aristolochia manshuriensis kom inhibits adipocyte differentiation by regulation of erk12 and akt pathway马兜铃manshuriensis卡尔玛抑制脂肪细胞的分化,调节erk12和akt通路.pdfVIP

Aristolochia Manshuriensis Kom Inhibits Adipocyte Differentiation by Regulation of ERK1/2 and Akt Pathway Dong Hoon Kwak, Ji-Hye Lee, Taesoo Kim, Hyo Sun Ahn, Won-Kyung Cho, Hyunil Ha, Youn- Hwan Hwang, Jin Yeul Ma* Traditional Korean Medicines (TKM)-Based Herbal Drug Research, Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea Abstract Aristolochia manshuriensis Kom (AMK) is a traditional medicinal herb used for the treatment of arthritis, rheumatism, hepatitis, and anti-obesity. Because of nephrotoxicity and carcinogenicity of AMK, there are no pharmacological reports on anti-obesity potential of AMK. Here, we showed AMK has an inhibitory effect on adipocyte differentiation of 3T3-L1 cells along with significantly decrease in the lipid accumulation by downregulating several adipocyte-specific transcription factors including peroxisome proliferation-activity receptor c (PPAR-c), CCAAT/enhancer binding protein a (C/EBP-a) and C/ EBP-b, which are critical for adipogenesis in vitro. AMK also markedly activated the extracellular signal-regulated protein kinase 1/2 (ERK1/2) pathway including Ras, Raf1, and mitogen-activated protein kinase kinase 1 (MEK1), and significantly suppressed Akt pathway by inhibition of phosphoinositide-dependent kinase 1 (PDK1). Aristolochic acid (AA) and ethyl acetate (EtOAc) fraction of AMK with AA were significantly inhibited TG accumulation, and regulated two pathway (ERK1/2 and Akt) during adipocyte differentiation, and was not due to its cytotoxicity. These two pathways were upstream of PPAR-c and C/EBPa in the adipogenesis. In addition, gene expressions of secreting factors such as fatty acid synthase (FAS), adiponectin, lipopreotein lipase (LPL), and aP2 were significantly inhibited by treatment of AMK during adipogenesis. We used