cytokines play a key role in many inflammatory conditions. This study was aimed to investigate the mechanisms involved in the anti-inflammatory effect of EA.
Materials and Methods: Carrageenan-induced mouse paw edema model was used for induction of inflammation.
Results: The results showed that intraplantar injection of carrageenan led to time-dependent development of peripheral inflammation, which resulted in a significant increase in the levels of tumor necrosis factor α (TNF-α) and interleukin 1 (IL-1) β, nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) and also iNOS and COX-2 protein expression in inflamed paw. However, systemic administration of EA (1-30 mg/kg, intraperitoneal [i.p.]) could reduce edema in a dose-dependent fashion in inflamed rat paws with ED50 value 8.41 (5.26-14.76) mg/kg. It decreased the serum concentration of NO, PGE 2 , aspartate aminotransferase and alanine aminotransferase, and suppress the protein expression of iNOS, COX-2 enzymes, and attenuated the formation of PGE 2, TNF-α and IL-1 β in inflamed paw tissue. We also demonstrated that EA significantly decreased the malondialdehyde (MDA) level in liver at 5 h after carrageenan injection. Moreover, histopathological studies indicated that EA significantly diminished migration of polymorphonuclear leukocytes into site of inflammation, as did indomethacin.
Conclusions: Collectively, the anti-inflammatory mechanisms of EA might be related to the decrease in the level of MDA, iNOS, and COX-2 in the edema paw via the suppression of pro-inflammatory cytokines (TNFα, IL1 β), NO and PGE 2 overproduction.
Keywords: Carrageenan, ellagic acid, inducible nitric oxide synthase, prostaglandin E 2 , Rat
How to cite this article:
Mansouri MT, Hemmati AA, Naghizadeh B, Mard SA, Rezaie A, Ghorbanzadeh B. A study of the mechanisms underlying the anti-inflammatory effect of ellagic acid in carrageenan-induced paw edema in rats. Indian J Pharmacol 2015;47:292-8 |
How to cite this URL:
Mansouri MT, Hemmati AA, Naghizadeh B, Mard SA, Rezaie A, Ghorbanzadeh B. A study of the mechanisms underlying the anti-inflammatory effect of ellagic acid in carrageenan-induced paw edema in rats. Indian J Pharmacol [serial online] 2015 [cited 2023 Mar 30];47:292-8. Available from: https://www.ijp-online.com/text.asp?2015/47/3/292/157127 |
Mohammad Taghi Mansouri, Ali Asghar Hemmati
These authors are equally contributed to the work
| » Introduction | |  |
Inflammation is the body's response against invading pathogens, which is typically characterized by redness, swelling, pain, and heat. Several reports have provided evidence that inflammation is involved in the pathogenesis of many diseases including aging, [1] cancer, [2] cardiovascular dysfunction, [3] and other life-threatening and debilitating disorders.
Acute inflammation is a process that involved the overproduction of free radicals, activation of a complex enzymes, and release of several inflammatory and pro-inflammatory mediators. The carrageenan-induced paw edema is a well-known acute model of inflammation that is widely used for screening novel anti-inflammatory compounds. Carrageenan injection into the subplantar surface of rat paw induced a biphasic edema. The early phase observed around 1 h is related to the release of histamine, serotonin, bradykinin, and to a less extent prostaglandins produced by cyclooxygenase enzymes (COX), whereas the delayed phase (after 1 h) is attributed to neutrophil infiltration, and the continuing of the prostaglandin generation. [4] Release of the neutrophil-derived free radicals, nitric oxide (NO) and pro-inflammatory cytokines such as tumor necrosis factor (TNF-α), and interleukin-1 β (IL-1 β) also involved in the delayed phase of carrageenan-induced acute inflammation. [5] Different observations suggest that drugs targeting COX enzyme, free radical formation and pro-inflammatory protein expression (e.g. inducible nitric oxide synthase; iNOS) might provide a better control over inflammatory states than the therapeutic agents currently available. [6]
Plant polyphenols play an important role in human nutrition. There is increasing evidence that dietary phenolic compounds have biological properties including antioxidant, anti-inflammatory, anticancer and antiatherosclerotic effects. [7] Among these phytochemicals, ellagic acid (EA; 2, 3, 7, 8 tetrahydroxy [1] benzopyranol [5, 4, 3-cde] [1] benzopyran-5,10-dione) is a naturally-synthesized polyphenolic compound that present in fruits and nuts such as raspberries, strawberries, pomegranates, cranberries, walnuts, pecans, and other plant foods as EA-glycosides, or bound as ellagitannins. [8] Extracts from red raspberry leaves or seeds, pomegranates, or various other sources containing high levels of EA are commercially available as dietary supplements. This compound exhibits anti-carcinogenic, [9] anti-oxidative, [10] antinociceptive and anti-inflammatory [11],[12] activities. Furthermore, it has been shown that EA suppress the release of NO and prostaglandine E 2 (PGE 2 ) by down-regulating inducible NOS and COX, respectively in the endothelial cells and also rat model of colon cancer. [13]
Based on the mentioned above, this study was aimed to assess the mechanisms involved in the anti-inflammatory effect of EA in carrageenan-induced paw edema in rats.
| » Materials and Methods | | |
Animals
Adult male Wistar rats (160-200 g) were housed at controlled temperature (22 ± 2°C) and allowed free access to food and drinking water. Testing took place in the middle of the light period of a 12 h/12 h light/dark cycle. All animal experiments were carried out in accordance with the National Institutes of Health Guide for Care and Use of Laboratory Animals. The Institutional Animal Ethical Committee of Jundishapur University, formed under Committee for Purpose of Control and Supervision of Experiments on Animals (CPCSEA, Reg. No. PRC150) approved the pharmacological protocols. The animals were used only once and then euthanized.
Drugs and Chemicals
Ellagic acid, 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS), phenylmethylsulfonyl fluoride (PMSF), λ-carrageenan, thiobarbituric acid (TBA), aprotinin, pepstatin, and leupeptin were purchased from Sigma-Aldrich Co. (St. Louis, MO, USA). Indomethacin was donated by Iran Daru Pharmaceutical Co. (Tehran, Iran). TNF-α and IL1 β kits were purchased from eBioscience, USA. Anti-iNOS, anti-COX-2, and anti-β-actin antibody were obtained from Abcam Biochemical Co. (Cambridge, UK).
Carrageenan-induced Rat Paw Edema
Paw edema was induced in a right hind paw of each rat by intraplantar injection of 100 μl of 1% (suspension in saline) lambda carrageenan. EA (1, 3, 10 and 30 mg/kg) and indomethacin (5 mg/kg) were intraperitoneally administered 30 min before the carrageenan injection. The paw volume of rats was measured by plethysmometer (Ugo Basile, Varese, Italy), before and after injection of carrageenan at different time intervals (1, 2, 3, 4, and 5 h). The degree of edema induced was assessed by a − b, where a and b were the volume of the right hind paw after and before carrageenan treatment, respectively. After 5 h, the animals were sacrificed and the carrageenan-induced edema feet were dissected and stored at − 80°C. The whole liver tissue was rinsed in ice-cold normal saline, and immediately were homogenized in cold KCl solution (1.5%) to give a 10% homogenate suspension used for measuring malondialdehyde (MDA). Furthermore, blood was withdrawn and serum expressed from the clotted blood was kept at −80°C for measuring PGE 2 and NO levels.
Measurement of the Tumor Necrosis Factor α and Interleukin 1 β Level in Paw Tissue
Paw tissue were homogenized in 500 μl of buffer containing protease inhibitors, and IL-1 β and TNF-α levels were determined using a commercially available ELISA kit (eBioscience, USA) according to the instructions of the manufacturer.
