inflammation is the first response of the immune system to infection or irritation that helps the body to protect itself against an injurious stimulus . it can be evoked by a variety of noxious agents , ( e.g. infections , antibodies or physical injuries ) . inflammation may be acute or chronic , depending on the nature of the stimulus and the effectiveness of the initial reaction in eliminating the stimulus or the damaged tissues . acute inflammation is rapid in onset ( typically minutes ) and is of short duration , chronic inflammation may follow acute inflammation or be insidious in onset . it is of longer duration and is associated with the presence of lymphocytes , macrophages , proliferation of blood vessels , fibrosis , and tissue destruction ( 1 , 2 ) . nonsteroidal anti - inflammatory drugs ( nsaids ) , opioids and corticosteroids are the group of drugs , which are used presently for management of pain and inflammatory conditions . the adverse drug reactions associated with nsaids are the gastrointestinal problems due to direct and indirect irritation of the gastrointestinal tract , the most common being gastrointestinal bleeding and peptic ulcers . therefore , despite the currently available anti - inflammatory drugs , there is a need for safer alternatives . the use of natural remedies for the treatment of inflammatory and painful conditions has a long history in ayurveda and other systems of traditional medicine ( 3 - 5 ) . royal jelly ( rj ) , a honey bee secretion used in the nutrition of larvae as well as adult queens , is secreted from the glands in the hypopharynx of worker bees and fed to all larvae in the colony ( 6 ) . it is collected and sold as a dietary supplement , claiming to have various health benefits because of components like b - complex vitamins , such as pantothenic acid ( vitamin b5 ) and vitamin b6 ( pyridoxine ) ( 7 , 8) . it has also been reported to stimulate the growth of glial cells and neural stem cells in the brain ( 8) . preliminary evidences show that it has cholesterol - lowering , anti - inflammatory , wound - healing , and antibiotic effects . researches also suggest that the 10-hydroxy-2-decenoic acid ( 10-hda ) found in rj may inhibit the vascularization of tumors ( 7 , 9 ) . royal jelly is said to improve fertility in both men and women , in men by increasing the quality of their sperm , and in women by increasing the quality of their ovules ( 10 , 11 ) . it is also found to have antifungal activity against candida spp . and trichosporon spp . studies suggest the hepatoprotective and antioxidant activities of the rj against carbon tetrachloride ( ccl4)- induced acute liver injury ( 12 ) . earlier biological investigations have shown that rj has insulin - like activity and was found to be responsible for the lowering impact of honey on blood glucose levels ( 13 ) . in the present study , the anti - inflammatory properties of rj were investigated in formalin - induced rat paw edema . the rj used in this study was purchased from santa cruz biotechnology inc , usa . aspirin and formalin were obtained from darou - pakhsh ( iran ) and merck ( germany ) , respectively . albino wistar male rats ( weighing between 150 - 200 g ) were purchased from animal house of ahvaz jundishapur university of medical sciences . the animals were maintained under normal laboratory condition of humidity ( 50% ) , temperature ( 23  2c ) and a 12-hour light / dark cycle , and allowed free access to food and water ad libithum . the animals were randomly allocated into 5 groups ( n = 6 ) . at first , the volume of intact rats paw was measured in all groups using a plethysmometer . the first group served as a negative control ( normal saline 5 ml / kg i.p . ) while the second , third and the forth groups received different doses ( 25 , 50 and 100 mg / kg ) of rj and the fifth group received aspirin ( 300 mg / kg i.p . ) as a positive control group , respectively . edema was induced on the right hind paw of the rat by a subplantar injection of 0.1 ml of formalin ( 2.5 % ) 30 minutes after drug administration . swelling of formalin - injected foot was measured using a plethysmometer ( ugo basile , italy ) hourly during the first and fifth hours after the formalin injection ( 14 ) . the ability of anti - inflammatory agents to suppress paw inflammation was expressed as a percent inhibition of paw edema and calculated according to the following equation : where v1 = the animal paw volume before formalin injection and v2 = the paw volume after drugs and formalin injection at different time points . the data of this study were statistically analyzed using one - way anova and tukey tests . the rj used in this study was purchased from santa cruz biotechnology inc , usa . aspirin and formalin were obtained from darou - pakhsh ( iran ) and merck ( germany ) , respectively . albino wistar male rats ( weighing between 150 - 200 g ) were purchased from animal house of ahvaz jundishapur university of medical sciences . the animals were maintained under normal laboratory condition of humidity ( 50% ) , temperature ( 23  2c ) and a 12-hour light / dark cycle , and allowed free access to food and water ad libithum . the animals were randomly allocated into 5 groups ( n = 6 ) . at first , the volume of intact rats paw was measured in all groups using a plethysmometer . the first group served as a negative control ( normal saline 5 ml / kg i.p . ) while the second , third and the forth groups received different doses ( 25 , 50 and 100 mg / kg ) of rj and the fifth group received aspirin ( 300 mg / kg i.p . ) as a positive control group , respectively . edema was induced on the right hind paw of the rat by a subplantar injection of 0.1 ml of formalin ( 2.5 % ) 30 minutes after drug administration . swelling