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Free Radical Biology & Medicine May 2022The bioavailability of apigenin and its O-glycosides in humans was investigated with apigenin-4'-glucuronide (Ap-4'-GlcUA), apigenin-7-glucuronide and apigenin-7-sulfate... (Clinical Trial)
Clinical Trial
The bioavailability of apigenin and its O-glycosides in humans was investigated with apigenin-4'-glucuronide (Ap-4'-GlcUA), apigenin-7-glucuronide and apigenin-7-sulfate being identified as in vivo metabolites. Apigenin per se was poorly absorbed with metabolites equivalent to 0.5% of intake excreted in urine 0-24 h post-intake. Consumption of a parsley drink containing apigenin-7-O-(2″-O-apiosyl)glucoside resulted in the peak plasma concentration (C) of Ap-4'-GlcUA occurring after 4 h, indicative of absorption in the lower gastrointestinal tract (GIT). Urinary excretion of the three metabolites corresponded to 11.2% of intake. Ingestion of dried powdered parsley leaves with yogurt extended the C of Ap-4'-GlcUA to 6 h. Consumption of chamomile tea containing apigenin-7'-O-glucoside resulted in a 2 h C of Ap-4'-GlcUA, in keeping with absorption in the upper GIT. Urinary excretion was equivalent to 34% of intake. Intake of the parsley drink provided information on intra- and inter-individual variations in the level of excretion of the apigenin metabolites. CLINICAL TRAIL REGISTRATION NUMBER: This trail was registered at clinicaltrials.gov as NCT03526081.
Topics: Adult; Apigenin; Biological Availability; Glucosides; Glucuronides; Glycosides; Humans; Male
PubMed: 35452808
DOI: 10.1016/j.freeradbiomed.2022.04.007 -
International Journal of Biological... 2023Apigenin is the active ingredient in Ludangshen. Although previous studies reported the cardioprotective actions of apigenin against doxorubicin (Dox)-induced...
Apigenin is the active ingredient in Ludangshen. Although previous studies reported the cardioprotective actions of apigenin against doxorubicin (Dox)-induced cardiomyopathy, the underlying mechanisms remain incompletely understood. Since apigenin beneficially regulates various aspects of mitochondrial function and dynamics, we asked whether apigenin improves heart function in mice with Dox-induced cardiomyopathy by regulating the mitochondrial unfolded protein response (UPR). Co-administration of apigenin significantly restored heart function, reduced myocardial swelling, inhibited cardiac inflammation, increased cardiac transcription of UPR-related genes, and promoted cardiomyocyte survival in Dox-treated mice. In turn, blockade of UPR abolished the mito- and cytoprotective effects of apigenin, evidenced by decreased ATP production, suppressed mitochondrial antioxidant capacity, and increased apoptosis, in Dox-treated, cultured HL-1 cardiomyocytes. Furthermore, apigenin treatment prevented Dox-induced downregulation of Sirt1 and Atf5 expression, and the beneficial effects of apigenin were completely nullified in knockout (KO) mice or after siRNA-mediated knockdown . We thus provide novel evidence for a promotive effect of apigenin on UPR via regulation of the Sirt1/Atf5 pathway. Our findings uncover that apigenin seems to be an effective therapeutic agent to alleviate Dox-mediated cardiotoxicity.
Topics: Mice; Animals; Apigenin; Sirtuin 1; Myocytes, Cardiac; Cardiotoxicity; Cardiomyopathies; Mice, Knockout; Doxorubicin; Apoptosis; Oxidative Stress
PubMed: 37928261
DOI: 10.7150/ijbs.85204 -
BMC Ophthalmology Jul 2023Diabetic retinopathy (DR) is a common cause of visual impairment. Apigenin has been shown to have antiangiogenic effects in various diseases. Our study aimed to...
BACKGROUND
Diabetic retinopathy (DR) is a common cause of visual impairment. Apigenin has been shown to have antiangiogenic effects in various diseases. Our study aimed to investigate the role of apigenin in DR and elucidate the underlying mechanism.
METHODS
Human retinal microvascular endothelial cells (HRMECs) were exposed to high glucose (HG) to establish a DR model. HRMECs were treated with apigenin. Then we knocked down or overexpressed miR-140-5p and HDAC3, and added PI3K/AKT inhibitor LY294002. The expression levels of miR-140-5p, HDAC3, and PTEN were measured using qRT-PCR. Western blot analysis was performed to assess the expression of HDAC3, PTEN, and PI3K/AKT pathway-related proteins. Finally, cell proliferation and migration were evaluated using MTT, wound-healing assay, and transwell assay, while angiogenesis was examined using the tube formation assay.
