Retrofractamide C Derived from Piper longum Alleviates Xylene-Induced Mouse Ear Edema and Inhibits Phosphorylation of ERK and NF-κB in LPS-Induced J774A.1

Abstract

Many studies have reported the biological activities of retrofractamide C (RAC). However, few studies have investigated the anti-inflammatory effect of RAC. In the present study, we investigated the anti-inflammatory effect of RAC using lipopolysaccharide (LPS)-induced J774A.1 cells and a xylene-induced mouse ear edema model. Treatment with RAC decreased LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) secretion and inducible NO synthase (iNOS) and cyclooxygenase 2 (COX2) protein expression. It also downregulated the LPS-induced production of interleukin-1β (IL-1β) and interleukin-6 (IL-6) but not tumor necrosis factor α (TNF-α). In the LPS-induced signaling pathway, RAC inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB) but not c-Jun N-terminal kinase (JNK) or p38. In a xylene-induced mouse ear edema model, RAC treatment alleviated edema formation and inflammatory cell infiltration. In conclusion, the present study indicates that RAC has the potential to have anti-inflammatory effects and could be a prospective functional food.

Analgesic and Anti-Inflammatory Potential of Essential Oil of Eucalyptus camaldulensis Leaf: In Vivo and in Silico Studies

“…edema. 36 In our study, it was shown that the essential oil of E. camaldulensis at 400 mg/kg dose can markedly inhibit (67.75%) the formation of xylene-induced ear edema while the standard diclofenac Na was found to show the highest inhibition 83.67%.…”

“…This method has been frequently used to initiate acute inflammatory response which leads to serious edematous changes and vasodilation of skin when topically applied to the surfaces of the ears of mice. 36,37 Xylene initiates the release of inflammatory mediators, which promotes vasodilation and increasing vascular permeability, and causes ear Values are presented as mean ± SEM (n = 6). One-way ANOVA followed by Dunnett's multiple comparisons was performed to analyze this dataset.…”

Piper longum L.: A comprehensive review on traditional uses, phytochemistry, pharmacology, and health‐promoting activities

“…Interleukin‐1β (IL‐1β) and interleukin‐6 (IL‐6) expression were downregulated and phosphorylation of extracellular signal‐regulated kinase (ERK) and nuclear factor kappa light chain enhancer of activated B cells (NF‐κB) were inhibited. RAC treatment also alleviated oedema formation and inflammatory cell infiltration in the xylene‐induced mouse ear oedema model (Lim et al, 2020).…”

Development and In Vitro - In Vivo Evaluation of Composite Hydrogel-Forming Microneedles Containing Diclofenac Sodium with Box-Behnken Design Using SLA 3D-Printed Microneedle Molds

“…PGE-2 is one of the major inflammatory mediators in the tissue. It is known that following the xylene application, the level of PGE-2 increases, causing vasodilation and swelling of the ear tissue in combination with the effects of various mediators [68,69]. PGE-2 is also involved in numerous skinrelated conditions (including cancer, aging, UV-light exposure, etc.)…”