Western Blot Analysis of Inducible Nitric Oxide Synthase and Cyclooxygenase 2
Soft tissues were removed from rats paw and homogenized in a lysis solution containing 10 mM CHAPS, 1 mM PMSF, 5 μg/ml aprotinin, 1 μM pepstatin, and 10 μM leupeptin. The homogenates were centrifuged at 12,000 g for 20 min, and 30 μg of protein from the supernatants was then separated on 10% SDS-PAGE using a standard method and transferred to polyvinylidene difluoride membranes. The membranes were then incubated with anti-iNOS, anti-COX-2 or anti-β-actin antibodies in 5% skim milk in TBST for 2 h at room temperature. The membranes were then incubated with horseradish peroxidase-conjugated secondary antibody. The immunoreactive protein bands were detected by enhanced chemiluminescence (ECL) using hyperfilm and ECL reagent.
Measurement of Prostaglandine E 2 and Nitric Oxide Level in Paw Tissue and Serum
Tissue levels of PGE 2 were determined using a commercially available ELISA kit, following the manufacturer's guidelines (Abcam Biochemical, UK). Furthermore, nitrate reductase enzyme was used to measure NO products following the manufacture's guidelines (Cayman, USA). Values obtained by this procedure represented the sums of nitrite and nitrate. Similarly, PGE 2 and NO levels in serum were measured.
Hepatic Malondialdehyde Assay
Malondialdehyde levels, an index of lipid peroxidation, produced by free radicals were measured to check the hepatoprotective and antioxidant activity of EA in carrageenan-induced liver injury. MDA reacts with TBA to produce a red colored complex that has peak absorbance at 532 nm. 1, 1, 3, 3-tetramethoxypropane was used as a standard. [14]
Hepatic Assessment of the Aspartate Aminotransferase and Alanine Aminotransferase Levels
Plasma levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured as indicators of liver function parameters using commercial diagnostic assay kits from Bionik (Tehran, Iran) following the instructions of the manufacturer.
Histopathological Examination
After 5 h of carrageenan treatment, rats were sacrificed, and the tissue of the paws was removed and fixed in 10% neutral-buffered formaldehyde solution. Each sample was embedded in paraffin wax, sectioned at 5 μm and stained with H and E. A representative area was selected for qualitative light microscopic analysis of the inflammatory cellular response with a ×40 objective.
Statistical Analysis
All experimental results are given as means ± standard error of the mean for 6-8 animals per group. The statistical analyses were performed using one-way ANOVA, followed by Tukey's post-hoc test. The ED 50 value for the anti-inflammatory effect of EA accompanied by its respective 95% confidence limits were determined by linear regression from individual experiments using GraphPad Prism 5.0 software (San Diego, CA, USA).
| » Results | | |
Effects of Ellagic Acid on Carrageenan-induced Rat Paw Edema
Intraplantar injection of carrageenan in rats resulted in a time-dependent increase in paw volume [Figure 1]. However, treatment with EA reduced the paw edema in a dose-dependent manner at 1, 2, 3, 4 and 5 h after an injection of carrageenan. ED 50 values with 95% confidence intervals for the anti-inflammatory effect of EA were 8.41 (5.26-14.76) mg/kg. As expected, the reference drug, indomethacin (5 mg/kg), caused a significant inhibition of postcarrageenan edema [Figure 1]. | Figure 1: Effects of ellagic acid (EA) on hind paw edema induced by carrageenan (Carr) in rats. Each value represents the mean ± standard error of the mean. *P < 0.05 as compared to the Carr group (one-way ANOVA followed by Tukey's test). VEH: Vehicle, EA: Ellagic acid (1-30 mg/kg, intraperitoneal [i.p.]), Indo: Indomethacin (5 mg/kg, i.p.)
Click here to view |
Effects of Ellagic Acid on Cytokine Secretion
As shown in [Figure 2]a and b, carrageenan increased the level of TNF-α and IL-1 β in paw edema, respectively. Meanwhile, in the range dose 1-30 mg/kg, EA could inhibit the level of TNF-α and IL-1 β to 40-17% and 68-36% of that observed in carrageenan group, respectively. Moreover, indomethacin (5 mg/kg) significantly decreased TNF-α level in the rat edema paw. | Figure 2: Effects of ellagic acid (EA) on carrageenan (Carr)-induced (A) tumor necrosis factor-α and (B) interleukin 1 β concentrations in paw tissue at 5 h in rats. Each value represents the mean ± standard error of the mean. #P < 0.05 and *P < 0.05 as compared to the VEH and Carr group, respectively (one-way ANOVA followed by Tukey's test). VEH: Vehicle, EA: Ellagic acid, Indo: Indomethacin (5 mg/kg, intraperitoneal)
Click here to view |
Effects of Ellagic Acid on Inducible Nitric Oxide Synthase and Cyclooxygenase 2 Expression
To determine whether the inhibition of NO and PGE 2 production was due to a decreased iNOS and COX-2 protein level, the effect of EA on iNOS and COX-2 protein expression was studied using Western blotting analysis. The results showed that treatment with EA at 30 mg/kg for 5 h after carrageenan injection reduced iNOS and COX-2 proteins expression in the rat paw edema [Figure 3]. In addition, the protein expression showed a reduction of iNOS and COX-2 protein expression after treatment with indomethacin at 5 mg/kg compared with the carrageenan-induced alone [Figure 3]. | Figure 3: Inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) protein expression by ellagic acid (EA) induced by carrageenan (Carr) in rat paw edema for 5 h. Tissue hemogenated were then prepared and subjected to western blotting using an antibody specific for iNOS and COX-2. â-actin was used as an internal control. EA: Ellagic acid (30 mg/kg, intraperitoneal [i.p.]), Indo: Indomethacin (5 mg/kg, i.p.)
Click here to view |
Effects of Ellagic Acid on the Nitric Oxide Level
As shown in [Figure 4]a and b, injection of carrageenan into the rat hind paw induced a marked increase in the hind paw and also serum NO level 5 h after injection. The i.p. treatment of rats with EA (10 and 30 mg/kg) and indomethacin (5 mg/kg, i.p.) caused a significant reduction of increased NO generation by carrageenan in serum (P < 0.05). However, EA had no effect on NO level in edema paw tissue ([Figure 4]a, P > 0.05). | Figure 4: Effects of ellagic acid (EA) on carrageenan (Carr)-induced nitric oxide (NO) in (a) paw tissue and (b) serum at 5 h in rats. Each value represents the mean ± standard error of the mean. #P < 0.05 and *P < 0.05 as compared to the VEH and Carr group, respectively (one-way ANOVA followed by Tukey's test). VEH: Vehicle, EA: Ellagic acid, Indo: Indomethacin (5 mg/kg, intraperitoneal)
Click here to view |
Effects of Ellagic Acid on the Prostaglandine E 2 Level
[Figure 5]a and b show the PGE 2 level increased significantly in the paw tissue and serum 5 h after carrageenan injection (P < 0.05). The i.p. treatment of rats with EA (10 and 30 mg/kg) and indomethacin (5 mg/kg, i.p.) caused a significant reduction of increased PGE 2 level by carrageenan in serum (P < 0.05). However, the effect of EA in paw tissue was more potent than that of serum. | Figure 5: Effects of ellagic acid (EA) on carrageenan (Carr)-induced prostaglandine E2 in (a) paw tissue and (b) serum at 5 h in rats. Each value represents the mean ± standard error of the mean. #P < 0.05 and *P < 0.05 as compared to the VEH and Carr group, respectively (one-way ANOVA followed by Tukey's test). VEH: Vehicle, EA: Ellagic acid, Indo: Indomethacin (5 mg/kg, intraperitoneal)
Click here to view |
Effects of Ellagic Acid on the Malondialdehyde, Alanine Aminotransferase and Aspartate Aminotransferase Level
To determine whether the anti-inflammatory effect of EA was partly due to antioxidant activity, the hepatoprotective properties of EA were assessed by measurement the MDA levels as an index of lipid peroxidation and plasma contents of AST and ALT enzymes. As shown in [Figure 6]a, The MDA level increased significantly in liver tissue of rats at 5 h after carrageenan injection (P < 0.05). However, the MDA level was decreased significantly by treatment with EA. Furthermore, injection of carrageenan into the rat hind paw induced an increase in the serum levels of AST and ALT enzymes 5 h after injection compared with control group (P < 0.05). EA (1-30 mg/kg, i.p.) resulted in a significant reduction in AST and ALT levels [Figure 6]b and c. | Figure 6: Effects of ellagic acid (EA) on carrageenan (Carr)-induced (a) malondialdehyde (MDA), (b) aspartate aminotransferase (AST) and (c) alanine aminotransferase (ALT) concentrations at 5 h in rats. MDA was measured in liver homogenate. AST and ALT were measured in serum. Each value represents the mean ± standard error of the mean. #P < 0.05 and *P < 0.05 as compared to the VEH and Carr group, respectively (one-way ANOVA followed by Tukey's test). VEH: Vehicle, EA: Ellagic acid, Indo: Indomethacin (5 mg/kg, intraperitoneal)
