Shujun Sun

Urinary metabonomics characterization of liver fibrosis induced by CCl4 in rats and intervention effects of Xia Yu Xue Decoction

Xia Yu Xue Decoction (XYXD) is a traditional Chinese medicine which has been widely used in clinic practice for treating liver disease. However, its mechanism of action remains unknown. In this study, a urinary metabonomic method, based on gas chromatography coupled with mass spectrometry (GC/MS), was developed to investigate the effect of XYXD on liver fibrosis. Pattern recognition analysis, including principal component analysis (PCA) and partial least square discriminant analysis (PLS-DA), showed that metabolic perturbations induced by CCl(4) were restored after treatment with XYXD. Ten potential biomarkers associated with modulation of energy metabolism, microflora metabolism, amino acid and fatty acid metabolism were identified, suggesting that the mechanism of action of XYXD may involve these processes. Our findings indicate that metabonomic methods based on GC/MS may provide a useful means of exploring biomarkers involved in liver fibrosis and for elucidating the mechanisms of action of therapies used in traditional Chinese medicine.

Metabonomic Evaluation of ZHENG Differentiation and Treatment by Fuzhenghuayu Tablet in Hepatitis-B-Caused Cirrhosis

In Traditional Chinese Medicine (TCM), treatment based on ZHENG (also called TCM syndrome and pattern) differentiation has been applied for about 3 thousand years, while there are some difficulties to communicate with western medicine. In the present work, metabonomic methods were utilized to differentiate ZHENG types and evaluate the therapeutic efficiency of Fuzhenghuayu (FZHY) tablet in hepatitis-B-caused cirrhosis (HBC). Urine samples of 12 healthy volunteers (control group, CG) and 31 HBC patients (HBCG) were analyzed by gas chromatography mass spectrometry (GC/MS) and multivariate statistical analysis. The significantly changed metabolites between CG and HBCG were selected by PLS-DA loading plot analysis. Moreover, 4 ZHENGs were differentiated mutually, suggesting that there was urine metabolic material basis in ZHENG differentiation. The efficiency of FZHY tablet on subjects with spleen deficiency with dampness encumbrance syndrome (SDDES) and liver-kidney yin deficiency syndrome (LKYDS) was better than that of other syndromes. The efficiency of FZHY treatment based on ZHENG differentiation indicated that accurately ZHENG differentiating could guide the appropriate TCM treatment in HBC.

Applications of New Technologies and New Methods in ZHENG Differentiation

With the hope to provide an effective approach for personalized diagnosis and treatment clinically, Traditional Chinese Medicine (TCM) is being paid increasing attention as a complementary and alternative medicine. It performs treatment based on ZHENG (TCM syndrome) differentiation, which could be identified as clinical special phenotypes by symptoms and signs of patients. However, it caused skepticism and criticism because ZHENG classification only depends on observation, knowledge, and clinical experience of TCM practitioners, which is lack of objectivity and repeatability. Scientists have done fruitful researches for its objectivity and standardization. Compared with traditional four diagnostic methods (looking, listening and smelling, asking, and touching), in this paper, the applications of new technologies and new methods on the ZHENG differentiation were systemically reviewed, including acquisition, analysis, and integration of clinical data or information. Furthermore, the characteristics and application range of these technologies and methods were summarized. It will provide reference for further researches.

Current Understanding on Antihepatocarcinoma Effects of Xiao Chai Hu Tang and Its Constituents

Xiao Chai Hu Tang (XCHT), a compound formula originally recorded in an ancient Chinese medical book Shanghanlun, has been used to treat chronic liver diseases for a long period of time in China. Although extensive studies have been demonstrated the efficacy of this formula to treat chronic hepatitis, hepatic fibrosis, and hepatocarcinoma, how it works against these diseases still awaits full understanding. Here, we firstly present an overview arranging from the entire formula to mechanism studies of single herb in XCHT and their active components, from a new perspective of “separation study,” and we tried our best to both detailedly and systematically organize the antihepatocarcinoma effects of it, hoping that the review will facilitate the strive on elucidating how XCHT elicits its antihepatocarcinoma role.

