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Biomedicine & Pharmacotherapy =... Apr 2019Many food-derived phytochemicals and their derivatives represent a cornucopia of new anti-cancer compounds. Luteolin (3,4,5,7-tetrahydroxy flavone) is a flavonoid found... (Review)
Review
Many food-derived phytochemicals and their derivatives represent a cornucopia of new anti-cancer compounds. Luteolin (3,4,5,7-tetrahydroxy flavone) is a flavonoid found in different plants such as vegetables, medicinal herbs, and fruits. It acts as an anticancer agent against various types of human malignancies such as lung, breast, glioblastoma, prostate, colon, and pancreatic cancers. It also blocks cancer development in vitro and in vivo by inhibition of proliferation of tumor cells, protection from carcinogenic stimuli, and activation of cell cycle arrest, and by inducing apoptosis through different signaling pathways. Luteolin can additionally reverse epithelial-mesenchymal transition (EMT) through a mechanism that involves cytoskeleton shrinkage, induction of the epithelial biomarker E-cadherin expression, and by down-regulation of the mesenchymal biomarkers N-cadherin, snail, and vimentin. Furthermore, luteolin increases levels of intracellular reactive oxygen species (ROS) by activation of lethal endoplasmic reticulum stress response and mitochondrial dysfunction in glioblastoma cells, and by activation of ER stress-associated proteins expressions, including phosphorylation of eIF2α, PERK, CHOP, ATF4, and cleaved-caspase 12. Accordingly, the present review article summarizes the progress of recent research on luteolin against several human cancers.
Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Flavonoids; Humans; Luteolin; Neoplasms; Signal Transduction
PubMed: 30798142
DOI: 10.1016/j.biopha.2019.108612 -
Current Cancer Drug Targets Nov 2008Luteolin, 3',4',5,7-tetrahydroxyflavone, is a common flavonoid that exists in many types of plants including fruits, vegetables, and medicinal herbs. Plants rich in... (Review)
Review
Luteolin, 3',4',5,7-tetrahydroxyflavone, is a common flavonoid that exists in many types of plants including fruits, vegetables, and medicinal herbs. Plants rich in luteolin have been used in Chinese traditional medicine for treating various diseases such as hypertension, inflammatory disorders, and cancer. Having multiple biological effects such as anti-inflammation, anti-allergy and anticancer, luteolin functions as either an antioxidant or a pro-oxidant biochemically. The biological effects of luteolin could be functionally related to each other. For instance, the anti-inflammatory activity may be linked to its anticancer property. Luteolin's anticancer property is associated with the induction of apoptosis, and inhibition of cell proliferation, metastasis and angiogenesis. Furthermore, luteolin sensitizes cancer cells to therapeutic-induced cytotoxicity through suppressing cell survival pathways such as phosphatidylinositol 3'-kinase (PI3K)/Akt, nuclear factor kappa B (NF-kappaB), and X-linked inhibitor of apoptosis protein (XIAP), and stimulating apoptosis pathways including those that induce the tumor suppressor p53. These observations suggest that luteolin could be an anticancer agent for various cancers. Furthermore, recent epidemiological studies have attributed a cancer prevention property to luteolin. In this review, we summarize the progress of recent research on luteolin, with a particular focus on its anticancer role and molecular mechanisms underlying this property of luteolin.
Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Flavonoids; Humans; Luteolin; Neoplasms; Signal Transduction
PubMed: 18991571
DOI: 10.2174/156800908786241050 -
Life Sciences Mar 2021Ulcerative colitis (UC) is a chronic inflammatory bowel disease related to intestinal dysbiosis. Luteolin has been reported to reduce inflammation. However, it remains...
Ulcerative colitis (UC) is a chronic inflammatory bowel disease related to intestinal dysbiosis. Luteolin has been reported to reduce inflammation. However, it remains unclear whether luteolin ameliorates UC and regulates gut microbiota. In this study, we investigated the effects of luteolin on colonic structure and inflammation of dextran sulfate sodium (DSS)-induced rats using hematoxylin-eosin staining, immunohistochemistry and enzyme-linked immunosorbent assay and evaluated the effects of luteolin on gut microbiota using 16S rDNA sequencing. We found that luteolin treatment significantly reduced colonic damage, and inhibited colonic inflammation in UC rats, evidenced by the decreased levels of NF-κB, IL-17 and IL-23 in UC rats and the increased level of PPAR-γ. In addition, the 16S rDNA sequencing analysis revealed that luteolin treatment could alter diversity and composition of gut microbiota in UC rats. Lactobacillus, Bacteroides, Roseburia and Butyricicoccus were dominant genera in the luteolin group. Luteolin treatment reduced DSS-induced increased ratios of Lactobacillus and Prevotella_9. Furthermore, KEGG analysis revealed that gut microbiota was mainly related to DNA repair and recombination proteins, ribosome, purine metabolism, peptidases, and pyrimidine metabolism. In conclusion, our results revealed that luteolin could alleviate DSS-induced colitis in rats, and gut microbiota had the potential to serve as promising biomarkers for uncovering the mechanism by which luteolin improved UC.
