title: Sustained antidiabetic effects of a berberine-containing Chinese herbal medicine through regulation of hepatic gene expression.
abstract: Diabetes and obesity are complex diseases associated with insulin resistance and fatty liver. The latter is characterized by dysregulation of the Akt, AMP-activated protein kinase (AMPK), and IGF-I pathways and expression of microRNAs (miRNAs). In China, multicomponent traditional Chinese medicine (TCM) has been used to treat diabetes for centuries. In this study, we used a three-herb, berberine-containing TCM to treat male Zucker diabetic fatty rats. TCM showed sustained glucose-lowering effects for 1 week after a single-dose treatment. Two-week treatment attenuated insulin resistance and fatty degeneration, with hepatocyte regeneration lasting for 1 month posttreatment. These beneficial effects persisted for 1 year after 1-month treatment. Two-week treatment with TCM was associated with activation of AMPK, Akt, and insulin-like growth factor-binding protein (IGFBP)1 pathways, with downregulation of miR29-b and expression of a gene network implicated in cell cycle, intermediary, and NADPH metabolism with normalization of CYP7a1 and IGFBP1 expression. These concerted changes in mRNA, miRNA, and proteins may explain the sustained effects of TCM in favor of cell survival, increased glucose uptake, and lipid oxidation/catabolism with improved insulin sensitivity and liver regeneration. These novel findings suggest that multicomponent TCM may be a useful tool to unravel genome regulation and expression in complex diseases.
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China. zhaohailu@yahoo.com
authors.forename: Hai-Lu
authors.initials: HL
authors.lastname: Zhao
authors.forename: Yi
authors.initials: Y
authors.lastname: Sui
authors.forename: Chun-Feng
authors.initials: CF
authors.lastname: Qiao
authors.forename: Kevin Y
authors.initials: KY
authors.lastname: Yip
authors.forename: Ross K K
authors.initials: RK
authors.lastname: Leung
authors.forename: Stephen K W
authors.initials: SK
authors.lastname: Tsui
authors.forename: Heung-Man
authors.initials: HM
authors.lastname: Lee
authors.forename: Harriet K T
authors.initials: HK
authors.lastname: Wong
authors.forename: Xun
authors.initials: X
authors.lastname: Zhu
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Siu
authors.forename: Lan
authors.initials: L
authors.lastname: He
authors.forename: Jing
authors.initials: J
authors.lastname: Guan
authors.forename: Li-Zhong
authors.initials: LZ
authors.lastname: Liu
authors.forename: Hong-Xi
authors.initials: HX
authors.lastname: Xu
authors.forename: Peter C Y
authors.initials: PC
authors.lastname: Tong
authors.forename: Juliana C N
authors.initials: JC
authors.lastname: Chan
mesh_terms: D000818:Animals; D001599:Berberine / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose; D002851:Chromatography, High Pressure Liquid; D003920:Diabetes Mellitus / Q000188:drug therapy*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011924:Rats, Zucker; D015203:Reproducibility of Results
chemical_list: D001786:Blood Glucose; D004365:Drugs, Chinese Herbal; D007004:Hypoglycemic Agents; D001599:Berberine