Cis-urocanic acid

Hawthorn fruit, renowned as both a functional food and herbal medicine with lipid-lowering effects, is abundant in polysaccharides. However, there is limited research on the effects and mechanisms of hawthorn fruit polysaccharides (HP) in addressing non-alcoholic fatty liver disease (NAFLD).

This study aims to investigate the effects of HP on NAFLD both in vivo and in vitro, and to elucidate the underlying mechanisms by which HP exerts its anti-NAFLD activity.

NAFLD mice induced by a high-fat diet were employed as the in vivo model, while oleate/palmitate-induced HepG2 cells served as the in vitro model. H&E and Oil Red O staining were employed to examine fat accumulation in hepatocytes. Serum aminotransferase (ALT), aspartate aminotransferase (AST), hepatic malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) were measured using corresponding ELISA kits. Hepatic metabolomics analysis based on UHPLC-QTOF/MS was utilized to examine the role of HP in improving hepatic metabolic disorders. 16S rRNA sequencing was conducted to explore the effect of HP in alleviating gut microbiota dysbiosis. GC-MS was applied to detect short-chain fatty acids (SCFAs) to clarify the impact of HP in NAFLD mice.

HP significantly inhibited weight gain and hepatic fat accumulation in NAFLD mice. The reduction in serum ALT and AST levels indicated that HP mitigated liver function damage, while the decreased MDA levels and increased SOD activity suggested that HP alleviated hepatic oxidative stress. Furthermore, HP diminished the release of inflammatory cytokines such as IL-1β and IL-6 in the liver. HP significantly regulated metabolic pathways related to amino acids, lipids, and vitamins. Key metabolites such as l-tyrosine, urocanic acid, undecanedioic acid, oleamide, vitamin A, and vitamin B7 were restored to near-normal levels under the regulatory effects of HP. Gut microbiota dysbiosis in NAFLD mice was also ameliorated by HP, with genera such as unclassified_f__Lachnospiraceae and Dubosiella being notably affected. Correlation analysis indicated a significant correlation between the regulatory effects of HP on liver metabolism and gut microbiota. Additionally, HP showed no effect in vitro but increased acetic acid level in the gut of NAFLD mice.

These findings demonstrate that HP exhibits its anti-NAFLD effects, including alleviating lipid accumulation, liver dysfunction, oxidative stress, and inflammation. Mechanistically, HP primarily improves gut microbiota dysbiosis, thereby elevating intestinal SCFA levels and restoring hepatic metabolic disorders in NAFLD mice.

Bronchial asthma is the most common multifactorial and heterogeneous disease in childhood. The glucocorticoid dexamethasone is a classic treatment for asthma. Research indicates that group 2 innate lymphoid cells (ILC2s) are crucial to the pathogenesis of asthma. However, few studies have focused on ILC2s metabolism and transcription. This study aims to establish an ovalbumin (OVA)-induced asthma model and a dexamethasone-treated asthma model to explore the regulation of lung ILC2s at the genetic and metabolic levels during the progression and remission of asthma, utilizing single-cell metabolomics and transcriptomics approaches. The results showed that ILC2s regulated the metabolic pathways and transcriptional levels of amino acids (such as arginine, proline, and histidine) and linoleic acid, as well as the metabolic biomarkers of arginine, urocanic acid, and linoleic acid in asthma. Additionally, the cytokine pathways and NF-γB pathways have been altered at the genetic level. At the same time, we revealed that dexamethasone regulates ILC2s amino acid and aminoacyl tRNA metabolism, as well as related genes, thereby alleviating asthma symptoms. Furthermore, we identified the genes Eno3 and Tap1, which are significantly associated with asthma. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the accuracy of the RNA sequencing results. This study, for the first time, revealed the mechanistic changes of ILC2s in the development and treatment of asthma using multiomics techniques, laying a foundation for targeted therapies in asthma.