Peng Ji

Metabonomics study on the hepatoprotective effect of polysaccharides from different preparations of Angelica sinensis.

ETHNOPHARMACOLOGICAL RELEVANCE Angelica sinensis (AS) has been used for thousands of years in Traditional Chinese Medicine (TCM). Processed products of AS mainly include charred Angelica, parching Angelica with oil, parching Angelica with wine, and parching Angelica with soil, which have been widely used in TCM prescriptions. Polysaccharides are important chemical substances of AS. These compounds effectively treat liver diseases, shows hepatoprotectivity, and contributes directly to the therapeutic effect of AS. However, the precise molecular mechanism of the effects of the different AS products polysaccharide has not been comprehensively explored. The present investigation was designed to assess the effects and possible mechanisms of polysaccharide in the different AS products against carbon tetrachloride-induced liver injury. MATERIALS AND METHODS Liver injury was induced by intraperitoneal injection with Carbon tetrachloride (CCl4) in the mice. Gas chromatography-mass spectrometry (GC-MS) combined with pattern recognition approaches, namely, principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA), were used to determine differentiating metabolites in plasma and liver tissue. RESULTS PCA and PLS-DA score plots of the liver injury group clustered separately from that of the control, while groups treated with polysaccharides from charred AS (ASTP), parching AS with soil (ASTUP), parching AS with wine (ASJP), parching AS with Sesame Oil (ASYP) clustered closely with the control. This result indicates that the metabolic profiles of the ASTP, ASTUP, ASJP, and ASYP groups are almost similar to those of the control. Potential metabolite biomarkers (six in the liver homogenates and seven in the plasma) were identified. These biomarkers include citric acid, succinic acid,glycine, palmitelaidic acid, arachidonic acid, fumaric acid, malic acid, valine, ananine, and hexadecanoic acid. Functional pathway analysis revealed that alterations in these metabolites are associated with lipid, amino acid, and energy metabolism. Notably, ASTP exhibited a potential pharmacological effect by regulating multiple perturbed pathways to the normal state. CONCLUSION It is likely that ASTP, ASTUP, ASJP, ASYP intervenes the metabolic process of liver injury mice by affecting the lipid and amino acid metabolism. Metabonomics is a robust and promising for the identification of biomarkers and elucidation of the mechanisms of a disease, thereby highlighting its importance in drug discovery.

Metabolomics research on the hepatoprotective effect of Angelica sinensis polysaccharides through gas chromatography-mass spectrometry.

Angelica sinensis polysaccharides (ASP) have an established hepatoprotective effect, but the mechanism for this effect remains unclear. A novel approach using biochemical parameters coupled with metabolomics based on gas chromatography-mass spectrometry (GC-MS) and chemometrics was established in this study to explain the hepatoprotective effect mechanism of ASP. The superoxide dismutase activity, malonaldehyde content, alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transpeptidase in plasma were measured. Pathological changes in the liver were observed. Plasma and liver homogenate obtained from mice were analyzed using GC-MS. Distinct changes in metabolite patterns in the plasma and liver homogenate after being induced by carbon tetrachloride and drug intervention were observed using principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA). Potential biomarkers were found using PLS-DA and T-test. The results of the pathological changes observed in the liver, the biochemical parameters in plasma, and the metabolomics of the plasma and liver homogenate all showed that liver injury was successfully reproduced, ASP exhibited hepatoprotective effect, and the medium dose of ASP exhibited the best. Nine endogenous metabolites in the liver homogenate and ten endogenous metabolites in the plasma were all considered as potential biomarkers. They were considered to be in response to hepatoprotective effects of ASP involved in the amino acids metabolism, energy metabolism, and lipids metabolism. Therefore metabolomics is a valuable tool in measuring the efficacy and mechanisms of action of traditional Chinese medicines.

