ABSTRACT
OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) occurs when excess fat storage in the liver and it is strongly linked with metabolic syndrome including obesity, insulin resistance, dyslipidemia and hypertension. Curcumin5-8 (CUR5-8) is a synthetic derivative of naturally active curcumin (CUR) that has anti-oxidative and anti-inflammatory properties. In the present study, we investigated the effects of CUR5-8, a novel CUR analog, on hepatic steatosis in mice with high-fat diet (HFD)-induced obesity. METHODS: Based on their diets for 13â¯weeks, the mice were categorized into the following six groups: regular diet (RD, nâ¯=â¯10), RD with CUR (RDâ¯+â¯CUR, 100â¯mg/kg/day, nâ¯=â¯10), RD with CUR5-8 (RDâ¯+â¯CUR5-8, 100â¯mg/kg/day, nâ¯=â¯10), high-fat diet-induced obese mice (HFD, nâ¯=â¯10), HFD with CUR (HFDâ¯+â¯CUR, 100â¯mg/kg/day, nâ¯=â¯10), and HFD with CUR5-8 (HFDâ¯+â¯CUR5-8, 100â¯mg/kg/day, nâ¯=â¯10) for 13â¯weeks. Hematoxylin and eosin (H&E) staining of the sections revealed hepatic steatosis. RESULTS: CUR5-8 administration prevented increase in body and liver weights in mice with HFD-induced obesity. Compared to the HFD group, insulin resistance was significantly improved in the HFDâ¯+â¯CUR5-8 group. Serum alanine aminotransferase level, which is an indicator of liver damage, was also decreased after CUR5-8 administration. H&E staining revealed that CUR5-8 treatment decreased hepatic steatosis in mice with HFD-induced obesity. Interestingly, CUR5-8, and not CUR, decreased the elevated liver triglyceride level induced by the HFD. CONCLUSIONS: These findings suggest that CUR5-8 ameliorates insulin resistance and hepatic steatosis in mice with HFD-induced obesity.
Subject(s)
Curcumin , Diet, High-Fat , Non-alcoholic Fatty Liver Disease/drug therapy , Obesity/drug therapy , Animals , Autophagy/drug effects , Cells, Cultured , Curcumin/analogs & derivatives , Curcumin/pharmacology , Cytoprotection/drug effects , Lipid Metabolism/drug effects , Liver/drug effects , Liver/metabolism , Liver/pathology , Male , Mice , Mice, Inbred C57BL , Mice, Obese , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/pathology , Obesity/etiology , Weight Gain/drug effectsABSTRACT
A novel curcumin mimic library (14a-14h and 15a-15h) possessing variously substituted benzimidazole groups was synthesized through the aldol reaction of (E)-4-(4-hydroxy-3-methoxyphenyl)but-3-en-2-one (7) or (E)-4-(3-hydroxy-4-methoxyphenyl)but-3-en-2-one (13) with diversely substituted benzimidazolyl-2-carbaldehyde (12a-12h). The MTT assay of the cancer cells MCF-7, SH-SY5Y, HEP-G2, and H460 showed that compound 14c with IC(50) of 1.0 and 1.9µM has a strong inhibitory effect on the growth of SH-SY5Y and Hep-G2 cells, respectively, and that compound 15h with IC(50) of 1.9µM has a strong inhibitory effect on the growth of MCF-7 cancer cells.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Benzimidazoles/chemistry , Benzimidazoles/pharmacology , Curcumin/chemistry , Curcumin/pharmacology , Small Molecule Libraries/pharmacology , Antineoplastic Agents/chemistry , Benzimidazoles/chemical synthesis , Cell Line, Tumor , Cell Proliferation/drug effects , Curcumin/chemical synthesis , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Molecular Mimicry , Molecular Structure , Small Molecule Libraries/chemical synthesis , Small Molecule Libraries/chemistry , Structure-Activity RelationshipABSTRACT
In order to discover novel small vasodilatory molecules for potential use in the treatment of vascular disease, we tested the vasodilatation effect of two types of synthetic curcumin mimics, amide type (3) and sulfonyl amide type (4), upon the basilar artery of rabbits. In general, the sulfonyl amide type mimic (4) is more potent than the amide type (3). Curcumin (1) and compounds 12 and 20 effectively dilated the basilar artery of white rabbits.
Subject(s)
Basilar Artery/physiology , Curcumin/chemical synthesis , Molecular Mimicry , Sulfinic Acids/chemical synthesis , Vasodilation/physiology , Animals , Basilar Artery/drug effects , Curcumin/pharmacology , Dose-Response Relationship, Drug , In Vitro Techniques , Male , Molecular Mimicry/physiology , Rabbits , Sulfinic Acids/pharmacology , Vasodilation/drug effects , Vasodilator Agents/chemical synthesis , Vasodilator Agents/pharmacologyABSTRACT
In order to discover novel multidrug resistance (MDR) reversal agents for efficient cancer chemotherapy, the unsymmetrical curcumin mimics with various amide moieties (6-19) were synthesized and evaluated their MDR reversal activities in MDR cell line KBV20C. Among the tested compounds, 13, 16, and 17 showed potent MDR reversal activities by inhibiting drug efflux function of P-glycoprotein in KB20C cells, and almost recovered the cytotoxicity of vincristine and paclitaxel against KBV20C cell to the degree of potency against drug sensitive KB cells.
Subject(s)
Curcumin/analogs & derivatives , Curcumin/pharmacology , Drug Resistance, Multiple/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Cross-Linking Reagents/chemistry , Curcumin/chemical synthesis , Curcumin/chemistry , Drug Resistance, Neoplasm/drug effects , Humans , Molecular Structure , StereoisomerismABSTRACT
Novel curcumin mimics with asymmetrical units phenyl group with alkyl amide, chloro-substituted benzamide, or heteroaromatic amide moieties were synthesized and their anti-angiogenic activity was evaluated with the proliferation and tube formation inhibitory activity on the human umbilical vein endothelial cells. Compounds 5, 14, 17, and 18 showed potent growth inhibitory activity and tube formation inhibitory activity.
