The injection into the rat paws induces inflammation and

The results of the present study confirmed our previous findings that N. officinale extract shows a remarkable anti-inflammatory function against the carrageenan-induced paw edema in rats (an acute animal model of inflammation) (Sadeghi et al., 2014). Furthermore, the extract produced a considerable anti-inflammatory effect on two sub-acute models of inflammation (e.g. formalin-induced paw edema in rat and ear edema by multiple topical application of TPA in ear mouse).

Carrageenan-evoked paw edema is mostly used as an experimental animal model for the acute inflammation studies. Carrageenan induces inflammation processes in a biphasic time-dependent manner. The first phase which includes 0–1 h after injection is regulated by histamine, bradykinin, and serotonin (Crunkhorn and Meacock, 1971; Vinegar et al., 1969). The second phase which is immediately located next to the first phase is mediated by overproduction of prostaglandins, infiltration of neutrophil and the synthesis of the neutrophil-derived free radicals, including hydrogen peroxide, superoxide, and hydroxyl radicals. Carrageenan also induces the synthesis of several leading pro-inflammatory cytokines including TNF-? and IL-1? (Halici et al., 2007; Nacife et al., 2004). To confirm the proinflammatory effects of N. officinale extract via upregulation of the proinflammatory cytokines, IL-1? and TNF-? in the carrageenan-treated paw were measured. Our results clearly indicated an elevated level of TNF-? and IL-1? in in the carrageenan-inflamed paws; it may imply that both cytokines mediate inflammatory signaling in carrageenan-induced paw edema. These findings are thoroughly inconsistent with the previous works (Beloeil et al., 2005; Loram et al., 2007; Sadeghi et al., 2011; 2013). Hajhashemi et al. reported that subplantar injection of carrageenan-induced the TNF-? and IL-1? secretion from the rat paw (Hajhashemi et al., 2010). All doses of the extract significantly reduced the elevation of the IL-1? in paw due to carrageenan challenge, but the extract did not alter the TNF-? levels.  Phytochemical screening of the extract showed that there were phenols and flavonoids in the plant. Phenolics and flavonoids exert an anti-inflammatory effect through reduction of the pro-inflammatory mediators (Ford et al., 2013; Yoon and Baek, 2005)Accordingly, these phenolic and flavonoid seem to underlie the anti-inflammatory activities by N. officially in this study.

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The formalin injection into the rat paws induces inflammation and pain (Arzi et al., 2015). The paw edema induction by formalin in rats is a primary model of sub-chronic inflammation studies;  this is a common model for evaluation of the anti-proliferative activities and also screening the anti-arthritic and anti-inflammatory compounds since it is highly similar to human arthritis (Banerjee et al., 2000; Greenwald, 1991). After 7 days continuous application of N. officinale (500 mg/kg, p.o.) and indomethacin (10 mg/kg, p.o.) formaldehyde-induced paw edema was remarkably inhibited. Therefore, it could be argued that N. officinale is a potential source of drugs against arthritis. These results confirmed by histopathological findings.

The TPA induced-skin inflammation by a single of is shown by erythema, edema, and polymorphonuclear leukocyte migration,; however, multiple doses of TPA produces edema, infiltration of the inflammatory cell and also epidermal hyperplasia. Cyclooxygenase, lipoxygenase, and phospholipase A inhibitors and corticosteroids considerably inhibit the acute inflammation while the chronic process did not suppress by the usual cyclooxygenase inhibitors (Giner-Larza et al., 2001). Some works have shown that the skin carcinogenicity of TPA is strongly related to is pro-inflammatory effects reincluding generation of pro-inflammatory cytokines and also upregulation of COX-2 and iNOS (Murakami et al., 2000). NF-?B regulates the inflammatory ear induce by TPA  in the mouse (Seo et al., 2002; Surh et al., 2001). Additionally, several other studies revealed that MAPKs played an important role in the activation of NF-?B in the TPA-inflammatory skin mouse (Chun et al., 2003; Khan et al., 2013). The extract of was effective in both the acute (Sadeghi et al., 2014) and chronic TPA models. Therefore, it is plausible that the extract in some way interferes with the MAPKs pathway. Also, the topical anti-inflammatory role of the extract may indicate a lipophilic anti-inflammatory component which can cross the skin barrier and exhibit antiphlogistic action (Asuzu et al., 1999).

histological findings showed that extract efficiently inhibits neutrophil infiltration into the skin in both acute and chronic inflammations (Sadeghi et al., 2014). This character would represent a basis for developing a product with cutaneous anti-inflammatory effect.


Currently, a pile of evidence shows that a wide range of the tissue damages such as inflammation, asthma, arthritis, and cancer is mediated by reactive oxygen species (ROS) (Conner and Grisham, 1996). inflammation is regarded as the main site for generation of the different type of oxidants (Reuter et al., 2010). It has been reported that N. officinale showed a potent antioxidative activity in vitro and in vivo conditions. Watercress ingestion has been shown to exert protective effects against the DNA damage and lipid peroxidation (Fogarty et al., 2013); water and ethanol as the main components of the Watercress extracts are shown to play  an effective antioxidant role in the linoleic acid, liver, brain, and kidney homogenate model systems (Ozen, 2008). Moreover, Phenolics and flavonoids which are mostly located in the plants, have a remarkable anti-oxidant role(Pourmorad et al., 2006). It was detected Phenolic and flavonoid contents of N. officinale extract to be 68 ± 8.16 Gallic acid equivalents/g dried extract and 90.26±4.81 mg rutin equivalents/g dried extract, respectively. Based on this, it seems to be possible that beneficial effects of N. officinale in reducing of inflammation development were mediated through its antioxidant properties.

In conclusion, the finding of the resent study demonstrated that N. officinale extract exerts topical and systemic anti-inflammatory activities in some acute and chronic models of inflammation; these activities are probably imposed through inhibition of the action/release of the cytokine, neutrophils infiltration and interferes with the MAPKs pathway. Further studies are necessary to verify the exact mechanism of action and isolate and characterize its active ingredients.