Isoquercetin (IQ), a glucoside derivative of quercetin, has been reported to have beneficial effects in nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the potential improvement of IQ in liver lipid accumulation, inflammation, oxidative condition, and activation in Kupffer cells (KCs) on a high-fat diet (HFD) induced NAFLD models. Male Sprague-Dawley (SD) rats were induced by HFD, lipopolysaccharides/free fatty acids (LPS/FFA) induced co-culture cells model between primary hepatocytes and Kupffer cells was used to test the effects and the underlying mechanism of IQ. Molecular docking was performed to predict the potential target of IQ. Significant effects of IQ were found on reduced lipid accumulation, inflammation, and oxidative stress. In addition, AMP-activated protein kinase (AMPK) pathway was activated by IQ, and is plays an important role in lipid regulation. Meanwhile, IQ reversed the increase of activated KCs which caused by lipid overload, and also suppression of Transforming growth factor beta (TGF-β) signaling by TGF-β Recptor-1 and SMAD2/3 signaling. Finally, TGF-βR1 and TGF-βR2 were both found may involve in the mechanism of IQ. IQ can improve hepatic lipid accumulation and decrease inflammation and oxidative stress by its activating AMPK pathway and suppressing TGF-β signaling to alleviate NAFLD.

Non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is the most common chronic liver disease in the world. However, there are still no drugs for NAFLD/NASH in the market. Gastrodin (GAS) is a bioactive compound that is extracted from Gastrodia elata, which is used as an active compound on nervous system diseases. Recent reports showed that GAS and Gastrodia elata possess anti-oxidant activity and lipid regulating effects, which makes us curious to reveal the anti-NAFLD effect of GAS. A high cholesterol diet (HCD) was used to induce a NAFLD larval zebrafish model, and the lipid regulation and anti-oxidant effects were tested on the model. Furthermore, qRT-PCR studied the underlying mechanism of GAS. To conclude, this study revealed a lipid regulation and anti-oxidant insights of GAS on NAFLD larval zebrafish model and provided a potential therapeutic compound for NAFLD treatment.

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease with a global prevalence of 25%. However, the medicines approved by the FDA or EMA are still not commercially available for the treatment of NAFLD. The NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome plays a crucial role in inflammatory responses, and the mechanisms related to steatohepatitis have been sufficiently clarified. NLRP3 has been widely evaluated as a potential target for multiple active agents in treating NAFLD. As a quercetin glycoside, isoquercitrin (IQ) has a broad inhibitory effect on oxidative stress, cancers, cardiovascular diseases, diabetes, and allergic reactions in vitro and in vivo. This study aimed to investigate the undercover mechanism of IQ in the treatment of NAFLD, particularly in anti-steatohepatitis, by suppressing the NLRP3 inflammasome. In this study, a methionine-choline-deficient induced steatohepatitis mice model was used to explore the effect of IQ on NAFLD treatment. Further mechanism exploration based on transcriptomics and molecular biology revealed that IQ inhibited the activated NLRP3 inflammasome by down-regulating the expression of heat shock protein 90 (HSP90) and suppressor of G-two allele of Skp1 (SGT1). In conclusion, IQ could alleviate NAFLD by inhibiting the activated NLRP3 inflammasome by suppressing the expression of HSP90.

5-Hydroxytryptamine (also known as 5-HT, serotonin) is one of the monoamine neurotransmitters which is distributed widely in plasma and brain of mammals and plays important roles in physiological manipulations. In the present method, we describe the development of a simple, efficient and rapid high performance liquid chromatographic method coupled with ultraviolet (HPLC–UV) detector for the qualitative and quantitative analysis of 5-HT in both cell extract and cell culture medium (RIN-14B). The experiments use repeated freeze–thaw cycles followed by centrifugation and direct injection of the supernatant into the chromatography. An analytical C18 column (Agilent Zorbax Extend, 4.6 × 250 mm, 5 μm.) was taken for chromatographic separation; the mobile phase was 0.05 mol/L potassium dihydrogen phosphate (KH2PO4)/acetonitrile (90:10 v/v). Isocratic elution is established at the flow rate of 1.0 mL/min. The time required for this chromatographic run is 8 min. Over the concentration range of 0.1–10 μg/mL, the calibration curve is linear in this method. Other unique characteristics and advantages include high accuracy (92.02–103.28%) and high precision (intra- and inter-day coefficients of variation ≤ 4.69%). This method is applicable for the investigation of drug/condition–response relationships in the function of synthesis and secretion of 5-HT in cultured RIN-14B cells in various in vitro studies.

Cichorium glandulosum Boiss. et Huet (CG) and Cichorium intybus L. (CI) are widely used as the main raw material of functional food with hepatoprotective and hypoglycemic effects. Due to the lack of comparison on the chemical ingredients and efficacy, they were often used imprecisely and interchangeably. It is necessary to distinguish between them. With the plant metabolomics based on high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-QTOF-MS) and multivariate chemometric techniques, the chemical ingredients were characterized and 59 compounds between CG and CI were classified. As for antioxidative and hypoglycemic activities in vitro, CI extraction exhibited better antioxidant activity than CG, while CG extraction showed stronger hypoglycemic activity. Furthermore, a bivariate correlation between the chemical composition and efficacy of the extract was also analyzed, and three differentially strong correlation components between CI and CG were prepared, and the antioxidative and hypoglycemic efficacies were compared in vivo and different active phenotypes were obtained. Finally, we revealed chemical and biological differences between CG and CI, providing a basis for achieving better quality control and developing more effective functional foods.

Objective: To evaluate the effects of Knoxia roxburghii on blood glucose levels in diabetic rats and to investigate its underlying mechanisms of action using proteomics and metabolomics.Methods: Streptozotocin (STZ)-induced diabetic rats were treated with different doses of K. roxburghii extract. Proteomics and metabolomics analyses were performed using pancreatic proteins and serum samples, and the proteomics findings were validated via parallel reaction monitoring (PRM).Results: Compared with the model group, rats in the treatment group showed improved diabetic symptoms. Fasting blood glucose (FBG), glycated serum protein (GSP), pancreatic malondialdehyde (MDA), and the area under the curve of oral glucose tolerance test (OGTT-AUC) were significantly decreased (P < 0.01, P < 0.05), while superoxide dismutase (SOD), homeostasis model assessment of β-cell function (HOMA-β), and fasting insulin (FINS) were significantly increased (P < 0.01, P < 0.05). Histological analysis revealed an increased pancreatic islet cell area in the treatment group. Proteomic analysis identified six significantly downregulated proteins validated by PRM: Ethylmalonyl-CoA Decarboxylase 1 (ECHDC1), Calcium - Dependent Protein Kinase II Delta (CAMK2D), DNA Damage - Binding Protein 1 (DDB1), Ubiquitin-Like Modifier-Activating Enzyme 6(UBA6), Baculoviral IAP Repeat - Containing Protein6(BIRC6), and Hexokinase 1(HK1). These proteins were associated with six key metabolic pathways, including butyric acid metabolism, propionic acid metabolism, and the mTOR signaling pathway.Conclusion: The ethyl acetate extract of K. roxburghii reduces endogenous glucose production by inhibiting gluconeogenesis, alleviates oxidative stress in pancreatic cells, and preserves pancreatic islet architecture. These effects contribute to increased insulin secretion, improved glycemic control, and alleviation of diabetic symptoms in STZ-induced rats. These findings not only provide mechanistic insights into the ethnopharmacological basis for the traditional use of K. roxburghii in diabetes management, but also establish a scientific rationale supporting its clinical application through the regulation of hepatic gluconeogenesis and pancreatic β-cell preservation.