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Metabolites Mar 2023It has been demonstrated that cancer stem cells (CSCs) go through metabolic changes that differentiate them from non-CSCs. The altered metabolism of CSCs plays a vital... (Review)
Review
It has been demonstrated that cancer stem cells (CSCs) go through metabolic changes that differentiate them from non-CSCs. The altered metabolism of CSCs plays a vital role in tumor initiation, progression, immunosuppression, and resistance to conventional therapy. Therefore, defining the role of CSC metabolism in carcinogenesis has emerged as a main focus in cancer research. Two natural flavonoids, apigenin and isovitexin, have been shown to act synergistically with conventional chemotherapeutic drugs by sensitizing CSCs, ultimately leading to improved therapeutic efficacy. The aim of this study is to present a critical and broad evaluation of the anti-CSC capability of apigenin and isovitexin in different cancers as novel and untapped natural compounds for developing drugs. A thorough review of the included literature supports a strong association between anti-CSC activity and treatment with apigenin or isovitexin. Additionally, it has been shown that apigenin or isovitexin affected CSC metabolism and reduced CSCs through various mechanisms, including the suppression of the Wnt/β-catenin signaling pathway, the inhibition of nuclear factor-κB protein expression, and the downregulation of the cell cycle via upregulation of p21 and cyclin-dependent kinases. The findings of this study demonstrate that apigenin and isovitexin are potent candidates for treating cancer due to their antagonistic effects on CSC metabolism.
PubMed: 36984844
DOI: 10.3390/metabo13030404 -
Frontiers in Nutrition 2022Apigenin is a flavonoid with antioxidant, anti-inflammatory, and anti-apoptotic activity. In this study, the potential effects of apigenin on cardiometabolic diseases... (Review)
Review
Apigenin is a flavonoid with antioxidant, anti-inflammatory, and anti-apoptotic activity. In this study, the potential effects of apigenin on cardiometabolic diseases were investigated and . Potential signaling networks in different cell types induced by apigenin were identified, suggesting that the molecular mechanisms of apigenin in cardiometabolic diseases vary with cell types. Additionally, the mechanisms of apigenin-induced biological response in different cardiometabolic diseases were analyzed, including obesity, diabetes, hypertension and cardiovascular diseases. This review provides novel insights into the potential role of apigenin in cardiometabolic diseases.
PubMed: 35495935
DOI: 10.3389/fnut.2022.875826 -
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 -
Journal of Oral Science Jul 2023Enterococcus faecalis (E. faecalis) is one of the major microorganisms that causes failure of endodontic treatment. This study aimed to investigate the antibacterial...
PURPOSE
Enterococcus faecalis (E. faecalis) is one of the major microorganisms that causes failure of endodontic treatment. This study aimed to investigate the antibacterial activity of apigenin and its synergistic effect with reduced graphene oxide (RGO) in treating E. faecalis biofilms.
METHODS
The antibacterial activities were characterized by viability analysis including colony forming units and confocal laser scanning microscopy (CLSM) analyses. The effect on biofilm biomass was measured using a crystal violet staining method. Live and dead bacteria bio-volumes were determined by CLSM analysis, and the morphology of E. faecalis biofilm after treatment with apigenin and apigenin + RGO was observed by scanning electron microscopy (SEM).
RESULTS
The viability of E. faecalis in biofilms decreased by apigenin treatment in a dose-dependent manner. While apigenin alone did not significantly affect the biofilm biomass, apigenin + RGO reduced the biomass in an apigenin concentration-dependent manner. Likewise, the bio-volume of live bacteria decreased and the bio-volume of dead bacteria increased in apigenin-treated biofilms. According to SEM images, apigenin + RGO-treated samples showed less E. faecalis in biofilms than apigenin-only treated samples.
CONCLUSION
The results suggested that the combined use of apigenin and RGO could be a potential strategy for effective endodontic disinfection.
Topics: Enterococcus faecalis; Apigenin; Biofilms; Anti-Bacterial Agents; Root Canal Irrigants
PubMed: 37211399
DOI: 10.2334/josnusd.22-0459 -
Scientific Reports May 2023Apigenin (APN), a flavone found in several plant foods with various biological properties such as anti-obesity, anti-inflammation and other abilities, alleviates...
