stimuli (Cho et al. 2009). Many cells and mediators are instrumental in the proceeding of inflammation (Asgarpanah and Kazemivash 2013).
Macrophages are crucial in the immune responses and participate in both innate
and acquired immunity (Asgarpanah and Kazemivash 2013; Woods et al. 2009).
When activated by stimulants, macrophages secrete pro-inflammatory products
including nitric oxide, prostaglandin E2, interleukin (IL)-6, and IL-1β, tumor necrosis factor (TNF)-α, granulocyte/macrophage colony-stimulating factor (GM-CSF)
and other inflammatory mediators in response to cell signaling (Tetley 2005;
Asgarpanah and Kazemivash 2013).
An excessive immune response is undesirable and can be involved in the pathogenesis of various diseases including arthritis, atherosclerosis, inflammatory bowel
diseases, etc. (Moilanen and Vapaatalo 1995; Guzik et al. 2003). Therefore, apposite
countermeasures are required against the overproduction of inflammatory mediators.
Despite the presence of many steroidal or non-steroidal anti-inflammatory drugs,
researchers are looking for natural products to develop them into anti-inflammatory
agents because of the side-effects produced by chemical drugs.
Serotonin derivatives from safflower seeds have been reported to exhibit antiinflammatory effects. Serotonin derivatives for ethyl acetate extract of safflower
seeds have been isolated and among them, N-feruloylserotonin has been found to be
most potent in inhibiting lipopolysaccharide (LPS)-induced production of nitric
oxide and prostaglandin E2, (IL)-6, and IL-1β in RAW 264.7 macrophages
(Jo et al. 2017).
70% ethanol extracts of safflower seeds inhibited the production of nitric oxide
and prostaglandin E2 in LPS-stimulated RAW 246.7 macrophages. While the
expression of TNF-α, IL-1β, and IL-6 was significantly reduced. Due to the significant effects on inflammatory factors, the study suggested safflower as a potential
anti-inflammatory therapeutic agent (Kim et al. 2013).
Ethyl acetate extracts of safflower, mainly employing cosmosiin, acacetin, N-( pcoumaroyl) serotonin, and N-feruloyl serotonin, were found to exhibit effective antiinflammatory effects against LPS-stimulated RAW 264.7 macrophages. All of the
four compounds were found to significantly inhibit the production of LPS-stimulated
nitric oxide and pro-inflammatory cytokines (Kim et al. 2015).
Apart from above-mentioned mediators, other mediators can also be involved in
inflammation and can be a target of anti-inflammatory compounds. Jun and colleagues have reported the anti-inflammatory effects of methanol extracts of safflower. These extracts were reported to produce anti-inflammatory effects by
inducing heme oxygenase-1 expression and inhibiting nuclear factor kappa B
(NF-κB) activity (Jun et al. 2011). Serotonin derivatives, N-( p-coumaroyl) serotonin
and N-( p-coumaroyl) tryptamine, from safflower seed extracts have been shown to
inhibit the production of pro-inflammatory cytokines including IL-1α, IL-1β, IL-6,
IL-8, and TNF-α, produced by lipopolysaccharide-stimulated human monocytes
(Takii et al. 2003). Seeds of safflower also exhibit neuroprotective effects through
inhibition of the secretion of pro-inflammatory cytokines including nitric oxide and
prostaglandin E2 (Asgarpanah and Kazemivash 2013).
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M. Nazir et al.
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