Apigenin Research Articles

Ameliorative effects of apigenin on a rat model of endometriosis

Objectives: Apigenin and parthenolide as natural products have potent antioxidant and anti-inflammatory outcomes that could make them a perfect option for endometriosis therapy. This study aimed to determine the effects of apigenin and parthenolide on created endometrial implants in a rat model of endometriosis. Methods: Thirty-nine mature, female Sprague-Dawley rats were assigned randomly to six experimental groups four weeks after endometriosis induction. Group 1 (n = 5): Control (CTRL) that opened and closed the abdomen; Group 2 (n = 6): Peritoneal and ovarian endometriosis (POE) + drug-free; Group 3 (n = 7): POE+ Apigenin (APG) (50 mg/kg); Group 4 (n = 7): POE+ Parthenolide (PTL) (10 mg/kg); Group 5 (n = 7): POE+ Apigenin (APG) (50 mg/kg) + Parthenolide (PTL) (10 mg/kg); Group 6 (n = 7): POE+ DMSO. An endometriosis model was created, and histopathological analysis and biochemical evaluation were performed. Serum and peritoneal levels of pro-and-anti-inflammatory cytokine, and oxidative stress of implant tissue were measured. Results: Serum IL-37 levels decreased significantly in the APG-treated group compared to the drug-free group (p = 0.016). The peritoneum and ovary endometriosis histopathologic scores were significantly lower in APG-treated (p = 0.001) and PTL-treated (p = 0.001) groups in comparison to the drug-free group. The oxidative stress index (OSI) values were increased statistically significantly in ovary endometriosis tissue in the drug-free group, (p = 0.001). However, compared to the drug-free group, OSI values decreased statistically significantly in the APG-treated group (p = 0.003). Conclusions: The application of apigenin caused a decrease in oxidative stress and an improvement in histopathological grade. Apigenin may be a novel therapeutic agent for the treatment of endometriosis.

Theoretical exploration on the molecular configurations, solubilities and chemical reactivities of four flavonoid-based co-crystals

Four flavonoid-based co-crystals containing the active pharmaceutical ingredients Apigenin (AP), 4′,7-Dihydroxyflavone (DH), Genistein (GE), Daidzein (DA) and the co-crystal former Theophylline (TH) were constructed as the stoichiometric ratio of 1:2 form in theory. The structural parameters and chemical reactivities of the four co-crystals were systematically explored via the density functional theory (DFT) and quantum theory of atoms in molecules (QTAIM) methods. The intermolecular hydrogen bond lengths, frontier molecular orbitals, absorption spectra, electrostatic potential population, binding energies, solvent energies and global reactivity descriptors of the monomers and co-crystal systems were studied. In addition, the topological analysis of bond critical point based on the QTAIM, interaction region indicator and infrared (IR) spectrum analysis were adopted to investigate the intermolecular interaction between the APIs and CCF. The calculated results indicate that the APIs and CCF are bound via the intermolecular hydrogen bond interaction, and the drug activity and solubility of all co-crystals are significantly improved compared with that of the monomers. Interestingly, the isoflavone-based co-crystals (DA-TH and GE-TH) show the more excellent drug activities than that of the flavonoid-based co-crystals (AP-TH and DH-TH). This work can provide the reliable theoretical basis for the experimental synthesis of flavonoid-based drug co-crystal with more outstanding properties.

Hepatoprotective Mechanism of Apigenin via Suppression of Oxidative Inflammatory Signaling and Apoptosis against Hepatotoxicity Induced by CCl4 in Rats

Background: Carbon tetrachloride (CCl4) is a critical hepatotoxicant causing liver injury and fibrosis via hepatic production of reactive oxygen species (ROS). Apigenin (APG) is a natural bioactive compound and flavonoid antioxidant. We, therefore, evaluated whether APG could mitigate CCl4-mediated hepatotoxicity. Methods: Rats were randomly divided and administered APG and/or CCl4 in Control group, CCl4 group, APG + CCl4 groups (APG: 10 and 20 mg/kg bw) and APG groups (APG: 10 and 20 mg/kg bw) 2 times per week for 7 consecutive weeks. Result: Rats exposed to CCl4 demonstrated marked increases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and monoamine oxidase (MAO) activities and decreased hepatic malondialdehyde (MDA) level compared to control. The hepatic activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) decreased appreciably. The CCl4 intoxication caused significant increases in inflammatory cytokines (IL-6 and TNF-α) and apoptosis markers, while the anti-inflammatory cytokines (IL-4 and IL-10) decreased with evident histopathological lesions compared to control. APG-dose-dependently-prevented these hepatic alterations.

