Exploring the potential mechanism of Rhodomyrtus tomentosa (Ait.) Hassk fruit phenolic rich extract on ameliorating nonalcoholic fatty liver disease by integration of transcriptomics and metabolomics profiling.

Nonalcoholic fatty liver disease (NAFLD), as the commonest form of chronic liver disease, is accompanied by liver oxidative stress and inflammatory responses. Rhodomyrtus tomentosa (Ait.) Hassk fruit phenolic rich extract (RTE) possesses multiple pharmacological effects in management of chronic diseases. In this study, the liver-protective effect of RTE on mice with high-fat-diet (HFD)-induced NAFLD was investigated for the first time, and the underlying molecular mechanism was explored via integration of transcriptomics and metabolomics. The results showed that RTE mitigated liver damage, which was evidenced by declined inflammatory cell infiltration in liver, decreased liver function markers, oxidative stress indexes, lipid profile levels and inflammatory cytokines levels. The differential metabolites by metabonomics illustrated supplementation of RTE affected metabolomics pathways including tryptophan metabolism, alanine, aspartate and glutamate metabolism, D-glutamine and D-glutamate metabolism, cysteine and methionine metabolism, arginine and proline metabolism, which are all involved in oxidative stress and inflammation. Furthermore, the five differential expression genes (DEGs) through liver transcriptomics were screened and recognized, namely Tnfrsf21, Ifit1, Inhbb, Mapk15 and Gadd45g, which revealed that HFD induced Cytokine-cytokine receptor interaction pathway, NF-κB signaling pathway NOD-like receptor pathway, TNF signaling pathway. Integrated analysis of transcriptomics and metabolomics confirmed the supplementation of RTE had significantly regulatory effects on the metabolic pathways involved in inflammatory responses. Additionally, RT-PCR and western blot authenticated RTE intervention regulated the mRNA levels of liver genes involved in inflammation response and inhibited the liver endotoxin-TLR4-NF-κB pathway triggered by HFD, thus alleviating NAFLD. Our findings strongly support the possibility that RTE can be regarded as a potential therapeutic method for obesity-associated NAFLD.

Wang R ，Yao L ，Lin X ，Hu X ，Wang L ... -  《-》

Exploring the potential mechanism of Rubus corchorifolius L. fruit polyphenol-rich extract in mitigating non-alcoholic fatty liver disease by integration of metabolomics and transcriptomics profiling.

Qin Y ，Fan R ，Liu Y ，Qiu S ，Wang L ... -  《-》

Rhodomyrtus tomentosa (Ait.) Hassk fruit phenolic-rich extract mitigates intestinal barrier dysfunction and inflammation in mice.

Wang R ，Yao L ，Meng T ，Li C ，Wang L ... -  《-》

Noni (Morinda citrifolia L.) fruit phenolic extract supplementation ameliorates NAFLD by modulating insulin resistance, oxidative stress, inflammation, liver metabolism and gut microbiota.

The liver-protective activity of phenolics has been consistently reported, but the underlying protective mechanism of phenolic extract from noni fruit (NFE) against high-fat-diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) remains unclear. Mice were fed with HFD or combination of HFD and NFE for 10 weeks, and then the gut microbiota and liver metabolites were compared. In this study, NFE supplementation alleviated HFD-induced liver injury and metabolic comorbidities, as evidenced by reduced liver function markers, decreased lipid profile levels, and improved obesity and insulin resistance. NFE supplementation restored the composition of gut microbiota with a remarkable elevation in the relative abundance of Parabacteroides, Lactobacillus, Roseburia, Akkermansia and a significant reduction in Helicobacter, norank_f_Desulfovibrionaceae, Desulfovibrio, Mucispirillum at the genus level. Liver metabolomics demonstrated that NFE supplementation favorably regulated the metabolic pathways involved in oxidative stress and inflammation, including purine metabolism, glutathione metabolism, primary bile acid biosynthesis, glycerophospholipid metabolism, pentose phosphate pathway, ascorbate and aldarate metabolism, galactose metabolism etc. Furthermore, NFE supplementation inhibited the HFD-induced activation of the liver endotoxin - TLR4 - NF-κB pathway, and alleviated liver inflammation. In conclusion, the findings of this study provide new evidences supporting that NFE can be used as a therapeutic approach for HFD-induced NAFLD via modulating the gut microbiota composition, liver metabolite profile and suppressing inflammatory reaction.

Wang R ，Wang L ，Wu H ，Zhang L ，Hu X ，Li C ，Liu S ... -  《-》

Integrative transcriptomics and metabolomics explore the mechanism of kaempferol on improving nonalcoholic steatohepatitis.

Lu Y ，Shao M ，Xiang H ，Zheng P ，Wu T ，Ji G ... -  《-》