alisol-b-monoacetate and Disease-Models--Animal

The ligand-activated nuclear receptor, farnesoid X receptor (FXR), plays a pivotal role in regulating renal function. Activation of FXR by its specific agonists exerts renoprotective action in animals with acute kidney injury (AKI). In the present study, we aimed to identify naturally occurring agonists of FXR with potential as therapeutic agents in renal ischemia-reperfusion injury. In vitro and in vivo FXR activation was determined by a dual-luciferase assay, docking analysis, site-directed mutagenesis, and whole kidney transcriptome analysis. Wild-type (WT) and FXR knockout (

Topics: Acute Kidney Injury; Animals; Apoptosis; Cholestenones; Disease Models, Animal; Drugs, Chinese Herbal; HEK293 Cells; Hep G2 Cells; Humans; Inflammation Mediators; Kidney; Ligands; Male; Mice, Inbred C57BL; Mice, Knockout; Oxidative Stress; Receptors, Cytoplasmic and Nuclear; Reperfusion Injury; Signal Transduction

Hunting for natural compounds that can modulate the structure of the intestinal flora is a new hotspot for colitis-associated cancer (CAC) prevention or treatment. Alisol B 23-acetate (AB23A) is a natural tetracyclic triterpenoid found in

Topics: Animals; Azoxymethane; China; Cholestenones; Colitis; Colitis-Associated Neoplasms; Dextran Sulfate; Disease Models, Animal; Gastrointestinal Microbiome; Male; Mice; Mice, Inbred C57BL; Sulfates

Atherosclerosis (AS) is characterized by dyslipidemia and chronic inflammation. In the high-fat environment, the lipid metabolism of dendritic cells (DCs) is abnormal, which leads to abnormal immune function, promotes the occurrence of immune inflammatory reactions, and promotes the development of AS. Alisol B 23-acetate (23B) is a triterpenoid in the rhizomes of Alisma, which is a traditional Chinese medicine. Here, we identified cholesterol metabolism-related targets of 23B through a virtual screen, and further transcriptome analysis revealed that 23B can change antigen presentation and cholesterol metabolism pathways in cholesterol-loaded DCs. In vitro experiments confirmed that 23B promoted cholesterol efflux from ApoE

Topics: Animals; Aorta; Apolipoproteins E; Atherosclerosis; Cholestenones; Cholesterol; Cytokines; Dendritic Cells; Disease Models, Animal; Dyslipidemias; Humans; Hypercholesterolemia; Inflammation; Lipid Metabolism; Male; Mice; Signal Transduction; T-Lymphocytes, Regulatory; T-Lymphocytopenia, Idiopathic CD4-Positive

Intrahepatic cholestasis is a clinical syndrome with systemic and intrahepatic accumulation of excessive toxic bile acids that ultimately cause hepatobiliary injury. Appropriate regulation of bile acids in hepatocytes is critically important for protection against liver injury. In the present study, we characterized the protective effect of alisol B 23-acetate (AB23A), a natural triterpenoid, on alpha-naphthylisothiocyanate (ANIT)-induced liver injury and intrahepatic cholestasis in mice and further elucidated the mechanisms in vivo and in vitro. AB23A treatment dose-dependently protected against liver injury induced by ANIT through reducing hepatic uptake and increasing efflux of bile acid via down-regulation of hepatic uptake transporters (Ntcp) and up-regulation of efflux transporter (Bsep, Mrp2 and Mdr2) expression. Furthermore, AB23A reduced bile acid synthesis through repressing Cyp7a1 and Cyp8b1, increased bile acid conjugation through inducing Bal, Baat and bile acid metabolism through an induction in gene expression of Sult2a1. We further demonstrate the involvement of farnesoid X receptor (FXR) in the hepatoprotective effect of AB23A. The changes in transporters and enzymes, as well as ameliorative liver histology in AB23A-treated mice were abrogated by FXR antagonist guggulsterone in vivo. In vitro evidences also directly demonstrated the effect of AB23A on FXR activation in a dose-dependent manner using luciferase reporter assay in HepG2 cells. In conclusion, AB23A produces protective effect against ANIT-induced hepatotoxity and cholestasis, due to FXR-mediated regulation of transporters and enzymes.

