Search

Lignans from Schisandra chinensis (Turcz.) Baill (LFS) has been proved to improve impaired cognitive ability thereby show potential in treating Alzheimer's disease (AD). In this study, UHPLC-Q-TOF-MS and UHPLC-QQQ-MS were adopted cooperatively to establish a method synchronously detecting 10 kinds of LFS monomers in rat plasma samples. And this method was further applied for pharmacokinetic study to compare the metabolism of LFS in normal and AD rats. The results indicated that AD rats showed an observably better absorption of LFS compared to normal rats. Based on time-varying plasma concentration of LFS, metabolomics was used to establish a plasma concentration-time-endogenous metabolite connection. In total 54 time-varying endogenous metabolites were screened and most of which were closely associated with AD. And LFS exerted a concentration dependent regulating effect to most of these metabolites. Through biomarker related pathways and biological function analysis, LFS might treat AD through neuroprotection, antioxidant damage and regulating the metabolism of unsaturated fatty acids. This is the first study connecting LFS absorbtion and endogenous metabolite changes with the time lapse. The pharmacokinetics and metabolic profile differences between normal and AD rats were firstly investigated as well. This study provides a novel perspective in exploring the effect and mechanism of LFS in treating AD., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Gancao Fuzi decoction (GFD) is a classic Chinese medicine formula for the treatment of rheumatic and rheumatoid arthritis. The main active components of GFD are alkaloids, flavonoids and saponins. This study aimed to clarify the pharmacodynamic effects of the active components in GFD and investigate the mechanism of them treating rheumatoid arthritis rats by the method of metabonomics. Seven groups were studied, named as the normal group (NG), the model group (MG), the Gancao Fuzi decoction treatment group (GFDe), the alkaloids group (ALK), the compatibility of alkaloids with flavonoids group (AF), the compatibility of alkaloids with saponins group (AS) and the compatibility of alkaloids with flavonoids and saponins group (AFS), respectively. Firstly, the anti-inflammatory and analgesic effects of these groups were studied. Besides, urinary metabonomics based on ultra high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was employed for delineation of metabolic alterations in the rats. Based on our results, it is concluded that AFS showed better anti-inflammatory and analgesic activities in GFD. Urinary metabonomic study and multivariate statistical analyses were used to investigate the mechanism of different groups. 26 potential biomarkers have been identified. By the analysis of heat map combined with score plot, the AFS group was the closest group to the NG group after treatment in GFD. The changes of urinary endogenous metabolites showed that AFS exhibited better effect on regulating the taurine and hypotaurine metabolism, phenylalanine metabolism, TCA cycle, tryptophan metabolism, fatty acid metabolism, vitamin B6 metabolism, arginine and proline metabolism and purine metabolism pathways. The pharmacodynamics results showed that three components of flavonoids, saponins and alkaloids in GFD played an overall efficacy. Metabonomics studies showed that the compatibility of three components in GFD achieved the therapeutic effect by regulating the perturbations of multiple metabolic pathways., (Copyright © 2018. Published by Elsevier B.V.)

Rheumatoid arthritis (RA) is a chronic disease with pain, swelling, and limitation in the motion and function of multiple joints thus leading to high disability. Previous studies have shown that flavonoids and saponins are the most abundant and active constituents in Glycyrrhiza, which possess a wide range of pharmacological effects such as anti-inflammatory, antioxidant and anti-bacteria. But the mechanisms of those actions are not entirely clear. In order to clarify the mechanisms of those actions, the pharmacodynamical assessments of extraction of water-soluble components and flavonoids and saponins obtained from Glycyrrhiza were investigated. Combining the pharmacodynamical researches, we found that flavonoids obtained from Glycyrrhiza had more significant therapeutic effects on acute inflammation, chronic inflammation and inflammatory pain than that of extraction of water-soluble components and saponins obtained from Glycyrrhiza. The results indicated that flavonoids are the main medicinal ingredients in Glycyrrhiza. In order to further investigate the mechanism of the action of flavonoids in Glycyrrhiza on treating RA, a urine metabolomics method based on ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was established to observe the metabolic variations in adjuvant-induced arthritis (AIA) rats and investigate the therapeutic effect of flavonoids in Glycyrrhiza on RA. As a result, twenty potential biomarkers were found by comparison with the model group (MG) and flavonoid treated group (FG). We associated these compounds with related metabolic pathways, the results showed that these biomarkers were mainly associated with purine metabolism, taurine and hypotaurine metabolism, tryptophan metabolism, phenylalanine metabolism, tricarboxylic acid cycle (TCA cycle), pantothenate and coenzyme A (CoA) biosynthesis. The results about the pharmacodynamics and metabolomics provided a theoretical basis for clarifying the mechanism of flavonoids in Glycyrrhiza in the treatment of RA., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Fenugreek is a traditional plant for the treatment of diabetes. Galactomannan, an active major component in fenugreek seeds, has shown hypoglycemic activity. The present study was performed to investigate the therapeutic mechanism underlying fenugreek galactomannan (F-GAL) in treating diabetes, using a metabonomics approach based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). The F-GAL used for study was highly purified, and its yield, purity, and galactose/mannose ratio were characterized by capillary zone electrophoresis (CZE) and a modified phenol-sulfuric acid method. After treatment of streptozotocin (STZ)-induced diabetic rats with F-GAL for 28days, urine and serum samples were analyzed by UPLC-QTOF/MS. Multivariate statistical approaches such as principal component analysis (PCA) and orthogonal projection to latent structures squares-discriminant analysis (OPLS-DA) were applied to distinguish the non-diabetic/untreated, diabetic/untreated, and diabetic/F-GAL-treated groups. Then, potential biomarkers were identified that may help elucidate the underlying therapeutic mechanism of F-GAL in diabetes. The results demonstrated that there was a clear separation among the three groups in the PCA model. Fourteen potential biomarkers were identified by OPLS-DA, and they were determined to be produced in response to the therapeutic effects of F-GAL. These biomarkers were involved in histidine metabolism, tryptophan metabolism, energy metabolism, phenylalanine metabolism, sphingolipid metabolism, glycerophospholipid metabolism, and arachidonic acid metabolism. In conclusion, our study demonstrates that a metabonomics approach is a powerful, novel tool that can be used to evaluate the underlying therapeutic mechanisms of herb extracts., (Copyright © 2016 Elsevier B.V. All rights reserved.)