Metabolomics study of hematopoietic function of Angelica sinensis on blood deficiency mice model

ETHNOPHARMACOLOGICAL RELEVANCE Angelica sinensis (AS) has been used in traditional Chinese medicine for thousands of years to enrich and invigorate blood. In this study, the aim is to investigate the influence of AS on metabolism of blood deficiency mice model and to explore its anti-blood deficiency mechanism. MATERIALS AND METHODS The blood deficiency mice model was induced by being hypodermically injected with N-acetyl phenylhydrazine (APH) and being intraperitoneally injected with cyclophosphamide (CTX). Gas chromatography-mass spectrometry (GC-MS), principle component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were used to identify potential biomarkers in plasma and splenic tissue. RESULTS The levels of white blood cell (WBC), red blood cell (RBC), hemoglobin (HGB) and platelet (PLT) showed a trend to return to control group after administrating with AS, while the dose of 10g/kg showed the best effect. Potential metabolite biomarkers (nine in the plasma and nine in the spleen homogenates) were identified in this study. These biomarkers were mainly related to five metabolic pathways, such as arachidonic acid metabolism, valine, leucine and isoleucine biosynthesis, glycine, serine and threonine metabolism, arginine and proline metabolism and TCA cycle. CONCLUSION Metabolomics was used to reflect an organism׳s physiological and metabolic state comprehensively, indicating that metabolomics was a potentially powerful tool to reveal the anti-blood deficiency mechanism of AS.

Metabonomic analysis of the anti-inflammatory effects of volatile oils of Angelica sinensis on rat model of acute inflammation

Metabonomics based on GC-MS was used to study the possible anti-inflammatory mechanisms of volatile oils of Angelica sinensis (VOAS) in rats with acute inflammation. Acute inflammation was induced by subcutaneous injection of carrageenan in rats. The levels of prostaglandin E2 (PGE2 ), histamine (HIS) and 5-hydroxytryptamine (5-HT) in the inflammatory fluid were detected. Principal component analysis and orthogonal partial least squares-discriminant analysis models were performed for pattern recognition analysis. After the administration of VOAS, the levels of PGE2 , HIS, and 5-HT returned to levels observed in normal group. According to GC-MS analysis, the intervention of VOAS in rats with acute inflammation induced substantial and characteristic changes in their metabolic profiles. Fourteen metabolite biomarkers, namely, lactic acid, malic acid, citric acid, trans-dehydroandrosterone, aldosterone, linoleic acid, hexadecanoic acid, pregnenolone, octadecenoic acid, myristic acid, l-histidine, octadecanoic acid, arachidonic acid (AA) and l-tryptophan, were detected in the inflammatory fluid. The levels of all biomarkers either increased or decreased significantly in model groups. VOAS possibly intervened in the metabolic process of inflammation by altering histidine metabolism, tryptophan metabolism, AA metabolism, steroid hormone biosynthesis, fatty acid metabolism and energy metabolism. Metabonomics was used to reflect an organisms physiological and metabolic state comprehensively, and it is a potentially powerful tool that reveals the anti-acute-inflammatory mechanism of VOAS.

Characterization and antioxidative activities of polysaccharide in Chinese angelica and its processed products

Five polysaccharides from unprocessed Chinese angelica (UCAP), parched one with alcohol (ACAP), soil (SCAP), sesame oil (OCAP) and parched into charred (CCAP) were extracted and purified. Their structures were identified by Fourier transform-infrared spectroscopy (FT-IR), compositions were analyzed by gas chromatography-mass spectrometry (GC-MS) and antioxidative activities were compared by determining MDA contents and SOD activities of liver tissue in mice damaged with CCl4 after gavage. The results showed that the FT-IR spectra of CCAP and OCAP displayed lower transmittance at around 1050cm(-1) in comparison with that of UCAP. Five polysaccharides were all composed of rhamnose, arabinose, mannose, glucose and galactose. In CCAP, ACAP, OCAP and SCAP, the proportions of arabinose were significantly increased in comparison with that of UCAP. The SOD activities in CCAP and SCAP groups were significantly enhanced, and MDA contents in CCAP, OCAP and SCAP groups were significantly decreased as compared with UCAP group. This indicated that processing could change the structure, composition and enhance antioxidative activity of polysaccharide in Chinese angelica, and CCAP possessed the strongest antioxidative activity.

The investigation of anti-inflammatory activity of volatile oil of Angelica sinensis by plasma metabolomics approach.

