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Xudong Di,Danica M.K. Andrews,Charles J. Tucker,Linda Yu,Alicia B. Moore,Xiaolin Zheng,Lysandra Castro,Tonia Hermon,Hang Xiao,Darlene Dixon 생화학분자생물학회 2012 Experimental and molecular medicine Vol.44 No.4
Previously, we found that high doses of genistein show an inhibitory effect on uterine leiomyoma (UtLM) cell proliferation. In this study, using microarray analysis and Ingenuity Pathways AnalysisTM, we identified genes (up- or down-regulated, ≥ 1.5 fold, P ≤ 0.001),functions and signaling pathways that were altered following treatment with an inhibitory concentration of genistein (50 μg/ml) in UtLM cells. Downregulation of TGF-β signaling pathway genes, activin A, activin B,Smad3, TGF-β2 and genes related to cell cycle regulation,with the exception of the upregulation of the CDK inhibitor P15, were identified and validated by real-time RT-PCR studies. Western blot analysis further demonstrated decreased protein expression of activin A and Smad3 in genistein-treated UtLM cells. Moreover, we found that activin A stimulated the growth of UtLM cells, and the inhibitory effect of genistein was partially abrogated in the presence of activin A. Overexpression of activin A and Smad3 were found in tissue samples of leiomyoma compared to matched myometrium, supporting the contribution of activin A and Smad3 in promoting the growth of UtLM cells. Taken together, these results suggest that downregulation of activin A and Smad3, both members of the TGF-β pathway, may offer a mechanistic explanation for the inhibitory effect of a high-dose of genistein on UtLM cells, and might be potential therapeutic targets for treatment of clinical cases of uterine leiomyomas.
Triterpenoid saponins from Clinopodium chinense (Benth.) O. Kuntze and their biological activity
Yin-Di Zhu,Jing-Yi Hong,Feng-Da Bao,Na Xing,Ling-Tian Wang,Zhong-Hao Sun,Yun Luo,Hai Jiang,Xudong Xu,Nai-Liang Zhu,Hai-Feng Wu,Gui-Bo Sun,Jun-Shan Yang 대한약학회 2018 Archives of Pharmacal Research Vol.41 No.12
Four new ursane-type triterpenoid saponins, clinopoursaponins A–D (1–4), six new oleanane-type triterpenoid saponins, clinopodiside VII–XII (5–10), as well as eight known triterpene analogues (11–18), were isolated from the aerial parts of Clinopodium chinense (Benth.) O. Kuntze. The structures of the new compounds were determined based on extensive spectral analyses, including 1D (1H and 13C) and 2D NMR experiments (COSY, NOESY, HSQC, 2D TOCSY, HSQC-TOCSY and HMBC), HR-ESI-MS and chemical methods. Compounds 1–18 were evaluated for their protective effects against anoxia/reoxygenation-induced apoptosis in H9c2 cells and cytotoxicities against murine mammary carcinoma cell line 4T1. Compounds 8, 9 and 18 exhibited significant protective effects, while compound 1 exhibited cytotoxic activity with IC50 value of 7.4 μm compared to 7.6 μm for the positive control 10-hydroxycamptothecin.