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Nutrient or energy deprivation, especially glucose restriction, is a promising anticancer therapeutic approach. However, establishing a precise and potent deprivation strategy remains a formidable task. The Golgi morphology is crucial in maintaining the function of transport proteins (such as GLUT1) driving glycolysis. Thus, in this study, we present a "Golgi-customized Trojan horse" based on tellurium loaded with apigenin (4′,5,7-trihydroxyflavone) and human serum albumin, which was able to induce GLUT1 plasma membrane localization disturbance via Golgi dispersal leading to the inhibition of tumor glycolysis. Diamond-shaped delivery system can efficiently penetrate into cells as a gift like Trojan horse, which decomposes into tellurite induced by intrinsically high H 2 O 2 and GSH levels. Consequently, tellurite acts as released warriors causing up to 3.8-fold increase in Golgi apparatus area due to the down-regulation of GOLPH3. Further, this affects GLUT1 membrane localization and glucose transport disturbance. Simultaneously, apigenin hinders ongoing glycolysis and causes significant decrease in ATP level. Collectively, our "Golgi-customized Trojan horse" demonstrates a potent antitumor activity because of its capability to deprive energy resources of cancer cells. This study not only expands the applications of tellurium-based nanomaterials in the biomedicine but also provides insights into glycolysis restriction for anticancer therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

SUMMARY Acacetin, a flavonoid compound, possesses a wide range of pharmacological effects, including antimicrobial, immune regulation, and anticancer effects. Some key steps in its biosynthetic pathway were largely unknown in flowering plants. Here, we present the first haplotype‐resolved genome of Chrysanthemum indicum, whose dried flowers contain abundant flavonoids and have been utilized as traditional Chinese medicine. Various phylogenetic analyses revealed almost equal proportion of three tree topologies among three Chrysanthemum species (C. indicum, C. nankingense, and C. lavandulifolium), indicating that frequent gene flow among Chrysanthemum species or incomplete lineage sorting due to rapid speciation might contribute to conflict topologies. The expanded gene families in C. indicum were associated with oxidative functions. Through comprehensive candidate gene screening, we identified five flavonoid O‐methyltransferase (FOMT) candidates, which were highly expressed in flowers and whose expressional levels were significantly correlated with the content of acacetin. Further experiments validated two FOMTs (CI02A009970 and CI03A006662) were capable of catalyzing the conversion of apigenin into acacetin, and these two genes are possibly responsible acacetin accumulation in disc florets and young leaves, respectively. Furthermore, combined analyses of ancestral chromosome reconstruction and phylogenetic trees revealed the distinct evolutionary fates of the two validated FOMT genes. Our study provides new insights into the biosynthetic pathway of flavonoid compounds in the Asteraceae family and offers a model for tracing the origin and evolutionary routes of single genes. These findings will facilitate in vitro biosynthetic production of flavonoid compounds through cellular and metabolic engineering and expedite molecular breeding of C. indicum cultivars. [ABSTRACT FROM AUTHOR]

Apigenin, a naturally derived flavonoid, is increasingly being acknowledged for its potential therapeutic applications, especially in oncology. This research explores apigenin's capacity to modulate cancer cell viability, emphasizing its roles beyond its minimal antioxidant activity attributed to its basic molecular structure devoid of hydroxyl groups. We investigated apigenin's effects on two breast cancer cell lines, estrogen-dependent MCF-7 and non-estrogen-dependent MDA-MB-231 cells. Our findings reveal that apigenin exerts a dose-dependent cytotoxic and anti-migratory impact on these cells. Interestingly, both apigenin and doxorubicin—a standard chemotherapeutic agent—induced lipid droplet accumulation in a dose-dependent manner in MDA-MB-231 cells. This phenomenon was absent in MCF-7 cells and not evident when doxorubicin and apigenin were used concurrently, suggesting distinct cellular responses to these treatments that imply that their synergistic effects might be mediated through mechanisms unrelated to lipid metabolism. A further chemoinformatics analysis indicated that apigenin and doxorubicin might interact primarily at the level of ATP-binding cassette (ABC) transporter proteins, with potential indirect influences from the AKT and MYC signaling pathways. These results highlight the importance of understanding the nuanced interactions between apigenin and conventional chemotherapeutic drugs, as they could lead to more effective strategies for cancer treatment. This study underscores apigenin's potential as a modulator of cancer cell dynamics through mechanisms independent of its direct antioxidant effects, thereby contributing to the development of flavonoid-based adjunct therapies in cancer management. [ABSTRACT FROM AUTHOR]

Apigenin, a natural flavonoid compound found in chamomile (Matricaia chamomilla L.) from the Asteraceae family, has been shown in our previous study to possess antimyocardial hypertrophy and anti‐cardiac fibrosis effects. However, its effects and mechanisms on the pyroptosis of cardiomyocytes induced by doxorubicin (DOX) are poorly understood. The objective of this study was to investigate the role of GSK‐3β and the effects of apigenin in DOX‐induced cardiotoxicity. H9c2 cells stimulated with DOX were treated with SB216763 and apigenin. Additionally, a mouse model of DOX‐induced cardiotoxicity was prepared and further treated with apigenin and SB216763 for 30 days. The findings revealed that treatment with SB216763 or apigenin resulted in a significant reduction in the levels of pyroptosis‐related factors. Furthermore, the phosphorylation of GSK‐3β was enhanced while the phosphorylation of nuclear factor‐kB (NF‐κB) p65 was reduced following treatment with either SB216763 or apigenin. Conversely, the effects of apigenin treatment were nullified in siRNA‐GSK‐3β‐transfected cells. Results from computer simulation and molecular docking analysis supported that apigenin could directly target the regulation of GSK‐3β. Therefore, our study confirmed that the inhibition of GSK‐3β and treatment with apigenin effectively suppressed the pyroptosis of cardiomyocytes in both DOX‐stimulated H9c2 cells and mice. These benefits may be attributed in part to the decrease in GSK‐3β expression and subsequent reduction in NF‐κB p65 activation. Overall, our findings revealed that the pharmacological targeting of GSK‐3β may offer a promising therapeutic approach for alleviating DOX‐induced cardiotoxicity. [ABSTRACT FROM AUTHOR]

This study aimed to extract apigenin and luteolin from celery seeds using 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) based ultrasonic-assisted technique. Optimal extraction conditions were determined through the integration of support vector regression combined with various optimization algorithms, including Genetic Algorithm, Particle Swarm Optimization, Gray Wolf Optimizer, Bat Algorithm, Firefly Algorithm, and Cuckoo Search Algorithm. The identified optimal conditions included an extraction time of 52 min, an HP-β-CD concentration of 24 mg/mL, and a solvent-to-solid ratio of 24 mL/g. Under these conditions, the predicted apigenin and luteolin content in the extract were 0.156 and 0.814 mg/g, respectively, closely aligning with the actual values of 0.158 ± 0.005 mg/g and 0.807 ± 0.008 mg/g. Notably, the HP-β-CD/water extract exhibited significantly higher concentrations of active ingredients and antioxidant activity compared to the water extract, with the content of apigenin and luteolin in the water extract being only 25 and 45%, respectively, compared to the HP-β-CD/water extract. Regarding the antioxidant effect, the water extract displayed a 50% scavenging capacity (SC50) of 331.29 ± 20.5 g/mL, whereas the SC50 for the HP-β-CD/water extract was 89.04 ± 4.70 g/mL. Molecular modeling and IR spectra analysis also suggested the formation of inclusion complexes between HP-β-CD and apigenin/luteolin. These findings suggested that HP-β-CD could be a preferable alternative to conventional solvents due to its advantages, such as easier control, safety, and cost-effectiveness. In addition, the use of support vector regression and nature-inspired optimization algorithms could be promising alternatives to traditional response surface methodology. [ABSTRACT FROM AUTHOR]