Differences of Excess and Deficiency Zheng in Patients with Chronic Hepatitis B by Urinary Metabonomics

Traditional Chinese medicine (TCM) physicians stratify patients with the same disease into different subtypes in order to guide the appropriate treatment, which is called Zheng (TCM syndrome) classification. Excess and deficiency ZHENG is a couple of basic ZHENGs of maladjusted body nature, reflecting the struggling state of human body and pathogenic factor and is important and prevalently exists in the ZHENG classification of many diseases. The present work using chronic hepatitis B (CHB) as an entry point explored the substance connotation of excess and deficiency ZHENG with the metabonomic technology based on gas chromatography-mass spectrometry (GC-MS). The different substantial basis of two ZHENGs suggested that CHB patients could be categorized into two groups with diverse pathogenesis. The differential metabolites and disturbed pathways compared to not-obvious ZHENG characters patients (without ZHENG group/WZ) were selected in both of the two ZHENGs. The ROC analysis demonstrated that five metabolites had a greater potential to be the clinic biomarkers of EZ or DZ. And excess ZHENG revealed a higher level of immune function than deficiency ZHENG. We are eager to transform the concept of traditional excess and deficiency ZHENGs to modern therapeutic approaches, with the prospect to help to promote personalized medicine.

Differences in Metabolites of Different Tongue Coatings in Patients with Chronic Hepatitis B

Tongue coating is one of the important foundations of tongue diagnosis in traditional Chinese medicine (TCM) and plays an important role in reflecting the occurrence, development, and prognosis of the disease. However, its material basis is still poorly understood. In this study, a urinary metabonomic method based on gas chromatography coupled to mass spectrometry (GC/MS) was developed. The distinct clustering in metabolic profile was observed from Group A (thick yellow coating in patients with chronic hepatitis B), Group B (thick white coating in patients with chronic hepatitis B), and Group C (thin white coating with healthy humans) using orthogonal projections to latent structures (OPLS). Based on the variable of importance in the project (VIP) values, some significantly changed metabolites have been identified. These changes were related to the disturbance in energy metabolism, amino acid metabolism, nucleotide metabolism, and gut microflora, which were helpful to understand the material basis leading to the formation of tongue coating. This study demonstrated that tongue coating may have an objective material basis.

Metabolomics study of renal fibrosis and intervention effects of total aglycone extracts of Scutellaria baicalensis in unilateral ureteral obstruction rats

ETHNOPHARMACOLOGICAL RELEVANCE Scutellariae Radix (Scutellaria baicalensis Georgi) is a well-known Traditional Chinese Medicine (TCM) which mainly contains flavonoids. Our previous studies have demonstrated that total aglycone extracts of Scutellaria baicalensis (TAES) can improve kidney disease in rats. AIM OF THE STUDY To investigate the renal fibrosis (RF) pathogenesis and TAES treatment mechanism in unilateral ureteral obstruction (UUO) rats, using a metabolomics approach based on gas chromatography-mass spectrometry (GC/MS). METHODS Rats with RF were divided into 6 groups with rats subjected to sham operation as normal control. The effects of TAES on some RF closely related parameters in UUO rats were investigated. A metabolomics method, based on GC/MS, was developed to monitor metabolic alterations in urine. Multivariate data analysis was utilized to identify biomarkers potentially associated with RF and the anti-RF activity of TAES. Ontology-based enrichment analysis by BiNChE and pathway analysis by MetPA aid in the interpretation of difference metabolites. RESULTS After 10 days of treatment, the parameters of renal function begin returning to normal, and the abnormal high expressions of genes associated with extracellular matrix (ECM) were relived. In the metabolomics study, metabolic perturbations induced by UUO were reversed after treatment and TAES showed a dose-dependent therapy effect on RF, meanwhile, 18 potential biomarkers associated with RF were identified. Enrichment analysis of metabolites shows an over representation of mostly alkane-alpha, omega-diamine and alpha, omega-dicarboxylic acid, and these biomarkers are primarily involved in Glycine, serine and threonine metabolism, Retinol metabolism, Arginine and proline metabolism and Fructose and mannose metabolism. CONCLUSIONS Our findings indicate that TAES have positive effects on UUO-induced RF in rats, meanwhile, metabolomics method coupled with metabolites enrichment analysis is a useful tool for revealing the pathogenesis of diseases and action mechanism of TCM on the whole body.

