Inhibition of MDM2 expression by rosmarinic acid in TSLP-stimulated mast cell.

Rosmarinic acid (RA) has an anti-inflammatory property while thymic stromal lymphopoietin (TSLP) has an important role in mast cell-mediated inflammatory responses. Thus, the aim of this study was to determine the regulatory effect of RA in TSLP-stimulated human mast cell line, HMC-1 cells, and short ragweed pollen-induced allergic conjunctivitis mouse model. As a result, we found that RA significantly decreased the TSLP-induced mast cell proliferation and murine double minute (MDM) 2 expression. RA significantly decreased the levels of interleukin (IL)-13 and phosphorylated the signal transducer and activation of transcription 6 in the TSLP-stimulated HMC-1 cells. RA induced the increment of p53 levels, caspase-3 activation, and poly-ADP-ribose polymerase cleavage and the reduction of the procaspase-3 and Bcl2. RA significantly reduced the production of tumor necrosis factor-α, IL-1ß, and IL-6 on the TSLP-stimulated HMC-1 cells. In addition, RA significantly reduced the levels of IgE, IL-4, and TSLP in the short ragweed pollen-induced allergic conjunctivitis mouse model. In conclusion, the results of the study suggest that RA has a significant anti-inflammatory effect on TSLP-induced inflammatory reactions. These effects of RA are likely to be mediated through inhibiting the MDM2 increased by TSLP.

Protective effect of porcine placenta in a menopausal ovariectomized mouse.

Menopause is a significant physiological phase that occurs as women's ovaries stop producing ovum and the production of estrogen declines. Human placenta and some amino acids are known to improve menopausal symptoms. In this study, we investigated that porcine placenta extract (PPE) and arginine (Arg), a main amino acid of PPE, would have estrogenic activities in ovariectomized (OVX) mice as a menopause mouse model, human breast cancer cell line (MCF-7) cells, and human osteoblast cell line (MG-63) cells. PPE or Arg significantly inhibited the body weight and increased the vagina weight compared to the OVX mice. PPE or Arg ameliorated the vaginal atrophy in the OVX mice. The levels of 17ß-estradiol and the activities of alkaline phosphatase (ALP) were significantly increased by PPE or Arg in the serum of OVX mice. Trabecular bone parameters such as bone mineral density and porosity were also improved by PPE or Arg in the OVX mice. In the MCF-7 and MG-63 cells, PPE or Arg significantly increased the cell proliferation, estrogen receptor ß mRNA expression, and estrogen-response elements luciferase activity. Finally, PPE or Arg increased the activations of ALP and extracellular signal-regulated kinase 1/2 in the MG-63 cells. These results indicate that PPE or Arg would have estrogenic and osteoblastic activity. Therefore, PPE or Arg may be useful as new pharmacological tools for treating menopausal symptoms including osteoporosis. Free Korean abstract: A Korean translation of this abstract is freely available at http://www.reproduction-online.org/content/150/3/173/suppl/DC1.