Abstract
In addition to the previous investigations of bioactivity of aqueous extract of the edible Gracilaria tenuistipitata (AEGT) against H2O2-induced DNA damage and hepatitis C virus replication, the purpose of this study is to evaluate the potential therapeutic properties of AEGT against inflammation and hepatotoxicity using lipopolysaccharide (LPS)-stimulated mouse RAW 264.7 cells, primary rat peritoneal macrophages and carbon tetrachloride (CCl4)-induced acute hepatitis model in rats. AEGT concentration-dependently inhibited the elevated RNA and protein levels of inducible nitric oxide synthase and cyclooxygenase-2, thereby reducing nitric oxide and prostaglandin E2 levels, respectively. Moreover, AEGT significantly suppressed the production of LPS-induced proinflammatory cytokines, including interleukin (IL)-1β, IL-6 and tumor necrosis factor-α. These inhibitory effects were associated with the suppression of nuclear factor-kappa B activation and mitogen-activated protein kinase phosphorylation by AEGT in LPS-stimulated cells. In addition, we highlighted the hepatoprotective and curative effects of AEGT in a rat model of CCl4-intoxicated acute liver injury, which was evident from reduction in the elevated serum aspartate aminotransferase and alanine aminotransferase levels as well as amelioration of histological damage by pre-treatment or post-treatment of AEGT. In conclusion, the results demonstrate that AEGT may serve as a potential supplement in the prevention or amelioration of inflammatory diseases.
Highlights
Inflammation, considered an innate immune response beneficial to host survival, is a complex biological response of living organisms to harmful stimuli, such as infection, cellular damage, and tissue injury [1]
We evaluated the anti-inflammatory effect of aqueous extract of the edible Gracilaria tenuistipitata (AEGT) using LPS-stimulated RAW264.7 and primary rat peritoneal macrophages, and found that AEGT exerted prophylactic and curative effects of anti-inflammatory activity by reducing inducible nitric oxide synthase (iNOS), COX-2, tumor necrosis factor-a (TNF-a), IL-1b, and IL-6 expression
The results indicated that 800 mg/ml AEGT decreased nitric oxide (NO) and PGE2 production to 6.360.8 mM and 2.860.5 ng/ml, respectively, compared to LPS which stimulated NO and PGE2 production to 14.262.2 mM and 6.660.9 ng/ml, respectively (Fig. 2E and 2F)
Summary
Inflammation, considered an innate immune response beneficial to host survival, is a complex biological response of living organisms to harmful stimuli, such as infection, cellular damage, and tissue injury [1]. The inflammatory reaction includes a number of cellular and biochemical alterations involving the downstream regulation of proinflammatory protein expression and the upregulation of anti-inflammatory protein expression that facilitate the recruitment of immune cells, whereas pro-inflammatory cytokines facilitate this process [2,3]. Two important mediators of inflammation, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), regulate the inflammatory process by producing nitric oxide (NO) and prostaglandins (PG) E2 (PGE2), respectively [5]. In LPS-induced inflammation, the binding of LPS to the toll-like receptor 4 (TLR4)/CD14/MD2 complex stimulates the recruitment of both cytoplasmic MyD88 and TRIF adaptor proteins, which activates nuclear factor-kappa B (NF-kB) and mitogen-activated protein kinase (MPAK) signaling [6]. Persistent activation of the MAPK signaling pathway has been revealed to increase the development of human inflammatory diseases due to the induction of iNOS expression [10]. Targeting the NFkB and MAPK signaling pathways is considered as an attractive therapeutic strategy for the development of anti-inflammatory drugs
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