Cinnamomum cassia (Lauraceae) has long been used as one of the most frequently used traditional oriental medicines for the treatment of gastritis, diabetes, blood circulation disturbance and inflammatory diseases. Cinnamomulactone (1), a new butyrolactone was isolated from the twigs of C. cassia together with nine known compounds, coumarin (2), trans-cinnamic acid (3), cinnamaldehyde (4), 2-hydroxycinnamaldehyde (5), 2-methoxycinnamaldehyde (6), 2-hydroxy-cinnamyl alcohol (7), benzoic acid (8), (+)-syringaresinol (9) and phenethyl (E)-3-[4-methoxyphenyl]-2-propenoate (10). The planar structure of 1 was elucidated on the basis of spectroscopic data analysis and its configurations were determined by coupling constant ( J ) analysis and a comparison with specific rotation data of related compounds on the literatures. The structures of known compounds were confirmed by the comparison of their spectroscopic data to the reported values. Compound 10 was isolated for the first time from this plant. Compounds 1, 2, 4, and 9 showed inhibitory activity against matrix metalloproteinases (MMPs) gene expression. Among them, compound 1 has been revealed to suppress the gene expression of MMP-3 and interleukin (IL)-1β as well as MMP-1 in tumor necrosis factor (TNF)-α stimulated rheumatoid arthritis synovial fibroblasts.
Background: Psoriasis is a common chronic inflammatory skin disease characterized by an external red rash that is caused by abnormal proliferation and differentiation of keratinocytes and immune T cells. This study aimed to elucidate the role of aminooxy acetic acid (AOA) in alleviating psoriasis from the perspective of immunology and metabolomics. Therefore, contributing to the development of new drugs as candidates for psoriasis treatment.Methods: To investigate the symptom-alleviating effects and the related mechanisms of AOA on the treatment of psoriasis, we used a 12-O-tetradecanoylphorbol-13-acetate-induced psoriasis-like skin mouse model and interleukin (IL)-17-stimulated human keratinocytes.Results: The results showed that AOA ameliorated psoriasis-related symptoms and decreased inflammation-associated antimicrobial peptides and T-helper 17 (Th17)-associated cytokines in a mouse model of psoriasis. Furthermore, AOA inhibited the activation of mechanistic target of rapamycin (mTOR) by suppressing serine metabolism-related genes. Importantly, mTOR inhibition ameliorated psoriatic disease by affecting the differentiation of various T cells and normalizing the Th17/regulatory T (Treg) cell balance. In addition, IL-17-stimulated human keratinocytes showed the same results as in the in vivo experiments.Conclusion: Taken together, these results suggest that targeting the serine metabolism pathway in the treatment of psoriasis is a novel strategy, and that AOA could be utilized as a novel biologic to treat psoriasis.
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