title: The effects of apigenin on lipopolysaccharide-induced depressive-like behavior in mice.
abstract: Increasing evidence shows that inflammation may contribute to the pathophysiology of depression. Apigenin, one type of natural flavone, has a number of biological actions including anti-inflammatory effects. Although it has potential antidepressant activity in a chronic mild stress model, the mechanisms of antidepressant effect for apigenin remain unclear. Here, we examined the effects of apigenin on lipopolysaccharide (LPS)-induced depressive-like behavior in male mice. A single administration of LPS (0.5mg/kg, i.p.) increased the immobility time in the tail suspension test (TST) and reduced sucrose preference without changing spontaneous locomotor activity in open field test (OFT). Pre-treatment with apigenin (25, 50mg/kg, i.p.) or fluoxetine (positive control drug, 20mg/kg, i.p.) once daily for 7 consecutive days prevented the abnormal behavior induced by LPS. Apigenin or fluoxetine also effectively attenuated LPS-induced production of pro-inflammatory cytokines IL-1β (interleukin-1β) and TNF-α (tumor necrosis factor-α). Moreover, apigenin or fluoxetine significantly suppressed the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression at both the mRNA and protein level via the modulation of nuclear factor-κB (NF-κB) activation in the prefrontal cortex. Additionally, apigenin (50mg/kg, i.p.) or fluoxetine (20mg/kg, i.p.) effectively reversed the depressive-like behavior induced by TNF-α (0.1fg/site, i.c.v.) without altering the locomotor activity. These results demonstrate that apigenin exhibits antidepressant-like effects in LPS treated mice, partially due to its anti-inflammatory properties.
authors: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, PR China.
authors: Ruipeng
authors: R
authors: Li
authors: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, PR China.
authors: Di
authors: D
authors: Zhao
authors: Discipline of Chinese and Western Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210046, PR China.
authors: Rong
authors: R
authors: Qu
authors: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: fuqiang@cpu.edu.cn.
authors: Qiang
authors: Q
authors: Fu
authors: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: spma@cpu.edu.cn.
authors: Shiping
authors: S
authors: Ma
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D003863:Depression / Q000188:drug therapy* / Q000276:immunology / Q000523:psychology; D005518:Food Preferences; D019417:Hindlimb Suspension; D053583:Interleukin-1beta / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D013395:Sucrose / Q000008:administration & dosage; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D000928:Antidepressive Agents; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D016211:Transforming Growth Factor alpha; D013395:Sucrose; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2
keywords: Apigenin; Depression; Inflammation; Lipopolysaccharide; NF-κB