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The Metabolic Changes of Artesunate and Ursolic Acid on Syrian Golden Hamsters Fed with the High-Fat Diet.

ABSTRACT: Artesunate was well known as an antimalarial drug. Our previous research found that it has hypolipidemia effects in rabbits fed with a high-fat diet, especially combined with ursolic acid. In this study, we reconfirmed the lipid-lowering effect of artesunate and ursolic acid in hamsters and analyzed the metabolic changes using gas chromatography time-of-flight mass spectrometry (GC/TOF MS). Compared with the model group, a variety of different metabolites of artesunate and ursolic acid, alone or in combination, were found and confirmed. These differential metabolites, including fatty acids, lipids, and amino acids, were involved in lipid metabolism, energy metabolism, and amino acid metabolism. It indicated that two agents of artesunate and ursolic acid could attenuate or normalize the metabolic transformation on these metabolic pathways.

SUBMITTER: Pu S

PROVIDER: S-EPMC7144559 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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The Metabolic Changes of Artesunate and Ursolic Acid on Syrian Golden Hamsters Fed with the High-Fat Diet.

Pu Shichen S Liu Yumin Y Liang Shan S Liu Pin P Qian Hongmei H Wu Qian Q Wang Yuliang Y

Molecules (Basel, Switzerland) 20200318 6

Artesunate was well known as an antimalarial drug. Our previous research found that it has hypolipidemia effects in rabbits fed with a high-fat diet, especially combined with ursolic acid. In this study, we reconfirmed the lipid-lowering effect of artesunate and ursolic acid in hamsters and analyzed the metabolic changes using gas chromatography time-of-flight mass spectrometry (GC/TOF MS). Compared with the model group, a variety of different metabolites of artesunate and ursolic acid, alone or ...[more]

PMID: 32197531

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Project description:Aim: The objective of this study was to characterize the early effects of high fructose diets (with and without high fat) on both the composition of the gut microbiota and lipid metabolism in Syrian hamsters, a reproducible preclinical model of diet-induced dyslipidemia. Methods: Eight-week-old male hamsters were fed diets consisting of high-fat/high-fructose, low-fat/high-fructose or a standard chow diet for 14 days. Stool was collected at baseline (day 0), day 7 and day 14. Fasting levels of plasma triglycerides and cholesterol were monitored on day 0, day 7 and day 14, and nonfasting levels were also assayed on day 15. Then, 16S rRNA sequencing of stool samples was used to determine gut microbial composition, and predictive metagenomics was performed to evaluate dietary-induced shifts in deduced microbial functions. Results: Both high-fructose diets resulted in divergent gut microbiota composition. A high-fat/high-fructose diet induced the largest shift in overall gut microbial composition, with dramatic shifts in the Firmicute/Bacteroidetes ratio, and changes in beta diversity after just seven days of dietary intervention. Significant associations between genus level taxa and dietary intervention were identified, including an association with Ruminococceace NK4A214 group in high-fat/high-fructose fed animals and an association with Butryimonas with the low-fat/high-fructose diet. High-fat/high-fructose feeding induced dyslipidemia with increases in plasma triglycerides and cholesterol, and hepatomegaly. Dietary-induced changes in several genus level taxa significantly correlated with lipid levels over the two-week period. Differences in microbial metabolic pathways between high-fat/high-fructose and low-fat/high-fructose diet fed hamsters were identified, and several of these pathways also correlated with lipid profiles in hamsters. Conclusions: The high-fat/high-fructose diet caused shifts in the host gut microbiota. These dietary-induced alterations in gut microbial composition were linked to changes in the production of secondary metabolites, which contributed to the development of metabolic syndrome in the host.

Project description:Effects of polyomavirus SV40 microRNA on pathogenesis of viral infections in vivo are not known. Syrian golden hamsters are the small animal model for studies of SV40. We report here effects of SV40 microRNA and influence of the structure of the regulatory region on dynamics of SV40 DNA levels in vivo. Outbred young adult hamsters were inoculated by the intracardiac route with 1×10? plaque-forming units of four different variants of SV40. Infected animals were sacrificed from 3 to 270 days postinfection and viral DNA loads in different tissues determined by quantitative real-time polymerase chain reaction assays. All SV40 strains displayed frequent establishment of persistent infections and slow viral clearance. SV40 had a broad tissue tropism, with infected tissues including liver, kidney, spleen, lung, and brain. Liver and kidney contained higher viral DNA loads than other tissues; kidneys were the preferred site for long-term persistent infection although detectable virus was also retained in livers. Expression of SV40 microRNA was demonstrated in wild-type SV40-infected tissues. MicroRNA-negative mutant viruses consistently produced higher viral DNA loads than wild-type SV40 in both liver and kidney. Viruses with complex regulatory regions displayed modestly higher viral DNA loads in the kidney than those with simple regulatory regions. Early viral transcripts were detected at higher levels than late transcripts in liver and kidney. Infectious virus was detected infrequently. There was limited evidence of increased clearance of microRNA-deficient viruses. Wild-type and microRNA-negative mutants of SV40 showed similar rates of transformation of mouse cells in vitro and tumor induction in weanling hamsters in vivo. This report identified broad tissue tropism for SV40 in vivo in hamsters and provides the first evidence of expression and function of SV40 microRNA in vivo. Viral microRNA dampened viral DNA levels in tissues infected by SV40 strains with simple or complex regulatory regions.

Dataset Information

The Metabolic Changes of Artesunate and Ursolic Acid on Syrian Golden Hamsters Fed with the High-Fat Diet.

Publications

The Metabolic Changes of Artesunate and Ursolic Acid on Syrian Golden Hamsters Fed with the High-Fat Diet.

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