Thyme (Thymus quinquecostatus Celak) Polyphenol-Rich Extract (TPE) Alleviates HFD-Induced Liver Injury in Mice by Inactivating the TLR4/NF-κB Signaling Pathway through the Gut-Liver Axis.

Non-alcoholic fatty liver disease (NAFLD) represents a significant and urgent global health concern. Thyme (Thymus quinquecostatus Celak) is a plant commonly used in cuisine and traditional medicine in Asian countries and possesses potential liver-protective properties. This study aimed to assess the hepatoprotective effects of thyme polyphenol-rich extract (TPE) on high-fat diet (HFD)-induced NAFLD and further explore possible mechanisms based on the gut-liver axis. HFD-induced liver injury in C57 mice is markedly ameliorated by TPE supplementation in a dose-dependent manner. TPE also regulates the expression of liver lipid metabolic genes (i.e., Hmgcr, Srebp-1, Fasn, and Cyp7a1), enhancing the production of SCFAs and regulating serum metabolites by modulating gut microbial dysbiosis. Furthermore, TPE enhances the intestinal barrier function and alleviates intestinal inflammation by upregulating tight junction protein expression (i.e., ZO-1 and occluding) and inactivating the intestinal TLR4/NF-κB pathway in HFD-fed mice. Consequently, gut-derived LPS translocation to the circulation was blocked, the liver TLR4/NF-κB signaling pathway was repressed, and subsequent pro-inflammatory cytokine production was restrained. Conclusively, TPE might exert anti-NAFLD effects through the gut-liver axis and has the potential to be used as a dietary supplement for the management of NAFLD.

Water extract of Ferula lehmanni Boiss. prevents high-fat diet-induced overweight and liver injury by modulating the intestinal microbiota in mice.

Obesity, often accompanied by hepatic steatosis, has been associated with an increased risk of health complications such as fatty liver disease and certain cancers. Ferula lehmannii Boiss., a food and medicine homologue, has been used for centuries as a seasoning showing anti-bacterial and anti-oxidant effects on digestive discomfort. In the present study, we sought to investigate whether a short-term oral administration of water extract of Ferula lehmanni Boiss. (WEFL) could prevent high-fat diet (HFD)-induced abnormal weight gain and hepatic steatosis in mice and its underlying mechanisms. WEFL reduced HFD-increased body weight, liver injury markers and inflammatory cytokines (i.e. IL-6 and IL-1ß), and inhibited the elevation of AMPKα, SREBP-1c and FAS in HFD. Moreover, WEFL reconstructed the gut microbiota composition by increasing the relative abundances of beneficial bacteria, e.g. Akkermansia spp., while decreasing Desulfovibrio spp. and so on, thereby reversing the detrimental effects of HFD in mice. Removal of the gut microbiota with antibiotics partially eliminated the hepatoprotective effects of WEFL. Notably, WEFL substantially promoted the levels of short-chain fatty acids, especially butyric acid. To clarify the functional components at play in WEFL, we used UPLC-MS/MS to comprehensively detect its substance composition and found it to be a collection of polyphenol-rich compounds. Together, our findings demonstrate that WEFL prevented HFD-induced obesity and liver injury through the hepatic-microbiota axis, and such health-promoting value might be explained by the enriched abundant polyphenols.

Herba Houttuyniae Extract Benefits Hyperlipidemic Mice via Activation of the AMPK/PGC-1α/Nrf2 Cascade.

Hyperlipidemia is associated with metabolic disorders, but the detailed mechanisms and related interventions remain largely unclear. As a functional food in Asian diets, Herba houttuyniae has been reported to have beneficial effects on health. The present research was to investigate the protective effects of Herba houttuyniae aqueous extract (HAE) on hyperlipidemia-induced liver and heart impairments and its potential mechanisms. Male C57BL/6J mice were administered with 200 or 400 mg/kg/day HAE for 9 days, followed by intraperitoneal injection with 0.5 g/kg poloxamer 407 to induce acute hyperlipidemia. HAE treatment significantly attenuated excessive serum lipids and tissue damage markers, prevented hepatic lipid deposition, improved cardiac remodeling, and ameliorated hepatic and cardiac oxidative stress induced by hyperlipidemia. More importantly, NF-E2 related factor (Nrf2)-mediated antioxidant and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α)-mediated mitochondrial biogenesis pathways as well as mitochondrial complex activities were downregulated in the hyperlipidemic mouse livers and hearts, which may be attributable to the loss of adenosine monophosphate (AMP)-activated protein kinase (AMPK) activity: all of these changes were reversed by HAE supplementation. Our findings link the AMPK/PGC-1α/Nrf2 cascade to hyperlipidemia-induced liver and heart impairments and demonstrate the protective effect of HAE as an AMPK activator in the prevention of hyperlipidemia-related diseases.

Effects of ellagic acid-rich extract of pomegranates peel on regulation of cholesterol metabolism and its molecular mechanism in hamsters.

The study investigated the effect of pomegranates ellagic acid (PEA) on blood cholesterol and investigated its effects on LXR/RXR/PPAR-ABCA1 nuclear receptors-signaling pathways of cholesterol metabolism on molecular level in hamsters. In this experiment, hamsters were randomly divided into two groups: the first group (NG, n = 9) was always fed the normal diet, whereas the other group (HFG, n = 45) was fed a high fat diet during the first 4 weeks and then fed the normal diet for the last 4 weeks. In HFG, which was divided into five groups (n = 9) during the last 4 weeks, three groups were treated with PEA at 44 mg per kg bw, 88 mg per kg bw and 177 mg per kg bw, one group was treated with simvastatin at 1.77 mg per kg bw, and one was given sterile double-distilled water. The data validated that PEA dose-dependently decreased plasma total cholesterol and triglyceride level accompanied by a greater excretion of fecal bile acid. The result of RT-PCR revealed that PEA up-regulated liver X receptor (LXRα), peroxisome proliferator-activated receptor α (PPARα), peroxisome proliferator-activated receptor γ (PPARγ) and their downstream gene ATP-binding cassette transporter A1 (ABCA1), with no effect on retinoid X receptor (RXRα). PEA promoted cholesterol removal by enhancing fecal bile acid and up-regulation of the two pathways, LXR/PPAR-ABCA1. Moreover, PEA was stronger than simvastatin in some aspects.