Topics: Animals; Bacteria; Colitis, Ulcerative; Colon; Discriminant Analysis; Gastrointestinal Microbiome; Inflammation; Inflammation Mediators; Luteolin; Male; Principal Component Analysis; Rats, Wistar; Rats
PubMed: 33434535
DOI: 10.1016/j.lfs.2020.119008 -
Acta Pharmacologica Sinica Apr 2022Luteolin is a flavonoid in a variety of fruits, vegetables, and herbs, which has shown anti-inflammatory, antioxidant, and anti-cancer neuroprotective activities. In...
Luteolin is a flavonoid in a variety of fruits, vegetables, and herbs, which has shown anti-inflammatory, antioxidant, and anti-cancer neuroprotective activities. In this study, we investigated the potential beneficial effects of luteolin on memory deficits and neuroinflammation in a triple-transgenic mouse model of Alzheimer's disease (AD) (3 × Tg-AD). The mice were treated with luteolin (20, 40 mg · kg · d, ip) for 3 weeks. We showed that luteolin treatment dose-dependently improved spatial learning, ameliorated memory deficits in 3 × Tg-AD mice, accompanied by inhibiting astrocyte overactivation (GFAP) and neuroinflammation (TNF-α, IL-1β, IL-6, NO, COX-2, and iNOS protein), and decreasing the expression of endoplasmic reticulum (ER) stress markers GRP78 and IRE1α in brain tissues. In rat C6 glioma cells, treatment with luteolin (1, 10 µM) dose-dependently inhibited LPS-induced cell proliferation, excessive release of inflammatory cytokines, and increase of ER stress marker GRP78. In conclusion, luteolin is an effective agent in the treatment of learning and memory deficits in 3 × Tg-AD mice, which may be attributable to the inhibition of ER stress in astrocytes and subsequent neuroinflammation. These results provide the experimental basis for further research and development of luteolin as a therapeutic agent for AD.
Topics: Alzheimer Disease; Animals; Cognitive Dysfunction; Disease Models, Animal; Endoplasmic Reticulum Stress; Endoribonucleases; Luteolin; Mice; Mice, Transgenic; Neuroinflammatory Diseases; Protein Serine-Threonine Kinases; Rats
PubMed: 34267346
DOI: 10.1038/s41401-021-00702-8 -
Bioengineered Dec 2021Stroke is a leading cause of morbidity and mortality worldwide. As the most common type of stroke cases, treatment effectiveness is still limited despite intensive...
Stroke is a leading cause of morbidity and mortality worldwide. As the most common type of stroke cases, treatment effectiveness is still limited despite intensive research. Recently, traditional Chinese medicine has attracted attention because of potential benefits for stroke treatment. Among these, luteolin, a natural plant flavonoid compound, offers neuroprotection following against ischemic stroke, although the specific mechanisms are unknown. Here we used network pharmacology, molecular docking, and experimental verification to explore the mechanisms whereby luteolin can benefit stroke recovery. The pharmacological and molecular properties of luteolin were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The potential targets of luteolin and ischemic stroke were collected from interrogating public databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed by Funrich and Database for Annotation, Visualization and Integrated Discovery respectively, a luteolin-target-pathway network constructed using Cytoscape, Autodock vina was used for molecular docking simulation with Discovery Studio was used to visualize and analyze the docked conformations. Lastly, we employed an in vitro model of stroke injury to evaluate the effects of luteolin on cell survival and expression of the putative targets. From 95 candidate luteolin target genes, our analysis identified six core targets . KEGG analysis of the candidate targets identified that luteolin provides therapeutic effects on stroke through TNF signaling and other pathways. Our experimental analyses confirmed the conclusions analyzed above. In summary, the molecular and pharmacological mechanisms of luteolin against stroke are indicated in our study from a systematic perspective.