Effects of Apigenin on Pharmacokinetics of Dasatinib and Probable Interaction Mechanism.

Dasatinib (DAS), a narrow-therapeutic index drug, Bcr-Abl, and Src family kinases multitarget inhibitor have been approved for chronic myelogenous leukemia (CML) and Ph-positive acute lymphocytic leukemia (Ph+ ALL). Apigenin (APG) has a long history of human usage in food, herbs, health supplements, and traditional medicine, and it poses low risk of damage. The concomitant use of APG containing herbs/foods and traditional medicine may alter the pharmacokinetics of DAS, that probably lead to possible herb-drug interactions. The pharmacokinetic interaction of APG pretreatment with DAS in rat plasma following single and co-oral dosing was successfully deliberated using the UPLC-MS/MS method. The in vivo pharmacokinetics and protein expression of CYP3A2, Pgp-MDR1, and BCPR/ABCG2 demonstrate that APG pretreatment has potential to drastically changed the DAS pharmacokinetics where escalation in the Cmax, AUC(0-t), AUMC(0-inf_obs), T1/2, Tmax, and MRT and reduction in Kel, Vd, and Cl significantly in rats pretreated with APG 40 mg/kg, thus escalating systemic bioavailability and increasing the rate of absorption via modulation of CYP3A2, Pgp-MDR1, and BCPR/ABCG2 protein expression. Therefore, the concomitant consumption of APG containing food or traditional herb with DAS may cause serious life-threatening drug interactions and more systematic clinical study on herb-drug interactions is required, as well as adequate regulation in herbal safety and efficacy.

Optimization of apigenin nanoparticles prepared by planetary ball milling: In vitro and in vivo studies

Abstract This study intended to optimize apigenin (APG) nanoparticle formulation prepared by planetary ball milling to enhance its dissolution rate and bioavailability using a design of experiment (DoE). In this study, polyvinyl pyrrolidone (PVP K30) was used as a nanoparticle stabilizer. The independent parameters of milling speed, milling ball size, and drug to solvent ratio were evaluated for their impacts on APG nanoparticles concerning the nanoparticle size (Y1), zeta potential (Y2), and drug dissolution efficiency after 60 min, notated as % DE60 (Y3). The milling ball size showed a significant antagonistic effect (P = 0.0210) on the size of APG nanoparticles, while milling speed had an agonistic effect on the zeta potential values of drug nanoparticles, ranging from low to medium speed levels. In addition, ANOVA analysis indicated that the effect of the drug-to-solvent ratio on the % DE60 of APG from the nanoparticle formulations was antagonistically significant (P = 0.015), and the quadratic effect of milling speed (AA) also had a significant antagonistic effect (P = 0.025) on the % DE60. Risk assessment analytical tools revealed that milling ball size and milling speed significantly affect the nanoparticle size. The drug/solvent ratio exerted a strong impact on % DE60. Furthermore, the maximum plasma concentration (C max) of the optimized APG nanoparticle formula increased by four folds. In addition, AUC0–t (ng·mL−1·h−1) for APG nanoparticle (353.7 ± 185.3 ng·mL−1·h−1) was higher than that noticed in the case of the untreated drug (149 ± 137.5 ng·mL−1·h−1) by more than two folds.