Click here to view |
Histopathological Examination
As shown in [Figure 7]a, there was no sign of inflammation in the paw tissue of normal rats. Paw tissue of vehicle-treated rats showed an acute inflammation with extensive extravasations, mainly polymorphonuclear leukocytes [Figure 7]b. As observed in [Figure 7]c and d, treatment of rats with EA at 30 mg/kg and indomethacin (5 mg/kg, i.p.) exhibited a significant decrease in the number of cellular infiltrates. | Figure 7: Histopathologic examination of paw tissue of rats treated with EA, 5 h after injection of carrageenan (Carr). (a) Normal rats show the normal appearance of epidermis and dermis without any lesion. (b) Carrageenan-injected paw tissue in control group. Vasodilatation with edema, and migration of neutrophil were observed. (c and d) Carrageenan-injected paw of rats treated with EA (30 mg/kg, intraperitoneal [i.p.]) and indomethacin (5 mg/kg, i.p.), respectively. The migration of neutrophil and edema reduced. Sections were stained with H and E, ×40. 1: Neutrophil, 2: Edema, 3: Vessel
Click here to view |
| » Discussion | | |
The results of this study showed that EA significantly suppressed the rat hind paw edema induced by intraplantar injection of carrageenan, indicating marked anti-acute inflammatory efficacy. In the current study, the anti-inflammatory effect of EA was further evaluated to elucidate the underlying mechanisms involved in this animal model. We demonstrated that the effect may be due to inhibition of the pro-inflammatory cytokines release, inflammatory enzymes (iNOS and COX-2) expression and also their products (NO and PGE 2 ). Furthermore, we showed that EA could prevent liver damage induced by carrageenan through the anti-oxidative mechanisms.
The carrageenan-induced paw edema is a well-defined model of acute inflammation that a variety of inflammatory mediators involves in its development and has wildly been used to evaluate the anti-edematous effect of natural products. In the present study, we showed that EA produced anti-inflammatory effects in carrageenan-induced rat paw edema dose-dependently. Our results confirmed previous findings that EA exhibit a noticeable anti-inflammatory effect in experimental models. [15] On the other hand, it is well characterized that neutrophil infiltration plays a key role in the inflammation induced by carrageenan in hind paw. [4] Our results indicated that EA elicited a marked reduction in the infiltration of neutrophils into the carrageenan-treated paws, according to a histopathological examination.
A growing lines of evidence have demonstrated that flavonoids, phenolic acids, and triterpenoid possessed antinociceptive and anti-inflammatory effects in animal models. [16] Studies have also reported that flavonoids such as rutin, quercetin, luteolin produced significant antinociceptive and anti-inflammatory activities. [17] Hence, it was suggested that the antioxidant and anti-inflammatory activities of EA may be related to its phenolic content.
The expression of the inducible isoform of NO synthase (iNOS) has been proposed as an important mediator of inflammation. Moreover, a large amount of NO is produced from L-arginine by iNOS, thereby causing detrimental effects. Although physiological NO production has beneficial anti-microbial and anti-tumor effects, excessive NO produced by iNOS is a mediator of the inflammatory diseases and causes cell injury by generating reactive radicals, such as peroxynitrite. [18] Our finding revealed that EA suppressed carrageenan-induced production of iNOS and its product, NO. So, we suggest the anti-inflammatory mechanism of EA may be through the L-arginine-NO pathway because EA significantly inhibits the NO production by iNOS. In accordance with this data, we previously showed the involvement of L-arginine-NO pathway in the anti-nociceptive effect of EA in acetic acid-induced visceral pain. [11] Furthermore, Dhingra and Chhillar suggested the role of iNOS in antidepressant-like activity of EA. [19] Moreover, it has been indicated that EA inhibit the release of NO by down-regulating iNOS. [13]
In vitro and in vivo studies have been indicated an existing cross talk between the release of NO and PGs in the modulation of inflammation. [20] Data indicate that NO has a profound effect on COX-2 catalytic activity. [21] However, the mechanisms of this effect have not been elucidated. One possibility is that NO increases COX-2 half-life by generating free radicals and inhibiting COX-2 autoinactivation. [20] Another possibility is that lipid peroxidation initiated by peroxynitrite, the product of the reaction of NO with superoxide, liberates arachidonic acid from the cell membrane, which in turn activates COX-2. [22] PGE 2 , a product of COX-2, is considered as one of the strongest inflammatory mediators in the inflammatory response. Our study showed that EA could inhibit PGE 2 production and reduce the COX-2 expression significantly in carrageenan-induced rat paw edema suggested that the anti-inflammatory effect of EA might be associated to its inhibitive effect on PGE 2 production through blocking COX-2 protein expression. On the other hand, carrageenan injection also provokes the release of some important pro-inflammatory cytokines such as TNF-α and IL-1 β. [23] TNF-α triggers the release of IL-1 β and cytokine-induced neutrophil chemo-attractant 1. These mediators are responsible for stimulation of the PGs synthesis by COX-2. Moreover, TNF-α induces NO synthesis by activating iNOS and augments the responses of neutrophils to inflammatory stimuli. [5],[24] Our findings demonstrated that EA considerably reduced the TNF-α and IL-1 β levels in the carrageenan-injected paw tissues. Inhibition of cytokine production by EA might account for the inhibition of COX-2 expression because both cytokines induce it. [25] Also, EA has been found to inhibit the activation of transcription factor NF-κB and, therefore, reduced expression of COX-2 protein. [26] Karin and Ben-Neriah showed that transcription of pro-inflammatory mediators such as iNOS, COX-2, TNF-α, and IL-1 β is regulated by activation of NF-κB. [27]
Free radical has been proposed to play an important role in the carrageenan-induced acute inflammatory response. [28] In a number of pathophysiological conditions associated with inflammation or oxidative stress, free radical have been proposed to mediate cell damage in the liver. [29] As a marker of oxidative damage, lipid peroxidation indicates changes in membrane fluidity and permeability and thus increases in rates of protein degradation, which will eventually lead to cell lysis. One of the consequences of lipid peroxidation can also result in enzyme activity changes. [30] MDA is a metabolic product of lipid peroxidation, the level of which is raised in oxidative stress. The present results showed that EA reduce the severity of liver damage by lowering MDA level. Furthermore, there were significant decreases in AST and ALT level with EA treatment. We assume that the suppression of AST and ALT level is probably due to the inhibition of lipid peroxidation. A growing body of evidence suggests the anti-oxidative effect of EA, which is consistent with our results. [8],[10]
In conclusion, the results of the current study suggested that EA possessed anti-inflammatory effects in carrageenan-induced rat paw edema, which is comparable to indomethacin. The anti-inflammatory mechanism of EA may be related to the reduction of TNF-α and IL-1 β that could result in inhibition of iNOS and COX-2 expression and its product (NO and PGE 2 ). Furthermore, the protective effect of EA on liver damage may result from anti-oxidative effects. Our findings provide new perspectives on the therapeutic use EA in the management of inflammatory diseases.
