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ObjectiveTo explore the impact of Gegen Qinliantang（GQT） on the fecal short-chain fatty acids（SCFAs） metabolism in antibiotic-associated diarrhea（AAD） through targeted metabolomics. MethodA total of 240 SD rats were randomly divided into six groups（n=40， half male and half female）， including blank group， model group， bifidobiogen group（0.15 g·kg-1）， and GQT high-， medium-， and low-dose groups（10.08， 5.04， 2.52 g·kg-1）， except for the blank group， clindamycin（250 mg·kg-1） was given to all groups by gavage for modeling every day for 7 d. After successful modeling， each administered group was gavaged with the corresponding dose of the drug， and the blank and model groups were gavaged with an equal volume of normal saline solution， 1 time/d， for 14 d. At 0， 3， 7， 14 d after the drug intervention， eight rats were randomly selected from each group， respectively. Gas chromatography-time-of-flight mass spectrometry（GC-TOF-MS） was used to perform targeted metabolomic analysis of SCFAs in the feces of rats， and partial least squares-discriminant analysis（PLS-DA） was applied to compare the differences in metabolic profiles between groups at different treatment times， and to compare the changes in the contents of SCFAs in rat feces between groups. ResultPLS-DA results showed that the blank group could be clearly distinguishable from the model group， with GQT exhibiting a closer proximity to the blank group after 7 d of treatment. After further analyzing the composition of SCFAs， it was found that the proportion of acetic acid increased and the proportions of butyric acid， valeric acid， hexanoic acid and isovaleric acid decreased in the model group compared with the blank group. After the treatment with GQT， the proportions of butyric acid， isobutyric acid， valeric acid， and isovaleric acid increased， and the proportions of acetic acid， propionic acid and caproic acid decreased. Subsequent differential analysis revealed that GQT could significantly improve the content of butyric acid， and had a certain retrogressive effect on the contents of valeric acid and hexanoic acid. ConclusionThe medium dose group of GQT can improve the contents of SCFAs in AAD feces after 7 days of treatment， which may be related to the improvement of the composition ratio of SCFAs and the contents of butyric acid， valeric acid and caproic acid.
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Objective: Corydalis bungeana (CB) is a well-used medicinal herb in Mongolian folk medicine and has been traditionally applied as an antiobesity agent. However, the evidence-based pharmacological effects of CB and its specific metabolic alterations in the obese model are not entirely understood. This study aimed to utilize untargeted metabolomic techniques to identify biomarkers and gain mechanistic insight into the serum metabolite alterations associated with weight loss and lipid metabolism in obese rats. Methods: A high-fat high-sugar (HFHS) diet was used to induce obese models in rats. CB extract was orally gavaged at 0.18, 0.9 and 1.8 g/kg doses for six weeks, and feed intake, body weight, fat pad weight, and blood indexes were measured. Blood serum metabolites were evaluated by gas chromatography/quadrupole time-of-flight tandem mass spectrometry (GC-TOF/MS). Results: The results showed that compared with the obese group, the administration of CB extract caused significant decreases in body weight (P < 0.05), feed intake, Lee's index, and perirenal, mesenteric, epididymal fat weight. CB extract also reduced blood triglyceride and total cholesterol levels (P < 0.05) of obese rats. Metabolomic findings showed that nine differential metabolites, including pyruvic acid, D-glucuronic acid, malic acid, dimethylglycine, oxoglutaric acid, pantothenic acid, sorbitol acid, fumaric acid and glucose 6-phosphate were identified under CB treatment and altered metabolic pathways such as TCA cycle, pantothenate and CoA biosynthesis, and glycolysis/gluconeogenesis. Conclusion: This study demonstrated weight loss and lipid lowering effects of CB on HFHS diet-induced obese rats and identified nine metabolites as potential biomarkers for evaluating the favorable therapeutic mechanism of CB via regulation of lipid and glucose metabolism.