Apigenin (APN), a flavone found in several plant foods with various biological properties such as anti-obesity, anti-inflammation and other abilities, alleviates atherosclerosis and non-alcoholic fatty liver disease (NAFLD) induced by a high fat diet (HFD) in mice. However, the underlying mechanisms have not been fully understood. In this study, we investigated the role of NLRP3 in anti-atherosclerosis and anti-NAFLD effect of APN in mouse models with NLRP3 deficiency. Atherosclerosis and NAFLD models were established by treatment of low density lipoprotein receptor-deficient (Ldlr) mice and NLRP3 Ldlr mice with a HFD diet (20% fat and 0.5% cholesterol) with or without APN. En face lipid accumulation analysis, plasma lipid levels, hepatic lipid accumulation and inflammation were analyzed and quantified. For in vitro experiments, HepG2 cells were stimulated by LPS plus oleic acid (OA) in the absence or presence of APN (50 μM). Lipid accumulation and the effect of APN on the NLRP3/NF-κB signaling pathway were investigated. APN administration partly reversed atherosclerosis and hepatic lipid accumulation, and decreased body weight and plasma lipid levels in Ldlr mice when fed a HFD. Compared with Ldlr mice, NLRP3 Ldlr mice showed more severe atherosclerosis and hepatic lipid accumulation. Treating the HepG2 cells with APN reduced lipid accumulation. APN also inhibited activation of the NLRP3/ NF-κB signaling pathway stimulated by OA together with LPS. Our results indicate that APN supplementation prevents atherosclerosis and NAFLD via NLRP3 inhibition in mice, and suggest that APN might be a potential therapeutic agent for the prevention of atherosclerosis and NAFLD.
Topics: Animals; Mice; Non-alcoholic Fatty Liver Disease; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Apigenin; NF-kappa B; Lipopolysaccharides; Liver; Atherosclerosis; Diet, High-Fat; Mice, Inbred C57BL
PubMed: 37198205
DOI: 10.1038/s41598-023-34654-2 -
Food Science & Nutrition Nov 2023Colon cancer (CC) is one of the most common and deadly cancers worldwide. Oncologists are facing challenges such as development of drug resistance and lack of suitable... (Review)
Review
Colon cancer (CC) is one of the most common and deadly cancers worldwide. Oncologists are facing challenges such as development of drug resistance and lack of suitable drug options for CC treatment. Flavonoids are a group of natural compounds found in fruits, vegetables, and other plant-based foods. According to research, they have a potential role in the prevention and treatment of cancer. Apigenin is a flavonoid that is present in many fruits and vegetables. It has been used as a natural antioxidant for a long time and has been considered due to its anticancer effects and low toxicity. The results of this review study show that apigenin has potential anticancer effects on CC cells through various mechanisms. In this comprehensive review, we present the cellular targets and signaling pathways of apigenin indicated to date in in vivo and in vitro CC models. Among the most important modulated pathways, Wnt/β-catenin, PI3K/AKT/mTOR, MAPK/ERK, JNK, STAT3, Bcl-xL and Mcl-1, PKM2, and NF-kB have been described. Furthermore, apigenin suppresses the cell cycle in G2/M phase in CC cells. In CC cells, apigenin-induced apoptosis is increased by inhibiting the formation of autophagy. According to the results of this study, apigenin appears to have the potential to be a promising agent for CC therapy, but more research is required in the field of pharmacology and pharmacokinetics to establish the apigenin effects and its dosage for clinical studies.
PubMed: 37970406
DOI: 10.1002/fsn3.3645 -
Journal of Translational Medicine May 2024Retinal ischemia/reperfusion (RIR) is implicated in various forms of optic neuropathies, yet effective treatments are lacking. RIR leads to the death of retinal ganglion...
BACKGROUND
Retinal ischemia/reperfusion (RIR) is implicated in various forms of optic neuropathies, yet effective treatments are lacking. RIR leads to the death of retinal ganglion cells (RGCs) and subsequent vision loss, posing detrimental effects on both physical and mental health. Apigenin (API), derived from a wide range of sources, has been reported to exert protective effects against ischemia/reperfusion injuries in various organs, such as the brain, kidney, myocardium, and liver. In this study, we investigated the protective effect of API and its underlying mechanisms on RGC degeneration induced by retinal ischemia/reperfusion (RIR).
METHODS
An in vivo model was induced by anterior chamber perfusion following intravitreal injection of API one day prior to the procedure. Meanwhile, an in vitro model was established through 1% oxygen and glucose deprivation. The neuroprotective effects of API were evaluated using H&E staining, spectral-domain optical coherence tomography (SD-OCT), Fluoro-Gold retrograde labeling, and Photopic negative response (PhNR). Furthermore, transmission electron microscopy (TEM) was employed to observe mitochondrial crista morphology and integrity. To elucidate the underlying mechanisms of API, the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, flow cytometry assay, western blot, cell counting kit-8 (CCK-8) assay, lactate dehydrogenase (LDH) assay, JC-1 kit assay, dichlorofluorescein-diacetate (DCFH-DA) assay, as well as TMRE and Mito-tracker staining were conducted.