Topics: 1-Naphthylisothiocyanate; Animals; Bile Acids and Salts; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Cholestenones; Cytoprotection; Disease Models, Animal; Dose-Response Relationship, Drug; Gene Expression Regulation, Enzymologic; Hep G2 Cells; Homeostasis; Humans; Liver; Male; Membrane Transport Proteins; Mice, Inbred C57BL; Protective Agents; Receptors, Cytoplasmic and Nuclear; Signal Transduction; Time Factors; Transfection

To investigate protective effects of alisol B 23-acetate (AB23A) against hepatotoxity and cholestasis induced by 17α-ethinylestradiol (EE) in association with farnesoid X receptor (FXR) activation in vivo and in vitro.. The cholestatic liver injury model was established by subcutaneous injections of EE in C57BL/6 mice. Serum biomarkers, bile flow assay and H&E staining were used to identify the amelioration of cholestasis after AB23A treatment. Mice primary hepatocytes culture, gene silencing experiment, real-time PCR and Western blot assay were used to elucidate the mechanisms underlying AB23A hepatoprotection.. AB23A treatment protected against liver injury induced by EE through increasing hepatic efflux and reducing uptake of bile acid via an induction in efflux transporters (Bsep and Mrp2) and an inhibition in hepatic uptake transporter (Ntcp) expression. AB23A also reduced bile acid synthesis through repressing Cyp7a1 and Cyp8b1, and increased bile acid metabolism through an induction in gene expression of Sult2a1. We further demonstrated that the changes in transporters and enzymes, as well as ameliorative liver histology in AB23A-treated mice were abrogated by FXR antagonist guggulsterone in vivo and were abrogated after FXR was silenced in vitro.. AB23A produces protective effects against EE-induced cholestasis, due to FXR-mediated gene regulation.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 11; ATP-Binding Cassette Transporters; Chemical and Drug Induced Liver Injury; Cholestasis; Cholestenones; Cholesterol 7-alpha-Hydroxylase; Disease Models, Animal; Ethinyl Estradiol; Hepatocytes; Liver Function Tests; Male; Membrane Transport Proteins; Mice, Inbred C57BL; Multidrug Resistance-Associated Protein 2; Multidrug Resistance-Associated Proteins; Organic Anion Transporters, Sodium-Dependent; Primary Cell Culture; Receptors, Cytoplasmic and Nuclear; Steroid 12-alpha-Hydroxylase; Symporters

The 70% ethanol extract of the rhizome of Alisma orientale (Alismatis rhizome) (AOE) was prepared and found to significantly inhibit 5-lipoxygenase (5-LOX)-catalyzed leukotriene (LT) production from rat basophilic leukemia (RBL)-1 cells and β-hexosaminidase release by antigen-stimulated RBL-2H3 cells. It also attenuated delayed-type hypersensitivity (DTH) reaction in mice. Among the three major triterpene constituents isolated (i.e., alisol B, alisol B 23-acetate, alisol C 23-acetate) as active principles, alisol B and its 23-acetate strongly and significantly inhibited LT production and β-hexosaminidase release between 1-10 µM. On the other hand, all these alisol derivatives significantly and strongly inhibited DTH response after oral administration. In addition, AOE (200 mg/kg/d) was for the first time found to considerably alleviate hapten-induced dermatitis symptoms in NC/Nga mice, an animal model of atopic dermatitis. These results indicate that alisol derivatives possess inhibitory activities on immediate-type as well as delayed-type hypersensitivity reactions and may contribute to the anti-allergic action of AOE.

Topics: Alisma; Animals; Antigens; Arachidonate 5-Lipoxygenase; beta-N-Acetylhexosaminidases; Cell Line, Tumor; Cholestenones; Dermatitis, Atopic; Disease Models, Animal; Haptens; Hypersensitivity, Delayed; Leukemia; Leukotrienes; Male; Mice; Mice, Inbred ICR; Mice, Inbred Strains; Phytotherapy; Plant Extracts; Rhizome