Polyphenols from the Lonicera caerulea L. berry have shown protective effects on experimental non-alcoholic fatty liver disease (NAFLD) in our previous studies. As endotoxins from gut bacteria are considered to be the major trigger of inflammation in NAFLD, this study aims to clarify the regulatory effects of L. caerulea L. berry polyphenols (LCBP) on gut microbiota in a high fat diet (HFD)-induced mouse model. C57BL/6N mice were fed with a normal diet, HFD, or HFD containing 0.5–1% of LCBP for 45 days. The results revealed that supplementation with LCBP decreased significantly the levels of IL-2, IL-6, MCP-1, and TNF-α in serum, as well as endotoxin levels in both serum and liver in HFD-fed mice. Fecal microbiota characterization by high throughput 16S rRNA gene sequencing revealed that a HFD increased the Firmicutes/Bacteroidetes ratio, and LCBP reduced this ratio by increasing the relative abundance of Bacteroides, Parabacteroides, and another two undefined bacterial genera belonging to the order of Bacteroidales and family of Rikenellaceae, and also by decreasing the relative abundance of six bacterial genera belonging to the phylum Firmicutes, including Staphylococcus, Lactobacillus, Ruminococcus, and Oscillospira. These data demonstrated that LCBP potentially attenuated inflammation in NAFLD through modulation of gut microbiota, especially the ratio of Firmicutes to Bacteroidetes.

Fisetin, a dietary flavonoid, is reported to have cellular antioxidant activity with an unclear mechanism. In this study, we investigated the effect of fisetin on the nuclear factor, erythroid 2-like 2 (Nrf2) signaling pathway in HepG2 cells to explore the cellular antioxidant mechanism. Fisetin upregulated the mRNA expression of heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase modifier subunit (GCLM), and NAD(P)H quinone oxidoreductase-1 (NQO1), and induced the protein of HO-1 but had no significant effect on the protein of GCLC, GCLM and NQO1. Moreover, nuclear accumulation of Nrf2 was clearly observed by immunofluorescence analysis and western blotting after fisetin treatment, and an enhanced luciferase activity of antioxidant response element (ARE)-regulated transactivation was obtained by dual-luciferase reporter gene assays. In addition, fisetin upregulated the protein level of Nrf2 and downregulated the protein level of Kelch-like ECH-associated protein 1 (Keap1). However, fisetin had no significant effect on Nrf2 mRNA expression. When protein synthesis was inhibited with cycloheximide (CHX), fisetin prolonged the half-life of Nrf2 from 15 min to 45 min. When blocking Nrf2 degradation with proteasome inhibitor MG132, ubiquitinated proteins were enhanced, and fisetin reduced ubiquitination of Nrf2. Taken together, fisetin translocated Nrf2 into the nucleus and upregulated the expression of downstream HO-1 gene by inhibiting the degradation of Nrf2 at the post-transcriptional level. These data provide the molecular mechanism to understand the cellular antioxidant activity of fisetin.

Non-alcoholic fatty liver disease (NAFLD) is a manifestation of metabolic syndrome closely linked to dyslipidemia and gut microbiome dysbiosis. Bilberry anthocyanins (BA) have been reported to have preventive effects against metabolic syndrome. This study aimed to investigate the protective effects and mechanisms of BA in a Western diet (WD)-induced mouse model. The results revealed that supplementation with BA attenuated the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein cholesterol (LDL-c), fat content in liver, 2-thiobarbituric acid reactive substances (TBARS) and α-smooth muscle actin (α-SMA) caused by WD. Furthermore, gut microbiota characterized by 16S rRNA sequencing revealed that BA reduced remarkably the ratio of Firmicutes/Bacteroidetes (F/B) and modified gut microbiome. In particular, BA increased the relative abundance of g_Akkermansia and g_Parabacteroides. Taken together, our data demonstrated that BA might ameliorate WD-induced NAFLD by attenuating dyslipidemia and gut microbiome dysbiosis.

Blue honeysuckle is rich in polyphenols, and recently receiving attention because of its potential antioxidant and anti-inflammatory properties. Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease that develops hepatic inflammation and metabolic syndrome. The present study aims to study the effect of blue honeysuckle extract (BHE) on fat deposition and hepatic lipid peroxidation in a high-fat-diet (HFD)-induced mouse model. Mice were fed a normal diet (ND) or a HFD containing 0.5% or 1% of BHE or not for 45 d. Liver sections were stained by hematoxylin-eosin staining. Serum lipids were measured by a clinical analyzer. Insulin was examined by ELISA, and hepatic proteins were detected by Western blotting. Dietary supplementation of BHE dose-dependently suppressed HFD-induced obesity and hepatic fat deposition. Moreover, BHE improved glucose metabolism by increasing insulin sensitivity and attenuated oxidative stress potentially by up-regulating nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated pathway.

This study investigated whether rosemary extract (RE) supplementation selectively reshapes ruminal butyrate-producing microbiota and enhances functional milk properties in lactating dairy goats. Twenty-four goats were fed a control diet or a diet supplemented with 2.14 g/kg RE (n = 12) during a 42-day feeding trial. Rumen fermentation parameters, bacterial community composition, and milk quality indices - including bioactive proteins, amino acid and fatty acid profiles, and somatic cell count - were analyzed. RE supplementation significantly increased butyrate concentration and tended to elevate valeric acid. The relative abundances of fibrolytic bacteria (Ruminococcus albus and Fibrobacter succinogenes) and butyrate-producing taxa (i.e., Butyrivibrio) were significantly enriched (p < 0.05) in the RE group. Notably, dietary RE markedly elevated milk bioactive proteins, including lactoferrin, α-lactalbumin, and β-lactoglobulin (p < 0.05), and reduced somatic cell count (p < 0.05). These findings reveal a microbiota-mediated pathway through which RE enhances the functional quality of goat milk and support the potential of phytogenic feed additives.