| » Acknowledgments | | |
This paper is issued from Ph.D. thesis of (Behnam Ghorbanzadeh) and financial support was provided by the Vice Chancellor of Research, Ahvaz Jundishapur University of Medical Sciences (grant no. PRC150).
| » References | | |
| 1. | Finch CE. Developmental origins of aging in brain and blood vessels: An overview. Neurobiol Aging 2005;26:281-91.  |
| 2. | Caruso C, Lio D, Cavallone L, Franceschi C. Aging, longevity, inflammation, and cancer. Ann N Y Acad Sci 2004;1028:1-13. |
| 3. | Rus H, Niculescu FI. Inflammation, aspirin, and the risk of cardiovascular disease. N Engl J Med 1997;337:423. |
| 4. | Gilligan JP, Lovato SJ, Erion MD, Jeng AY. Modulation of carrageenan-induced hind paw edema by substance P. Inflammation 1994;18:285-92. |
| 5. | Halici Z, Dengiz GO, Odabasoglu F, Suleyman H, Cadirci E, Halici M. Amiodarone has anti-inflammatory and anti-oxidative properties: An experimental study in rats with carrageenan-induced paw edema. Eur J Pharmacol 2007;566:215-21. |
| 6. | Ronchetti D, Borghi V, Gaitan G, Herrero JF, Impagnatiello F. NC×2057, a novel NO-releasing derivative of ferulic acid, suppresses inflammatory and nociceptive responses in in vitro and in vivo models. Br J Pharmacol 2009;158:569-79. |
| 7. | Handique JG, Baruah JB. Polyphenolic compounds: An overview. React Funct Polym 2002;52:163-88. |
| 8. | Priyadarsini KI, Khopde SM, Kumar SS, Mohan H. Free radical studies of ellagic acid, a natural phenolic antioxidant. J Agric Food Chem 2002;50:2200-6. |
| 9. | Glauert HP, Calfee-Mason K, Stemm DN, Tharappel JC, Spear BT. Dietary antioxidants in the prevention of hepatocarcinogenesis: A review. Mol Nutr Food Res 2010;54:875-96. |
| 10. | Park SH, Kim JL, Lee ES, Han SY, Gong JH, Kang MK, et al. Dietary ellagic acid attenuates oxidized LDL uptake and stimulates cholesterol efflux in murine macrophages. J Nutr 2011;141:1931-7. |
| 11. | Taghi Mansouri M, Naghizadeh B, Ghorbanzadeh B, Farbood Y. Central and peripheral antinociceptive effects of ellagic acid in different animal models of pain. Eur J Pharmacol 2013;707:46-53. |
| 12. | Mansouri MT, Naghizadeh B, Ghorbanzadeh B. Sildenafil enhances the peripheral antinociceptive effect of ellagic acid in the rat formalin test. Indian J Pharmacol 2014;46:404-8. [ PUBMED]  |
| 13. | Umesalma S, Sudhandiran G. Differential inhibitory effects of the polyphenol ellagic acid on inflammatory mediators NF-kappaB, iNOS, COX-2, TNF-alpha, and IL-6 in 1,2-dimethylhydrazine-induced rat colon carcinogenesis. Basic Clin Pharmacol Toxicol 2010;107:650-5. |
| 14. | Naghizadeh B, Mansouri MT, Ghorbanzadeh B, Farbood Y, Sarkaki A. Protective effects of oral crocin against intracerebroventricular streptozotocin-induced spatial memory deficit and oxidative stress in rats. Phytomedicine 2013;20:537-42. |
| 15. | Mansouri MT, Naghizadeh B, Ghorbanzadeh B. Involvement of opioid receptors in the systemic and peripheral antinociceptive actions of ellagic acid in the rat formalin test. Pharmacol Biochem Behav 2014;120:43-9. |
| 16. | Arslan R, Bektas N, Ozturk Y. Antinociceptive activity of methanol extract of fruits of Capparis ovata in mice. J Ethnopharmacol 2010;131:28-32. |
| 17. | Deliorman Orhan D, Hartevioglu A, Küpeli E, Yesilada E. In vivo anti-inflammatory and antinociceptive activity of the crude extract and fractions from Rosa canina L. fruits. J Ethnopharmacol 2007;112:394-400. |
| 18. | Huang GJ, Bhaskar Reddy MV, Kuo PC, Huang CH, Shih HC, Lee EJ, et al. A concise synthesis of viscolin, and its anti-inflammatory effects through the suppression of iNOS, COX-2, ERK phosphorylation and proinflammatory cytokines expressions. Eur J Med Chem 2012;48:371-8. |
| 19. | Dhingra D, Chhillar R. Antidepressant-like activity of ellagic acid in unstressed and acute immobilization-induced stressed mice. Pharmacol Rep 2012;64:796-807. |
| 20. | Salvemini D, Settle SL, Masferrer JL, Seibert K, Currie MG, Needleman P. Regulation of prostaglandin production by nitric oxide; an in vivo analysis. Br J Pharmacol 1995;114:1171-8. |
| 21. | Wu KK. Inducible cyclooxygenase and nitric oxide synthase. Adv Pharmacol 1995;33:179-207. |
| 22. | Davidge ST, Baker PN, Laughlin MK, Roberts JM. Nitric oxide produced by endothelial cells increases production of eicosanoids through activation of prostaglandin H synthase. Circ Res 1995;77:274-83. |
| 23. | Nacife VP, Soeiro Mde N, Gomes RN, D'Avila H, Castro-Faria Neto HC, Meirelles Mde N. Morphological and biochemical characterization of macrophages activated by carrageenan and lipopolysaccharide in vivo. Cell Struct Funct 2004;29:27-34. |
| 24. | Subramanian N, Bray MA. Interleukin 1 releases histamine from human basophils and mast cells in vitro. J Immunol 1987;138:271-5. |
| 25. | Cunha TM, Verri WA Jr, Silva JS, Poole S, Cunha FQ, Ferreira SH. A cascade of cytokines mediates mechanical inflammatory hypernociception in mice. Proc Natl Acad Sci U S A 2005;102:1755-60. |
| 26. | Marín M, María Giner R, Ríos JL, Recio MC. Intestinal anti-inflammatory activity of ellagic acid in the acute and chronic dextrane sulfate sodium models of mice colitis. J Ethnopharmacol 2013;150:925-34. |
| 27. | Karin M, Ben-Neriah Y. Phosphorylation meets ubiquitination: The control of NF-[kappa] B activity. Annu Rev Immunol 2000;18:621-63. |
| 28. | Salvemini D, Wang ZQ, Bourdon DM, Stern MK, Currie MG, Manning PT. Evidence of peroxynitrite involvement in the carrageenan-induced rat paw edema. Eur J Pharmacol 1996;303:217-20. |
| 29. | Huang GJ, Huang SS, Lin SS, Shao YY, Chen CC, Hou WC, et al. Analgesic effects and the mechanisms of anti-inflammation of ergostatrien-3beta-ol from Antrodia camphorata submerged whole broth in mice. J Agric Food Chem 2010;58:7445-52. |
| 30. | Rauchová H, Drahota Z, Koudelová J. The role of membrane fluidity changes and thiobarbituric acid-reactive substances production in the inhibition of cerebral cortex Na+/K+-ATPase activity. Physiol Res 1999;48:73-8. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
