Exploration of costunolide derivatives as potential anti-inflammatory agents for topical treatment of atopic dermatitis by inhibiting MAPK/NF-κB pathways.

Atopic dermatitis (AD) is a common inflammatory disease and it is very difficult to treat. In the present work, a series of costunolide derivatives have been prepared, and in vitro and in vivo anti-inflammatory activities have evaluated. The results showed that most derivatives displayed good inhibition of NO generation with low cytotoxicity, and 7d could inhibit the phosphorylation of P38, P65 NF-κB and IκB-α in LPS-induced RAW264.7 model. The in vivo researches showed that 7d could improve skin injury symptoms, decrease Th2-type cytokine levels, inhibit HIS levels, alleviate scratching and repaire the damaged skin barrier through the inhibition of phosphorylation of MAPK and NF-κB signaling pathways on MC903-induced AD model. Therefore, costunolide derivatives may be new potent anti-AD agents for further study.

Vasicine alleviates 2,4-dinitrochlorobenzene-induced atopic dermatitis and passive cutaneous anaphylaxis in BALB/c mice.

Atopic dermatitis (AD), a type of skin inflammation, is associated with immune response mediated by T-helper 2 (Th2) cells, and mast cells. Vasicine is an alkaloid isolated from Adhatoda vasica, a popular Ayurvedic herbal medicine used for treating inflammatory conditions. In the present study, the anti-AD effects of vasicine were evaluated on 2,4-dinitrochlorobenzene-induced AD-like skin lesions in BALB/c mice. The potential anti-allergic effects of vasicine were also assessed using the passive cutaneous anaphylaxis (PCA) test. The results showed that the oral administration of vasicine improved the severity of AD-like lesional skin by decreasing histopathological changes and restoring epidermal thickness. Vasicine also inhibited the infiltration of mast cells in the skin and reduced the levels of pro-Th2 and Th2 cytokines as well as immunoglobulin E in the serum. Finally, vasicine inhibited the expression of pro-Th2 and Th2 cytokines in skin tissues, indicating the therapeutic potential of vasicine for AD.

[3, 4- dinitro-furazan-based oxidation furazan acute and subchronic toxicity studies].

OBJECTIVE: To study the 3, 4- dinitro-furazan-based oxidation furazan (DNTF) of sub-acute toxicity and chronic toxicity, to determine the acute toxicity classification DNTF, the nature of toxic effects and major target organ for the development provide the basis for occupational exposure limits. METHODS: ( 1) Acute toxicity: The oral gavage method once infected, symptoms of poisoning of animals observed to calculate the LD50DNTF and 95% confidence limits. ( 2) sub-chronic experiment: selection of 96 healthy SD rats were randomly divided into four groups, doses of 25, 56.2, 125 mg/kg and the negative control group, Exposure for ninety days,five days a week, once a day, The rats were killed at end of Exposure, heart, liver, spleen, lung, kidney, brain,testis, uterus were taken to observe the pathological changes. RESULTS: ( 1) Acute oral toxicity test results indicate that DNTF rat oral LD50 greater than 5000 mg/kg, DNTF mice treated by oral LD50 4589 mg/kg, 95%confidence limit for the 4026-5230 mg/kg, Acute toxicity grade level is low toxicity compounds. (2) Sub-chronic toxicity experiment, the high-dose male rats, high, medium and low-dose group female rats weight gain than the negative control group, compared with the control group, the difference was statistically significant (P<0.05).125 mg/kg of serum alanine aminotransferase, aspartate aminotransferase was significantly higher. 125 mg/kg dose groups, liver, kidney, lung, testicular factor was significantly higher. Liver, kidney, lung histological examination showed obvious morphological changes. CONCLUSION: Acute toxicity grade DNTF low toxicity level compounds, target organ toxicity of liver, kidney and lung.