Effect of apigenin in combination with oxymatrine on non-small cell lung cancer and mechanism

This study explores the effect of apigenin(APG), oxymatrine(OMT), and APG+OMT on the proliferation of non-small cell lung cancer cell lines and the underlying mechanisms. Cell counting kit-8(CCK-8) assay was used to detect the vitality of A549 and NCI-H1975 cells, and colony formation assay to evaluate the colony formation ability of the cells. EdU assay was employed to examine the proliferation of NCI-H1975 cells. RT-qPCR and Western blot were performed to detect the mRNA and protein expression of PLOD2. Molecular docking was carried out to explore the direct action ability and action sites between APG/OMT and PLOD2/EGFR. Western blot was used to study the expression of related proteins in EGFR pathway. The viability of A549 and NCI-H1975 cells was inhibited by APG and APG+OMT at 20, 40, and 80 μmol·L~(-1) in a dose-dependent manner. The colony formation ability of NCI-H1975 cells was significantly suppressed by APG and APG+OMT. The mRNA and protein expression of PLOD2 was significantly inhibited by APG and APG+OMT. In addition, APG and OMT had strong binding activity with PLOD2 and EGFR. In APG and APG+OMT groups, the expression of EGFR and proteins in its downstream signaling pathways was significantly down-regulated. It is concluded that APG in combination with OMT could inhibit non-small lung cancer, and the mechanism may be related to EGFR and its downstream signaling pathways. This study lays a new theoretical basis for the clinical treatment of non-small cell lung cancer with APG in combination with OMT and provides a reference for further research on the anti-tumor mechanism of APG in combination with OMT.

Molecular Mechanism of the Role of Apigenin in the Treatment of Hyperlipidemia: A Network Pharmacology Approach.

The therapeutic effect of apigenin (APG) on hyperlipidemia was investigated using network pharmacology combined with molecular docking strategy, and the potential targets of APG in the treatment of hyperlipidemia were explored. Genetic Ontology Biological Process (GOBP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway enrichment analysis of common targets were performed. Then, molecular docking was used to predict the binding mode of APG to the target. Finally, Sprague Dawley rats were used to establish a hyperlipidemia model. The expression levels of insulin (INS) and vascular endothelial growth factor A (VEGFA) mRNA in each group were detected by quantitative reverse transcription-polymerase chain reaction. Network pharmacological studies revealed that the role of APG in the treatment of hyperlipidemia was through the regulation of INS, VEGFA, tumor necrosis factor, epidermal growth factor receptor, matrix metalloprotein 9, and other targets, as well as through the regulation of the hypoxia-inducible factor 1 (HIF-1) signaling pathway, fluid shear stress, and atherosclerosis signaling pathways, vascular permeability; APG also participated in the regulation of glucose metabolism and lipid metabolism, and acted on vascular endothelial cells, and regulated vascular tone. Molecular docking showed that APG binds to the target with good efficiency. Experiments showed that after APG treatment, the expression levels of INS and VEGFA mRNA in the model group were significantly decreased (p<0.01). In conclusion, APG has multiple targets and affects pathways involved in the treatment of hyperlipidemia by regulating the HIF-1 signaling pathway, fluid shear stress, and the atherosclerosis pathway.

Four Different Structural Dietary Polyphenols, Especially Dihydromyricetin, Possess Superior Protective Effect on Ethanol-Induced ICE-6 and AML-12 Cytotoxicity: The Role of CYP2E1 and Keap1-Nrf2 Pathways.

Polyphenols have received attention as dietary supplements for the relief of alcoholic liver disease (ALD) due to various bioactivities. Ethanol-induced rat small intestinal epithelial cell 6 (IEC-6) and alpha mouse liver 12 (AML-12) cell models were pretreated with four dietary polyphenols with different structures to explore their effects on cytotoxicity and potential protective mechanisms. The results showed that polyphenols had potential functions to inhibit ethanol-induced AML-12 and IEC-6 cell damage and oxidative stress, and restore ethanol-induced IEC-6 permeability and tight junction gene expression. Especially, dihydromyricetin (DMY) had the best protective effect on ethanol-induced cytotoxicity, followed by apigenin (API). Western blot results showed that DMY and API had the best ability to inhibit CYP2E1 and Keap1, and promote nuclear translocation of Nrf2, which might be the potential mechanism by which DMY and API attenuate ethanol-induced cytotoxicity. Moreover, the molecular docking results predicted that DMY and API could bind more tightly to the amino acid residues of CYP2E1 and Keap1, which might be one of the inhibitory modes of dietary polyphenols on CYP2E1 and Keap1. This study provided a rationale for the subsequent protective effect of dietary polyphenols on alcohol-induced liver injury in animal models and provided new clues on bioactive components for ALD-protection based on the gut-liver axis.

Apigenin ameliorates non-eosinophilic inflammation, dysregulated immune homeostasis and mitochondria-mediated airway epithelial cell apoptosis in chronic obese asthma via the ROS-ASK1-MAPK pathway

BackgroundObese asthma is one of the important asthma phenotypes that have received wide attention in recent years. Excessive oxidative stress and different inflammatory endotypes may be important reasons for the complex symptoms, frequent aggravation, and resistance to traditional treatments of obese asthma. Apigenin (API), is a flavonoid natural small molecule compound with good anti-inflammatory and antioxidant activity in various diseases and proved to have the potential efficacy to combat obese asthma. MethodsIn vivo, this study fed C57BL/6 J mice with high-fat diets(HFD)for 12 weeks and then stimulated them with OVA for 6 weeks to establish a model of chronic obese asthma, while different doses of oral API or dexamethasone were used for therapeutic interventions. In vitro, this study used HDM to stimulate human bronchial cells (HBEs) to establish the model and intervened with API or Selonsertib (SEL). ResultsThis study clarified that OVAinduced a type of mixed granulocytic asthma with elevated neutrophils and eosinophils in obese male mice fed with long-term HFD, which also exhibited mixed TH17/TH1/TH2 inflammation. Apigenin effectively suppressed this complex inflammation and acted as a regulator of immune homeostasis. Meanwhile, apigenin reduced AHR, inflammatory cell infiltration, airway epithelial cell apoptosis, airway collagen deposition, and lung oxidative stress via the ROS-ASK1-MAPK pathway in an obese asthma mouse model. In vitro, this study found that apigenin altered the binding status of TRAF6 to ASK1, inhibited ASK1 phosphorylation, and protected against ubiquitin-dependent degradation of ASK1, suggesting that ROS-activated ASK1 may be an important target for apigenin to exert anti-inflammatory and anti-apoptotic effects. To further verify the intervention mechanism, this study clarified that apigenin improved cell viability and mitochondrial function and inhibited apoptosis by interfering with the ROS-ASK1-MAPK pathway. ConclusionsThis study demonstrates for the first time the therapeutic effect of apigenin in chronic obese asthma and further clarifies its potential therapeutic targets. In addition, this study clarifies the specificity of chronic obese asthma and provides new options for its treatment.

Apigenin attenuates depressive-like behavior via modulating monoamine oxidase A enzyme activity in chronically stressed mice

Chronic stress is a risk factor for depression and is characterized by elevated levels of brain monoamine oxidase A (MAOA). Mounting evidence has shown that MAOA is a biochemical link between stress and depression. Apigenin (API), a natural flavonoid, as demonstrated in vitro inhibitory effect on MAOA, is suggestive of antidepressant-like activity. However, the in vivo inhibitory effect of API on MAOA and how it affects depression still remain unclear. Here, we report the probable mechanisms of action of API in chronic unpredictable mild stress (CUMS)-induced depression in mice. Treatment with API reversed anhedonia, and reduced anxiety and immobility time in behavioral studies. API reduced brain corticosterone and malondialdehyde (MDA) levels but increased brain levels of glutathione and superoxide dismutase. Furthermore, interleukin-6 and tumor necrosis factor-α were attenuated by API. It also restored cell loss and inhibited the activity of MAOA in the hippocampal brain regions and prefrontal cortex. Comparative binding affinity of API for MAOA (-7.7 kcal/mol) through molecular docking studies was greater than that of reference compound, clorgyline (-6.8 kcal/mol). Favorable hydrophobic interactions important to API binding at MAOA binding cavity was revealed to include conventional hydrogen bond (Cys323 and Tyr444), π-Sulfur (Cys323), π-π Stacked (Tyr407), π-π T-shaped (Phe208), π-lone pair and π-alkyl (Ile335, Ile180) interactions. These results suggest that API is a potent, selective, reversible inhibitor of MAOA with capability of attenuating CUMS-induced depression via inhibiting MAOA enzyme activity and altering other pathomechanisms.