| This article has been cited by | | 1 |
Analgesic and Anti-Inflammatory Effects of 80% Methanol Extract and Solvent Fractions of the Leaves of Vernonia auriculifera Hiern. (Asteraceae) |
|
| Ephrem Ashenafi, Teferra Abula, Solomon Mequanente Abay, Mahlet Arayaselassie, Samson Taye, Rekik Ashebir Muluye | | Journal of Experimental Pharmacology. 2023; Volume 15: 29 | | [Pubmed] | [DOI] | | | 2 |
Evaluation of the anti-inflammatory, antioxidant, and cytotoxic potential of Cardamine amara L. (Brassicaceae): A comprehensive biochemical, toxicological, and in silico computational study |
|
| Abdul Basit, Saeed Ahmad, Kashif ur Rehman Khan, Hanan Y. Aati, Asmaa E. Sherif, Chitchamai Ovatlarnporn, Safiullah Khan, Huma Rao, Muhammad Adeel Arshad, Muhammad Nadeem Shahzad, Shagufta Perveen | | Frontiers in Chemistry. 2023; 10 | | [Pubmed] | [DOI] | | | 3 |
Bee Pollen as Functional Food: Insights into Its Composition and Therapeutic Properties |
|
| Asmae El Ghouizi, Meryem Bakour, Hassan Laaroussi, Driss Ousaaid, Naoual El Menyiy, Christophe Hano, Badiaa Lyoussi | | Antioxidants. 2023; 12(3): 557 | | [Pubmed] | [DOI] | | | 4 |
Ginger (Zingiber officinale) Root Capsules Enhance Analgesic and Antioxidant Efficacy of Diclofenac Sodium in Experimental Acute Inflammation |
|
| Ioana Boarescu, Raluca Maria Pop, Paul-Mihai Boarescu, Ioana Corina Boc?an, Dan Gheban, Adriana Elena Bulboaca, Anca Dana Buzoianu, Sorana D. Bolboaca | | Antioxidants. 2023; 12(3): 745 | | [Pubmed] | [DOI] | | | 5 |
Anti-Inflammatory and Analgesic Effects of Curcumin Nanoparticles Associated with Diclofenac Sodium in Experimental Acute Inflammation |
|
| Ioana Boarescu, Raluca Maria Pop, Paul-Mihai Boarescu, Ioana Corina Boc?an, Dan Gheban, Ruxandra-Mioara Râjnoveanu, Armand Râjnoveanu, Adriana Elena Bulboaca, Anca Dana Buzoianu, Sorana D. Bolboaca | | International Journal of Molecular Sciences. 2022; 23(19): 11737 | | [Pubmed] | [DOI] | | | 6 |
The Antioxidant Potential of Ficus Umbellata Vahl (Moraceae) That Accelerates In Vitro and the In Vivo Anti-Inflammatory Protective Effects |
|
| Kevine Kamga Silihe, Zingue Stephane, Marius Trésor Kemegne Sipping, Anna Busuioc Cazanevscaia, Andreea Veronica Dediu Botezatu, Dieudonne Njamen, Rodica Mihaela Dinica | | Applied Sciences. 2022; 12(18): 9070 | | [Pubmed] | [DOI] | | | 7 |
Ethyl Acetate Fraction of Bixa orellana and Its Component Ellagic Acid Exert Antibacterial and Anti-Inflammatory Properties against Mycobacterium abscessus subsp. massiliense |
|
| Roberval Nascimento Moraes-Neto, Gabrielle Guedes Coutinho, Ana Caroline Santos Ataíde, Aline de Oliveira Rezende, Camila Evangelista Carnib Nascimento, Rafaela Pontes de Albuquerque, Cláudia Quintino da Rocha, Adriana Sousa Rêgo, Maria do Socorro de Sousa Cartágenes, Ana Lúcia Abreu-Silva, Igor Victor Ferreira dos Santos, Cleydson Breno Rodrigues dos Santos, Rosane Nassar Meireles Guerra, Rachel Melo Ribeiro, Valério Monteiro-Neto, Eduardo Martins de Sousa, Rafael Cardoso Carvalho | | Antibiotics. 2022; 11(6): 817 | | [Pubmed] | [DOI] | | | 8 |
Computational Studies and Biological Evaluation on Synthesized Lead 1,3-
diphenyl-4,5-dihydro-1H-pyrazole Moiety as Anti-Infective Agents |
|
| Elangovan Manickavalli, Natarajan Kiruthiga, Lalitha Vivekanandan, Anitha Roy, Thangavel Sivakumar | | Anti-Infective Agents. 2022; 20(5) | | [Pubmed] | [DOI] | | | 9 |
Ellagic acid production by solid-state fermentation (SSF) using pomegranate peels as a substrate: a review |
|
| C.N. Aguilar, J.A. Ascacio-Valdés, J.J. Buenrostro, L. Sepúlveda, M.L. Chávez-González, A. Prado-Barragán | | Acta Horticulturae. 2022; (1349): 559 | | [Pubmed] | [DOI] | | | 10 |
Isolation and Identification of Anti-Inflammatory Peptide from Goose Blood Hydrolysate to Ameliorate LPS-Mediated Inflammation and Oxidative Stress in RAW264.7 Macrophages |
|
| Yeye Du, Shuangjie Zhu, Ran Wang, Xingyong Chen, Kezhou Cai | | Molecules. 2022; 27(24): 8816 | | [Pubmed] | [DOI] | | | 11 |
Pioneering Role of Marine Macroalgae in Cosmeceuticals |
|
| Haresh S. Kalasariya, Leonel Pereira, Nikunj B. Patel | | Phycology. 2022; 2(1): 172 | | [Pubmed] | [DOI] | | | 12 |
Inhibition of Carrageenan-Induced Acute Inflammation in Mice by the Microgramma vacciniifolia Frond Lectin (MvFL) |
|
| Leydianne Leite de Siqueira Patriota, Dalila de Brito Marques Ramos, Mariana Gama e Silva, Angela Caroline Lima Amorim dos Santos, Yasmym Araújo Silva, Patrícia Maria Guedes Paiva, Emmanuel Viana Pontual, Lidiane Pereira de Albuquerque, Rosemairy Luciane Mendes, Thiago Henrique Napoleão | | Polymers. 2022; 14(8): 1609 | | [Pubmed] | [DOI] | | | 13 |
Antioxidant and anti-inflammatory activities of Ganoderma resinaceum (Boud) fruiting bodies extracts |
|
| Marius Trésor Kemegne Sipping, Francine Kengne Mediesse, Annette Yannuvie Natia Sombes, Adamou Mfopa, Thaddée Boudjeko | | Journal of Herbmed Pharmacology. 2022; 11(3): 348 | | [Pubmed] | [DOI] | | | 14 |
Anti-inflammatory Activity of Water Extract of Luvunga sarmentosa (BI.) Kurz Stem in the Animal Models |
|
| Sabar Deyulita, Hilkatul Ilmi, Hanifah Khairun Nisa, Lidya Tumewu, Aty Widyawaruyanti, Achmad Fuad Hafid | | Borneo Journal of Pharmacy. 2022; 5(1): 56 | | [Pubmed] | [DOI] | | | 15 |
Anti-inflammatory activity of Indonesian polyherbal product containing Curcuma zanthorrhiza and Vitex trifolia as the main ingredients in carrageenan- and histamine-induced inflammation in Wistar rats |
|
| Zullies Ikawati, Triana Hertiani, Yesiska Kristina Hartanti, Niken Laras Sigalih | | Journal of Medicinal Plants. 2022; 21(84): 39 | | [Pubmed] | [DOI] | | | 16 |
Caralluma tuberculata exhibits analgesic and anti-arthritic potential by downregulating pro-inflammatory cytokines and attenuating oxidative stress |
|
| Syed Ihtisham Haider, Awais Asif, Hafiz Muhammad Farhan Rasheed, Adnan Akram, Qaiser Jabeen | | Inflammopharmacology. 2022; | | [Pubmed] | [DOI] | | | 17 |
Synthesis and Anti-Inflammatory Activity Evaluation of Some Benzimidazole Derivatives |
