Anti-Inflammatory Activity of Cnidoscolus aconitifolius (Mill.) Ethyl Acetate Extract on Croton Oil-Induced Mouse Ear Edema

Nowadays, there is a growing interest in the development of medicinal plant-based therapies to diminish the ravages of the inflammatory process related to diseases and tissue damage. Most therapeutic effects of these traditional medicinal plants are owed to their phenolic and antioxidant properties. C. aconitifolius is a traditional medicinal plant in Mexico. Previous characterization reports have stated its high nutritional and antioxidant components. The present study aimed to better understand the biological activity of C. aconitifolius in inflammation response. We developed an ethyl acetate extract of this plant to evaluate its anti-inflammatory capacity and its flavonoid content. The topical anti-inflammatory effect of the ethyl acetate extract of C. aconitifolius was determined by the croton oil-induced mouse ear edema test, while flavonoid detection and concentration were determined by thin layer chromatography and the aluminum chloride colorimetric assay, respectively. Topical application of the extract showed significant inhibition of the induced-ear edema (23.52 and 49.41% for 25 and 50 mg/kg dose, respectively). The extract also exhibited the presence of flavonoids. The finding of the anti-inflammatory activity exerted by the C. aconitifolius and the identification of its active principles may suggest and support its use for inflammation treatment.

Ex Vivo and In Vivo Anti-inflammatory Evaluations of Modulated Flavanones Solutions

Interest has developed in natural molecules due to their clinically proven effects on skin diseases. Flavanones display several biological activities, and recently have been the focus of studies due to their anti-inflammatory effect. To improve their pharmacological profile, four flavanones (A, B, C, and D) were synthesized by structural modification of one natural flavanone 1 (semi-systematic name: (2S)-5,7-dihydroxy-6-prenylflavanone) extracted from Eysenhardtia platycarpa. The hydroalcoholic flavanone solutions (FS) were assayed to investigate their anti-inflammatory effect on two in vivo cutaneous inflammation models. Materials and methods: the topical anti-inflammatory effects of FS were evaluated against models of 12-O-tetradecanoylphorbol acetate (TPA)-induced mouse ear edema and arachidonic acid (AA) in rat ear edema. Results: The vinylogous cyclized derivative (flavanone D) caused edema inhibition in the TPA-induced models with an inhibition of 96.27 ± 1.93%; equally effective and potent in inhibiting the mouse ear edema as indomethacin had been. In addition, the AA-induced increase in ear thickness was reduced the most by the topical application of modulated ether (flavanone B). Conclusions: The in vivo and histology results suggest that flavanones B and D are effective as topical anti-inflammatory agents in inflammatory processes. Thus, this new compound represents a promising agent for the management of skin diseases with an inflammatory component.

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

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.

Rosa davurica Pall. Improves Propionibacterium acnes-Induced Inflammatory Responses in Mouse Ear Edema Model and Suppresses Pro-Inflammatory Chemokine Production via MAPK and NF-κB Pathways in HaCaT Cells

Acne, also known as acne vulgaris, is a common disorder of human skin involving the sebaceous gland and Propionibacterium acnes (P. acnes). Although there are a number of treatments suggested for acne, many of them have limitations in their safety and have efficacy issues. Therefore, there is a high demand to develop safe and effective novel acne treatments. In the present study, we demonstrate the protective effects of Rosa davurica Pall. leaves (RDL) extract against P. acnes-induced inflammatory responses in vitro and in vivo. The results showed that RDL dose-dependently inhibited the growth of skin bacteria, including P. acnes (KCTC3314) and aerobic Staphylococcus aureus (KCTC1621) or Staphylococcus epidermidis (KCTC1917). The downregulation of proinflammatory cytokines by RDL appears to be mediated by blocking the phosphorylations of mitogen-activated protein kinase (MAPK) and subsequent nuclear factor-kappa B (NF-κB) pathways in P. acnes-stimulated HaCaT cells. In a mouse model of acne vulgaris, histopathological changes were examined in the P. acnes-induced mouse ear edema. The concomitant intradermal injection of RDL resulted in the reduction of ear swelling in mice along with microabscess but exerted no cytotoxic effects for skin cells. Instrumental analysis demonstrated there were seven major components in the RDL extract, and they seemed to have important roles in the anti-inflammatory and antimicrobial effects of RDL. Conclusively, our present work showed for the first time that RDL has anti-inflammatory and antimicrobial effects against P. acnes, suggesting RDL as a promising novel strategy for the treatment of acne, including natural additives in anti-acne cosmetics or pharmaceutical products.

Quantification of prostaglandins E2 and D2 using liquid chromatography-tandem mass spectrometry in a mouse ear edema model

A sensitive, specific, and accurate high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed and validated for the quantification of prostaglandins D2 (PGD2) and E2 (PGE2) in a mouse ear edema model.

Co-Stimulation of Purinergic P2X4 and Prostanoid EP3 Receptors Triggers Synergistic Degranulation in Murine Mast Cells

Mast cells (MCs) recognize antigens (Ag) via IgE-bound high affinity IgE receptors (FcεRI) and trigger type I allergic reactions. FcεRI-mediated MC activation is regulated by various G protein-coupled receptor (GPCR) agonists. We recently reported that ionotropic P2X4 receptor (P2X4R) stimulation enhanced FcεRI-mediated degranulation. Since MCs are involved in Ag-independent hypersensitivity, we investigated whether co-stimulation with ATP and GPCR agonists in the absence of Ag affects MC degranulation. Prostaglandin E2 (PGE2) induced synergistic degranulation when bone marrow-derived MCs (BMMCs) were co-stimulated with ATP, while pharmacological analyses revealed that the effects of PGE2 and ATP were mediated by EP3 and P2X4R, respectively. Consistently, this response was absent in BMMCs prepared from P2X4R-deficient mice. The effects of ATP and PGE2 were reduced by PI3 kinase inhibitors but were insensitive to tyrosine kinase inhibitors which suppressed the enhanced degranulation induced by Ag and ATP. MC-dependent PGE2-triggered vascular hyperpermeability was abrogated in a P2X4R-deficient mouse ear edema model. Collectively, our results suggest that P2X4R signaling enhances EP3R-mediated MC activation via a different mechanism to that involved in enhancing Ag-induced responses. Moreover, the cooperative effects of the common inflammatory mediators ATP and PGE2 on MCs may be involved in Ag-independent hypersensitivity in vivo.