Here's a more recent article about luteolin and cognition:
Front Neurosci. 2015 Jul 3;9:225. doi: 10.3389/fnins.2015.00225. eCollection 2015.
Brain "fog," inflammation and obesity: key aspects of neuropsychiatric disorders improved by luteolin.
Theoharides TC1, Stewart JM2, Hatziagelaki E3, Kolaitis G4.
1 Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine Boston, MA, USA ; Departments of Internal Medicine, Tufts University School of Medicine and Tufts Medical Center Boston, MA, USA ; Psychiatry, Tufts University School of Medicine and Tufts Medical Center Boston, MA, USA ; Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine Boston, MA, USA.
2 Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine Boston, MA, USA.
3 Second Department of Internal Medicine, Attikon General Hospital, Athens Medical School Athens, Greece.
4 Department of Child Psychiatry, University of Athens Medical School, Aghia Sophia Children's Hospital Athens, Greece.
Brain "fog" is a constellation of symptoms that include reduced cognition, inability to concentrate and multitask, as well as loss of short and long term memory. Brain "fog" characterizes patients with autism spectrum disorders (ASDs), celiac disease, chronic fatigue syndrome, fibromyalgia, mastocytosis, and postural tachycardia syndrome (POTS), as well as "minimal cognitive impairment," an early clinical presentation of Alzheimer's disease (AD), and other neuropsychiatric disorders. Brain "fog" may be due to inflammatory molecules, including adipocytokines and histamine released from mast cells (MCs) further stimulating microglia activation, and causing focal brain inflammation. Recent reviews have described the potential use of natural flavonoids for the treatment of neuropsychiatric and neurodegenerative diseases. The flavone luteolin has numerous useful actions that include: anti-oxidant, anti-inflammatory, microglia inhibition, neuroprotection, and memory increase. A liposomal luteolin formulation in olive fruit extract improved attention in children with ASDs and brain "fog" in mastocytosis patients. Methylated luteolin analogs with increased activity and better bioavailability could be developed into effective treatments for neuropsychiatric disorders and brain "fog."
brain; cognition; cytokines; fog; histamine; inflammation; luteolin; mast cells
PMID: 26190965 [PubMed] PMCID: PMC4490655 Free PMC Article
The full article is available here:
Snippets from the full article:
Flavonoids (Figure (Figure2)2) are naturally occurring compounds mostly found in green plants and seeds (Middleton et al., 2000). Unfortunately, our modern life diet contains progressively fewer flavonoids and under these conditions, the average person cannot consume enough to make a positive impact on health. Moreover, less than 10% of orally ingested flavonoids are absorbed (Passamonti et al., 2009; Thilakarathna and Rupasinghe, 2013) and are extensively metabolized to inactive ingredients in the liver (Chen et al., 2014).
Luteolin (5,7-3′5′-tetrahydroxyflavone) has potent antioxidant, anti-inflammatory (Middleton et al., 2000) and MC inhibitory activities (Kimata et al., 2000; Kempuraj et al., 2005; Asadi et al., 2010) and also inhibits auto-immune T cell activation (Verbeek et al., 2004; Kempuraj et al., 2008) (Table (Table2).2). Luteolin also inhibits microglial IL-6 release (Jang et al., 2008), microglial activation and proliferation (Chen et al., 2008; Dirscherl et al., 2010; Kao et al., 2011), as well as microglia-induced neuron apoptosis (Zhu et al., 2011).
Flavonoids can also inhibit acetylcholinesterase (Tsai et al., 2007; Boudouda et al., 2015), which will increase acetylcholine and improve memory (Table (Table1).1). It is of interest that luteolin further inhibits release of the excitatory neurotransmitter glutamate (Lin et al., 2011), while it activates receptors for the inhibitory neurotransmitter γ-amino butyric acid (GABA) independent of GABA, suggesting it may also have a calming effect (Hanrahan et al., 2011). In fact, benzodiazepines that act by activating GABA receptors were shown to bind to MCs (Miller et al., 1988).
Flavonoids are generally considered safe (Kawanishi et al., 2005; Harwood et al., 2007; Seelinger et al., 2008; Corcoran et al., 2012; Theoharides et al., 2014). Unfortunately, some of the cheaper sources of flavonoids found in dietary supplements are from peanut shells and fava beans and may lead to anaphylactic reactions or hemolytic anemia to allergic and G6PD-deficient individuals, respectively. Flavonoids are extensively metabolized (Chen et al., 2014) primarily through glucoronidation, methylation, and sulphation (Hollman et al., 1995; Hollman and Katan, 1997). Therefore, flavonoids must be used with caution when administered with other natural polyphenolic molecules (e.g., curcumin, resveratrol) or drugs metabolized by the liver as they may affect the blood levels of themselves or of other drugs (Theoharides and Asadi, 2012). Tetramethoxyluteolin is already methylated and less likely to affect liver metabolism, is more stable (Walle, 2007), and has better bioavailability (Wei et al., 2014). Intranasal tetramethoxyluteolin preparations would offer the additional advantage of delivering the flavonoid directly to the brain through the cribriform plexus as was shown for some other compounds (Zhuang et al., 2011).