|
| Alok Kumar Moharana, Rudra Narayan Dash, Nimai Charan Mahanandia, Bharat Bhusan Subudhi | | Pharmaceutical Chemistry Journal. 2022; | | [Pubmed] | [DOI] | | | 18 |
Evaluation of anti-inflammatory response of berberine-loaded gum nanocomplexes in carrageenan-induced acute paw edema in rats |
|
| Jyoti Bakshi, Prity Lathar, Meenakshi Mehra, Sapna Grewal, Dinesh Dhingra, Santosh Kumari | | Pharmacological Reports. 2022; | | [Pubmed] | [DOI] | | | 19 |
New mechanistic insights on Justicia vahlii Roth: UPLC-Q-TOF-MS and GC-MS based metabolomics, in-vivo, in-silico toxicological, antioxidant based anti-inflammatory and enzyme inhibition evaluation |
|
| Abdul Basit, Saeed Ahmad, Kashif ur Rehman Khan, Asmaa E Sherif, Hanan Y Ati, Chitchamai Ovatlarnporn, Mohsin Abbas Khan, Huma Rao, Imtiaz Ahmad, Muhammad Nadeem Shahzad, Bilal Ahmed Ghalloo, Hassan Shah, Kifayatullah Khan, Rizwana Dilshad | | Arabian Journal of Chemistry. 2022; : 104135 | | [Pubmed] | [DOI] | | | 20 |
Design, Characterization and In Vivo Performance of Solid Lipid Nanoparticles (SLNs)-Loaded Mucoadhesive Buccal Tablets for Efficient Delivery of Lornoxicam in Experimental Inflammation |
|
| Moataz B. Zewail, Gihan F.Asaad, Salma M. Swellam, Sama M. Abd-allah, Sahar K.Hosny, Salma K. Sallah, Jehan E.Eissa, Salma S.Mohamed, Walaa A. El-Dakroury | | International Journal of Pharmaceutics. 2022; : 122006 | | [Pubmed] | [DOI] | | | 21 |
Systemic and topical Ginkgo biloba leaf extract (Egb-761) ameliorated rat paw inflammation in comparison to dexamethasone |
|
| Rania A. Abdel-Emam, Ahmed M. Abd-Eldayem | | Journal of Ethnopharmacology. 2022; 282: 114619 | | [Pubmed] | [DOI] | | | 22 |
Anti-inflammatory effects of Pikad Tri-phol-sa-mut-than remedy, consisting of dried fruits of Aegle marmelos (L.) Corrêa, Coriandrum sativum L., and Morinda citrifolia L. |
|
| Bing Tan, Natthakarn Chiranthanut, Sunee Chansakaow, Seewaboon Sireeratawong, Parirat Khonsung, Wutigri Nimlamool, Mingkwan Na Takuathung, Nirush Lertprasertsuke | | Journal of Ethnopharmacology. 2022; : 115639 | | [Pubmed] | [DOI] | | | 23 |
Exploring the anti-inflammatory potential of Colocasia esculenta root extract in in-vitro and in-vivo models of inflammation |
|
| Momita Rani Baro, Manas Das, Anuradha Kalita, Bhabajyoti Das, Kishore Sarma | | Journal of Ethnopharmacology. 2022; : 116021 | | [Pubmed] | [DOI] | | | 24 |
Australian native fruits and vegetables: Chemical composition, nutritional profile, bioactivity and potential valorization by industries |
|
| Indeewarie Hemamali Dissanayake, Valeria Zak, Kirandeep Kaur, Kayla Jaye, Zahra Ayati, Dennis Chang, Chun Guang Li, Deep Jyoti Bhuyan | | Critical Reviews in Food Science and Nutrition. 2022; : 1 | | [Pubmed] | [DOI] | | | 25 |
Viburnum opulus fruit extract-capped gold nanoparticles attenuated oxidative stress and acute inflammation in carrageenan-induced paw edema model |
|
| Cristina Bidian, Gabriela Adriana Filip, Lumini?a David, Bianca Moldovan, Ioana Baldea, Diana Olteanu, Mara Filip, Pompei Bolfa, Monica Potara, Alina Mihaela Toader, Simona Clichici | | Green Chemistry Letters and Reviews. 2022; 15(2): 319 | | [Pubmed] | [DOI] | | | 26 |
Evaluating the anti-arthritic potential of walnut (
Juglans regia
L.) in
FCA
induced Sprague Dawley rats
|
|
| Komal Javed, Allah Rakha, Masood Sadiq Butt, Muhammad Naeem Faisal, Urwa Tariq, Makkia Saleem | | Journal of Food Biochemistry. 2022; | | [Pubmed] | [DOI] | | | 27 |
Phytochemicals, Antiinflammatory, and Analgesic Effects of the Ethanol Extract From the Leaves of Premna Flavescens Wall. ex C. B. Clarke |
|
| Ha Minh Le, Phuong Thi Ngo, Anh Tuan Nguyen, Huyen Thi Thanh Do | | Natural Product Communications. 2022; 17(7): 1934578X22 | | [Pubmed] | [DOI] | | | 28 |
Anti-inflammatory, Analgesic, and Cytotoxic Effects of The Phytexponent: A Polyherbal Formulation |
|
| Halvince O. Odira, Simon O. Mitema, Isaac M. Mapenay, Gervason A. Moriasi | | Journal of Evidence-Based Integrative Medicine. 2022; 27: 2515690X22 | | [Pubmed] | [DOI] | | | 29 |
Analgesic, anti-inflammatory and NF-?B inhibitory activity of aerial parts of Cestrum diurnum |
|
| Amina Khatun, Mahmudur Rahman, Mst. Luthfun Nesa, Chung Yeng Looi, Won Fen Wong, Hazrina Hazni, Mohamad Azrul bin Mahdzir, Shaikh Jamal Uddin, Khalijah Awang, Jamil A. Shilpi | | Clinical Phytoscience. 2022; 8(1) | | [Pubmed] | [DOI] | | | 30 |
Pharmacological activities and mechanisms of action of Pogostemon cablin Benth: a review |
|
| Chen Junren, Xie Xiaofang, Li Mengting, Xiong Qiuyun, Li Gangmin, Zhang Huiqiong, Chen Guanru, Xu Xin, Yin Yanpeng, Peng Fu, Peng Cheng | | Chinese Medicine. 2021; 16(1) | | [Pubmed] | [DOI] | | | 31 |
Protective Effects of Anwulignan against HCl/Ethanol-Induced Acute Gastric Ulcer in Mice |
|
| Jiawei Liu, Huijiao Lin, Liwei Yuan, Dan Wang, Chunmei Wang, Jinghui Sun, Chengyi Zhang, Jianguang Chen, He Li, Shu Jing, Hua Li | | Evidence-Based Complementary and Alternative Medicine. 2021; 2021: 1 | | [Pubmed] | [DOI] | | | 32 |
Investigation of the anti-inflammatory effects of caffeic acid phenethyl ester in a model of ?-Carrageenan–induced paw edema in rats |
|
| Halil Sezgin Semis, Cihan Gur, Mustafa Ileriturk, Ozgur Kaynar, Fatih Mehmet Kandemir | | Human & Experimental Toxicology. 2021; : 0960327121 | | [Pubmed] | [DOI] | | | 33 |
In vivo anti-inflammatory effects of Prasiola japonica ethanol extract |
|
| Chae Young Lee, Sang Hee Park, Hye Yeon Lim, Seok Gu Jang, Kyung Ja Park, Dong Sam Kim, Ji Hye Kim, Jae Youl Cho | | Journal of Functional Foods. 2021; 80: 104440 | | [Pubmed] | [DOI] | | | 34 |
Regulation of the redox signaling and inflammation by Terminalia myriocarpa leaves and the predictive interactions of it's major metabolites with iNOS and NF-?B |
|
| Md Afjalus Siraj, Md Sariful Islam Howlader, Md Arman Islam, Tanzira Irin, Jesus Simal-Gandara | | Journal of Ethnopharmacology. 2021; 280: 114459 | | [Pubmed] | [DOI] | | | 35 |