Summary: Apigenin (AP) is a natural flavonoid with multiple health benefits that can be used in functional foods. However, the hydrophobicity and poor aqueous solubility of AP have hindered its food application. With ethanol injection and spray drying, encapsulated AP in dried chitosan‐coated liposomes could be promising in delivering AP via foods. By comparing with the unencapsulated AP, this study examined the potential of spray‐dried chitosan‐coated apigenin liposomes (SCAL) in preserving the AP content and antioxidant capacity against food‐related heat, pH, light, oxygen and salt conditions. The moisture sorption isotherms and storage stability of SCAL were also investigated. The results show that the encapsulated AP in SCAL had better stability against pH (pH 2, pH 4, pH 6 and pH 7), light, oxygen and salt stress (0.1, 0.3 and 0.5 M NaCl) than the unencapsulated AP. The limits of relative humidity (RH) for SCAL storage were found to be <50% at 25 °C, <60% at 35 °C and <70% at 45 °C. SCAL could preserve AP over 90 days in room (86.55–95.42%) and chilled (91.54–95.79%) conditions. These findings suggest the potential of spray‐dried chitosan‐coated liposomes in improving the stability of AP, hence SCAL is promising for delivering AP in functional foods. [ABSTRACT FROM AUTHOR]

A total of 43 compounds, including phenolic acids, flavonoids, lignans, and diterpene, were identified and characterized using UPLC‐ESI‐Q‐TOF‐MS coupled with UNIFI software. The identified flavonoids were mostly isomers of luteolin, apigenin, and quercetin, which were elucidated and distinguished for the first time in pepper cultivars. The use of multivariate data analytics for sample discrimination revealed that luteolin derivatives played the most important role in differentiating pepper cultivars. The content of phenolic acids and flavonoids in immature green peppers was generally higher than that of mature red peppers. The pepper extracts possessed significant antioxidant activities, and the antioxidant activities correlated well with phenolic contents and their molecular structure. In conclusion, the findings expand our understanding of the phytochemical components of the Chinese pepper genotype at two maturity stages. Moreover, a UPLC‐ESI‐Q‐TOF‐MS in negative ionization mode rapid methods for characterization and isomers differentiation was described. [ABSTRACT FROM AUTHOR]

Due to its propensity to metastasize, cancer remains one of the leading causes of death worldwide. Thanks in part to their intrinsic low cytotoxicity, the effects of the flavonoid family in the prevention and treatment of various human cancers, both in vitro and in vivo, have received increasing attention in recent years. It is well documented that Apigenin (4′,5,7-trihydroxyflavone), among other flavonoids, is able to modulate key signaling molecules involved in the initiation of cancer cell proliferation, invasion, and metastasis, including JAK/STAT, PI3K/Akt/mTOR, MAPK/ERK, NF-κB, and Wnt/β-catenin pathways, as well as the oncogenic non-coding RNA network. Based on these premises, the aim of this review is to emphasize some of the key events through which Apigenin suppresses cancer proliferation, focusing specifically on its ability to target key molecular pathways involved in angiogenesis, epithelial-to-mesenchymal transition (EMT), maintenance of cancer stem cells (CSCs), cell cycle arrest, and cancer cell death. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Peroxynitrite (ONOO−) is an oxidant linked with several human pathologies. Apigenin, a natural flavonoid known for its health benefits, remains unexplored in relation to ONOO− effects. This study investigated the potential of apigenin to structurally protect fibrinogen, an essential blood clotting factor, from ONOO−-induced damage. Methods: Multi-approach analyses were carried out where fibrinogen was exposed to ONOO− generation while testing the efficacy of apigenin. The role of apigenin against ONOO−-induced modifications in fibrinogen was investigated using UV spectroscopy, tryptophan or tyrosine fluorescence, protein hydrophobicity, carbonylation, and electrophoretic analyses. Results: The findings demonstrate that apigenin significantly inhibits ONOO−-induced oxidative damage in fibrinogen. ONOO− caused reduced UV absorption, which was reversed by apigenin treatment. Moreover, ONOO− diminished tryptophan and tyrosine fluorescence, which was effectively restored by apigenin treatment. Apigenin also reduced the hydrophobicity of ONOO−-damaged fibrinogen. Moreover, apigenin exhibited protective effects against ONOO−-induced protein carbonylation. SDS-PAGE analyses revealed that ONOO−treatment eliminated bands corresponding to fibrinogen polypeptide chains Aα and γ, while apigenin preserved these changes. Conclusions: This study highlights, for the first time, the role of apigenin in structural protection of human fibrinogen against peroxynitrite-induced nitrosative damage. Our data indicate that apigenin offers structural protection to all three polypeptide chains (Aα, Bβ, and γ) of human fibrinogen. Specifically, apigenin prevents the dislocation or breakdown of the amino acids tryptophan, tyrosine, lysine, arginine, proline, and threonine and also prevents the exposure of hydrophobic sites in fibrinogen induced by ONOO−. [ABSTRACT FROM AUTHOR]

Neuroinflammation, a hallmark of various central nervous system disorders, is often associated with oxidative stress and neuronal or oligodendrocyte cell death. It is therefore very interesting to target neuroinflammation pharmacologically. One therapeutic option is the use of nutraceuticals, particularly apigenin. Apigenin is present in plants: vegetables (parsley, celery, onions), fruits (oranges), herbs (chamomile, thyme, oregano, basil), and some beverages (tea, beer, and wine). This review explores the potential of apigenin as an anti-inflammatory agent across diverse neurological conditions (multiple sclerosis, Parkinson's disease, Alzheimer's disease), cancer, cardiovascular diseases, cognitive and memory disorders, and toxicity related to trace metals and other chemicals. Drawing upon major studies, we summarize apigenin's multifaceted effects and underlying mechanisms in neuroinflammation. Our review underscores apigenin's therapeutic promise and calls for further investigation into its clinical applications. [ABSTRACT FROM AUTHOR]

Objective: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age and is one of the main causes of ovulation infertility, affecting 5-10% of women. Inflammation, hormonal imbalances, and disruption of the oxidant-antioxidant balance are the main factors in the pathophysiology of PCOS. This study was designed to answer the question of whether apigenin and chrysin have therapeutic effects on the dehydroepiandrosterone (DHEA)-induced rat model of PCOS. Materials and Methods: The experimental PCOS model was created by administering 6 mg/100g DHEA subcutaneously to 21-day-old female Wistar rats for 28 days, followed by treatment with natural agents 50 mg/kg apigenin and 50 mg/kg chrysin by oral gavage twice a week for one month. The predominant cell type was determined by microscopic analysis in vaginal smears daily from day 10 to day 28 of the experiment. In tissue supernatants, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities, and malondialdehyde (MDA) levels were obtained by spectrophotometric method with appropriate manual methods; follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone, interleukin (IL)-18, IL-1β, and IL-13 levels were determined by enzyme-linked immunosorbent assay (ELISA) method. In addition, histological sections obtained from ovarian tissue samples were stained with hematoxylin-eosin and examined under a light microscope. Results: The results showed that treatment with apigenin and chrysin alone and in combination reduced MDA, LH, FSH, progesterone, IL-1β, IL-13, and IL-18 levels compared with PCOS rats. Furthermore, enzymatic activities of antioxidants including CAT, SOD, and GPx in the ovaries increased in therapeutic groups compared to the PCOS group. Conclusion: In conclusion, this study demonstrates the potential therapeutic efficacy of apigenin and chrysin, either alone or in combination, in alleviating the hormonal imbalances, inflammation, and oxidative stress in DHEA-induced PCOS rats. Apigenin, in particular, emerges as a promising agent for PCOS treatment, showing superiority over chrysin and combination treatments in ameliorating cystic follicles and improving various parameters associated with PCOS pathophysiology. These findings suggest that apigenin holds promise as a novel therapeutic agent for PCOS and warrants further investigation in clinical settings. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that has a high prevalence worldwide. Apigenin is a flavonoid present in several vegetables and fruits and has anti-inflammatory, anti-oxidant, and anti-MetS properties. This study aims to systematically review the effects of apigenin against MetS and the relevant molecular and cellular mechanisms of action, pharmacokinetics features, and potential structure-activity relationship. Electronic databases including Scopus, PubMed, Science Direct and Cochrane Library were searched for in vivo, and in vitro, and human studies with the following keywords: "apigenin" and "metabolic syndrome or insulin resistance syndrome", "fatty liver", "hypertension or blood pressure", "diabetes or blood glucose", "dyslipidemia", "heart or cardiovascular" and "obesity" in title/abstract. Data were collected from 2000 until 2021 (up to April). Only papers published in the English language were included. Forty-six full-text articles out of 1016 retrieved papers were reviewed and underwent quality assessment by investigators. Antiobesity activity of apigenin is mainly through attenuating adipocyte differentiation by suppressing the mitotic clonal expansion and the adipogenesis-related factors. Its anti-diabetic effects can be exerted through inhibition of protein tyrosine phosphatase1B expression, maintaining the activity of anti-oxidant enzymes, reducing intracellular ROS production, cellular DNA damage, protein carbonylation, and attenuating ß-cell apoptosis. Moreover, apigenin could attenuate dyslipidemia and subsequent atherosclerotic conditions through down-regulating sterol regulatory elementbinding proteins (SREBP)-1c, SREBP-2, stearyl-CoA desaturase-1, and 3-hydroxy-3-methyl-glutaryl- CoA reductase. Apigenin as a dietary bioactive compound would be a promising candidate for improving MetS and its components. [ABSTRACT FROM AUTHOR]

Flavonoids are a diverse set of natural products with promising bioactivities including anti-inflammatory, anti-cancer, and neuroprotective properties. Previously, the oleaginous host Yarrowia lipolytica has been engineered to produce high titers of the base flavonoid naringenin. Here, we leverage this host along with a set of E. coli bioconversion strains to produce the flavone apigenin and its glycosylated derivative isovitexin, two potential nutraceutical and pharmaceutical candidates. Through downstream strain selection, co-culture optimization, media composition, and mutant isolation, we were able to produce168 mg/L of apigenin, representing a 46% conversion rate of 2-(R/S)-naringenin to apigenin. This apigenin platform was modularly extended to produce isovitexin by addition of a second bioconversion strain. Together, these results demonstrate the promise of microbial production and modular bioconversion to access diversified flavonoids. [Display omitted] • Apigenin and its flavone C-glucosides are promising bioactive natural products. • Apigenin produced through delayed multi-organism co-culture. • Bioconversion enhanced by host choice, media optimization, and mutant isolation. • Co-culture modularity enables downstream diversification to isovitexin. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is a metastatic disease and a formidable treatment challenge as it does not respond to existing therapies. Epigenetic regulators play a crucial role in the progression and metastasis by modulating the expression of anti-apoptotic, pro-apoptotic markers and related miRNAs in TNBC cells. We have investigated the anti-TNBC potential of dietary flavonoid 'Apigenin' and its combination with Vorinostat on MDA-MB-231 cells. At Apigenin generated ROS, inhibited cell migration, arrested the cell cycle at subG0/G1 phases, and induced apoptotic-mediated cell death. Apigenin reduced the expression of the class-I HDACs at the transcriptomic and proteomic levels. In the immunoblotting study, Apigenin has upregulated pro-apoptotic markers and downregulated anti-apoptotic proteins. Apigenin inhibited the enzymatic activity of HDAC/DNMT and increased HAT activity. Apigenin has manifested its effect on miRNA expression by upregulating the tumor-suppressor miR-200b and downregulation oncomiR-21. Combination study reduced the growth of TNBC cells synergistically by modulating the expression of epigenetic and apoptotic regulators. Molecular docking and MD simulations explored the mechanism of catalytic inhibition of HDAC1 and HDAC3 and supported the in-vitro studies. The overall studies demonstrated an anti-TNBC potential of Apigenin and may help to design an effective strategy to treat metastatic phenotype of TNBC. [ABSTRACT FROM AUTHOR]

Self-nanoemulsifying drug delivery systems (SNEDDS) have been used to improve the oral bioavailability of various drugs. In the current study, apigenin was developed as SNEDDS to solve its dissolution problem and enhance oral bioavailability and antioxidant potential. SNEDDS were prepared by mixing Gelucire 44/14, Tween 80, and PEG 400 under controlled conditions. The droplet of diluted SNEDDS demonstrated a spherical shape with a size of less than 100 nm and a neutral charge. The very fast self-emulsification was obtained within 32 s, and the transmittance values exceeded 99%. The highest drug loading was 90.10 ± 0.24% of the initial load with the highest %encapsulation efficiency of 84.20 ± 0.03%. FT-IR and DSC spectra showed no interaction between components. The dissolution in buffer pH 1.2, 4.5, and 6.8 showed significantly higher dissolved apigenin than the apigenin coarse powder. The dissolution profiles were fitted to the Korsmeyer–Peppas kinetics. The cellular antioxidant activities in Caco-2 cells were approximately 52.25–54.64% compared to no treatment and were higher than the apigenin coarse powder (12.70%). Our work highlights the potential of SNEDDS to enhance the dissolution and permeability of apigenin and promote antioxidant efficacy, which has a strong chance of being developed as a bioactive compound for nutraceuticals. [ABSTRACT FROM AUTHOR]

Studying the involvement of nicotinic acetylcholine receptors (nAChRs), specifically α7-nAChRs, in neuropsychiatric brain disorders such as autism spectrum disorder (ASD) has gained a growing interest. The flavonoid apigenin (APG) has been confirmed in its pharmacological action as a positive allosteric modulator of α7-nAChRs. However, there is no research describing the pharmacological potential of APG in ASD. The aim of this study was to evaluate the effects of the subchronic systemic treatment of APG (10–30 mg/kg) on ASD-like repetitive and compulsive-like behaviors and oxidative stress status in the hippocampus and cerebellum in BTBR mice, utilizing the reference drug aripiprazole (ARP, 1 mg/kg, i.p.). BTBR mice pretreated with APG (20 mg/kg) or ARP (1 mg/g, i.p.) displayed significant improvements in the marble-burying test (MBT), cotton-shredding test (CST), and self-grooming test (SGT) (all p < 0.05). However, a lower dose of APG (10 mg/kg, i.p.) failed to modulate behaviors in the MBT or SGT, but significantly attenuated the increased shredding behaviors in the CST of tested mice. Moreover, APG (10–30 mg/kg, i.p.) and ARP (1 mg/kg) moderated the disturbed levels of oxidative stress by mitigating the levels of catalase (CAT) and superoxide dismutase (SOD) in the hippocampus and cerebellum of treated BTBR mice. In patch clamp studies in hippocampal slices, the potency of choline (a selective agonist of α7-nAChRs) in activating fast inward currents was significantly potentiated following incubation with APG. Moreover, APG markedly potentiated the choline-induced enhancement of spontaneous inhibitory postsynaptic currents. The observed results propose the potential therapeutic use of APG in the management of ASD. However, further preclinical investigations in additional models and different rodent species are still needed to confirm the potential relevance of the therapeutic use of APG in ASD. [ABSTRACT FROM AUTHOR]

After ovulation, senescent oocytes inevitably experience reduced quality and defects in embryonic development. Apigenin (API) is a flavonoid with a wide range of pharmacological effects. Therefore, this study examined the protective effects of API on the quality of porcine oocytes during in-vitro ageing and the underlying mechanisms. The results showed that API treatment could reduce the activation rate after aging for 48 h. In addition, API significantly reduced reactive oxygen species, abnormal distribution of mitochondria, early apoptosis in ageing oocytes, increased glutathione, and mitochondrial adenosine triphosphate levels in ageing oocytes. Importantly, API increased the embryonic development rate in aged oocytes. We also examined molecular changes, finding decreased sirtuin 1 expression in in-vitro postovulatory oocytes, but API reversed this effect. Our results suggest that API attenuates the deterioration of oocyte quality during in-vitro ageing, possibly by reducing oxidative stress through the upregulation of sirtuin 1. [Display omitted] [ABSTRACT FROM AUTHOR]

This study aimed to investigate the potential anti-inflammatory and antioxidant effects of apigenin in rats with acute lung injury (ALI). We also examined changes in levels of inflammatory and antioxidant factors after apigenin treatment in a rat model of ALI. Methods: We searched several databases, including PubMed, Scopus, EMBASE, Web of Science, ProQuest, and GoogleScholar, to retrieve relevant articles for our systematic review and meta-analysis. Five studies with 226 rat models of ALI were included in this study. We investigated inflammatory factors and oxidative stress with the corresponding 95% confidence interval in three groups: 1. Group1 (control vs. ALI), 2. Group2 (ALI vs. apigenin10), and 3. Group3 (ALI vs. apigenin20). Estimating the correlation and 95% confidence intervals for the inflammatory agents and oxidative stress in the intervention group (ALI), compared with that in the control group, respectively (correlation: 0.194; 95% confidence intervals, 0.101–0.282, p value =.001, z-value= 4.08) and (correlation: 0.099; 95% confidence intervals, 0.016–0.182, p value =.020, z value= 2.325). Estimating the correlation and 95% confidence intervals for the inflammatory agents and oxidative stress in the intervention group (apigenin 10 mg/kg), compared with that in the control group (ALI), respectively (correlation: 0.476; 95% confidence intervals, 0.391–0.553, p value =.001, z-value= 9.678) and (correlation: 0.415; 95% confidence intervals, 0.313–0.508, p value=.001, z-value= 7.349). Apigenin may have potential anti-inflammatory and antioxidant effects in rat models of ALI. However, the efficacy of apigenin as a therapeutic strategy requires further investigation through prospective controlled randomized trials. [ABSTRACT FROM AUTHOR]

The development of two-dimensional chromatography systems is crucial in many scientific fields as it provides improved separation efficiency and selectivity of complex mixtures. By separating compounds based on two independent properties, these systems can offer a more detailed understanding of sample composition. This increased level of detail is particularly useful in industries such as pharmaceuticals, environmental analysis, and proteomics, where complex mixtures with similar properties need to be differentiated. A new chromatography system with two dimensions was developed to separate and quantify specific flavonoids in German wine samples. The first dimension used a homemade hydrophilic interaction liquid chromatographic column, while the second dimension used a reversed-phase liquid chromatographic column. This 2D ZIC-HILIC x RP technique was able to address the problem of peak overlapping that commonly occurs in one-dimensional liquid chromatography, especially for natural products. The study presents analytical and statistical data for both techniques, and suggests that the use of two-dimensional chromatography can improve the resolution of conventional one-dimensional liquid chromatography. In a conventional ZIC-HILIC-HPLC system, apigenin and naringenin were detected together but were successfully separated and measured using a 2DLC system. The limits of detection (LOD) for apigenin and naringenin were found to be 0.0705 µg/mL and 0.1300 µg/mL, respectively, while the limits of quantification (LOQ) were 0.2136 µg/mL and 0.3939 µg/mL, respectively. The recovery rate for both compounds was over 99%, with a relative standard deviation (RSD) of less than 1.5%. The linearity range for both compounds was between 0.005 µg/mL to 10 µg/mL, and the correlation coefficient (r2) was determined to be 0.9998. For hesperidin and rutin, the LOD and LOQ were found to be 0.0336 µg/mL and 0.1018 µg/mL, and 0.0120 µg/mL and 0.0363 µg/mL, respectively. The linearity range for both compounds was between 0.005 µg/mL to 12 µg/mL, and the correlation coefficient (r2) was determined to be 0.9999. [ABSTRACT FROM AUTHOR]

Background and Objective: Antioxidant apigenin (AP) is a natural, non-mutagenic, and less toxic flavonoid with pharmacological anti-cancer, anti-viral, anti-bacterial, anti-apoptotic, and anti-inflammatory activities. This antioxidant is easily received by the cell, binds to sperm DNA, and forms a DNA-AP complex, thereby protecting sperm DNA. The present study was conducted to determine the antioxidant effect of AP on human sperm quality after freezing-thawing. Methods: In this descriptive-analytical study, 10 normozoospermic samples underwent freezing-thawing conditions, and sperm functional tests were investigated in different AP concentrations, including 0.4 mM, 0.2 mM, 0.1 mM, and 0.05 mM. Results: The quality of total sperm parameters and functional tests decreased after freezing compared to before freezing. Among the AP concentrations, only in the 0.2 mM AP concentration, the improvement of the additional histone percentage, protamine deficiency, and sperm DNA health were observed compared to the control; this finding was not statistically significant. Conclusion: The use of AP with a concentration of 0.2 mM during freezing-thawing culminates in improving sperm functional tests. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a chronic inflammatory disorder affecting the colon, with symptomatology influenced by factors including environmental, genomic, microbial, and immunological interactions. Gut microbiota dysbiosis, characterized by bacterial population alterations, contributes to intestinal homeostasis disruption and aberrant immune system activation, thereby exacerbating the inflammatory state. This study assesses the therapeutic efficacy of intraperitoneal (IP) injected flavonoids (apigenin, luteolin, and xanthohumol) in the reduction of inflammatory parameters and the modulation of the gut microbiota in a murine model of ulcerative colitis. Flavonoids interact with gut microbiota by modulating their composition and serving as substrates for the fermentation into other anti-inflammatory bioactive compounds. Our results demonstrate the effectiveness of luteolin and xanthohumol treatment in enhancing the relative abundance of anti-inflammatory microorganisms, thereby attenuating pro-inflammatory species. Moreover, all three flavonoids exhibit efficacy in the reduction of pro-inflammatory cytokine levels, with luteolin strongly demonstrating utility in alleviating associated physical UC symptoms. This suggests that this molecule is a potential alternative or co-therapy to conventional pharmacological interventions, potentially mitigating their adverse effects. A limited impact on microbiota is observed with apigenin, and this is attributed to its solubility constraints via the chosen administration route, resulting in its accumulation in the mesentery. [ABSTRACT FROM AUTHOR]

Background: Liver fibrosis is an irreversible liver destruction. Apigenin (API) has different pharmacological properties as anticancer, anti-inflammatory, and antioxidant; however, API hepatoprotective and therapeutic effects are not often studied. This study assesses protective and therapeutic API effects on hepatic injuries produced by thioacetamide (TAA) in rats. Methods: Forty-nine rats were sorted into seven groups (7 in each): negative control (G1), positive control (G2, TAA), API group (G3), TAA+API group (G4), TAA+SL group (G5), API+TAA group (G6), and SL+TAA group (G7). API and SL effects on TAA-induced hepatotoxicity were examined by determined body weights, liver weights, complete blood count picture (white blood cells, red blood cells, hemoglobin, hematocrit, and platelets counts), liver function tests (alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, gamma glutamyl transferase, alkaline phosphatase, total proteins, albumin, and globulin), and oxidative stress markers (malonaldehyde, catalase, superoxide dismutase, and reduced glutathione) in serum and liver histological was assessed. Results: TAA decreased red blood cells, platelets, hemoglobin content, and hematocrit (p <0.001) and increased white blood cells count (p <0.001) versus control. Serum values of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, gamma glutamyl transferase, alkaline phosphatase, and malondialdehyde significantly elevated (p <0.001); meanwhile, total protein, albumin, globulin, catalase, superoxide dismutase, and glutathione S transferase decline (p <0.001) versus negative control. Hepatic structure of TAA group revealed fibrosis and hepatocyte destruction. Therapeutic or protective treating TAA-rats with API or SL ameliorate hematological values, liver functions, oxidative stress, and histological alterations especially therapeutic effects on hematological changes, liver function tests, and oxidative stress markers. Conclusions: Apigenin had therapeutic and protective effects on liver fibrosis due to its antioxidant activity with therapeutic better than protective effects. [ABSTRACT FROM AUTHOR]

Background: Glioma is a devastating disease with the worst prognosis among human malignant tumors. Although temozolomide (TMZ) improves the overall survival of glioma patients, there are still many glioma patients who are resistant to TMZ. In this study, we focused on the effect of apigenin (API) and TMZ on glioma cells in vitro and in vivo, and we studied the underlying molecular mechanisms. Materials and Methods: To investigate the effect of API on glioblastoma cell proliferation, cell viability was assessed after glioma cells were incubated with various concentrations of API with or without TMZ using MTT assays. Then, we explored the synergistic effect of API and TMZ on glioma cell cycle, apoptosis, and migration. To investigate the molecular mechanism behind the synergism of API and TMZ, we examined the related genes of the major signaling pathways involved in glioma pathogenesis by Western blotting. Results: In this study, we found that API significantly suppressed the proliferation of glioma cells in a dose- and time-dependent manner. Combining API and TMZ significantly induced glioma cells arrest at the G2 phase and inhibited glioma cells proliferation compared with API or TMZ alone. In addition, API promoted the ability of TMZ to induce glioma cells apoptosis and inhibit glioma cells invasion. Furthermore, compared with treatment with individual agents, the combination of API and TMZ significantly inhibited the growth of subcutaneous tumors in mice. These results implied that API could synergistically suppress the growth of glioma cells when combined with TMZ. Combining API and TMZ significantly inhibited the protein expression of p-AKT, cyclin D1, Bcl-2, Matrix Metallopeptidase 2, and Matrix Metallopeptidase 9. Conclusion: API and TMZ synergistically inhibited glioma growth through the PI3K/AKT pathway. [ABSTRACT FROM AUTHOR]

Aging impairs osteoblast function and bone turnover, resulting in age‐related bone degeneration. Stress granules (SGs) are membrane‐less organelles that assemble in response to stress via the recruitment of RNA‐binding proteins (RBPs), and have emerged as a novel mechanism in age‐related diseases. Here, we identified HuR as a bone‐related RBP that aggregated into SGs and facilitated osteogenesis during aging. HuR‐positive SG formation increased during osteoblast differentiation, and HuR overexpression mitigated the reduction in SG formation observed in senescent osteoblasts. Moreover, HuR positively regulated the mRNA stability and expression of its target β‐catenin by binding and recruiting β‐catenin into SGs. As a potential therapeutic target, HuR activator apigenin (API) enhanced its expression and thus aided osteoblasts differentiation. API treatment increased HuR nuclear export, enhanced the recruitment of β‐catenin into HuR‐positive SGs, facilitated β‐catenin nuclear translocation, and contributed osteogenesis. Our findings highlight the roles of HuR and its SGs in promoting osteogenesis during skeletal aging and lay the groundwork for novel therapeutic strategies against age‐related skeletal disorders. [ABSTRACT FROM AUTHOR]

Joint inflammation and damage can be caused by rheumatoid arthritis (RA), a systemic autoimmune disorder. Long-term RA affects the joints, causing pain, edema, and stiffness. Several studies have revealed that the exact origin of RA is still unidentified, but inherited disorder and external factors may contribute to the inflammatory condition. The incidence of RA is mostly caused by uncontrolled-production of proinflammatory cytokines under nuclear factor-kappa B (NF-κB) overexpression condition. The nuclear factor-kappa B plays an important role in inflammatory T cell activation, differentiation, and effector function. Therefore, the inhibition of NF-κB can be a strategy to reduce the adverse effects or incidence of RA. Red betel is a perennial herb native to Indonesia that is widely used by conventional healers. Many reports show that red betel leaf extracts contain several critical bioactive compounds such as Apigenin, Luteolin, Hydroxychavicol, Eugenol, and Chavibetol. This present study aims to evaluate and predict the therapeutic potential of those compounds as medication that reduce inflammation against RA by disturbing and inactivating the NF-κB molecular interaction. The LC-MS chromatography was used to evaluate the chemical contents of red betel leaves. Furthermore, in silico study, the 3D structure of the active compounds of red betel leaves is obtained from PubChem web server, while NF-κB is obtained from Protein Data Bank (PDB) website. Molecular docking was used to screen the potential compounds compared to aspirin as control. As a result, 2 compounds including Apigenin and Luteolin have smaller bond affinity values, -6.3 and -6.0 kcal/mol, respectively compared to aspirin. Based on molecular dynamics (MD) simulation, the root-mean-square deviation (RMSD) value of protein-ligand complexes have the similar pattern over 1000/ps except the NF-κB-Chavibetol complex which has an unstable pattern. On the other hand, the total energy of the protein-ligand complexes have similar average number of -1.69 kJ/mol. The simulation indicates the ligands have constant binding energy to the protein. Furthermore, numerous pharmacokinetic properties of compounds including absorption, distribution, metabolism, excretion and toxicity are exponentially greater than the control drugs. Finally, red betel active compounds can be used as alternative candidates of RA therapy medication. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Natural components that can exert a wide range of anti‐hair loss activity with fewer side effects are in high demand. The objective of this study was to investigate the anti‐hair loss potential of Silybum marianum flower extract (SMFE) in vitro and in vivo. Methods: The effect of SMFE on dermal papilla cells was evaluated by measuring cell proliferation and VEGF production in hair follicle dermal papilla cells (HFDPCs). In addition, to confirm the effect of SMFE on dermal papilla senescence, SA‐β‐gal staining and senescence associated secretory phenotype (SASP) production such as IL‐6 was observed in both replicative and hydrogen peroxide (H2O2)‐induced senescence models. In a clinical study, hair growth was determined by reconstitution analysis after shaving the hair of the clinical subject's scalp and hair area. Results: SMFE increased the proliferation and VEGF production of HFDPCs. It also suppressed cellular senescence of HFDPCs and IL‐6 production in replicative senescence and oxidative stress‐induced senescence models. The hair density and total hair count at 16 and 24 weeks after using hair shampoo containing SMFE were significantly increased compared with those of the placebo group. Conclusion: SMFE has the potential to be used as a natural ingredient for alleviating hair loss. [ABSTRACT FROM AUTHOR]

The present study standardized a green protocol for extracting apigenin from Biophytum poterioides. Natural deep eutectic solvents (NADES) and green extraction techniques like microwave-assisted extraction (MAE) and ultrasound-assisted extraction (UAE) were adopted and optimized by response surface methodology. Based on the statistically evaluated results, the optimal solvent was the choline chloride: oxalic acid (NADE 5) at a molar ratio 1:1 with 30% (v/v) of water. MAE using a solid-to-solvent ratio 1:10 for 6 min duration was identified as the optimum condition for the effective extraction of apigenin. A sixfold increase of apigenin was obtained using NADE 5 (1395.767 ± 5.083 mg/L) compared to ethanol (255.718 ± 2.930 mg/L) at the optimal condition. The FT-IR studies aided in confirming the interaction of apigenin with NADES 5. Furthermore, antioxidant studies demonstrated that the NADES 5 extract had a substantial ability to scavenge DPPH radical (IC50 =219.572 μg/ml). Appraisal of the greenness of the developed methods was evaluated using the novel Analytical GREEnness (AGREEprep) metric. The results confirmed that the combination of NADES and MAE offers a rapid and cheap alternative to conventional solvents for sustainable and green extraction and allows easy transfer of the proposed methodology to large-scale extraction of apigenin. [Display omitted] • An eco-friendly method for apigenin extraction has been developed. • Green solvent-mediated microwave and ultrasound-assisted extractions. • Higher yield and reproducibility of apigenin achieved using NADES than ethanol. • Response surface methodology was used for the protocol optimization. • Evaluation of greenness with Analytical GREEnness (AGREEprep) metric. [ABSTRACT FROM AUTHOR]

Despite the multiple health benefits, natural flavonoid apigenin has poor aqueous solubility that restricts its delivery in foods. This study investigated the potential of spray-dried chitosan-coated liposomes prepared from scalable methods for the food industry as the delivery carriers for apigenin. Apigenin-loaded small unilamellar liposomes produced from ethanol injection had an encapsulation efficiency of 74.88 ± 5.31%. They were electrostatically stabilised via chitosan coating (0.25% w/v) and spray-dried. Spray-dried chitosan-coated apigenin liposomes (SCAL) exhibited the following powder characteristics: yield 66.62 ± 3.08%, moisture content 4.33 ± 0.56%, water activity 0.2242 ± 0.0548, particle size 10.97 ± 1.55 μm, nearly spherical morphology with wrinkles and dents under microscopic observation. Compared with the unencapsulated apigenin, SCAL demonstrated improved aqueous solubility (10.22 ± 0.18 mg/L), higher antioxidant capacity, and stability against simulated gastrointestinal digestion. The chitosan coating gave a slower in-vitro release of apigenin in SCAL (77.0 ± 6.2%) than that of uncoated apigenin liposomes (94.0 ± 5.3%) at 12 h. The apigenin release kinetics from SCAL could be represented by the Korsmeyer-Peppas model (R2 = 0.971). These findings suggest that SCAL could be a promising delivery system of apigenin for functional food applications. [ABSTRACT FROM AUTHOR]

This study focuses on tumor therapy using two biocompatible silver nanoplatforms of chamomile extract and its active ingredient apigenin-7-glucoside. Chamomile silver nanoparticles (Ch-AgNPs) and apigenin 7- glucoside silver nanoparticles (Ap-AgNPs) were synthesized and characterized using different analytical techniques. On a stable nanoplatform with spherical nanoparticles in a narrow size range, both Ch-AgNP and Ap-AgNP exhibit potent cytotoxic effects against two different cell lines (HepG2 and MCF7). The synthesized NPs were radiolabeled with 131I giving high radiochemical purity. Biodistribution studies in tumor-bearing Albino mice showed higher accumulation in tumor sites compared to normal muscle. In conclusion, after further preclinical studies, both chamomile silver nanoparticles (Ch-AgNPs) and apigenin-7-glucoside silver nanoparticles (Ap-AgNPs) can be used as potential drugs for tumor theranostics. [ABSTRACT FROM AUTHOR]

The eight flavonoids, apigenin, chrysin, hesperidin, kaempferol, myricetin, quercetin, rutin and luteolin were tested for the inhibition of human parainfluenza virus type 2 (hPIV-2) replication. Three flavonoids out of the eight, kaempferol, quercetin and luteolin inhibited hPIV-2 replication. Kaempferol reduced the virus release (below 1/10,000), partly inhibited genome and mRNA syntheses, but protein synthesis was observed. It partly inhibited virus entry into the cells and virus spreading, and also partly disrupted microtubules and actin microfilaments, indicating that the virus release inhibition was partly caused by the disruption of cytoskeleton. Quercetine reduced the virus release (below 1/10,000), partly inhibited genome, mRNA and protein syntheses. It partly inhibited virus entry and spreading, and also partly destroyed microtubules and microfilaments. Luteolin reduced the virus release (below 1/100,000), largely inhibited genome, mRNA and protein syntheses. It inhibited virus entry and spreading. It disrupted microtubules and microfilaments. These results indicated that luteolin has the most inhibitory effect on hPIV-2 relication. In conclusion, the three flavonoids inhibited virus replication by the inhibition of genome, mRNA and protein syntheses, and in addition to those, by the disruption of cytoskeleton in vitro. [ABSTRACT FROM AUTHOR]

The stimulator of interferon genes (STING) signaling pathway is crucial for the pathogenesis of autoimmune and inflammatory disorders, including acute lung injury (ALI). Apigenin (4 ′ ,5,7-trihydroxyflavone) is a natural flavonoid widely found in fruits, vegetables, and Chinese medicinal herbs that exhibits a range of pharmacological effects, such as antibacterial and anti-inflammatory activities. However, the efficacy of apigenin in STING pathway-mediated diseases remains unclear. Accordingly, this study screened Chinese medicines to identify potent agents that reduced the synthesis of type I interferons (IFNs). The results revealed apigenin as a potent compound with low cytotoxicity that markedly reduced the synthesis of type I IFNs in response to STING pathway agonists. Besides, apigenin markedly suppressed innate immune responses triggered by the STING agonist SR-717. Mechanistically, apigenin downregulated IFN beta 1 (IFNB1) expression mediated by the STING pathway via dose-dependent inhibition of STING expression, reduction of dimerization, nuclear translocation of phosphorylated IRF3, and disruption of the association between STING and IRF3. Moreover, apigenin effectively mitigated pathological pulmonary inflammation and lung edema in lipopolysaccharide (LPS)-induced ALI in mice. Apigenin further strongly attenuated the hallmarks of immoderate inflammation (interleukin (IL)-6, IL-1 β , and tumor necrosis factor α) and innate immune responses (IFNB1, C-X-C motif chemokine ligand 10, and IFN-stimulated gene 15) by preventing the activation of the STING/IRF3 pathway both in vitro and in vivo. Importantly, SR-717 significantly reversed the inhibitory effects of apigenin in LPS-induced THP1-BlueTM ISG macrophages. Collectively, apigenin effectively alleviated innate immune responses and mitigated inflammation in LPS-induced ALI via inhibition of the STING/IRF3 pathway. These findings suggest the potential of apigenin as a prophylactic and therapeutic candidate for managing STING-mediated diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral Mucositis, a debilitating side effect of radio and chemotherapy for head and neck cancers, involves inflammation and ulceration of the mucous membranes in the oral cavity. This condition often leads to severe pain, difficulty in eating, and compromised quality of life for cancer patients. The use of natural compounds such as polyphenols has shown promise in preventing and alleviating Oral Mucositis as they possess anti-inflammatory, antioxidant, and healing properties, capable of mitigating the adverse effects of chemo and radiotherapy on the oral mucosa. The recent literature suggests that integrating these natural compounds into treatment regimens may help manage Oral Mucositis, offering a potential adjuvant therapy to improve a patient's quality of life and overall well-being during cancer treatment. Oral Mucositis (OM) is the most common side effect due to chemotherapy and radiotherapy, which are the conventional treatment options for head and neck cancers. OM is a severe inflammatory condition characterized by multifactorial etiopathogenesis. It further negatively affects patients' quality of life by severe impairment of normal oral functions. Consequently, it is mandatory to identify new effective therapeutic approaches to both prevent and treat OM while also avoiding any recurrence. Polyphenols recently attracted the interest of the scientific community due to their low toxicity and wide range of biological activities making them ideal candidates for several applications in the odontostomatological field, particularly against OM. This review collects the in vivo studies and the clinical trials conducted over the past 13 years evaluating the preventive and curative effects of several polyphenolic compounds towards chemo- and radiotherapy-induced OM, both when administered alone or as a plant-extracted phytocomplex. The literature fully confirms the usefulness of these molecules, thus opening the possibility of their clinical application. However, polyphenol limitations (e.g., unfavourable physicochemical properties and susceptibility to degradation) have emerged. Consequently, the interest of the scientific community should be focused on developing innovative delivery systems able to stabilize polyphenols, thus facilitating topical administration and maximizing their efficacy. [ABSTRACT FROM AUTHOR]

Two secoiridoid glycosides, lonicejaposide I (1) and secologanin dimethyl acetal (2), six flavonoids, isoorientin (3) hesperidin (4), apigenin 7-O-neohesperidoside (5), luteolin 7-O-B-D-glucopyranoside (6), kaempferol 3-O-(3",6"-di-(E)-p-coumaroyl)-β-D-glucopyranoside (7), and kaempferol 3-O-(3"-O-acetyl, 6"-O-(E)-p-coumaroyl)-β-D-glycopyranoside (8), two caffeoylquinic acid derivatives, chlorogenic acid (9) and 3,5-dicaffeoylquinic acid (10) were isolated from the EtOAc and H2O subextracts of the crude MeOH extract prepared from the aerial parts of Scabiosa atropurpurea. Their structures were identified by extensive 1D and 2D NMR experiments as well as ESI-MS analysis. Xanthine oxidase (XO) inhibitory and antioxidant activities of the isolated compounds were evaluated by in vitro tests. Compounds, 3, 5, 6, 9 and 10 showed mild-to-moderate inhibitory effects on XO enzyme. The highest antioxidant activity was found for compound 10 according to results of DPPH, FRAP and CUPRAC assays. This is the first study on the XO inhibitory activities for compounds 1, 2, 5, 7 and 8. [ABSTRACT FROM AUTHOR]

People's health benefits from andrographolide (ANDRO), apigenin (API), gallic acid (GA), and apocynin (APO) because they aid in the treatment of liver illness. The study mainly illustrated that a green approach is essential in the medical sector as well as the herbal sector with the help of "Green Analytical quality by design". The mobile phase combination Dichloromethane: Ethyl acetate: Formic acid (10:8:0.4)v/v/v was optimized with the aid of an analytical quality‐by‐design approach. The absorbance mode at 254 nm was chosen for densitometric analysis as it gives a compact spot of ANDRO, API, GA, and APO at RF values of 0.24, 0.55, 0.17, and 0.68. Linearity was obtained in the range of 200–800 ng for all four markers. After retardation factor, ANDRO, APO, API, and GA from the tablet were found 0.0433, 0.0020, 0.1356, and 0.0015 mg, respectively. The validation parameter of R2 value ranged from 0.998, 0.999, 0.996, and 0.998 for all four ANDRO, API, GA, and APO. The study's findings revealed that the "high‐performance thin layer chromatography" technology is an environmentally friendly analytical design that helps to maintain the stability of the medication. It was also acknowledged as a quality design and a fresh idea in the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