Topics: Animals; Caco-2 Cells; Cell Death; Cell Survival; Gene Expression Regulation; Gene Ontology; Glucose; Humans; Ischemic Stroke; Luteolin; Molecular Docking Simulation; Network Pharmacology; Oxygen; PC12 Cells; Protein Interaction Maps; Rats; Reproducibility of Results
PubMed: 34898370
DOI: 10.1080/21655979.2021.2006966 -
EBioMedicine Jan 2023Stroke is one of the most common neurological diseases in the world and is clinically manifested by transient or permanent brain dysfunction. It has a high mortality and...
BACKGROUND
Stroke is one of the most common neurological diseases in the world and is clinically manifested by transient or permanent brain dysfunction. It has a high mortality and disability rate, which severely affects people's health and diminishes the quality of life. However, there is no efficient treatment that can be considered curative and there are other less well-known theories of pathogenesis. Therefore, it is imperative to gain a full understanding of the pathophysiology of ischemia and to seek new therapeutic strategies.
METHODS
We first examined Kir4.1 channel and myelin based protein (MBP) expression in brain tissues from acute ischemic patients by Western blotting. We then established a transient ischemic mouse model (tMCAO) to conduct molecular, cell biological, transmission electron microscopy and pharmacokinetic studies, as well as in Kir4.1 cKO mice. Finally, neuroimaging and behavioral analyses were used to examine whether activation of Kir4.1 channel by luteolin could contribute to neuronal functional recovery in ischemic stroke.
FINDINGS
In acute ischemic stroke patients, we first demonstrated that Kir4.1 ion channels were greatly impaired and a severe demyelination of axons occurred in ischemic infarction area of cerebral cortex in these patients. Further evidence showed that the deficits of Kir4.1 channels in NG2 glia led to the myelin loss of axons in a transient ischemic mouse model (tMCAO). Treating ischemic mice with a natural botanical extract, luteolin augmented Kir4.1 channel currents in NG2 glia and consequently promoted remyelination of axons, alleviated the infarction area and ultimately improved motor function in a series of behavioral tests.
INTERPRETATION
Targeting Kir4.1 ion channels expressed in NG2 glial cells by luteolin treatment highlights an effective therapeutic strategy for a prompt brain functional recovery in ischemic stroke.
FUNDING
This work was supported by grants from the Ministry of Science and Technology China Brain Initiative (2022ZD0204702, to X.T.), the National Natural Science Foundation of China (82271466, 82171279, 31970904 and 31571063), the Program for Professor of Special Appointment (Eastern Scholar for Dr. X.T.) at Shanghai Institutions for Higher Learning (1510000084), Shanghai Pujiang Talent Award (15PJ1404600), Shanghai Municipal Science and Technology Major Project (2018SHZDZX05) and Shanghai Science and Technology Project (17411954000).
Topics: Mice; Animals; Ischemic Stroke; Luteolin; Quality of Life; Remyelination; China; Neuroglia; Stroke; Infarction
PubMed: 36527899
DOI: 10.1016/j.ebiom.2022.104406 -
International Journal of Molecular... Jan 2023Flavonoids have been shown to have anti-oxidative effects, as well as other health benefits (e.g., anti-inflammatory and anti-tumor functions). Luteolin (3', 4',... (Review)
Review
Flavonoids have been shown to have anti-oxidative effects, as well as other health benefits (e.g., anti-inflammatory and anti-tumor functions). Luteolin (3', 4', 5,7-tetrahydroxyflavone) is a flavonoid found in vegetables, fruits, flowers, and herbs, including celery, broccoli, green pepper, navel oranges, dandelion, peppermint, and rosemary. Luteolin has multiple useful effects, especially in regulating inflammation-related symptoms and diseases. In this paper, we summarize the studies about the immunopharmacological activity of luteolin on anti-inflammatory, anti-cardiovascular, anti-cancerous, and anti-neurodegenerative diseases published since 2018 and available in PubMed or Google Scholar. In this review, we also introduce some additional formulations of luteolin to improve its solubility and bioavailability.