RESULTS
HG treatment resulted in reduced miR-140-5p expression and overexpression of miR-140-5p suppressed proliferation, migration, and angiogenesis of the HG-induced HRMECs. Apigenin treatment significantly restored the decreased level of miR-140-5p caused by HG treatment and inhibited proliferation, migration, and angiogenesis of the HG-induced HRMECs by upregulating miR-140-5p. Moreover, miR-140-5p targeted HDAC3, and overexpression of miR-140-5p reversed the HG-inducted upregulation of HDAC3 expression. HDAC3 was found to bind to the promoter region of PTEN, inhibiting its expression. Knockdown of HDAC3 suppressed the PI3K/AKT pathway by elevating PTEN expression. Furthermore, apigenin inhibited angiogenesis in DR cell models through the regulating of the miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway.
CONCLUSIONS
Apigenin effectively suppressed angiogenesis in HG-induced HRMECs by modulating the miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway. Our study may contribute to the development of novel therapeutic approaches and identification of potential targets for the treatment of DR.
Topics: Humans; Proto-Oncogene Proteins c-akt; MicroRNAs; Phosphatidylinositol 3-Kinases; Apigenin; Signal Transduction; Endothelial Cells; Diabetic Retinopathy; Cell Proliferation; PTEN Phosphohydrolase
PubMed: 37415101
DOI: 10.1186/s12886-023-03046-5 -
European Journal of Pharmacology Aug 2024Apigenin and baicalein are structurally related flavonoids that have been reported to have multiple pharmacological activities. The aim of this study was to investigate...
Apigenin and baicalein ameliorate thoracic aortic structural deterioration and cognitive deficit via inhibiting AGEs/RAGE/NF-κB pathway in D-galactose-induced aging rats.
Apigenin and baicalein are structurally related flavonoids that have been reported to have multiple pharmacological activities. The aim of this study was to investigate the protective effects and potential mechanisms of apigenin and baicalein in D-galactose-induced aging rats. First, apigenin and baicalein showed remarkable antioxidant activity and anti-glycation activity in vitro. Secondly, the protective effects of apigenin and baicalein on aging rats were investigated. We found that apigenin and baicalein supplementation significantly ameliorated aging-related changes such as declines in the spatial learning and memory and histopathological damage of the hippocampus and thoracic aorta. In addition, our data showed that apigenin and baicalein alleviated oxidative stress as illustrated by decreasing MDA level, increasing SOD activity and GSH level. Further data showed that they significantly reduced the accumulation of advanced glycation end products (AGEs), inhibited the expression of RAGE, down-regulated phosphorylated nuclear factor (p-NF-κB (p65)). Our results suggested that the protective effects of apigenin and baicalein on aging rats were at least partially related to the inhibition of AGEs/RAGE/NF-κB pathway and the improvement of oxidative damage. Overall, apigenin and baicalein showed almost equal anti-aging efficacy. Our results provided an experimental basis for the application of apigenin and baicalein to delay the aging process.
Topics: Animals; Receptor for Advanced Glycation End Products; Glycation End Products, Advanced; Flavanones; Galactose; Apigenin; Aging; Male; NF-kappa B; Rats; Signal Transduction; Oxidative Stress; Aorta, Thoracic; Rats, Sprague-Dawley; Hippocampus; Cognitive Dysfunction; Antioxidants
PubMed: 38795756
DOI: 10.1016/j.ejphar.2024.176660 -
The Journal of Nutritional Biochemistry Nov 2023Apigenin, a flavonoid that widely existed in vegetables and fruits, possesses anticarcinogenic, low toxicity, and no mutagenic properties, suggesting that apigenin is a...
Apigenin, a flavonoid that widely existed in vegetables and fruits, possesses anticarcinogenic, low toxicity, and no mutagenic properties, suggesting that apigenin is a potential therapeutic agent for tumors. However, the underlying anti-cancer molecular target of apigenin is still unclear. Therefore, to reveal the direct target and amino acid site of apigenin against colorectal cancer is the focus of this study. In the present study, the results proved that the anti-CRC activity of apigenin was positively correlated with pyruvate kinase M2 (PKM2) expression, characterized by the inhibition of cell proliferation and increase of apoptotic effects induced by apigenin in LS-174T cells of knock down PKM2. Next, pull-down and MALDI-TOF/TOF analysis determined that apigenin might interact directly with PKM2 in HCT-8 cells. Further, the study confirmed that lysine residue 433 (K433) was a key amino acid site for PKM2 binding to apigenin. Apigenin restricted the glycolysis of LS-174T and HCT-8 cells by targeting the K433 site of PKM2, thereby playing an anti-CRC role in vivo and in vitro. Meanwhile, apigenin markedly attenuated tumor growth without any adverse effects. Taken together, these findings reveal that apigenin is worthy of consideration as a promising PKM2 inhibitor for the prevention of CRC.
