Safety investigation of Pulsatilla chinensis saponins from chronic metabonomic study of serum biomedical changes in oral treated rat. (10th May 2019)

• Record Type: Journal Article
• Authors: Song, Yonggui; Shan, Baixi; Li, Hanyun; Feng, Bingwei; Peng, Hong; Jin, Chen; Xu, Pengfei; Zeng, Qiang; Liao, Zhou; Mu, Pengqian; Su, Dan
• Is Part Of: Journal of ethnopharmacology. Volume 235(2019)
• Page Start: 435
• Page End: 445
• Publication Date: 2019-05-10
• Subjects: TCM Traditional Chinese Medicine -- P chinensis Pulsatilla chinensis -- PRS Pulsatilla chinensis saponins -- UPLC-QTOF-MS Ultra-Performance Liquid Chromatography/Quadrupole Time-Of-Flight Mass Spectrometry -- OPLS Optimized Potentials For Liquid Simulations -- PCA Principal Component Analysis -- ALT Alanine aminotransferase -- AST Aspartate aminotransferase -- ALP Alkaline phosphatase -- PG Pulsatilla Group -- HCG Healthy Control Group -- CMC-Na sodium carboxymethyl cellulose -- IDA Information-Dependent Acquisition -- MMDF Multiple Mass Defect Filter -- ACO Acyl-CoA Oxidase -- RSD Relative Standard Deviation -- HMDB Human metabolome database -- FGH9 Fibroblast growth factor -- SM Sphingomyelin -- ELSD Evaporative Light Scattering Detector -- B3 hederagenin 3-O- {α-L-rhamnopyranosyl(1→2) [β-D-glucopyranosyl(1→4)] α-L-arabinopyranoside} -- BD hederagenin 3-O-{α-L-rhamnopyranosyl (1→2) α-L-arabinopyranoside} -- B7 oleanolic acid 3-O- {β-D- glucopyranosyl(1→4) [α-L- rhamnopy- ranosyl(1→2)] α-L- arabinopyranoside} -- B9 oleanolic acid 3-O-{β-D-glucopyranosyl (1→4)[β-D- glucopyranosyl (1→3)] [α-L- rhamnopyranosyl(1→2)]α-L-arabinopyranoside} B10, oleanolic acid 3-O-{β-D- glucopyranosyl(1→3) [α-L-rhamnopyranosyl (1→2)] α-L- arabinopyranoside} -- B11 oleanolic acid 3-O-{α-L-rhamnopyranosyl(1→2)α-L-arabinopyranoside}; P. chinensis saponins -- UPLC-QTOF-MS -- Serum metabonomics -- Chronic liver injury; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2019.01.035
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Pulsatilla chinensis (Bunge) Regel is a valuable traditional Chinese medicine (TCM) which is widely used for the treatment of schistosomiasis, inflammatory, bacterial infections. In recent years, P chinensis has been reported to exhibit antitumor activities. However, the mechanisms underlying its toxic effects remain largely unresolved. This paper is designed to investigate the damage of long-term oral P. chinensis saponins (PRS) and to explore its potential damage mechanisms by serum metabonomics approach. Materials and methods: The serum samples from control and PRS treated rats were analyzed by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) in positive ionization mode and negative ionization mode. Liver function index of ALT, AST and ALP, blood biochemistry and biomarkers were examined to identify specific changes of injury. Acquired data were subjected to principal component analysis (PCA) for differentiating the control and PRS treated groups. Then, serum metabolic profiling was analyzed and pathway analysis performed on the biomarkers reversed after PRS treated and further integration of metabolic networks. Results: The results suggested that serum liver function indexes of ALT had significantly changed and stage increased. AST, ALP detection content show volatility changes. Changes in the 15 biomarkers found in the serum, such as acetaminophen glucuronide, 9 E, 11 E-linoleic acid, chenodeoxycholic acid, monoacylglycerides, sphingomyelin (SM), 7-ketodeoxycholic acid and 12-keto-deoxycholic acid, which were closely related to changes in liver injury. It could be seen clearly that with the change of the dosing time, the biomarkers in the serum have undergone obvious, regular and progressive changes through the score plot and corresponding loading plot. The underlying regulations of PRS-perturbed metabolic pathways were discussed according to the identified metabolites. Conclusion: The present study proves the potential of UPLC-QTOF-MS based metabonomics in mapping metabolic response. Long-term oral administration of P. chinensis saponins can cause chronic liver injury, and its safety needs further attention. It is of great significance in safeguarding human health to explore the damage mechanism of Pulsatilla chinensis saponins on liver by serum metabolomics. Graphical abstract: fx1