Potential mechanisms underlying the protective effects of Tricholoma matsutake singer peptides against LPS-induced inflammation in RAW264.7 macrophages |
|
| Mengqi Li, Liu Dong, Hanting Du, Zhijie Bao, Songyi Lin | | Food Chemistry. 2021; 353: 129452 | | [Pubmed] | [DOI] | | | 36 |
Dobera glabra (Forssk.) Poir. (Salvadoraceae); phenolic constituents of the aqueous leaves extract and evaluation of its anti-inflammatory, analgesic activities |
|
| Mahmoud Emam, Passant E. Moustafa, Ahmed Elkhateeb, Sameh R. Hussein, Mona M. Marzouk, Sahar S. Abd El-Rahman, El-Sayed S. Abdel-Hameed, Rehab F. Abdel-Rahman | | Heliyon. 2021; 7(2): e06205 | | [Pubmed] | [DOI] | | | 37 |
In vitro therapeutic evaluation of nanoliposome loaded with Xyloglucans polysaccharides from Tamarindus flower extract |
|
| Melappa Govindappa, Ruchitha Birawat, Akshatha K, Vinay B. Raghavendra, Uzma Munawer, Sunayana Ningaraju, Sarah Al-Rashed, Srinivas Chowdappa, Arivalagan Pugazhendhi | | International Journal of Biological Macromolecules. 2021; 178: 283 | | [Pubmed] | [DOI] | | | 38 |
Chaetomium globosum extract mediated gold nanoparticle synthesis and potent anti-inflammatory activity |
|
| Sunayana Ningaraju, Uzma Munawer, Vinay Basavegowda Raghavendra, Kyathegowdanadoddi Srinivasa Balaji, Govindappa Melappa, Kathirvel Brindhadevi, Arivalagan Pugazhendhi | | Analytical Biochemistry. 2021; 612: 113970 | | [Pubmed] | [DOI] | | | 39 |
Phytochemical profiling, in vitro and in vivo anti-inflammatory, analgesic and antipyretic potential of Sesuvium sesuvioides (Fenzl) Verdc. (Aizoaceae) |
|
| M. Sajid-ur-Rehman, Saiqa Ishtiaq, Mohsin Abbas Khan, Meshal Alshamrani, Muhammad Younus, Ghazala Shaheen, Muhammad Abdullah, Ghulam Sarwar, Muhammad Sohaib Khan, Faraza Javed | | Inflammopharmacology. 2021; 29(3): 789 | | [Pubmed] | [DOI] | | | 40 |
Metformin effect in models of inflammation is associated with activation of ATP-dependent potassium channels and inhibition of tumor necrosis factor-a production |
|
| Paulo S. A. Augusto, Tamires C. Matsui, Alysson V. Braga, Felipe F. Rodrigues, Marcela I. Morais, Marcela M. G. B. Dutra, Carla R. A. Batista, Ivo S. F. Melo, Sarah O. A. M. Costa, Caryne M. Bertollo, Márcio M. Coelho, Renes R. Machado | | Inflammopharmacology. 2021; | | [Pubmed] | [DOI] | | | 41 |
The Role of Creatine in the Development and Activation of Immune Responses |
|
| Eric C. Bredahl, Joan M. Eckerson, Steven M. Tracy, Thomas L. McDonald, Kristen M. Drescher | | Nutrients. 2021; 13(3): 751 | | [Pubmed] | [DOI] | | | 42 |
Anti-Inflammatory Effect of 4,5-Dicaffeoylquinic Acid on RAW264.7 Cells and a Rat Model of Inflammation |
|
| Goeun Jang, Seulah Lee, Joonho Hong, Boram Park, Dokyung Kim, Chunsung Kim | | Nutrients. 2021; 13(10): 3537 | | [Pubmed] | [DOI] | | | 43 |
Red Seaweed-Derived Compounds as a Potential New Approach for Acne Vulgaris Care |
|
| Adriana P. Januário, Rafael Félix, Carina Félix, João Reboleira, Patrícia Valentão, Marco F. L. Lemos | | Pharmaceutics. 2021; 13(11): 1930 | | [Pubmed] | [DOI] | | | 44 |
Phytochemical Profiling, Anti-inflammatory, Antioxidant and Antimicrobial Effects of Seven Indian Morinda Species |
|
| Bharat Singh, Pooran Sahu, Ram Sharma | | Current Bioactive Compounds. 2021; 17 | | [Pubmed] | [DOI] | | | 45 |
ANTI-INFLAMMATORY PROPERTIES OF UNEXPLORED PLANTS – CUSCUTA REFLEXA AND COCCULUS HIRSUTUS – AN EXPERIMENTAL STUDY |
|
| ANITA SINGH, VANDANA SINGH, DINESH KUMAR B | | Asian Journal of Pharmaceutical and Clinical Research. 2021; : 24 | | [Pubmed] | [DOI] | | | 46 |
Curcumin Nanoparticles Enhance Antioxidant Efficacy of Diclofenac Sodium in Experimental Acute Inflammation |
|
| Ioana Boarescu, Paul-Mihai Boarescu, Raluca Maria Pop, Ioana Corina Boc?an, Dan Gheban, Ruxandra-Mioara Râjnoveanu, Armand Râjnoveanu, Adriana Elena Bulboaca, Anca Dana Buzoianu, Sorana D. Bolboaca | | Biomedicines. 2021; 10(1): 61 | | [Pubmed] | [DOI] | | | 47 |
Antioxidant Serine-(NSAID) Hybrids with Anti-Inflammatory and Hypolipidemic Potency |
|
| Panagiotis Theodosis-Nobelos, Georgios Papagiouvannis, Paraskevi Tziona, Panos N. Kourounakis, Eleni A. Rekka | | Molecules. 2021; 26(13): 4060 | | [Pubmed] | [DOI] | | | 48 |
Anti-Inflammatory Activities of the Ethanol Extract of Prasiola japonica, an Edible Freshwater Green Algae, and Its Various Solvent Fractions in LPS-Induced Macrophages and Carrageenan-Induced Paw Edema via the AP-1 Pathway |
|
| Laily Rahmawati, Sang Hee Park, Dong Seon Kim, Hwa Pyoung Lee, Nur Aziz, Chae Young Lee, Seung A Kim, Seok Gu Jang, Dong Sam Kim, Jae Youl Cho | | Molecules. 2021; 27(1): 194 | | [Pubmed] | [DOI] | | | 49 |
Cashew (Anacardium occidentale L.) Nuts Counteract Oxidative Stress and Inflammation in an Acute Experimental Model of Carrageenan-Induced Paw Edema |
|
| Marika Cordaro, Rosalba Siracusa, Roberta Fusco, Ramona D’Amico, Alessio Filippo Peritore, Enrico Gugliandolo, Tiziana Genovese, Maria Scuto, Rosalia Crupi, Giuseppina Mandalari, Salvatore Cuzzocrea, Rosanna Di Paola, Daniela Impellizzeri | | Antioxidants. 2020; 9(8): 660 | | [Pubmed] | [DOI] | | | 50 |
Kunitz-Type Peptides from the Sea Anemone Heteractis crispa Demonstrate Potassium Channel Blocking and Anti-Inflammatory Activities |
|
| Irina Gladkikh, Steve Peigneur, Oksana Sintsova, Ernesto Lopes Pinheiro-Junior, Anna Klimovich, Alexander Menshov, Anatoly Kalinovsky, Marina Isaeva, Margarita Monastyrnaya, Emma Kozlovskaya, Jan Tytgat, Elena Leychenko | | Biomedicines. 2020; 8(11): 473 | | [Pubmed] | [DOI] | | | 51 |
Overview of Neurological Mechanism of Pain Profile Used for Animal “Pain-Like” Behavioral Study with Proposed Analgesic Pathways |
|
| Mun Fei Yam, Yean Chun Loh, Chuan Wei Oo, Rusliza Basir | | International Journal of Molecular Sciences. 2020; 21(12): 4355 | | [Pubmed] | [DOI] | | | 52 |
A Critical Review of the Abilities, Determinants, and Possible Molecular Mechanisms of Seaweed Polysaccharides Antioxidants |
|
| Zhiwei Liu, Xian Sun | | International Journal of Molecular Sciences. 2020; 21(20): 7774 | | [Pubmed] | [DOI] | | | 53 |
