Abstract
Huang-Lian-Jie-Du-Decoction, a traditional Chinese formula, has been reported to protect liver from various injuries. Two cholestasis models of rats induced by thioacetamide and by bile duct ligation were established and treated with Huang-Lian-Jie-Du-Decoction. Nuclear Magnetic Resonance-based urinary metabolic profiles were analyzed by orthogonal partial least squares discriminant analysis and univariate analysis to excavate differential metabolites associated with the injuries of the two models and the treatment effects of Huang-Lian-Jie-Du-Decoction. The two cholestatic models shared common metabolic features of excessive fatty acid oxidation, insufficient glutathione regeneration and disturbed gut flora, with specific characteristics of inhibited urea cycle and DNA damage in thioacetamide-intoxicated model, and perturbed Kreb's cycle and inhibited branched chain amino acid oxidation in bile duct ligation model. With good treatment effects, Huang-Lian-Jie-Du-Decoction could regain the balance of the disturbed metabolic status common in the two cholestasis injuries, e.g., unbalanced redox system and disturbed gut flora; and perturbed urea cycle in thioacetamide-intoxicated model and energy crisis (disturbed Kreb's cycle and oxidation of branched chain amino acid) in bile duct ligation model, respectively.
Highlights
Traditional Chinese medicine (TCM) has been used for healthcare for thousands of years in China (Cheung, 2011)
According to the conformity to normality, the statistical significance was calculated using either parametric (t-test) or non-parametric statistical test (Wilcoxon signed rank test) for metabolites between groups using R, with p < 0.05 as significant. It revealed no pathological alterations in hearts, spleens, lungs and brains for all groups and no noticeable changes in the livers and kidneys (Figures 1a–h) of Normal control rats (NC) and HLD rats
On the treatment of HLJDD, the collagenic exudation was strikingly attenuated in livers of BDL rats treated with HLJDD (BHD) rats at 48 h (Figure 1u) and recovered at 144 h (Figure 1v), and renal slices exhibited slight necrosis and moderate cholangiocyte proliferation at 48 h (Figure 1w), which was recovered to normal at 144 h (Figure 1x)
Summary
Traditional Chinese medicine (TCM) has been used for healthcare for thousands of years in China (Cheung, 2011). Metabolomics, an important component of systems biology, is a sensitive tool to detect various stimuli by snapshotting metabolic status of the body (Nicholson et al, 1999; Lindon et al, 2003; Lucio, 2009). The most common analytical techniques for metabolic profiling are nuclear magnetic resonance (NMR) spectroscopy, gas chromatography-mass spectrometry (GC-MS) and liquid chromatography mass spectrometry (LC-MS). Despite of a lower sensitivity than MS, NMR has been widely applied in metabolic profiling for its associated advantages such as nondestructive, non-biased, separation free, short analysis time, and rich in structural information (Barba et al, 2008; Wishart, 2008; Wheelock et al, 2013)
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