of formalin - injected foot was measured using a plethysmometer ( ugo basile , italy ) hourly during the first and fifth hours after the formalin injection ( 14 ) . the ability of anti - inflammatory agents to suppress paw inflammation was expressed as a percent inhibition of paw edema and calculated according to the following equation : where v1 = the animal paw volume before formalin injection and v2 = the paw volume after drugs and formalin injection at different time points . the data of this study were statistically analyzed using one - way anova and tukey tests . as shown in figure 1 the rj ( 50 and 100 mg / kg ) significantly ( p < 0.05 ) inhibited formalin - induced rat paw edema as compared to the control group . also , it was shown that there was no significant difference between 3rd and 4th groups ( 50 and 100 mg/ kg ) and the positive control group ( aspirin 300 mg / kg ) in inhibiting formalin - induced swelling ( p > 0.05 , figure 2 ) . moreover , 25 mg / kg of rj could not diminish paw swelling in response to formalin . royal jelly at doses 50 and 100 mg / kg showed comparable effects to aspirin ( 300 mg / kg ) to inhibit paw edema up to 60% . * p < 0.05 as compared to the normal saline group . * p < 0.05 as compared to the aspirin ( 300 mg / kg ) group . formalin test is a biphasic response where first phase is the direct effect of formalin , which involves neurogenic pain . the second phase is involved in the inflammatory reactions mediated by prostaglandin , serotonin , histamine , bradikinin and cytokines , such as interleukin-1 beta , interleukin-6 tumor necrosis factor - alpha eicosanoids , and nitric oxide ( 15 ) . in the present study , the formalin - induced paw edema model was used to investigate anti - inflammatory effects of rj in experimental rats . the results demonstrated that anti - inflammatory effects of rj was dose - dependent and the best anti - inflammatory effect was observed in the doses of 50 and 100 mg / kg . it was shown that 50 mg / kg rj was as efficient as 300 mg / kg of aspirin in attenuating formalin - induced edema . aspirin , a nonsteroidal anti - inflammatory agent , has been frequently used in experimental models as positive control to suppress inflammation . the results of the recent study confirm the findings of karaca et al . which showed rj inhibits colitis induced by acetic acid ( 16 ) . this effect can be attributed to the polyphenolic compounds in rj that are responsible for the functional properties , such as antioxidant and anti - inflammatory capacity as showed by kerem et al . ( 17 ) , almaraz - abarca et al . ( 18 ) , and wu et al . ( 19 ) . these compounds in rj are collected by bees from the plants where they gather nectar ( 20 ) . royal jelly has been shown to exhibit dna - protective and antitumor effects in experimental animals ( 21 , 22 ) . hamerlinck reported that rj exhibited immunomodulatory properties by stimulating antibody production and immunocompetent cell proliferation in mice or by depressing humoral immune functions in rats ( 23 ) . another report indicated that the protection by rj ingestion could be partly attributed to the presence of neopterin in rj ( 23 ) . the protection afforded by rj against the immunosuppression produced by increased prostaglandin e2 levels has been demonstrated in studies in vivo and in vitro ( 21 - 24 ) . el - nekeety et al . found a potential protective effect of rj against the toxic hazards of fumonisins ( 25 ) . reported that rj in the diet decreased the gene expression of cytochrome p450 4a14 ( cyp4a14 ) enzymes and detoxifying enzymes , which catalyse peroxidation of endogenous lipids , and increased the gene expression of glutathione s - transferase and glutathione peroxidase ( 26 ) . as a result , rj was found to diminish the formalin - induced paw edema in a dose - dependent manner . although it has been considered that it might exert the benefits through its antioxidant features , the exact mechanism of effect is yet unknown . in conclusion , it could be suggested that rj provides considerable anti - inflammatory effects and the efforts to focus on the underlying mechanism / s of rj may provide new opportunities for the development of new drugs .
background : royal jelly ( rj ) , a food item secreted by worker honeybees , is a mixture that contains protein , glucose , lipid , vitamins , and minerals ; it is widely used as a commercial medical product . 
 previous studies have shown that rj has a number of physiological effects , such as anti - inflammatory , antitumor , antiallergic and antioxidant activities.objectives:in the present study , the anti - inflammatory properties of rj were investigated in formalin - induced rat paw edema.materials and methods : in this study , 30 male wistar albino rats were divided into five equal groups ( n = 6 ) as follows : test groups received different doses ( 25 , 50 and 100 mg / kg , ip ) of rj and a negative control group received normal saline ( 5 ml / kg ) and a positive control group received aspirin ( 300 mg / kg , i.p ) . 
 edema was induced on the right hind paw of the rat by a subplantar injection of 100 l of formalin ( 2.5% ) after 30 minutes . 
 paw edema was measured in the rats received the drugs , saline and aspirin before and after the formalin injection during 5 hours , using a plethysmometer.results:the results showed that rj has a dose - dependent anti - inflammatory effect and the highest anti - inflammatory effect was observed in the doses of 50 and 100 mg / kg.conclusions : royal jelly has potent anti - inflammatory effects compared to aspirin and it could be used in the treatment of inflammation . however , 
 further studies are required to determine the active components in rj responsible for this effect and its mechanism of action .