Topics: Humans; Luteolin; Flavonoids; Anti-Inflammatory Agents; Vegetables; Chronic Disease
PubMed: 36768462
DOI: 10.3390/ijms24032136 -
International Journal of Molecular... Nov 2023Researchers are amazed at the multitude of biological effects of 3',4',5,7-tetrahydroxyflavone, more commonly known as luteolin, as it simultaneously has antioxidant and... (Review)
Review
Researchers are amazed at the multitude of biological effects of 3',4',5,7-tetrahydroxyflavone, more commonly known as luteolin, as it simultaneously has antioxidant and pro-oxidant, as well as antimicrobial, anti-inflammatory, and cancer-preventive, properties. The anticancer properties of luteolin constitute a mosaic of pathways due to which this flavonoid influences cancer cells. Not only is it able to induce apoptosis and inhibit cancer cell proliferation, but it also suppresses angiogenesis and metastasis. Moreover, luteolin succeeds in cancer cell sensitization to therapeutically induced cytotoxicity. Nevertheless, apart from its promising role in chemoprevention, luteolin exhibits numerous potential utilizations in patients with conditions other than neoplasms, which include inflammatory skin diseases, diabetes mellitus, and COVID-19. This review aims to present the multidimensionality of the luteolin's impact on both neoplastic and nonneoplastic diseases. When it comes to neoplasms, we intend to describe the complexity of the molecular mechanisms that underlay luteolin's anticancer effectiveness, as well as to prove the usefulness of integrating this flavonoid in cancer therapy via the analysis of recent research on breast, colon, and lung cancer. Regarding nonneoplastic diseases, this review aims to emphasize the importance of researching the potential of luteolin in areas such as diabetology, virology, and dermatology as it summarizes the most important discoveries in those fields regarding its application.
Topics: Humans; Luteolin; Neoplasms; Lung Neoplasms; Antioxidants; Chemoprevention; Apoptosis
PubMed: 37958980
DOI: 10.3390/ijms242115995 -
Contrast Media & Molecular Imaging 2022Pure plant extract luteolin has been demonstrated to possess numerous biological and immunological effects. However, how luteolin affects mice alveolar macrophages'...
Pure plant extract luteolin has been demonstrated to possess numerous biological and immunological effects. However, how luteolin affects mice alveolar macrophages' self-renewal and polarization closely related to inflammatory and immunomodulatory is still unknown. In our study, the transcriptomic analysis showed that several self-renewal-related pathways in luteolin-pretreated alveolar macrophages were inhibited compared to the granulocyte-macrophage colony-stimulating factor (GM-CSF)-treated group. Ki-67 staining and EdU assay indicated that luteolin inhibited GM-CSF-induced alveolar macrophage proliferation. Moreover, GM-CSF-induced expressions of c-Myc and KLF4 were significantly suppressed by luteolin at transcriptional and protein levels. Besides, we found that luteolin promoted M1 macrophage polarization induced by LPS plus IFN-. At the same time, it inhibited M2 macrophage polarization induced by IL-4 in both alveolar and bone marrow-derived macrophages by detecting macrophage polarization-related gene expressions at mRNA and protein levels. We found that luteolin inhibited self-renewal and altered the polarization of primary alveolar macrophages. Taken together, our data will aid in a better understanding of the immunomodulatory effects of luteolin on the primary alveolar macrophages.
Topics: Animals; Granulocyte-Macrophage Colony-Stimulating Factor; Luteolin; Macrophages; Macrophages, Alveolar; Mice
PubMed: 36051934
DOI: 10.1155/2022/3517020 -
Scientific Reports Jul 2022We have studied the physiological effects and health functions of luteolin, especially focusing on its absorption and metabolism. Recent studies have reported the...
We have studied the physiological effects and health functions of luteolin, especially focusing on its absorption and metabolism. Recent studies have reported the advantages of microemulsion to improve the bioavailability of poorly water-soluble compounds, including luteolin. In the present study, we aimed to evaluate the absorption and metabolic profile of luteolin delivered in microemulsion system via oral intake. First, we prepared water-dispersed luteolin (WD-L) using a microemulsion-based delivery system and confirmed that WD-L has superior water dispersibility compared to free luteolin (CO-L) based on their particle size distributions. Following administration of WD-L and CO-L to rats, we detected high level of luteolin-3'-O-β-glucuronide and lower levels of luteolin, luteolin-4'-O-β-glucuronide, and luteolin-7-O-β-glucuronide in plasma from both CO-L and WD-L groups, indicating that the metabolic profile of luteolin was similar for both groups. On top of that, we found a 2.2-fold increase in the plasma area under the curve (AUC) of luteolin-3'-O-β-glucuronide (main luteolin metabolite) in WD-L group (vs. CO-L). Altogether, our results suggested that delivering luteolin by microemulsion system improve its oral bioavailability without affecting its metabolite profile. This evidence thereby provides a solid basis for future application of microemulsion system for optimal delivery of luteolin.
Topics: Administration, Oral; Animals; Biological Availability; Emulsions; Glucuronides; Luteolin; Particle Size; Rats; Rats, Sprague-Dawley; Solubility; Water
PubMed: 35831358
DOI: 10.1038/s41598-022-16220-4