Angelica sinensis (AS) is an important medicinal plant, and volatile oil is the main pharmacologically active ingredient. This study was aimed to investigate the anti-inflammatory activity of the volatile oil of A. sinensis (VOAS) and explore its potential anti-inflammatory mechanism by plasma metabolomics approach. Rat acute inflammation was induced by subcutaneous injection of carrageenan in hind paws. Paw edema, histamine (HIS) and 5-hydroxytryptamine (5-HT) were detected. Then, we analyzed plasma metabolic profiling of acute inflammation and performed pathway analysis on the metabolite markers reversed after VOAS administration and further integration of metabolic networks. The results showed that VOAS could alleviate the paw edema and decrease plasma HIS and 5-HT levels. Fourteen metabolite markers of acute inflammation were screened, and the levels were all reversed to different degrees after VOAS administration. These metabolite markers mainly related to linoleic acid metabolism, ascorbate and aldarate metabolism, arachidonic acid metabolism, glyoxylate and dicarboxylate metabolism, and glycine, serine and threonine metabolism. In metabolic networks, glycine and arachidonic acid were node molecules. It indicated that VOAS could significantly inhibit systemic inflammatory response triggered by acute local stimulation and it exerted anti-inflammatory activity mainly through regulating the disturbed metabolic networks centered on glycine and arachidonic acid.

Evaluation of the anti-inflammatory effects of volatile oils from processed products of Angelica sinensis radix by GC–MS-based metabolomics

ETHNOPHARMACOLOGICAL RELEVANCE Roots of Angelica sinensis (Oliv.) Diels (AS) a commonly used herbal, always act as an anti-inflammatory drug in Chinese traditional therapy. In clinical use, AS is always processed before being used for the reason that processing can increase its therapeutic effect. Recent studies have shown that volatile oil of AS (VOAS), an important component in AS, has evident anti-inflammatory activities. AIM OF THE STUDY In this study, our aim is to evaluate the anti-inflammatory effects of volatile oils from processed products of AS. MATERIALS AND METHODS In this paper, volatile oils from stir-fried AS (C-VOAS), parched AS with alcohol (J-VOAS), parched AS with soil (T-VOAS), and parched AS with sesame oil (Y-VOAS) were applied to intervene the carrageenan-induced acute inflammation model rats. GC-MS based metabolomics was utilized to determine different metabolites in the inflammatory exudate and plasma samples. RESULTS The results showed that VOASs could significantly inhibit the release of PGE2, HIS, 5-HT and TNF-α, among which C-VOAS and J-VOAS expressed better effect. Otherwise, 14 potential biomarkers were identified respectively in inflammatory exudate and plasma, which changed highly significantly (P<0.01) in C-VOAS and J-VOAS groups. CONCLUSIONS We inferred that the anti-inflammatory effect of C-VOAS and J-VOAS were superior to other VOASs.

Integrated metabonomic–proteomic studies on blood enrichment effects of Angelica sinensis on a blood deficiency mice model

Abstract Context: Angelica sinensis (Oliv.) Diels (Umbelliferae) (AS) is a well-known Traditional Chinese Medicine (TCM) that enriches and regulates the blood. Objective: An integrated metabonomic and proteomic method was developed and applied to study the blood enrichment effects and mechanisms of AS on blood deficiency (BD) mouse model. Materials and methods: Forty mice were randomly divided into the control, BD, High-dose of AS (ASH), Middle-dose of AS (ASM), and Low-dose of AS (ASL) groups. BD model mice were established by injecting N-acetylphenylhydrazine (APH) and cyclophosphamide (CTX) (ip). The aqueous extract of AS was administered at three dose of 20, 10, or 5 g/kg b. wt. orally for 7 consecutive days before/after APH and CTX administration. Gas chromatography–mass spectrometry (GC-MS) combined with pattern recognition method and 2D gel electrophoresis (2-DE) proteomics were performed in this study to discover the underlying hematopoietic regulation mechanisms of AS on BD mouse model. Results: Unlike in the control group, the HSP90 and arginase levels increased significantly (p < 0.05) in the BD group, but the levels of carbonic anhydrase, GAPDH, catalase, fibrinogen, GSTP, carboxylesterase and hem binding protein in the BD group decreased significantly (p < 0.05). Unlike the levels in the BD group, the levels of these biomarkers were regulated to a normal state near the control group in the ASM group. Unlike in the control group, l-alanine, arachidonic acid, l-valine, octadecanoic acid, glycine, hexadecanoic acid, l-threonine, butanoic acid, malic acid, l-proline and propanoic acid levels increased significantly (p < 0.05) in the BD group, the levels of d-fructose in the BD group decreased significantly (p < 0.05). The relative concentrations of 12 endogenous metabolites were also significantly affected by the ASL, ASM, and ASH treatments. Notably, most of the altered BD-related metabolites were restored to normal state after ASM administration. Conclusion: AS can promote hematopoietic activities, inhibit production of reactive oxygen species, regulate energy metabolism, increase antiapoptosis, and potentially contribute to the blood enrichment effects of AS against APH- and CTX-induced BD mice.