RESULTS
API treatment protected retinal inner plexiform layer (IPL) and ganglion cell complex (GCC), and improved the function of retinal ganglion cells (RGCs). Additionally, API reduced RGC apoptosis and decreased lactate dehydrogenase (LDH) release by upregulating Bcl-2 and Bcl-xL expression, while downregulating Bax and cleaved caspase-3 expression. Furthermore, API increased mitochondrial membrane potential (MMP) and decreased extracellular reactive oxygen species (ROS) production. These effects were achieved by enhancing mitochondrial function, restoring mitochondrial cristae morphology and integrity, and regulating the expression of OPA1, MFN2, and DRP1, thereby regulating mitochondrial dynamics involving fusion and fission.
CONCLUSION
API protects RGCs against RIR injury by modulating mitochondrial dynamics, promoting mitochondrial fusion and fission.
Topics: Retinal Ganglion Cells; Apigenin; Animals; Reperfusion Injury; Neuroprotective Agents; Mitochondrial Dynamics; Male; Apoptosis; Mitochondria; Reactive Oxygen Species; Models, Biological; Mice, Inbred C57BL
PubMed: 38741132
DOI: 10.1186/s12967-024-05260-1 -
Frontiers in Cellular and Infection... 2023Current treatment for visceral leishmaniasis is based on drugs such as pentavalent antimony and amphotericin B. However, this treatment remains mostly ineffective and...
Current treatment for visceral leishmaniasis is based on drugs such as pentavalent antimony and amphotericin B. However, this treatment remains mostly ineffective and expensive, resulting in several side effects and generating resistance. Apigenin, a flavonoid present in fruits and vegetables, has demonstrated several biological functions. In the present study, we observed a concentration-dependent inhibition of the promastigote in the presence of apigenin, exhibiting an IC value of 29.9 µM. Its effect was also evaluated in -infected murine peritoneal macrophages, presenting an C value against intracellular amastigotes of 2.3 µM and a selectivity index of 34.3. In a murine model of visceral leishmaniasis, the effect of apigenin was measured using short-term and long-term treatment schemes. Treatment with apigenin demonstrated 99.7% and 94% reductions in the liver parasite load in the short-term and long-term treatment schemes, respectively. Furthermore, no alterations in serological and hematological parameters were observed. Taken together, these results suggest that apigenin is a potential candidate for visceral leishmaniasis chemotherapy by oral administration.
Topics: Animals; Mice; Leishmaniasis, Visceral; Apigenin; Leishmania infantum; Amphotericin B; Antiprotozoal Agents; Mice, Inbred BALB C
PubMed: 37091674
DOI: 10.3389/fcimb.2023.1066407 -
Molecules (Basel, Switzerland) Jan 2023Apigenin is a natural flavonoid with significant biological activity, but poor solubility in water and low bioavailability limits its use in the food and pharmaceutical...
Apigenin is a natural flavonoid with significant biological activity, but poor solubility in water and low bioavailability limits its use in the food and pharmaceutical industries. In this paper, apigenin-7--β-(6″-)-d-glucoside (AG) and apigenin-7--β-(6″--succinyl)-d-glucoside (SAG), rare apigenin glycosyl and succinyl derivatives formed by the organic solvent-tolerant bacteria WNJ02 were used in a 10.0% DMSO (v/v) system. The water solubility of SAG was 174 times that of apigenin, which solved the application problem. In the biotransformation reaction, the conversion rate of apigenin (1.0 g/L) was 100% at 24 h, and the yield of SAG was 94.2%. Molecular docking showed that the hypoglycemic activity of apigenin, apigenin-7-glucosides (AG), and SAG was mediated by binding with amino acids of α-glucosidase. The molecular docking results were verified by an in vitro anti-α-glucosidase assay and glucose consumption assay of active compounds. SAG had significant anti-α-glucosidase activity, with an IC of 0.485 mM and enhanced glucose consumption in HepG2 cells, which make it an excellent α-glucosidase inhibitor.
Topics: Hypoglycemic Agents; Glycosylation; Apigenin; Molecular Docking Simulation; alpha-Glucosidases; Glucose; Glucosides
PubMed: 36677592
DOI: 10.3390/molecules28020533