title: The effect of isoliquiritigenin on learning and memory impairments induced by high-fat diet via inhibiting TNF-α/JNK/IRS signaling.
abstract: Isoliquiritigenin (ILG), a chalcone from Glycyrrhiza uralensis, has various biological properties. ILG markedly inhibited inflammation, but the effects on the brain inflammation and insulin resistance induced by high-fat diet (HFD) are still unknown, so our study intended to investigate its effect on cognitive dysfunction induced by HFD and the relevant mechanisms. ICR mice were treated with HFD diet for 8 weeks to induce peripheral insulin resistance prior to being intervened with rosiglitazone, ILG (30, 60 mg/kg). 4 weeks later, Morris Water Maze (MWM) was used to assess the learning and memory, the insulin resistance index was measured, and the brain inflammation cytokines (IL-1β, TNF-α) were assessed. Meanwhile, the p-JNK, p-IRS Ser(307) protein expressions in the hippocampus were also detected using the western blot to explore the corresponding mechanisms. Our results suggested that ILG could significantly alleviate the cognitive impairments in the MWM test and attenuate peripheral insulin resistance. The IL-1β, TNF-α levels declined with the administration of ILG, meanwhile the p-IRS Ser(307) expression decreased with the inhibition of p-JNK. In conclusion, ILG could improve the spatial learning and memory lesions induced by HFD via the inhibition of TNF-α/JNK/IRS pathway.
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, 210009, PR China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, 210009, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, 210009, PR China.
authors.forename: Meiting
authors.initials: M
authors.lastname: Song
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, 210009, PR China. Electronic address: mashiping2014@163.com.
authors.forename: Shiping
authors.initials: S
authors.lastname: Ma
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D047188:Chalcones / Q000494:pharmacology*; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D053583:Interleukin-1beta / Q000378:metabolism; D007859:Learning Disabilities / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D018697:Nootropic Agents / Q000494:pharmacology*; D008517:Phytotherapy; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D047188:Chalcones; D055504:Insulin Receptor Substrate Proteins; D053583:Interleukin-1beta; D018697:Nootropic Agents; D014409:Tumor Necrosis Factor-alpha; C040920:isoliquiritigenin
keywords: High-fat diet; Inflammation; Insulin resistance; Isoliquiritigenin; Learning and memory