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Critical Reviews in Oncology/hematology Aug 2022Apigenin is being increasingly recognized as a cancer chemopreventive agent. We aimed to investigate the anticancer effects of Apigenin in in-vivo studies to know its... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Apigenin is being increasingly recognized as a cancer chemopreventive agent. We aimed to investigate the anticancer effects of Apigenin in in-vivo studies to know its present research status and how close or how far it is from the clinics.
METHODS
Several electronic databases such as PubMed, Springer, Cochrane, and ctri.gov.in were searched to fetch the relevant articles. We focused only on published animal studies that reported the anticancer effects of Apigenin against various cancers. Two reviewers independently assessed the risk of bias for each analysis, and the conflicting views were resolved later by consensus.
RESULTS
A total of 25 studies focused on the anticancer effects of Apigenin on various cancer types, including liver, prostate, pancreatic, lung, nasopharyngeal, skin, colon, colorectal, colitis-associated carcinoma, head and neck squamous cell carcinoma, leukemia, renal cell carcinoma, Ehrlich ascites carcinoma, and breast cancer were included. Overall, Apigenin reduces tumor volume (SMD=-3.597, 95% CI: -4.502 to -2.691, p < 0.001), tumor-weight (SMD=-2.213, 95% CI: -2.897 to -1.529, p < 0.001), tumor number (SMD=-1.081, 95% CI: -1.599 to -0.563, p < 0.001) and tumor load (SMD=-1.556, 95% CI: -2.336 to -0.776, p < 0.001). Further, it has no significant effect on the animal's body-weight (SMD=-0.345, 95% CI: -0.832 to 0.143, p = 0.165). Apigenin exerts anti-tumor effects mainly by inducing apoptosis/cell-cycle arrest.
CONCLUSIONS
Our analysis suggests that Apigenin has potential anticancer effects against various cancers. However, the poor symmetry of the funnel plot suggested publication bias. Thus, it warrants further research to evaluate the potential of Apigenin alone or as an adjuvant for cancer treatment.
Topics: Animals; Apigenin; Breast Neoplasms; Head and Neck Neoplasms; Humans; Male; Models, Animal; Squamous Cell Carcinoma of Head and Neck
PubMed: 35752426
DOI: 10.1016/j.critrevonc.2022.103751 -
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 -
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 -
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 -
Life Sciences Sep 2023Psoriasis is an immune-mediated skin disease characterized by keratinocytes hyperproliferation, abnormal differentiation and inflammation. Therefore, this study aimed to...
AIMS
Psoriasis is an immune-mediated skin disease characterized by keratinocytes hyperproliferation, abnormal differentiation and inflammation. Therefore, this study aimed to investigate in-vitro and in-vivo anti-inflammatory and anti-proliferative activity to evaluate anti-psoriatic potential of apigenin.
MAIN METHODS
For in-vivo study, 5 % imiquimod cream was used to induce psoriasis-like skin inflammation in BALB/c mice to mimic human psoriatic conditions. PASI score, CosCam score, histopathology, immunohistochemistry, qRT-PCR, and ELISA were done to evaluate the anti-psoriatic potential of topically applied apigenin. For in-vitro studies, LPS-induced inflammation in RAW 264.7 was done, and qRT-PCR, ELISA, and immunofluorescence were conducted to evaluate the anti-inflammatory activity of apigenin. Migration and cell doubling assay in HaCaT cells were performed to assess the anti-proliferative effect of apigenin. Acute dermal toxicity profile of apigenin has also been done as per OECD guidelines.
KEY FINDINGS
Results showed that apigenin significantly reduce the PASI and CosCam scores, ameliorate the deteriorating histopathology, and effectively downregulated the expression of CCR6, IL-17A, and NF-κB. Apigenin effectively downregulated the expression and secretion of pro-inflammatory cytokines through IL-23/IL-17/IL-22 axis. Apigenin suppressed nuclear translocation of NF-κB in LPS-induced RAW 264.7 cells. Cell migration and cell doubling assay in HaCaT cells showing the anti-proliferative potential of apigenin and it was found safe in acute dermal toxicity study.