Apigenin is one of the most widespread flavonoids in the plant kingdom. For centuries, apigenin-containing plant preparations have been used in traditional medicines to treat diseases that have an inflammatory and/or degenerative component. In the 1980s, apigenin was proposed to interfere with the process of carcinogenesis. Since then, more and more evidence has demonstrated its anticancer efficacy, both in vitro and in vivo. Apigenin has been shown to target signaling pathways involved in the development and progression of cancer, such as PI3K/Akt/mTOR, MAPK/ERK, JAK/STAT, NF-κB, and Wnt/β-catenin pathways, and to modulate different hallmarks of cancer, such as cell proliferation, metastasis, apoptosis, invasion, and cell migration. Furthermore, apigenin modulates PD1/PD-L1 expression in cancer/T killer cells and regulates the percentage of T killer and T regulatory cells. Recently, apigenin has been studied for its synergic and additive effects when combined with chemotherapy, minimizing the side effects. Unfortunately, its low bioavailability and high permeability limit its therapeutic applications. Based on micro- and nanoformulations that enhance the physical stability and drug-loading capacity of apigenin and increase the bioavailability of apigenin, novel drug-delivery systems have been investigated to improve its solubility. [ABSTRACT FROM AUTHOR]

Apigenin belongs to the class of compounds known as flavones. It possesses significant antioxidant, anti-inflammatory, and antitumor potential in various preclinical studies. Despite being a potent anticancer molecule, it suffers from significant pharmacokinetic limitations. As per Biopharmaceutical classification system, Apigenin has been categorized as a Class II drug. It has high permeability but low solubility which leads to lower bioavailability. To increase its bioavailability, it has to raise its solubility. Thus, the present work aimed to develop novel Apigenin loaded stealth liposomes to enhance its solubility, plasma residence time and better therapeutic efficacy. Apigenin loaded stealth liposomes (APISL) were prepared by utilizing the ethanol injection technique. The formulation was statistically optimized by DOE and evaluated for particle size, zeta potential, entrapment efficiency, morphology, in-vitro drug release study, in-vivo pharmacokinetic study and stability study. Among all of the preparations, the optimized stealth liposomal batch (APISL-L8) produced the best outcomes, with smallest particle size, the highest percent entrapment efficiency and the highest drug release percent at 48 h. The optimized Apigenin loaded stealth liposomes L8 was found to show higher percent drug release than the plain Apigenin as per Higuchi release model. According to in-vivo experiments, stealth liposomes had a longer exposure period in comparison to pure drug solution. When compared to standard drug, investigations revealed that Apigenin-loaded stealth liposomes demonstrated better plasma retention time and stability. Thus, the result reveals that, the Apigenin-loaded stealth liposome demonstrated an improved bioavailability with enhanced antitumor efficacy in the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

The composition of flavonoids of 12 species of plants of the genus Silene introduced into Western Siberia was studied for the first time. The C-diglycoside of apigenin, shaftoside, was isolated from the aboveground part of S. chalcedonica, the structure of which was identified by HPLC, mass spectrometry, and NMR spectroscopy. In all other studied species, the presence of shaftoside and other C-glycosides of flavones was established on the basis of HPLC data. C-Diglycoside of apigenin —vicenin-2 was first identified in S. sendtneri, S. roemeri, S. viridiflora, S. paradoxa, S. nemoralis, S. frivaldszkyana, S. colpophylla, S. linicola, S. caramanica. The most common in the studied Silene species are the apigenin monoglycosides vitexin and isovitexin and a number of their derivatives, luteolin derivatives orientin and others are found a little-less frequently. The highest content of flavonoids in the aboveground part of the studied species is characterized by S. nemoralis (6.75%); high—S. chalcedonica, S. paradoxa, S. frivaldszkyana, S. caramanica, S. sendtneri (3.35–5.15%). The major component in the sum of flavonoids is shaftoside, the proportion of which in most species ranges from 50 to 90%. It is shown that the composition of flavonoids changes during vegetative development. The phases of maximum accumulation of flavonoids in the aboveground part of 4 Silene species have been determined. In general, the studied Silene species are promising sources of C-glycosylflavones. [ABSTRACT FROM AUTHOR]

Natural drug research is one of the main directions for the discovery and development of new drugs. Underutilized vegetables with a rich source of medicinal value have drawn much attention from scientists in synthesizing new drugs and finding new pharmacological actions. Apigenin is a natural flavonoid with pharmacological effects including anti-inflammatory, anti-tumor, anti-oxidation, anti-radiation, antidepressant effect, cardiovascular protection, regulated glucose and lipid metabolism, protecting the kidneys, neuroprotection, antibacterial, etc. Thus, these pharmacological effects of apigenin and the interaction between apigenin and drugs were mainly reviewed in this paper. The pharmacological actions of apigenin are being elucidated not only on the molecular level but also on the apigenin-receptor interaction, changes in factors, enzymes, proteins, cells, or tissues. The apigenin derivatives and complexes with their pharmacological actions were also summarized, which is expected to provide a reference for the rational development and utilization of apigenin. [ABSTRACT FROM AUTHOR]

Seizures are common in preterm newborns and are associated with poor neurodevelopmental outcomes. Current anticonvulsants have poor efficacy, and many have been associated with upregulation of apoptosis in the developing brain. Apigenin, a natural bioactive flavonoid, is a potent inhibitor of hyaluronidase and reduces seizures in adult animal models. However, its impact on perinatal seizures is unclear. In the present study, we examined the effect of apigenin and S3, a synthetic, selective hyaluronidase inhibitor, on seizures after cerebral ischemia in preterm fetal sheep at 0.7 gestation (98–99 days, term ~147 days). Fetuses received sham ischemia (n = 9) or ischemia induced by bilateral carotid occlusion for 25 min. Immediately after ischemia, fetuses received either a continuous infusion of vehicle (0.036% dimethyl sulfoxide, n = 8) or apigenin (50 µM, n = 6). In a pilot study, we also tested infusion of S3 (2 µM, n = 3). Fetuses were monitored continuously for 72 h after ischemia. Infusion of apigenin or S3 were both associated with reduced numbers of animals with seizures, total seizure time, and mean seizure burden. S3 was also associated with a reduction in the total number of seizures over the 72 h recovery period. In animals that developed seizures, apigenin was associated with earlier cessation of seizures. However, apigenin or S3 treatment did not alter recovery of electroencephalographic power or spectral edge frequency. These data support that targeting brain hyaluronidase activity with apigenin or S3 may be an effective strategy to reduce perinatal seizures following ischemia. Further studies are required to determine their effects on neurohistological outcomes. [ABSTRACT FROM AUTHOR]

Background: Apigenin effectively inhibits the growth of human gastric carcinoma SGC-7901 cells and induces apoptosis as well. This study investigated the effects of ATF6 and PERK signaling pathways in unfolded protein response (UPR) and endoplasmic reticulum stress (ERS) on the apoptosis induced by apigenin in human gastric carcinoma SGC-7901 cells. Materials and Methods: SGC-7901 cells were cultured with apigenin and tunicamycin for 48 h or with apigenin for 12–48 h. CCK-8 was used to determine cell viability. The mRNA expression level was detected by RT-qPCR. The expression of related proteins was explored by Western blot. The apoptosis rate of cells and cell-cycle arrest were evaluated by flow cytometer. Results: The results of CCK-8 confirmed that apigenin could induce apoptosis of SGC-7901 cells. In the apigenin -treated cells group, the protein and mRNA levels of GRP78 and GRP94 dose- and time-dependently increased. Additionally, apigenin -activated UPR components PERK and ATF6. However, apigenin exerted no influence on CHOP expression or JNK activation. Pretreatment with 4-PBA significantly increased the apigenin -triggered apoptosis in SCG-7901 cells (p < 0.05). Conclusion: The results revealed the protective effect of UPR performance on apigenin -triggered apoptosis in SGC-7901 cells. [ABSTRACT FROM AUTHOR]