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Based on dehydrogenation of monocrotaline-induced Beagle dog model of pulmonary hypertension (PH), GC-TOF-MS metabolomics technique was used to identify potential biomarkers and biologically significant changes in the serum. Pattern recognition method was used for processing metabolomics data to compare PH Beagle dogs (n=11) versus healthy controls (n=8). The results show that 514 compounds were detected in the serum. The profiles of PH models and healthy controls can be distinguished clearly, indicating that there are significant differences in the metabolic profiles. Data analysis revealed 15 types of potential biomarkers, including amino acids glycine and 3-cyanoalanine, glucose, fructose, 1-monopalmitic acid glycerin, and malic acid. Diversified metabolites and their metabolic pathways have been analyzed. We found that different degrees of turbulence and disorganization occurred in glyoxylate and dicarboxylate metabolism, TCA cycle, starch and sucrose metabolism pathways in the Beagle dogs. A soluble guanylate cyclase activator, 4,6-diamino-2-[1-(3-fluorothiophen-2-yl)methyl-1H-pyrazolo[3,4-b]pyridin-3-yl]-5-pyrimidinyl-N-methyl methyl carbamate (sGC003), was administered (n=15) for comparison with the model and the control. We found that three groups were clearly clustered, indicating that there were differences in the three groups of metabolites. ANOVA statistical analysis results suggested that sGC003 exhibited pharmacodynamic effect, and at the same time, it also changed the endogenous metabolites to some extent. This study laid a foundation for the application of metabolomics in early diagnosis of pulmonary hypertension and provided experimental evidence for the application of sGC003 compound. In this study, the program of animal testing had been approved by Committee on the management of experimental animal in the Beijing Rixin Technology Co. Ltd.
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Anoectochilus roxburghii is a traditional Chinese medicine and natural health products. In the modern cultivation system, A. roxburghii is micropropagated in tissue culture, and the plants are transferred to soil cultivation for months. However, it remains unclear about the necessity of soil cultivation for the accumulation of health beneficial compounds. In this paper, we performed nontargeted metabolomic analysis using GC-TOF-MS and UPLC-Q-TOF-MS, on A. roxburghii plants at tissue culture stage or after 3 months of soil cultivation. The results showed that the primary metabolites such as alcohols and organic acids are abundant in the tissue culture plants. In contrast, polysaccharide, nucleoside, esters and secondary metabolites such as flavonoids, terpenoids were significantly accumulated in cultivated seedlings. Flavonoids and polysaccharides are considered as the principle effective components in A. roxburghii. Soil cultivation period is therefore essential for the accumulation of these metabolites.
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Aim To investigate the changes of serum metabolism after the treatment of DOA and DOO on myocardial ischemia reperfusion ( MI/R ) injury in rats, and to explore the pathogenesis of MI/R injury and drug action mechanism. Method The serum samples of Sham group, Model group, DOA group and DOO group of rats were acquired, gas phase time of flight mass spectrometry ( GC-TOF-MS) was applied to analyze the metabolic profiles of the samples. After da-ta preprocessing, they were processed into SIMCA 14. 1 software for multivariate statistical analysis. Results By principal components analysis ( PCA ) , partial least squares analysis ( PLS-DA) and orthogonal partial least squares analysis ( OPLS-DA ) , the Model group and Sham group were obviously separated, the drug in-tervention group and Model group were separated and close to Sham group. The therapeutic effect of DOO and DOA on MI/R injury in rats was proved. The ex-perimental results identified 13 endogenous biomark-ers, which were related to the glucose metabolism,lipid metabolism and amino acid metabolism pathway. Con-clusion DOA and DOO may protect the MI/R injured rats by regulating the glucose metabolism, lipid metab-olism and amino acid metabolism pathway.
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To observe the effect of total saponins of Clematidis Radix et Rhizoma (TSCR) on serum metabolic profile changes in adjuvant arthritis(AA) rats, and explore its possible action mechanism for AA rats. The AA rat models were induced by Freund's complete adjuvant(FCA), and their histopathological changes were observed. Gas chromatography-time-of-flight mass spectrometry (GC-TOF-MS), principal component analysis(PCA) and partial least squares-discriminant analysis (PLS-DA) were employed to analyze the metabolic profile among normal group, AA model group and TSCR group. Potential biomarkers in the serum were screened based on the variable importance projection(VIP) value>1, P<0.05. As compared with the normal group, 17 potential biomarkers such as aspartic acid, inositol and phenylacetaldehyde were found and identified in the serum of model group rats. As compared with the model group, the above biomarkers were regulated nearly to a normal state after TSCR administration for 16 days. Metabolomic analysis revealed that the total saponins of Clematidis Radix et Rhizoma has a certain therapeutic effect for AA rats, and the mechanism may be related to regulation of lipid metabolism, amino acid metabolism and energy metabolism.