Anti-inflammatory effect of deoxylapachol by regulating interleukin 17/Toll-like receptor/tumor necrosis factor...

Deoxylapachol (DLP), a natural product of marine origin, firstly isolated from the New Zealand brown algae, was firstly found has potent anti-inflammatory activities both in vitro and in vivo experiments. The study's objective is aimed at its prospective molecular mechanisms. Firstly, the anti-inflammatory effect of DLP was assessed in zebrafish models induced by copper sulfate, tail-cutting and lipopolysaccharide exposure, respectively. The results showed that DLP effectively alleviated the acute inflammatory response by inhibiting the migration of immune cells, and the elevation of reactive oxygen species and nitric oxide. Moreover, DLP regulated the mRNA expression of tumor necrosis factor-α, matrix metalloproteinase 9, signal transducer and activator of transcription 3, nuclear factor of kappa light polypeptide gene enhancer in B-cells, cyclooxygenase-2, caspase-3, myeloperoxidase‌, glycogen synthase kinase 3 beta, mitogen-activated protein kinase 14a‌, mitogen-activated protein kinase 1‌, and hypoxia-inducible factor 1 alpha genes related to the interleukin (IL)-17/Toll-like receptor/TNF signaling pathway, and inflammatory cytokines (transforming growth factor beta, nucleotide-binding domain, leucine-rich repeat containing family, pyrin domain containing 3‌, IL-1β, IL-4, IL-6, IL-8, IL-10, Toll-like receptor 2 [TLR2], TLR3, TLR4, IL-17a, and IL-17b). DLP also regulates the expressions of proteins such as Tumor Necrosis Factor-α, nuclear factor of kappa light polypeptide gene enhancer in B-cells, matrix metalloproteinase 9, cyclooxygenase-2, p-P38, signal transducer and activator of transcription 3, GSK3α/β, caspase-3, inducible nitric oxide synthase, IL-18, nucleotide-binding domain, leucine-rich repeat containing family, pyrin domain containing 3‌, peroxisome proliferator-activated receptor‌ and nuclear factor (erythroid-derived 2)-like 2‌. In conclusion, our finding indicated that DLP has the potential to be a candidate drug for the effective treatment of inflammation. SIGNIFICANCE STATEMENT: This study has shown that deoxylapachol exerts a potent anti-inflammatory effect in zebrafish inflammatory models. Deoxylapachol, a natural product of marine origin, has the potential to be an effective agent for anti-inflammatory treatment.