Effects of volatile oils of Angelica sinensis on an acute inflammation rat model

Abstract Context Despite several pharmacological studies of volatile oils of Angelica sinensis (Oliv.) Diels (Umbelliferae) (VOAS), its anti-inflammatory mechanism remains unknown. Objective The study investigates the effects of VOAS on the lipopolysaccharide (LPS)-induced acute inflammation rat model and analyzes its possible anti-inflammatory mechanisms. Materials and methods Fourty rats were randomly divided into the control, model, VOAS and dexamethasone (Dex) groups. The VOAS and Dex groups were given VOAS (0.176 mL/kg) and Dex (40 μg/kg), respectively. Rats in all groups except the control group were intraperitoneally injected with LPS (100 μg/kg), their exterior behaviour and liver pathological changes were observed, and the level of white blood cell (WBC), the number of neutrophils (NE)%, glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), alkaline phosphatase (ALP), tumour necrosis factor (TNF-α), interleukin (IL)-1β, IL-6, IL-10, histamine (HIS), 5-hydroxytryptamine (5-HT), nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) were detected. Results Compared with the model group, VOAS and Dex significantly accelerated the recovery of the exterior behaviour, the liver pathological changes of rats, and increased the level of IL-10, but decreased the level of WBC, NE%, GOT, GPT, ALP, TNF-α, IL-1β, IL-6, HIS, 5-HT, NO, PGE2, iNOS and COX-2 (p < 0.05). Conclusion VOAS exhibits anti-inflammatory and liver protection effects by inhibiting the secretion of the pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), the inflammatory mediators (HIS, 5-HT, PGE2 and NO), the inflammation-related enzymes (iNOS and COX-2), as well as promoting the production of the anti-inflammatory cytokines IL-10.

Effects of Tao-Hong-Si-Wu decoction on acute blood stasis in rats based on a LC-Q/TOF-MS metabolomics and network approach

A novel approach using metabolomics coupled with a metabolic network was used to investigate the effects of Tao-Hong-Si-Wu decoction (THSWD) on the rat model of acute blood stasis syndrome. Acute blood stasis syndrome was induced by placing the rats in ice-cold water following two injections with epinephrine. The hemorheological indicators [whole blood viscosity (WBV) and plasma viscosity (PV)] and the blood coagulation indicators [thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB)] were detected. The nonparametric univariate method and multivariate statistical analysis were performed for determining the potential biomarkers. A correlation map was structured between biochemical indicators and hub metabolites to explain the effects mechanism of THSWD. After the administration of THSWD, the levels of WBV, PV, TT, APTT and FIB returned to levels observed in the control group. According to metabolomics coupled with metabolic network analysis, the intervention of THSWD in rats with acute blood stasis syndrome induced substantial and characteristic changes in their metabolic profiles. Fifteen metabolites were screened, which mainly involved 10 pathways and five hub metabolites, namely, l-glutamate, l-phenylalanine, N-acylsphingosine, arachidonic acid and phosphatidate. The biochemical indicators and hub metabolites could be adjusted to close to normal levels by THSWD. Therefore, combining metabolomics and metabolic network helped to evaluate the effects of THSWD on acute blood stasis.