SIGNIFICANCE
Apigenin was found effective against psoriasis in both in-vitro and in-vivo models suggesting apigenin as a potential candidate for the development of anti-psoriatic agent.
Topics: Animals; Mice; Humans; Apigenin; HaCaT Cells; NF-kappa B; Mice, Inbred BALB C; Lipopolysaccharides; RAW 264.7 Cells; Psoriasis; Keratinocytes; Anti-Inflammatory Agents; Dermatitis; Inflammation; Disease Models, Animal
PubMed: 37414141
DOI: 10.1016/j.lfs.2023.121909 -
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 -
Molecules (Basel, Switzerland) Jul 2022Plant bioactive compounds, particularly apigenin, have therapeutic potential and functional activities that aid in the prevention of infectious diseases in many... (Review)
Review
Plant bioactive compounds, particularly apigenin, have therapeutic potential and functional activities that aid in the prevention of infectious diseases in many mammalian bodies and promote tumor growth inhibition. Apigenin is a flavonoid with low toxicities and numerous bioactive properties due to which it has been considered as a traditional medicine for decades. Apigenin shows synergistic effects in combined treatment with sorafenib in the HepG2 human cell line (HCC) in less time and statistically reduces the viability of tumor cells, migration, gene expression and apoptosis. The combination of anti-cancerous drugs with apigenin has shown health promoting potential against various cancers. It can prevent cell mobility, maintain the cell cycle and stimulate the immune system. Apigenin also suppresses mTOR activity and raises the UVB-induced phagocytosis and reduces the cancerous cell proliferation and growth. It also has a high safety threshold, and active (anti-cancer) doses can be gained by consuming a vegetable and apigenin rich diet. Apigenin also boosted autophagosome formation, decreased cell proliferation and activated autophagy by preventing the activity of the PI3K pathway, specifically in HepG2 cells. This paper provides an updated overview of apigenin's beneficial anti-inflammatory, antibacterial, antiviral, and anticancer effects, making it a step in the right direction for therapeutics. This study also critically analyzed the effect of apigenin on cancer cell signaling pathways including the PI3K/AKT/MTOR, JAK/STAT, NF-κB and ERK/MAPK pathways.
Topics: Animals; Apigenin; Apoptosis; Cell Line, Tumor; Cell Proliferation; Humans; Mammals; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction; TOR Serine-Threonine Kinases
PubMed: 35807549
DOI: 10.3390/molecules27134304 -
Scientific Reports Feb 2024This pioneering research investigated apigenin potential to augment rooster sperm cryosurvival in an extender model. Apigenin is a natural antioxidant flavonoid showing...
This pioneering research investigated apigenin potential to augment rooster sperm cryosurvival in an extender model. Apigenin is a natural antioxidant flavonoid showing promise for improved post-thaw sperm function. However, its effects on avian semen cryopreservation remain unexplored. This first study supplemented rooster sperm Lake extender with 0, 50, 100, 200, 400 μmol/L apigenin to determine the optimal concentrations for post-thaw quality. Supplementation with 100 μmol/L apigenin resulted in significant enhancements in total motility (from 41.5% up to 71.5%), progressive motility (18.1% to 29.1%) (p < 0.05), membrane integrity (40% to 68%), mitochondrial function (p < 0.001), viability (37% to 62%) and total antioxidant capacity (p < 0.001) compared to the control. It also substantially reduced percentages of abnormal morphology, reactive oxygen species and apoptosis (p < 0.001). Although 200 μmol/L apigenin significantly enhanced some attributes, effects were markedly lower than 100 μmol/L. Higher doses did not improve cryoprotective parameters. This indicates 100 μmol/L as the optimal apigenin concentration. This represents the first report of apigenin protecting rooster sperm from cryodamage. The natural antioxidant improved post-thaw sperm quality, likely by suppressing oxidative stress and apoptosis. Apigenin shows promise for enhancing rooster sperm cryosurvival.
