TY - JOUR
T1 - Screening identifies the chinese medicinal plant Caulis Spatholobi as an effective HAMP expression inhibitor1-3
AU - Guan, Yu
AU - An, Peng
AU - Zhang, Zhuzhen
AU - Zhang, Fan
AU - Yu, Yu
AU - Wu, Qian
AU - Shi, Yanbo
AU - Guo, Xin
AU - Tao, Yunlong
AU - Wang, Fudi
PY - 2013/7/1
Y1 - 2013/7/1
N2 - Hepcidin, the pivotal regulator of iron metabolism, plays a critical role in multiple diseases including anemia of chronic disease and hemochromatosis. Recent studies have focused on identifying antagonists of hepcidin. We hypothesized that bioactive extracts from Chinese medicinal plants may be efficacious in the inhibition of expression of the hepcidinencoding gene (HAMP) product, hepcidin. To test this, we measured the level of hepcidin expression in cultured cells treated with 16 different medicinal plant extracts, all of which are used to treat anemia-related disorders in traditional Chinese medicine. Among the extracts tested, that of Caulis Spatholobi (CS; also called Jixueteng, the stem of Spatholobus suberectus Dunn) showed the most potent inhibitory effect on HAMP expression in the Huh7 cell line and was therefore selected for further mechanistic study. In cells treated with 400 μg/mL of extract, phosphorylated mothers against decapentaplegic homolog proteins 1/5/8 levels were 80% less than those of controls (P < 0.001), and the inhibitory effect on interleukin-6-induced HAMP expression (65% inhibition) was weaker than the strong inhibition on bone morphogenetic protein 6-induced HAMP expression (97% inhibition). Seven-week-old C57BL/6 female mice were fed an AIN-76A diet containing 10.8% dried CS and then analyzed on d 0, 5, 10, or 15. On d 5, there was a 60% decrease in hepatic HAMP expression (P < 0.05), an 18% decrease in hepatic iron concentration, and a 100% increase in serum iron concentration (P < 0.05) compared with the d 0 group. In conclusion, we identify the extract of CS as a novel, potent HAMP expression inhibitor, which may be further modified and optimized to become a dietary supplement or a therapeutic option for the amelioration of hepcidin-overexpression-related diseases, including iron deficiency anemia.
AB - Hepcidin, the pivotal regulator of iron metabolism, plays a critical role in multiple diseases including anemia of chronic disease and hemochromatosis. Recent studies have focused on identifying antagonists of hepcidin. We hypothesized that bioactive extracts from Chinese medicinal plants may be efficacious in the inhibition of expression of the hepcidinencoding gene (HAMP) product, hepcidin. To test this, we measured the level of hepcidin expression in cultured cells treated with 16 different medicinal plant extracts, all of which are used to treat anemia-related disorders in traditional Chinese medicine. Among the extracts tested, that of Caulis Spatholobi (CS; also called Jixueteng, the stem of Spatholobus suberectus Dunn) showed the most potent inhibitory effect on HAMP expression in the Huh7 cell line and was therefore selected for further mechanistic study. In cells treated with 400 μg/mL of extract, phosphorylated mothers against decapentaplegic homolog proteins 1/5/8 levels were 80% less than those of controls (P < 0.001), and the inhibitory effect on interleukin-6-induced HAMP expression (65% inhibition) was weaker than the strong inhibition on bone morphogenetic protein 6-induced HAMP expression (97% inhibition). Seven-week-old C57BL/6 female mice were fed an AIN-76A diet containing 10.8% dried CS and then analyzed on d 0, 5, 10, or 15. On d 5, there was a 60% decrease in hepatic HAMP expression (P < 0.05), an 18% decrease in hepatic iron concentration, and a 100% increase in serum iron concentration (P < 0.05) compared with the d 0 group. In conclusion, we identify the extract of CS as a novel, potent HAMP expression inhibitor, which may be further modified and optimized to become a dietary supplement or a therapeutic option for the amelioration of hepcidin-overexpression-related diseases, including iron deficiency anemia.
UR - http://www.scopus.com/inward/record.url?scp=84879831628&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84879831628&partnerID=8YFLogxK
U2 - 10.3945/jn.113.174201
DO - 10.3945/jn.113.174201
M3 - Article
C2 - 23700338
AN - SCOPUS:84879831628
SN - 0022-3166
VL - 143
SP - 1061
EP - 1066
JO - Journal of Nutrition
JF - Journal of Nutrition
IS - 7
ER -