Junwei Fang

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.

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.

Total flavonoid aglycones extract in Radix scutellariae inhibits lung carcinoma and lung metastasis by affecting cell cycle and DNA synthesis

ETHNOPHARMACOLOGICAL RELEVANCE Radix Scutellariae (Scutellaria baicalensis Georgi, RS), a traditional herbal medicine commonly used to treat inflammation, hypertension, cardiovascular disease, bacterial and viral infections, is reported to treat lung cancer by supplements of modern medicine. The total flavonoid aglycones extract (TFAE) from RS is the most important composition for the pharmacodynamic effects. The present study was designed to evaluate the anti-lung tumor effect of TFAE on A549 cells and A549 cell nude mice xenografts. The aim of the study is to investigate the effect and mechanism of TFAE treating non-small cell lung cancer both in vitro and in vivo. MATERIALS AND METHODS The anti-tumor activity of TFAE in vitro was investigated using the MTT assay. The changes of cell invasion and migration were detected by Transwell assay and tube formation experiments were used to detect the anti-angiogenic effect. The anti-tumor effects of TFAE in vivo were evaluated in A549 cell nude mice xenografts. The mechanism of TFAE was detected by flow cytometry technology, western blot assay and immuno-histochemistry assay. RESULTS In vitro, TFAE inhibited the proliferation, invasion and migration of A549 cells in a dose- and time-dependent manner. In vivo, TFAE by oral administration at 100mg/kg for 30 days decreased the tumor volume and tumor weight in A549 cell xenograft by 25.5% with no statistical significance (P<0.05) compared to the cis-platinum positive control group (30.0%). The cell cycle and DNA synthesis experiment illustrated that TFAE could induce A549 cell cycle to arreste in S phase and DNA synthesis in A549 cells be inhibited, while TFAE had no influence on apoptosis of A549 cells. Western Blot assay demonstrated that the treatment of TFAE could make Cyclin D1 decrease and p53 increase both in vitro and in vivo. CONCLUSION TFAE displayed the inhibition effects of non-small cell lung cancer both in vitro and in vivo and the underlying mechanism might be related to the increased p53 protein expression and decreased Cyclin D1 expression, leading to cell cycle arrested in S phase and the decrease of DNA synthesis.

Exploration of Macro-Micro Biomarkers for Dampness-Heat Syndrome Differentiation in Different Diseases

Increased attention is being paid to traditional Chinese medicine (TCM) as a complementary and alternative medicine to provide an effective approach for personalized diagnosis and clinical treatment. TMC performs treatment based on differentiation of TCM syndrome (ZHENG), which may identify special phenotypes by symptoms and signs of patients even if they are in different diseases. There has, however, been skepticism and criticism because syndrome classification only depends on observation, knowledge, and clinical experience of TCM practitioners, which lacks objectivity and repeatability. In order to transform syndrome classification into mainstream medicine, we introduce a macro-micro approach that combines symptoms, clinical indicators, and metabolites. The present paper explores the macro-micro biomarkers of dampness-heat syndrome in chronic hepatitis B and nonalcoholic fatty liver patients, which could provide the basis for developing a possible population-screening tool for selecting target individuals and creating an evaluation index for personalized treatment.