Anti-inflammatory effects of luteolin: A review of in vitro, in vivo, and in silico studies. (28th October 2018)

• Record Type: Journal Article
• Authors: Aziz, Nur; Kim, Mi-Yeon; Cho, Jae Youl
• Is Part Of: Journal of ethnopharmacology. Volume 225(2018)
• Page Start: 342
• Page End: 358
• Publication Date: 2018-10-28
• Subjects: NF-κB nuclear factor kappa B -- AP-1 activator protein -- STAT3 signal transducer and activator of transcription 3 -- NK cells natural killer cells -- TNF-α tumor necrosis factor-α -- NO nitric oxide -- iNOS inducible nitric oxygen synthase -- ROS reactive oxygen species -- AKT protein kinase B -- MAPK mitogen-activated protein kinase -- ATP adenosine triphosphate -- Syk spleen tyrosine kinase -- Src proto-oncogene tyrosine-protein kinase -- IL-1β interleukin-1β -- CCL2 chemokine (C-C motif) ligand 2 -- CXCL2 chemokine (C-X-C motif) ligand 2 -- LDH lactate dehydrogenase -- LPS lipopolysaccharides -- SOD superoxide dismutase -- GSH glutathione -- IFN-β interferon-β -- HMGB1 high mobility group B1 -- PGE2 prostaglandin E2 -- COX-2 cyclooxygenase enzyme-2 -- BMMCs bone marrow-derived mast cells -- LTC4 leukotriene C4 -- MIP macrophage inflammatory protein -- JAK Janus tyrosine kinase -- PI3K phosphatidylinositide 3-kinases -- ERK1/2 extracellular signal-regulated protein kinases 1 and 2 -- IκB inhibitor of kappa B -- IKK IκB kinase -- PRV pseudorabies virus -- PMA phorbol 12-myristate 13-acetate -- HUVECs human umbilical vein endothelial cells -- HAT histone acetyltransferase -- HDAC histone deacetylase -- IP-10 interferon gamma-induced protein 10 -- TLR toll like receptor -- GFP green fluorescent protein -- IRF interferon regulatory transcription factor -- MyD88 myeloid differentiation primary response 88 -- TRIF TIR-domain-containing adapter-inducing interferon-β -- TBK1 TANK-binding kinase 1 -- JNK c-Jun N-terminal kinase -- NFAT nuclear factor of activated T-cells -- PKC protein kinase C -- HSP90 heat shock protein 90 -- CREB cAMP response element-binding protein -- SIRT1 NAD-dependent deacetylase sirtuin-1 -- SOCS suppressor of cytokine signaling -- MCP-1 monocyte chemoattractant protein-1 -- MMP matrix metalloproteinases -- HO-1 heme oxygenase-1 -- VCAM-1 vascular cell adhesion protein 1 -- ICAM-1 intercellular adhesion molecule 1 -- TIMP tissue inhibitors of metalloproteinases; Luteolin (PubChem CID: 5280445) -- Luteolin-5-O-glucoside (PubChem CID: 44258061) -- Luteolin-7-O-glucoside (PubChem CID: 5280637) -- Luteolin-8-C-glucoside (PubChem CID: 5281675) -- Luteolin-6-C-glucoside (PubChem CID: 49852298); Luteolin -- Flavonoid -- Inflammatory diseases -- Inflammatory signaling; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2018.05.019
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Luteolin (3′, 4′, 5, 7-tetrahydroxyflavone) has been identified as commonly present in plants. Plants with a high luteolin content have been used ethnopharmacologically to treat inflammation-related symptoms. Both isolated luteolin and extracts from luteolin-rich plants have been studied using various models and exhibited anti-inflammatory activity. Aim of the review: This paper uses recent research findings with a broad range of study models to describe the anti-inflammatory activity of luteolin, particularly its mechanisms at the molecular level; provide guidance for future research; and evaluate the feasibility of developing luteolin into an anti-inflammatory drug. Materials and methods: We summarize reports about the anti-inflammatory activity of luteolin published since 2009, which we found in MEDLINE/PubMed, Scopus, Web of Knowledge, and Google Scholar. To acquire broad information, we extended our search to online FDA documents. Results: Luteolin is a flavonoid commonly found in medicinal plants and has strong anti-inflammatory activity in vitro and in vivo . Some of its derivatives, such as luteolin-7-O-glucoside, have also shown anti-inflammatory activity. The action mechanism of luteolin varies, but Src in the nuclear factor (NF)-κB pathway, MAPK in the activator protein (AP)− 1 pathway, and SOCS3 in the signal transducer and activator of transcription 3( STAT3) pathway are its major target transcription factors. A clinical trial with a formulation containing luteolin showed excellent therapeutic effect against inflammation-associated diseases. Conclusion: In silico, in vitro, in vivo, and clinical studies strongly suggest that the major pharmacological mechanism of luteolin is its anti-inflammatory activity, which derives from its regulation of transcription factors such as STAT3, NF-κB, and AP-1. Much work remains to ensure the safety, quality, and efficacy of luteolin before it can be used to treat inflammation-related diseases in humans. Graphical abstract: