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.

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Depression is associated with behavioral disturbances and serotonergic and neuroendocrinological disfunctions.1,2) The brain serotonergic system is a very complicated control system playing an important role in the response to depression. 3)A number of factors have been proposed to account for a reduced functionality of serotonergic system in depression. Investigations based on this system have formed into currently available antidepressants.2) On the other hand, neuroendocrinological abnormality in depressed patients is hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis characterized by hypersecretion of corticotropin-releasing factor (CRF), which stimulates corticosterone release. 4,5) Successful antidepressant treatment could attenuate these alterations in clinical trials and animal experiments. [6][7][8][9] In addition, there is a close relationship between the serotonergic and HPA axis systems in major depression. [10][11][12][13] The impact of stress on the HPA axis is reviewed and evidence present that CRF is the stress neurotransmitter which plays an important role in the activation of serotonergic systems. 11,14) Psoralen (Fig. 1) is a main furocoumarin isolated from the seeds of Psoralea corylifolia, 15) which is a traditional Chinese medicine used to treat a wide range of diseases and conditions. Our previous studies demonstrated that the total furocoumarins extracts of P. corylifolia possessed the potent antidepressant properties by employing the forced swimming test (FST), a well-established animal model of depression. 7)These furocoumarins extracts depressed the hyperactive HPA axis induced by swim stress in mice.7) Furthermore, the total furocoumarins extracts and psoralen exhibited inhibitory actions on monoamine oxidase (MAO) A and B activities. 16,17) Per-orally administered psoralen increased the daytime levels of melatonin via the competitive inhibition of hepatic melatonin metabolism, indicating that psoralen might affect seasonal affective disorder patients under a low level of illumination.18) However, there is no study on antidepressant-like effects and related possible mechanisms of actions by psoralen. The aim of the current study was to investigate the effects of psoralen on the durations of immobility, climbing and swimming in the mouse FST after administrations for 1, 3, 7 and 14 d, respectively. We also examined the effects of 14-d psoralen treatment on serotonergic neurotransmitters serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) levels in frontal cortex and hippocampus of the mouse brain regions. The regulation of psoralen on the HPA axis including CRF and corticosterone concentrations was simultaneously studied in the mouse FST. MATERIALS AND METHODS MaterialsPsoralen was isolated and purified from the seeds of P. corylifolia as described in our previous reports. 19)The purity of the chemical was determined to beyond 98% by HPLC analysis. Amitriptyline was obtained from Changzhou Siyao Pharmaceuticals Co., Ltd. (P. R. China). All other chemical...

Two cyclolanostane-type saponins, astragalosides I and II, were first identified by TLC-MS/MS in the ethyl acetate extract of the roots of Astragalus membranaceus Bge var. mongholicus (Bge.) Hsiao without chemical reference substances. They were then isolated by high-speed counter-current chromatography with a two-step two-phase solvent system of ethyl acetate-2-propanol-water (5:1:5, 50:1:50, v/v/v). The quantities of astragalosides I and II isolated from 1 g of the crude extract were 30.2 mg and 16.5 mg, respectively. Their purities were found to be over 95% by HPLC-ELSD analysis. Their chemical structures were confirmed by 1H and 13C nuclear magnetic resonance analysis.