Topics: Humans; Amino Acids; Apigenin; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; Glycolysis; Pyruvate Kinase; Thyroid Hormone-Binding Proteins
PubMed: 37597817
DOI: 10.1016/j.jnutbio.2023.109430 -
Biomedicine & Pharmacotherapy =... Nov 2023Visceral hypersensitivity (VH) and gut microbiota dysbiosis significantly contribute to the occurrence and development of irritable bowel syndrome (IBS), exacerbated by...
Visceral hypersensitivity (VH) and gut microbiota dysbiosis significantly contribute to the occurrence and development of irritable bowel syndrome (IBS), exacerbated by stress. Apigenin, a natural flavonoid derived from plants, possesses a range of beneficial properties. However, additional research is necessary to investigate its potential in alleviating symptoms of IBS and elucidating its underlying mechanisms of action. Our study confirms that apigenin effectively reverses mast cell and microglial activation, regulates the composition and abundance of the gut microbiota, improves intestinal barrier function in rats induced with water-avoidance stress, and mitigates VH and colonic hypermotility. Furthermore, in vitro studies suggest a potential role of dysbiotic gut microbiota in activating mast cells at the cellular level. Notably, apigenin inhibits mast cell degranulation through the toll-like receptor 4 (TLR4) / myeloid differentiation primary response gene 88 (MyD88) / nuclear factor-kappa B (NF-κB) pathway. In conclusion, this study discusses the potential therapeutic effects of apigenin in alleviating VH and modulating the gut-brain axis in water-avoidance stress rats, providing a novel or alternative treatment approach for IBS.
Topics: Rats; Animals; Irritable Bowel Syndrome; Brain-Gut Axis; Mast Cells; Apigenin; Water
PubMed: 37801900
DOI: 10.1016/j.biopha.2023.115562 -
Antiviral Research Sep 2023Epstein-Barr virus (EBV) is a highly prevalent human herpesvirus that persists for life in more than 95% of the adult population. EBV usually establishes an asymptomatic...
Epstein-Barr virus (EBV) is a highly prevalent human herpesvirus that persists for life in more than 95% of the adult population. EBV usually establishes an asymptomatic life-long infection, but it is also associated with malignancies affecting B lymphocytes and epithelial cells mainly. The virus alternates between a latent phase and a lytic phase, both of which contribute to the initiation of the tumor process. So far, there is only a limited number of antiviral molecules against the lytic phase, most of them targeting viral replication. Recent studies provided evidence that EBV uses components of the NLRP3 inflammasome to enter the productive phase of its cycle following activation in response to various stimuli. In the present work, we demonstrate that shikonin, a natural molecule with low toxicity which is known to inhibit inflammasome, can efficiently repress EBV reactivation. Similar results were obtained with apigenin and OLT 1177, two other NLRP3 inflammasome inhibitors. It is shown herein that shikonin repressed the transcription of reactivation-induced NLRP3 thereby inhibiting inflammasome activation and EBV lytic phase induction.
Topics: Inflammasomes; Virus Activation; Herpesvirus 4, Human; Naphthoquinones; Apigenin; Anti-Inflammatory Agents, Non-Steroidal; Humans; Cell Line; NLR Family, Pyrin Domain-Containing 3 Protein; Cell Line, Tumor
PubMed: 37549849
DOI: 10.1016/j.antiviral.2023.105699 -
Cellular and Molecular Biology... Sep 2023Fungal colonization of the soft denture liner is the first step in the development of denture-induced stomatitis. The study aims to assess apigenin and seashell...
