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

Abstract

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.

Keywords: ALT; AS; ASJP; AST; ASTP; ASTUP; ASYP; Ananine (PubchemCID:5950); Angelica sinensis; Arachidonic acid (PubchemCID:444899); CCl(4); Citric acid (Pubchem CID:311); Fumaric acid (PubchemCID:444972); GC–MS; GC–MS hepatoprotective effect; Glycine (Pubchem CID:750); HE; Hexadecanoic acid (Pubchem CID:985); MSTFA; Malic acid (PubchemCID:525); Metabonomics; N-methy-N-(trimethylsilyl) trifluoroacetamide; PCA; PLS-DA; Palmitelaidic acid (Pubchem CID:4668); Polysaccharide; Succinic acid (Pubchem CID:1110); TMCS; VIP; VLDL; Valine (PubchemCID:6287); alanine aminotransferase; aspartate aminotransferase; carbon tetrachloride; gas chromatography–mass spectrometry; hematoxylin and eosin; partial least squares-discriminant analysis; polysaccharides form charred AS; polysaccharides form parching AS with Sesame Oil; polysaccharides form parching AS with soil; polysaccharides form parching AS with wine; principal component analysis; trimethylchlorosilane; variable importance in the projection; very low density lipoproteins.