A urine metabonomics study of chronic renal failure and intervention effects of total aglycone extracts of Scutellaria baicalensis in 5/6 nephrectomy rats

Chronic renal failure (CRF) is a severe disease that can lead to a decline of life quality. Radix Scutellariae is a well-known traditional Chinese medicine (TCM). Our previous study has demonstrated that the Total Aglycone Extracts of Scutellaria baicalensis (TAES), can improve renal fibrosis induced by mercuric chloride in rats. However, no research has investigated the efficacy and mechanism of TAES in treating CRF. In the present study, we investigated the effects of TAES on some closely related parameters in 5/6 nephrectomy CRF rats, and studied the pathogenesis of CRF and the mechanism of TAES treatment using a metabonomics method based on gas chromatography coupled with mass spectrometry (GC/MS). Rats with CRF were divided into six groups with rats subjected to a sham operation as the normal control. After eight weeks of treatment by TAES, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) were decreased, and the metabolic perturbations induced by 5/6 nephrectomy were reversed according to pattern recognition analysis. Meanwhile, 18 potential biomarkers associated with CRF were identified, and the affected metabolic pathways in 5/6 nephrectomy rats were extracted based on the differential metabolites. Our findings suggest that TAES have positive effects on 5/6 nephrectomy-induced CRF in rats and show therapeutic potentials in CRF treatment. Our findings also indicate that metabonomics analysis based on GC/MS is a useful tool for studying the effect of drugs on the whole body, exploring biomarkers involved in CRF and elucidating the potential therapeutic mechanisms of TCM.

Understanding Acupuncture Based on ZHENG Classification from System Perspective

Acupuncture is an efficient therapy method originated in ancient China, the study of which based on ZHENG classification is a systematic research on understanding its complexity. The system perspective is contributed to understand the essence of phenomena, and, as the coming of the system biology era, broader technology platforms such as omics technologies were established for the objective study of traditional chinese medicine (TCM). Omics technologies could dynamically determine molecular components of various levels, which could achieve a systematic understanding of acupuncture by finding out the relationships of various response parts. After reviewing the literature of acupuncture studied by omics approaches, the following points were found. Firstly, with the help of omics approaches, acupuncture was found to be able to treat diseases by regulating the neuroendocrine immune (NEI) network and the change of which could reflect the global effect of acupuncture. Secondly, the global effect of acupuncture could reflect ZHENG information at certain structure and function levels, which might reveal the mechanism of Meridian and Acupoint Specificity. Furthermore, based on comprehensive ZHENG classification, omics researches could help us understand the action characteristics of acupoints and the molecular mechanisms of their synergistic effect.

Similar Connotation in Chronic Hepatitis B and Nonalcoholic Fatty Liver Patients with Dampness-Heat Syndrome

The phenomenon that the same syndrome turns up in different diseases appears in the sight of people around the world, which raises the thought for possibility of “Same Treatment for Different Diseases.” Actually, treatment based on ZHENG classification in Traditional Chinese Medicine could bring revelation for the former finding. The dampness-heat syndrome in chronic hepatitis B and nonalcoholic fatty liver is regarded as the breakthrough point. We discussed the molecular mechanism of similar connotation that exists in chronic hepatitis B and nonalcoholic fatty liver by metabonomics to give the modern understanding of dampness-heat syndrome. Both urine and serum metabolic profiling revealed that obvious differences existed between dampness-heat syndrome and non-dampness-heat syndrome but the commonality was proved to appear in chronic hepatitis B and nonalcoholic fatty liver patients with dampness-heat syndrome. Furthermore, disorder of body fluid metabolism, decline in digestive capacity, and imbalance of intestinal flora were found to be the new guiding for treatment, with the hope to provide the basis for Chinese personalized medicine.