Fungal colonization of the soft denture liner is the first step in the development of denture-induced stomatitis. The study aims to assess apigenin and seashell nano-additives for their antifungal efficacy and their impact on the surface roughness of a soft denture liner. The study was accomplished in the Colleges of Dentistry in Duhok, Mosul and Hawler Medical Universities. The Antifungal efficacy against Candida albicans was performed by the minimum inhibition concentration (MIC), for apigenin the MIC was determined by agar well diffusion and set at (0.25%, 0.5% and 1%) while for seashells, MIC was determined by broth dilution and set at (1.25%, 2.5% and 5%). Fungal adhesion was conducted on seven groups (unmodified soft liner and six groups of the modified liner with the antifungal concentrations (three for each nanoparticle). A total of forty-nine square-shaped specimens (10*10*2mm) of (GC, Super-soft, heat-cured, USA) soft liner were prepared, the adherent fungal cells were enumerated under a light microscope for each specimen in four fields and the results were expressed as fungal cells/mm2. For the surface roughness, forty-nine specimens of (20*10*3 mm) of the soft liner were prepared and the average surface roughness was obtained in µm using a profilometer (Talysurf, Taylor Hobson, UK). Apigenin and seashell-modified soft liner observed a significant decrease in both fungal adhesion and surface roughness compared to the unmodified liner and the reduction was related directly to the concentration of both additives. Apigenin and seashell nano-additives were effective as antifungal agents beside improving the surface roughness of the soft liner.
Topics: Animals; Antifungal Agents; Denture Liners; Apigenin; Animal Shells; Surface Properties; Candida albicans
PubMed: 37807336
DOI: 10.14715/cmb/2023.69.9.6 -
Biomedicine & Pharmacotherapy =... Mar 2024Gastric Cancer (GC) is one of the most prevalent cancers worldwide. As the currently available therapeutic options are invasive, new and more benign options are being... (Review)
Review
Gastric Cancer (GC) is one of the most prevalent cancers worldwide. As the currently available therapeutic options are invasive, new and more benign options are being explored. One of which is Apigenin (Api), a natural flavonoid found in fruits and vegetables, such as celery, parsley, garlic, bell pepper and chamomile tea. Api has known anti-inflammatory, -oxidant, and -proliferative proprieties in several diseases and its potential as an anticancer compound has been explored. Here we systematize the available data regarding the effects of Api on GC cells, in terms of cell proliferation, apoptosis, Helicobacter pylori (H. pylori) infection, and molecular targets. From the literature it is possible to conclude that Api inhibits cell growth in a dose- and time-dependent manner, which is accompanied by the reduction of clone formation and induction of apoptosis. This occurs through the Akt/Bad/Bcl2/Bax axis that activates the mitochondrial pathway of apoptosis, resulting in restriction of cell proliferation. Additionally, it seems that the anti-proliferative potential of Api on GC cells is particularly relevant in a more aggressive GC phenotype but can also affect normal gastric cells. This indicate that this flavonoid must be used in low-to-moderate doses to avoid side-effects induced by disturbance of the normal epithelium. In H. Pylori-infected cells, the literature demonstrates that Api reduces inflammation by diminishing the levels of H. pylori colonization, by preventing NF-kB activation and by diminishing the production of reactive oxygen specimens (ROS). Accordingly, in GC Api seems to regulate different hallmarks of cancer, such as cell proliferation, apoptosis, cell migration, inflammation and oxidative stress, demonstrating its potential has an anti-GC compound.
Topics: Humans; Stomach Neoplasms; Apigenin; Apoptosis; Antioxidants; Inflammation
PubMed: 38330709
DOI: 10.1016/j.biopha.2024.116251 -
Nutrients Aug 2020This review summarizes the latest advancements in phytochemicals as functional antiviral agents. We focused on flavonoids, like apigenin, vitexin, quercetin, rutin and... (Review)
Review
This review summarizes the latest advancements in phytochemicals as functional antiviral agents. We focused on flavonoids, like apigenin, vitexin, quercetin, rutin and naringenin, which have shown a wide range of biological effects including antiviral activities. The molecular mechanisms of their antiviral effects mainly consist in the inhibition of viral neuraminidase, proteases and DNA/RNA polymerases, as well as in the modification of various viral proteins. Mixtures of different flavonoids or combination of flavonoids with antiviral synthetic drugs provide an enhancement of their antiviral effects. Recent strategies in drug delivery significantly contribute to overcoming the low bioavailability of flavonoids. Frequent viral infections worldwide have led to the need for new effective antiviral agents, which can be identified among the various phytochemicals. In this light, screening the antiviral activities of a cocktail of flavonoids would be advantageous in order to prevent viral infections and improve current antiviral therapies.
Topics: Antiviral Agents; Apigenin; Biological Availability; Drug Combinations; Drug Delivery Systems; Drug Evaluation, Preclinical; Drug Synergism; Flavanones; Flavonoids; Humans; Neuraminidase; Quercetin; Rutin; Viral Protease Inhibitors; Viral Proteins; Virus Diseases; Viruses
PubMed: 32825564
DOI: 10.3390/nu12092534