Antiallergic effects of ethanol extract of Cnidium monnieri (L.) Cuss. on DNCB-induced atopic dermatitis in mice

Purpose: To study the anti-allergic effects of ethanol extract of Cnidium monnieri (L.) Cuss. on 2, 4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis in mice.Method: Atopic dermatitis (AD) was induced by DNCB in Balb/c mice, and the mice randomly divided into normal group, negative control group, hydrocortisone group, and ethanol extract of Cnidium monnieri (L.) Cuss. (EECM) group. Ear swelling was determined by measuring the thicknesses of the left and right ears of each mouse. Spleen and thymus indices were calculated from spleen, thymus and body weight values. The levels of TNF-α and IgE in serum were determined by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (H & E) staining and toluidine blue staining were used to evaluate pathological changes in ear tissue, while high performance liquid chromatography (HPLC) was performed to ascertain the bioactive compounds in EECM.Results: Compared with the negative control group, EECM significantly alleviated skin lesions, reduced thickness of ear swelling, and decreased spleen and thymus indexes of mice (p < 0.05). Moreover, EECM significantly reduced epidermal thickness (p < 0.01). However, EECM did not significantly alter the number of mast cells (p > 0.05). The expressions of TNF-α and IgE in serum were also significantly down-regulated (p < 0.01, p < 0.05). Results from HPLC revealed that the contents of bergapten, imperatorin and osthole in EECM were 0.73, 3.69 and 9.40 mg/g, respectively.Conclusion: EECM ameliorates AD in mice via inhibition of inflammation and by a mechanism that might be related to the regulation of TNF-α and IgE levels. The major bioactive constituents of EECM are osthole, imperatorin and bergapten. Thus, this plant extract has a potential to be developed for the treatment of of atopic dermatitis

Mediator MED23 regulates inflammatory responses and liver fibrosis.

Liver fibrosis, often associated with cirrhosis and hepatocellular carcinomas, is characterized by hepatic damage, an inflammatory response, and hepatic stellate cell (HSC) activation, although the underlying mechanisms are largely unknown. Here, we show that the transcriptional Mediator complex subunit 23 (MED23) participates in the development of experimental liver fibrosis. Compared with their control littermates, mice with hepatic Med23 deletion exhibited aggravated carbon tetrachloride (CCl4)-induced liver fibrosis, with enhanced chemokine production and inflammatory infiltration as well as increased hepatocyte regeneration. Mechanistically, the orphan nuclear receptor RAR-related orphan receptor alpha (RORα) activates the expression of the liver fibrosis-related chemokines C-C motif chemokine ligand 5 (CCL5) and C-X-C motif chemokine ligand 10 (CXCL10), which is suppressed by the Mediator subunit MED23. We further found that the inhibition of Ccl5 and Cxcl10 expression by MED23 likely occurs because of G9a (also known as euchromatic histone-lysine N-methyltransferase 2 [EHMT2])-mediated H3K9 dimethylation of the target promoters. Collectively, these findings reveal hepatic MED23 as a key modulator of chemokine production and inflammatory responses and define the MED23-CCL5/CXCL10 axis as a potential target for clinical intervention in liver fibrosis