Acacetin

About: Acacetin is a research topic. Over the lifetime, 442 publications have been published within this topic receiving 10458 citations. The topic is also known as: 5,7-Dihydroxy-2-(4-methoxyphenyl)-4-benzopyrone & Linarigenin.

Flavonoid-induced morphological modifications of endothelial cells through microtubule stabilization

Abstract: Flavonoids are common components of the human diet and appear to be of interest in cancer prevention or therapy, but their structure-activity relationships (SAR) remain poorly defined. In this study, were compared 24 flavonoids for their cytotoxicity on cancer cells (B16 and Lewis lung) and their morphological effect on endothelial cells (EC) that could predict antiangiogenic activity. Ten flavonoids presented inhibitory concentrations for 50% of cancer cells (IC50, 48 h) below 50 microM: rhamnetin, 3',4'-dihydroxyflavone, luteolin, 3-hydroxyflavone, acacetin, apigenin, quercetin, baicalein, fisetin, and galangin. Important SAR for cytotoxicity included the C2-C3 double bond and 3',4'-dihydroxylation. Concerning the morphological effects on EC, only fisetin, quercetin, kaempferol, apigenin, and morin could induce the formation of cell extensions and filopodias at noncytotoxic concentrations. The SAR for morphologic activity differed from cytotoxicity and involved hydroxylation at C-7 and C-4'. Fisetin, the most active agent, presented cell morphology that was distinct compared to colchicine, combretastatin A-4, docetaxel, and cytochalasin D. Resistance to cold depolymerization and a 2.4-fold increase in acetylated alpha-tubulin demonstrated that fisetin was a microtubule stabilizer. In conclusion, this study disclosed several SAR that could guide the choice or the rational synthesis of improved flavonoids for cancer prevention or therapy.

Acacetin Protects Dopaminergic Cells against 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Neuroinflammation in Vitro and in Vivo

Abstract: Acacetin (5,7-dihydroxy-4′-methoxyflavone), a constituent of flavone naturally present in plants, has anti-cancer and anti-inflammatory activities. Neuroinflammation is thought to be one of the major pathological mechanisms responsible for Parkinson’s disease (PD), and has been a primary target in the development of treatment for PD. In the present study, we evaluated the neuroprotective effect of acacetin in PD induced by 1-methyl-4-phenylpyridine (MPP+)/or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and examined the related pathways in vitro and in vivo. In primary mesencephalic culture, acacetin protected dopaminergic (DA) cells and inhibited production of inflammatory factors such as nitric oxide, prostaglandin E2, and tumor necrosis factor-α against MPP+-induced toxicity in a dose-dependent manner. Then, we confirmed the effect of acacetin (10 mg/kg/d for 3 d, per os (p.o.)) in a mouse model of PD induced by MPTP (30 mg/kg/d for 5 d, intraperitoneally (i.p.)). In the behavioral test (pole test), the acacetin-treated mice showed decreased time of turning and locomotor activity, which were longer in MPTP-only treated mice. In addition, the acacetin-treated group inhibited degeneration of DA neurons and depletion of dopamine level induced by MPTP toxicity in the substantia nigra and striatum of the brain. Moreover, the acacetin-treated group inhibited microglia activation, accompanied by production of inducible nitric oxide synthases and cyclooxygenase-2. These results suggest that acacetin can protect DA neurons against the neurotoxicity involved in PD via its anti-inflammatory action.

Acacetin inhibits the invasion and migration of human non-small cell lung cancer A549 cells by suppressing the p38α MAPK signaling pathway

Abstract: Lung cancer is one of the most common malignancies in the world and its metastasis is the major cause of death in cancer patients. Acacetin (5,7-dihydroxy-4′-methoxyflavone), a flavonoid compound, has anti-peroxidative and anti-inflammatory effects. The effect of acacetin on invasion and migration in human NSCLC A549 cells was investigated. First, the result demonstrated acacetin could exhibit an inhibitory effect on the abilities of the adhesion, morphology/actin cytoskeleton arrangement, invasion, and migration by cell–matrix adhesion assay, immunofluorescence assay, Boyden chamber assay, and wound-healing assay. Molecular data showed that the effect of acacetin in A549 cells might be mediated via sustained inactivation of the phosphorylation of mixed-lineage protein kinase 3 (MLK3), mitogen-activated protein kinase kinases 3/6 (MKK3/6), and p38α MAPK signal involved in the downregulation of the expressions of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and urokinase-type plasminogen activator (u-PA). Next, acacetin significantly decreased in the phosphorylation and degradation of inhibitor of kappaBα (IκBα), and the nuclear levels of nuclear factor kappa B (NF-κB), c-Fos, and c-Jun. Also, the treatment with acacetin to A549 cells also leads to a concentration-dependent inhibition on the binding abilities of NF-κB and activator protein-1 (AP-1). Furthermore, the treatment of specific inhibitor for p38 MAPK (SB203580) to A549 cells could cause reduced activities of MMP-2/9 and u-PA. In addition, acacetin significantly decreased the levels of phospho-p38α MAPK, MMP-2/9, and u-PA in p38α-cDNA-transfected cells concomitantly with a marked reduction on cell invasion and migration. Our results revealed the anti-migration and anti-invasion effects of acacetin, which may act as a promising therapeutic agent for the treatment of lung cancer.

Acacetin attenuates neuroinflammation via regulation the response to LPS stimuli in vitro and in vivo.

Abstract: Under normal conditions in the brain, microglia play roles in homeostasis regulation and defense against injury. However, over-activated microglia secrete proinflammatory and cytotoxic factors that can induce progressive brain disorders, including Alzheimer's disease, Parkinson's disease and ischemia. Therefore, regulation of microglial activation contributes to the suppression of neuronal diseases via neuroinflammatory regulation. In this study, we investigated the effects of acacetin (5,7-dihydroxy-4'-methoxyflavone), which is derived from Robinia pseudoacacia, on neuroinflammation in lipopolysaccharide (LPS)-stimulated BV-2 cells and in animal models of neuroinflammation and ischemia. Acacetin significantly inhibited the release of nitric oxide (NO) and prostaglandin E(2) and the expression of inducible NO synthase and cyclooxygenase-2 in LPS-stimulated BV-2 cells. The compound also reduced proinflammatory cytokines, tumor necrosis factor-α and interleukin-1β, and inhibited the activation of nuclear factor-κB and p38 mitogen-activated protein kinase. In an LPS-induced neuroinflammation mouse model, acacetin significantly suppressed microglial activation. Moreover, acacetin reduced neuronal cell death in an animal model of ischemia. These results suggest that acacetin may act as a potential therapeutic agent for brain diseases involving neuroinflammation.