Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease worldwide; thus, a dietary supplement that can restrict hepatic fat accumulation is needed. Baicalein, a major component of Scutellaria baicalensis, is used as a dietary supplement in Eastern and Western cultures and can reduce hepatic fat accumulation. However, the detailed mechanism by which baicalein exerts this effect has yet to be elucidated in vivo and in vitro. In this study, we characterized the hepatic fat-lowering activity of baicalein and found that baicalein reduced hepatic fat accumulation by activating AMPK and suppressing SREBP1 cleavage, thus consequently inhibiting the transcriptional activity of SREBP1 and the synthesis of hepatic fat in oleic acid-induced HepG2 cells and high-fat diet-induced non-insulin-resistant mice. Moreover, baicalein improved NAFLD by decreasing TC, increasing HDLC, decreasing LDLC, affecting antioxidant activity, and exerting other effects. Therefore, the mechanism of baicalein with regard to NAFLD prevention and treatment might involve effects on multiple targets and pathways. Our study supports the use of baicalein as a dietary supplement due to its ability to reduce hepatic fat accumulation and to ameliorate NAFLD-related biochemical abnormalities.
Recently, deep eutectic solvents (DESs) have attracted much attention in the extraction and separation field because of their green characteristics, and they are widely used to extract various bioactive substances from plants. In this study, ten choline chloride (ChCl)-based mixtures were selected for extracting flavonoids from Houttuynia cordata. Then, the optimal conditions for the DES-based extraction of Houttuynia cordata flavonoids (HCFs) were determined through one-way experiments and response surface optimization (RSM). The optimal conditions were a 60 min extraction time, an extraction temperature of 40 °C, a water content of 30%, a solid−liquid ratio of 1:22 g·mL−1, a molar ratio of 1:2, and an ultrasound power of 420 W. The antioxidant capacities of HCFs in terms of ABTS radical, DPPH radical, and hydroxyl radical scavenging capacity and nitrite inhibition capacity were determined. DESs can be efficiently recycled after extraction. This study developed an effective and environmentally friendly method for HCF extraction, thereby also supporting the development and utilization of natural products.
Lipid metabolism disorders have become a major global public health issue. Due to the complexity of these diseases, additional research and drugs are needed. Oroxin A, the major component of Oroxylum indicum (L.) Kurz (Bignoniaceae), can improve the lipid profiles of diabetic and insulin-resistant (IR) rats. Because insulin resistance is strongly correlated with lipid metabolism, improving insulin resistance may also constitute an effective strategy for improving lipid metabolism. Thus, additional research on the efficacy and mechanism of oroxin An under non-IR conditions is needed. In this study, we established lipid metabolism disorder model rats by high-fat diet feeding and fatty HepG2 cell lines by treatment with oleic acid and evaluated the therapeutic effect and mechanism of oroxin A in vitro and in vivo through biochemical indicator analysis, pathological staining, immunoblotting, and immunofluorescence staining. Oroxin A improved disordered lipid metabolism under non-IR conditions, improved the plasma and hepatic lipid profiles, and enhanced the lipid-lowering action of atorvastatin. Additionally, oroxin A reduced the total triglyceride (TG) levels by inhibiting sterol regulatory element-binding protein 1 (SREBP1) expression and reducing the expression of acetyl coenzyme A carboxylase (ACC) and fatty acid synthase (FASN) in vivo and in vitro. Oroxin A also reduced the total cholesterol (TC) levels by inhibiting SREBP2 expression and reducing HMGCR expression in vivo and in vitro. In addition, oroxin A bound to low-density lipoprotein receptor (LDLR) and increased AMPK phosphorylation. Our results suggested that oroxin A may modulate the nuclear transcriptional activity of SREBPs by binding to LDLR proteins and increasing AMPK phosphorylation. Oroxin A may thus reduce lipid synthesis and could be used for the treatment and prevention of lipid metabolism disorders.
Hyperuricemia is a metabolic disease characterized by serum uric acid (UA) levels remaining above normal levels for a long period of time, which has become a huge challenge faced by society. The fruits of P. nigrum L. (P. nigrum) as traditional Indian medicine was used to treat various diseases. However, the anti-hyperuricemia effect and mechanism of the ethanol extract of P. nigrum (PE) and its primary component, piperine (PI) still need to be elaborated. In this study, we systematically evaluated the effects of PE and PI on hyperuricemia, as well as their underlying mechanisms in the hyperuricemic mouse and cell models. Our results showed that PE effectively prevented abnormal elevation of UA level, and restored renal function in hyperuricemic mouse model. Transcriptomic and western blot analysis revealed that PE respectively relieved hepatic synthesis of UA and enhanced renal excretion of UA through suppressing the expressions of xanthine dehydrogenase (XDH) and glucose transporter member 9 (GLUT9) in vitro and in vivo. Additionally, PE ameliorated renal inflammation by reducing the expressions of suppressor of cytokine signalling 3 (SOCS3) and TNF-α. Furthermore, the experimental results for PI were consistent with those observed for PE. Mechanistically, the gene overexpression of Janus Kinase 2 (JAK2), luciferase reporter gene and molecular docking results demonstrated that the anti-hyperuricemia effect of PE was associated with the blocking of the JAK2/ signal transducers and activators of transcription 3 (STAT3) signalling transduction, and PI could specifically bound to JAK2. These data suggested that PE could ameliorate hyperuricemia and hyperuricemia-related renal inflammation through suppressing the JAK2-STAT3-XDH/SOCS3/TNF-α signalling pathway, and the beneficial effects of PE presumably were attributed to PI. In summary, our study suggests that PE may be an effective natural product for improving hyperuricemia by restoring the metabolic balance of UA and suppressing renal inflammation.