1.Icaritin acts synergistically with epirubicin to suppress bladder cancer growth through inhibition of autophagy.
Pan XW1, Li L1, Huang Y1, Huang H1, Xu DF2, Gao Y1, Chen L1, Ren JZ1, Cao JW3, Hong Y1, Cui XG1. Oncol Rep. 2016 Jan;35(1):334-42. doi: 10.3892/or.2015.4335. Epub 2015 Oct 16.
Bladder cancer is one of the most commonly diagnosed urological malignancies. Acquired resistance to chemotherapy is a great barrier for achieving successful treatment of bladder cancer. In the present study, we investigated the effect and mechanisms of icaritin, a flavonol glycoside derived from genus Epimedium, against human bladder cancer cells. It was found that despite the low cytotoxicity in normal human HEK293 cells, icaritin significantly inhibited the proliferation and colony formation of BT5637 and T24 bladder cancer cells time- and dose-dependently compared to the DMSO vehicle control. Moreover, cell viability monitored through mitochondrial membrane potential was inhibited markedly after icaritin treatment. Further investigation indicated that icaritin may inhibit epirubicin (EPI)-induced autophagy, and acted synergistically with EPI to suppress the proliferation of BT5637 and T24 cells. These findings suggest that icaritin may prove to be a novel potent therapeutic agent for the treatment of bladder cancer.
2.Icaritin Inhibits Collagen Degradation-Related Factors and Facilitates Collagen Accumulation in Atherosclerotic Lesions: A Potential Action for Plaque Stabilization.
Zhang ZK1, Li J2, Yan DX3, Leung WN4, Zhang BT5. Int J Mol Sci. 2016 Jan 28;17(2). pii: E169. doi: 10.3390/ijms17020169.
Most acute coronary syndromes result from rupture of vulnerable atherosclerotic plaques. The collagen content of plaques may critically affect plaque stability. This study tested whether Icaritin (ICT), an intestinal metabolite of Epimedium-derived flavonoids, could alter the collagen synthesis/degradation balance in atherosclerotic lesions. Rabbits were fed with an atherogenic diet for four months. Oral administration of ICT (10 mg·kg(-1)·day(-1)) was started after two months of an atherogenic diet and lasted for two months. The collagen degradation-related parameters, including macrophages accumulation, content and activity of interstitial collagenase-1 (MMP-1), and the collagen synthesis-related parameters, including amount and distribution of smooth muscle cells (SMC) and collagen mRNA/protein levels, were evaluated in the aorta. ICT reduced plasma lipid levels, inhibited macrophage accumulation, lowered MMP-1 mRNA and protein expression, and suppressed proteolytic activity of pro-MMP-1 and MMP-1 in the aorta.
3.[Tissue distribution of glucuronidated icaritin metabolite in rats].
Zhang S, Sun L, Huang Z. Wei Sheng Yan Jiu. 2015 Jul;44(4):692-4.
OBJECTIVE: To establish an ultra-high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS )method for the quantification of glucuronidated icaritin (GICT), and investigate tissue distribution of GICT in rats following a single intraperitoneal administration.
4.The role of icaritin in regulating Foxp3/IL17a balance in systemic lupus erythematosus and its effects on the treatment of MRL/lpr mice.
Liao J1, Liu Y1, Wu H1, Zhao M1, Tan Y1, Li D1, Long H1, Dai Y2, Yung S3, Chan TM3, Lu Q4. Clin Immunol. 2016 Jan;162:74-83. doi: 10.1016/j.clim.2015.11.006. Epub 2015 Nov 18.
Systemic lupus erythematosus (SLE) is a female predominant autoimmune disease characterized by multi-organ dysfunctions. However, current available therapies control the disease at the cost of many potential adverse effects. The development of safer and more effective therapies for SLE is a critical unmet need. Icaritin (ICT) is an active monomer extracted from Chinese herbals named the Epimedium genus. In this study, we found that ICT exhibited the capacity of regulating Foxp3/IL17a balance, enhancing Treg cell suppressive activities, and inhibiting over-activation of CD4(+)T cells from SLE. We also observed that ICT regulated Foxp3/IL17a balance by increasing STAT5b expression and histone methylation modification. Subsequent experiments further confirmed that ICT-treated mice exhibited amelioration of renal damages and suggested that ICT may be a potential new drug for the treatment of SLE.