Evaluation of Analgesic and Anti-inflammatory Potential of 80% Methanol Leaf Extract of Otostegia integrifolia Benth (Lamiaceae) |
|
| Rediet Tesfaye, Abel Degu, Besufekad Abebe, Hiwot Ayalew | | Journal of Inflammation Research. 2020; Volume 13: 1175 | | [Pubmed] | [DOI] | | | 54 |
Astragalin attenuates oxidative stress and acute inflammatory responses in carrageenan-induced paw edema in mice |
|
| Mohamed A. Alblihed | | Molecular Biology Reports. 2020; 47(9): 6611 | | [Pubmed] | [DOI] | | | 55 |
Biosynthesis of copperoxide nanoparticles using Abies spectabilis plant extract and analyzing its antinociceptive and anti-inflammatory potency in various mice models |
|
| Hongtao Liu, SiMin Zheng, HongFei Xiong, Mona S Alwahibi, Xiaoli Niu | | Arabian Journal of Chemistry. 2020; 13(9): 6995 | | [Pubmed] | [DOI] | | | 56 |
Hydroxypropyl-ß-cyclodextrin-complexed naringenin by solvent change precipitation for improving anti-inflammatory effect in vivo |
|
| Tais Gratieri, Ludmila A G Pinho, Marlange Almeida Oliveira, Livia Lira Sa-Barreto, Ricardo N. Marreto, Izabel C. Silva, Guilherme M. Gelfuso, Jullyana de Souza Siqueira Quintans, Lucindo J. Quintans-Junior, Marcilio Cunha-Filho | | Carbohydrate Polymers. 2020; 231: 115769 | | [Pubmed] | [DOI] | | | 57 |
Antinociceptive and anti-inflammatory effect of Poincianella pyramidalis (Tul.) L.P. Queiroz |
|
| Sabrina Zelice da Cruz de Moraes, Andrea Yu Kwan Villar Shan, Marlange Almeida Oliveira Melo, Juliane Pereira da Silva, Fabiolla Rocha Santos Passos, Ariel de Souza Graça, Brancilene Santos de Araújo, Jullyana de Souza Siqueira Quintans, Lucindo José Quintans Júnior, Emiliano de Oliveira Barreto, Geraldo Célio Brandão, Charles dos Santos Estevam | | Journal of Ethnopharmacology. 2020; 254: 112563 | | [Pubmed] | [DOI] | | | 58 |
Modulatory effects of Cornus sanguinea L. mediated green synthesized silver nanoparticles on oxidative stress, COX-2/NOS2 and NFkB/pNFkB expressions in experimental inflammation in Wistar rats |
|
| Luminita David, Bianca Moldovan, Ioana Baldea, Diana Olteanu, Pompei Bolfa, Simona Clichici, Gabriela Adriana Filip | | Materials Science and Engineering: C. 2020; 110: 110709 | | [Pubmed] | [DOI] | | | 59 |
Exploring antiulcer and anti-inflammatory activities of methanolic leaves extract of an Indian mistletoe Helicantes elasticus (Desv.) Danser |
|
| Jacob Jincy, Christudas Sunil | | South African Journal of Botany. 2020; 133: 10 | | [Pubmed] | [DOI] | | | 60 |
Diallyl Disulfide Suppresses Inflammatory and Oxidative Machineries following Carrageenan Injection-Induced Paw Edema in Mice |
|
| Hongxing Zhang, Chi Shang, Zhao Tian, Hatem K. Amin, Rami B. Kassab, Ahmed E. Abdel Moneim, Yingang Zhang | | Mediators of Inflammation. 2020; 2020: 1 | | [Pubmed] | [DOI] | | | 61 |
Medicinal Plants as a Drug Alternative Source for the Antigout Therapy in Morocco |
|
| Nour Elhouda Daoudi, Mohamed Bouhrim, Hayat Ouassou, Mohamed Bnouham, Abdel Halim Salem | | Scientifica. 2020; 2020: 1 | | [Pubmed] | [DOI] | | | 62 |
Antihemorrhoidal activity of organic acids of
Capsella bursa-pastoris
on croton oil-induced hemorrhoid in rats
|
|
| Betul Apaydin Yildirim, Tuba Aydin, Saban Kordali, Serkan Yildirim, Ahmet Cakir, Fatih Yildirim | | Journal of Food Biochemistry. 2020; 44(9) | | [Pubmed] | [DOI] | | | 63 |
Synthesis, characterization, and investigation of the anti-inflammatory effect of 2,3-disubstituted quinazoline-4(1H)-one |
|
| Bhimrao Ghodge, Ajay Kshirsagar, Vijay Navghare | | Beni-Suef University Journal of Basic and Applied Sciences. 2020; 9(1) | | [Pubmed] | [DOI] | | | 64 |
In vivo evaluation of the toxicity, genotoxicity, histopathological, and anti-inflammatory effects of the purified bioglycerol byproduct in biodiesel industry |
|
| Wesam Taha Basal, Aliaa Mahmoud Issa, Shehab Eldin Sayed Mohammed, Saher Abd-Elhafeez Mazen | | Journal of Genetic Engineering and Biotechnology. 2020; 18(1) | | [Pubmed] | [DOI] | | | 65 |
Development, Characterization, and Pharmacological Investigation of Sesamol and Thymol Conjugates of Mefenamic Acid |
|
| Nija B., Arun Rasheed, Kottaimuthu A | | Journal of Evolution of Medical and Dental Sciences. 2020; 9(52): 3909 | | [Pubmed] | [DOI] | | | 66 |
Anti-inflammatory effect of trans-4-methoxycinnamaldehyde from Etlingera pavieana in LPS-stimulated macrophages mediated through inactivation of NF-?B and JNK/c-Jun signaling pathways and in rat models of acute inflammation |
|
| Klaokwan Srisook, Sakulrat Mankhong, Natthakarn Chiranthanut, Kittiya Kongsamak, Na-thanit Kitwiwat, Patsara Tongjurai, Pornpun Aramsangtienchai | | Toxicology and Applied Pharmacology. 2019; 371: 3 | | [Pubmed] | [DOI] | | | 67 |
Bioprospection of Eugenia brasiliensis, a Brazilian native fruit, as a source of anti-inflammatory and antibiofilm compounds |
|
| Josy Goldoni Lazarini, Janaina de Cássia Orlandi Sardi, Marcelo Franchin, Bruno Dias Nani, Irlan Almeida Freires, Juliana Infante, Jonas Augusto Rizzato Paschoal, Severino Matias de Alencar, Pedro Luiz Rosalen | | Biomedicine & Pharmacotherapy. 2018; 102: 132 | | [Pubmed] | [DOI] | | | 68 |
Ellagic acid: A promising protective remedy against testicular toxicity induced by arsenic |
|
| Saeed Mehrzadi, Nosrat Bahrami, Mehrnaz Mehrabani, Manijeh Motevalian, Esrafil Mansouri, Mehdi Goudarzi | | Biomedicine & Pharmacotherapy. 2018; 103: 1464 | | [Pubmed] | [DOI] | | | 69 |
Ellagic acid ameliorates learning and memory impairment in APP/PS1 transgenic mice via inhibition of ß-amyloid production and tau hyperphosphorylation |
|
| Lili Zhong, Hong Liu, Weijia Zhang, Xu Liu, Bo Jiang, Hongxin Fei, Zhongren Sun | | Experimental and Therapeutic Medicine. 2018; | | [Pubmed] | [DOI] | | | 70 |
Lipid peroxidation in rodents with exudative inflammation |
|
| ?.?. ???????, ?.?. ????????, ?.?. ???????, ?.?. ???????? | | Nauchno-prakticheskii zhurnal «Patogenez». 2017; (3()): 58 | | [Pubmed] | [DOI] | |
|
|
|
|
|
|
|
|