Topics: Male; Animals; Semen; Antioxidants; Apigenin; Semen Analysis; Chickens; Cryoprotective Agents; Semen Preservation; Spermatozoa; Cryopreservation; Dietary Supplements; Sperm Motility
PubMed: 38402367
DOI: 10.1038/s41598-024-55057-x -
Food & Function Oct 2020Apigenin, as a natural flavonoid, has been proved to have many biological effects. Our previous research has found the antiadipogenic effects of apigenin on HepG2 cells....
Apigenin, as a natural flavonoid, has been proved to have many biological effects. Our previous research has found the antiadipogenic effects of apigenin on HepG2 cells. Autophagy is intimately associated with the metabolism of lipid droplets (LDs) and is considered to be one of the lipid breakdown pathways. However, there is no study to elucidate the lipid-lowering mechanism of apigenin from the perspective of autophagy. Here, we investigated the possible role of apigenin in autophagy and lipid accumulation in palmitic acid (PA)-induced HepG2 cells. Our results showed that apigenin increased autophagosome formation and the LC3-II/I ratio, but decreased the p-mTOR/mTOR ratio and P62 protein expression. The effects of apigenin were blocked by chloroquine (CQ). Likewise, apigenin significantly stimulated autophagic flux in the cytoplasm. This effect also could be blocked by CQ. Moreover, apigenin decreased the lipid content and co-localization of LDs with LC3, and CQ could block these effects. Thus, we proposed that apigenin induced autophagy and stimulated autophagic lipid degradation in PA-treated HepG2 cells.
Topics: Apigenin; Autophagosomes; Autophagy; Hep G2 Cells; Humans; Lipid Metabolism; Microtubule-Associated Proteins; TOR Serine-Threonine Kinases
PubMed: 33030472
DOI: 10.1039/d0fo00949k -
Scientific Reports May 2022Apigenin is a dietary polyphenol found abundantly in fruit and vegetables, which sensitizes leukaemia cells to topoisomerase inhibitor agents (e.g., etoposide), and...
Apigenin is a dietary polyphenol found abundantly in fruit and vegetables, which sensitizes leukaemia cells to topoisomerase inhibitor agents (e.g., etoposide), and alkylating agents (e.g., cyclophosphamide), reducing ATP levels and inducing apoptosis; whilst being protective to control haematopoietic stem cells. This study analysed the expression profiles of intrinsic and extrinsic apoptosis-related genes and proteins to help elucidate the mechanisms of action of apigenin when used in combination with etoposide or cyclophosphamide in lymphoid and myeloid leukaemia cell lines (Jurkat and THP-1). Expression of apoptosis-related genes were measured using a TaqMan® Human Apoptosis Array and the StepOne Plus RT-qPCR System, whilst apoptosis-related proteins were determined using a protein profiler™-human apoptosis array and the LI-COR Odyssey Infrared Imaging System. Apigenin when combined with etoposide or cyclophosphamide-induced apoptosis via the mitochondrial pathway, increasing the expression of pro-apoptotic cytochrome c, SMAC/DIABLO, and HTRA2/OMI, which promoted caspase-9 and -3 activation. Targeting anti-apoptotic and/or pro-apoptotic members of the apoptotic pathways is a promising strategy to induce cancer cell death and improve sensitivity to chemotherapy agents. Here the apoptotic pathways induced by apigenin in combination with etoposide or cyclophosphamide were identified within human leukaemia cell lines, such applications could provide combination therapies for the treatment of leukaemia.
Topics: Apigenin; Apoptosis; Apoptosis Regulatory Proteins; Cell Line; Cyclophosphamide; Drug Therapy, Combination; Etoposide; Humans; Leukemia; Mitochondrial Proteins
PubMed: 35614109
DOI: 10.1038/s41598-022-11441-z