Niosomes (NS) are the promising and novel carrier of the drug for effective transdermal delivery. Apigenin (AN) is a natural bioactive compound and has various pharmacological activities. AN is poorly water soluble which directly affects therapeutic efficacy. The aim of this research work was to develop the AN-NS gel to improve transdermal delivery. The thin-film hydration method was used for the development of AN-NS. The optimized AN-NS (AN-NS2) has a vesicle size of 272.56 ± 12.49 nm, PDI is 0.249, zeta potential is -38.7 mV, and entrapment efficiency of 86.19 ± 1.51%. The FTIR spectra of the AN-NS2 depicted that AN encapsulated in the NS matrix. AN-NS2 formulation was successfully incorporated into chitosan gel and evaluated. The optimized AN-NS2 gel (AN-NS2G4) has 2110 ± 14cps of viscosity, 10.40 ± 0.21g.cm/sec of spreadability, and 99.65 ± 0.53% of drug content. AN-NS2G4 displayed significantly (p<0.05) higher AN released (67.64 ± 3.03%) than pure AN-gel (37.31 ± 2.87%). AN-NS2G4 showed the Korsmeyer Peppas release model. AN-NS2G4 displayed significantly (p<0.05) higher antioxidant activity (90.72%) than pure AN (64.53%) at 300 mg/ml. AN-NS2G4 displayed significantly (p<0.05) higher % inhibition of swelling than pane AN-gel in carrageenin-induced paw oedema in rats. The finding concluded that niosomes-laden gel is a good carrier of drugs to improve transdermal delivery and therapeutic efficacy. [ABSTRACT FROM AUTHOR]

The present study deals with the advanced in-silico analyses of several Apigenin derivatives to explore human papillomavirus-associated cervical cancer and DNA polymerase theta inhibitor properties by molecular docking, molecular dynamics, QSAR, drug-likeness, PCA, a dynamic cross-correlation matrix and quantum calculation properties. The initial literature study revealed the potent antimicrobial and anticancer properties of Apigenin, prompting the selection of its potential derivatives to investigate their abilities as inhibitors of human papillomavirus-associated cervical cancer and DNA polymerase theta. In silico molecular docking was employed to streamline the findings, revealing promising energy-binding interactions between all Apigenin derivatives and the targeted proteins. Notably, Apigenin 4′-O-Rhamnoside and Apigenin-4′-Alpha-l-Rhamnoside demonstrated higher potency against the HPV45 oncoprotein E7 (PDB ID 2EWL), while Apigenin and Apigenin 5-O-Beta-d-Glucopyranoside exhibited significant binding energy against the L1 protein in humans. Similarly, a binding affinity range of − 7.5 kcal/mol to − 8.8 kcal/mol was achieved against DNA polymerase theta, indicating the potential of Apigenin derivatives to inhibit this enzyme (PDB ID 8E23). This finding was further validated through molecular dynamic simulation for 100 ns, analyzing parameters such as RMSD, RMSF, SASA, H-bond, and RoG profiles. The results demonstrated the stability of the selected compounds during the simulation. After passing the stability testing, the compounds underwent screening for ADMET, pharmacokinetics, and drug-likeness properties, fulfilling all the necessary criteria. QSAR, PCA, dynamic cross-correlation matrix, and quantum calculations were conducted, yielding satisfactory outcomes. Since this study utilized in silico computational approaches and obtained outstanding results, further validation is crucial. Therefore, additional wet-lab experiments should be conducted under in vivo and in vitro conditions to confirm the findings. [ABSTRACT FROM AUTHOR]

Apigenin (API) possesses excellent antitumor properties but its limited water solubility and low bioavailability restrict its therapeutic impact. Thus, a suitable delivery system is needed to overcome these limitations and improve the therapeutic efficiency. Poly (lactic-co-glycolic acid) (PLGA) is a copolymer extensively utilized in drug delivery. Hyaluronic acid (HA) is a major extracellular matrix component and can specifically bind to CD44 on colon cancer cells. Herein, we aimed to prepare receptor-selective HA-coated PLGA nanoparticles (HA-PLGA-API-NPs) for colon cancers with high expression of CD44; chitosan (CS) was introduced into the system as an intermediate, simultaneously binding HA and PLGA through electrostatic interaction to facilitate a tighter connection between them. API was encapsulated in PLGA to obtain PLGA-API-NPs, which were then sequentially coated with CS and HA to form HA-PLGA-API-NPs. HA-PLGA-API-NPs had a stronger sustained-release capability. The cellular uptake of HA-PLGA-API-NPs was enhanced in HT-29 cells with high expression of CD44. In vivo, HA-PLGA-API-NPs showed enhanced targeting specificity towards the HT-29 ectopic tumor model in nude mice in comparison with PLGA-API-NPs. Overall, HA-PLGA-API-NPs were an effective drug delivery platform for API in the treatment of colon cancers with high expression of CD44. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is an autoimmune disease that leads to severe bowel symptoms and complications. Currently, there is no effective treatment, and the exact cause of IBD remains unclear. In the last decades, numerous studies have confirmed that flavonoids can have a positive impact on the treatment of IBD. Therefore, this study investigated the protective effect of a flavonoid combination of apigenin and epigallocatechin-3-gallate (EGCG) on IBD. In vitro studies in which Caco-2 cell monolayers were incubated with different concentrations of flavonoids found that the flavonoid-treated group exhibited increased transepithelial electrical resistance (TEER) at high concentrations, indicating a protective effect on the barrier function of the intestinal epithelium. In vivo studies showed that flavonoids significantly attenuated inflammatory levels in both chronic and acute hapten-mediated experimental colitis models in a time- and dose-dependent manner. In addition, the activity of myeloperoxidase (MPO) and the level of proinflammatory cytokines in the colon tissue were significantly reduced. Interestingly, the levels of anti-inflammatory cytokines were also dramatically increased. Finally, flavonoids were found to positively modulate the composition of the gut microbiota in the colon. Therefore, a combination of flavonoids could be a promising therapeutic agent for the future adjunctive treatment of IBD. [ABSTRACT FROM AUTHOR]

Occurrence of cancer is driving up on a global scale that exerts greater implications on the physical, psychological and economic stability of the human population. In the present context, numerous research studies are being conducted to explore and discover the drug molecule as an anticancer agent. Diverse scales of flavonoids entail the human diet, and they displayed prospective curative effects against an array of ailments. Among different categories of flavonoids, apigenin a trihydroxy flavone has been proven to have various pharmacological effects. Molecular docking is a key tool in structural molecular biology and computer assisted drug design. In this study, HDAC inhibitory action of apigenin and its probable toxicity was assessed by docking study using Auto dock platform. Molecular dynamics simulation was done by using iMODS server for elucidating the stability of the receptor-ligand complex. Toxicity predictions were evaluated by using tools such as CarcinoPred for carcinogenicity study, pkCSM for ADMET analysis, ProTox-II for rodent oral toxicity, lazar for estimating mutagenicity, BOILED Egg plot analysis for examining the gastrointestinal absorption and blood brain permeability, PASS prediction to identify the various biological functions and DruLiTo program to compute the drug likeness property. [ABSTRACT FROM AUTHOR]

Xanthine oxidase (XO) is a homodimeric enzyme found in many species, including humans responsible for catalyzing the synthesis of uric acid from hypoxanthine using oxygen as a substrate. Pogostemon cablin (Blanco) Benth. (P. cablin) has been widely used in traditional medicine for the treatment of gout. In this study, we used molecular docking method to find bioactive compounds from Pogostemon cablin (Blanco) Benth. for inhibiting the XO enzyme. 78 bioactive compounds were collected based on previous Pogostemon cablin (Blanco) Benth publications. and evaluated docking scores using Autodock vina software. Out of 78, four compounds had stronger inhibiting potential to XO target than positive controls. Lipinski’s rule of five and ADMET property prediction analysis revealed positive results with two compounds, acacetin and apigenin. Therefore, in vitro and in vivo studies should be carried out to verify these compounds' XO inhibitory potential for future drug development. [ABSTRACT FROM AUTHOR]

Four flavonoid C-glycosides, including two new diglycosides, dendrodiglycosides A (1) and B (2), along with known isoviolanthin (3) and apigenin 6-C-β-D-glucopyranosyl-(1→2)-α-L-arabinopyranoside (4), were isolated from the leaves of Dendrobium officinale (Orchidaceae). Their structures were elucidated by NMR and MS. Apigenin 6-C-β-D-glucopyranosyl-(1→2)-α-L-arabinopyranoside exhibited an inhibitory effect against tyrosinase with an IC50 value of 146.5 μg/mL. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]