cinidon-ethyl and Non-alcoholic-Fatty-Liver-Disease

Erhuangquzhi granules (EQG) have been clinically proven to be effective in nonalcoholic steatohepatitis (NASH) treatment. However, the active components and molecular mechanisms remain unknown. This study aimed to screen active components targeting tumor necrosis factor α (TNF-α) in EQG for the treatment of NASH by a surface plasmon resonance (SPR) biosensor-based active ingredient recognition system (SPR-AIRS). The amine-coupling method was used to immobilize recombinant TNF-α protein on an SPR chip, the specificity of the TNF-α-immobilized chip was validated, and nine medicinal herbs in EQG were prescreened. Nuciferine (NF), lirinidine (ID), and O-nornuciferine (NNF) from lotus leaves were found and identified as TNF-α ligands by UPLC‒MS/MS, and the affinity constants of NF, ID, and NNF to TNF-α were determined by SPR experiments (Kd = 61.19, 31.02, and 20.71 µM, respectively). NF, ID, and NNF inhibited TNF-α-induced apoptosis in L929 cells, the levels of secreted IL-6 and IL-1β were reduced, and the phosphorylation of IKKβ and IκB was inhibited in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. In conclusion, a class of new active small-molecule TNF-α inhibitors was discovered, which also provides a valuable reference for the material basis and mechanism of EQG action in NASH treatment.

Topics: Biosensing Techniques; Chromatography, Liquid; Humans; Immunologic Factors; Lotus; Non-alcoholic Fatty Liver Disease; Plant Leaves; Tandem Mass Spectrometry; Tumor Necrosis Factor-alpha

Lotus leaf (LL) is one of the traditional Chinese herbs which can be used for both pharmaceutical and food application, and it posses lipid regulating efficacy. To observe the effect of LL on experimental nonalcoholic fatty liver disease (NAFLD) and its potential mechanism, a NAFLD model was established by feeding SD rat with high-fat and high-glucose diet. LL was administrated to rats in experiment group at the same time. AST,ALT,Cr,BUN,GLU levels in serum were determined by automatic biochemical analyser and TNF-α,IL-6,INS,ADPN,LEP and liver NF-κB,TGF-β1 levels were determined by ELISA according to the specification of the kits. HE staining was applied for histopathological examination and RT-PCR,Western blot was applied for AdipoR2 mRNA and protein expression．Results have shown that LL could significantly decrease ALT,AST,IL-6 level in serum and NF-κB,TGF-β1 level in liver,promote adiponectin content in serum and AdipoR2 protein expression in liver and could alleviate hepatocyte lipid degeneration. These results indicating that LL has protective effect for NAFLD induced by high-fat and high-glucose diet via promoting AdipoR2 expression, improving insulin resistance and inhibiting inflammatory reaction.

Topics: Animals; Diet, High-Fat; Glucose; Inflammation; Insulin Resistance; Liver; Lotus; Non-alcoholic Fatty Liver Disease; Plant Leaves; Rats; Rats, Sprague-Dawley; Receptors, Adiponectin

This study investigated the protective properties of lotus seedpod oligomeric procyanidins (LSOPC) against nonalcoholic fatty liver disease (NAFLD) and its underlying mechanism. Sprague-Dawley (SD) male rats were fed a basic diet, a high-fat diet (HFD), or HFD plus 0.2 or 0.5% (w/w) LSOPC for 12 weeks. Administration of LSOPC markedly reduced serum and hepatic biochemical parameters and protein expression of advanced glycation endproducts (AGEs). Additionally, 0.5% (w/w) LSOPC treatment remarkably reversed the increasing tendency of receptor of advanced glycation endproduct (RAGE) to normal level. Furthermore, dietary LSOPC significantly decreased the protein levels of mitogen-activated protein kinases (MAPK) and nuclear factor-kappa B (NF-κB) and down-regulated genes involved in pro-inflammatory cytokines and adhesion molecules. Taken together, these findings demonstrate that LSOPC may protect obese rats with long-term HFD-induced NAFLD against RAGE-MAPK-NF-κB signaling suppression.

Topics: Animals; Biflavonoids; Catechin; Diet, High-Fat; Glycation End Products, Advanced; Humans; Lotus; Male; Mitogen-Activated Protein Kinases; NF-kappa B; Non-alcoholic Fatty Liver Disease; Plant Extracts; Proanthocyanidins; Rats; Rats, Sprague-Dawley; Receptor for Advanced Glycation End Products; Seeds; Signal Transduction