Apigenin: Exploring its neuroprotective potential in neurodegenerative disorders: Mechanisms and promising therapeutic applications

Neurodegenerative diseases pose significant challenges to global health-care systems, highlighting the urgent need for effective therapeutic strategies. Apigenin (API), a natural compound derived from various plant sources, has emerged as a potential treatment option due to its neuroprotective properties. This review article provides a comprehensive overview of API, focusing on its definition, natural sources, pharmacokinetics, and bioavailability, mechanisms of action, safety, and tolerability profile. API protects neurons in many ways, including its antioxidant activity, anti-inflammatory properties, ability to change cellular signaling pathways, ability to stop proteins from misfolding and sticking together, and ability to improve mitochondrial function. In vitro studies have demonstrated that API attenuates oxidative stress, inhibits the formation of protein aggregates, and suppresses neuroinflammation. Animal models, such as transgenic mice, rat models, and non-human primates, have provided valuable insights into the potential therapeutic benefits of API, including improved cognitive function, mitigation of motor impairments, and preservation of neuronal integrity. API’s safety and tolerability profile appears favorable based on preclinical and clinical studies, with minimal reported adverse effects. However, further investigation is required to determine optimal dosing regimens and assess potential drug interactions. In addition, while current treatment options for neurodegenerative diseases primarily focus on symptom management, API holds promise as a disease-modifying agent.

Imaging supermolecular interactions of the pharmaceutical-cocrystal of apigenin-nicotinamide binding with serum albumin.

In this paper, a new pharmaceutical cocrystal was synthesized using apigenin (AP) and pharmaceutically acceptable conformer nicotinamide (Nico), and the drug delivery between AP-Nico pharmaceutical cocrystal and human serum albumin (HSA) in vivo was studied at atomic scale. The pharmaceutical cocrystal was characterized using Fourier-transform infrared (FTIR) spectroscopy, 1H NMR spectroscopy, differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD), and the self-assembling mechanism was explored. The dissolution and cumulative release in vitro were investigated. Molecular dynamic (MD) simulation combined with fluorescence spectroscopy was used to study the delivery mechanism of AP-Nico to HSA. The results showed that AP was pharmaceutically cocrystallized with Nico, which formed a pharmaceutical cocrystal mainly through hydrogen interaction between the -OH groups of AP and -NH2 groups of Nico. The solubility of the AP-Nico was 3 times higher than raw AP and the cumulative release rate was 71%. The fluorescence spectroscopy results showed that the AP-Nico pharmaceutical cocrystal bind with Sudlow's site I inside the HSA molecule with hydrogen-bond interaction as the main force. The Sudlow's site I of HSA conjugated with AP-Nico explains the conformational changes of HSA in-silico. This study provided a useful reference for synthesizing flavonoid pharmaceutical cocrystal to improve solubility and exploring the interaction mechanism while understanding its delivery mechanism in vivo.

Comparison of Flavonoid and Flavonoid Glycoside in the Inhibition of the Starch Hydrolyzing Enzymes and AGEs; A Virtual Approaches.

Inhibition of α-amylase, α-glucosidase, and advanced glycation end products (AGEs) is considered a prospective method for the prevention of type II diabetes. As two flavonoids obtained from fruits, swertisin (SW) and apigenin (AP) have similar structures and display various pharmacological properties. To examine the effects of flavonoid structure on inhibition of AGEs adducts and carbohydrate hydrolyzing enzymes activity, molecular docking and molecular dynamic simulations (MDs) were used. The molecular docking method was performed by the Autodock program, and the ligand that showed the most negative binding energy was selected for further investigation. SW showed the potential ability to inhibit the AGEs formation and carbohydrate hydrolyzing enzymes activity. The stability of the receptor/SW complex was evaluated by MDs. Based on the findings of the present study, it was found that SW has the potential to reduce glycation and delay the activity of α-amylase and α-glucosidase enzymes.

Apigenin and its octoic acid diester attenuated glycidol-induced autophagic-dependent apoptosis via inhibiting the ERK/JNK/p38 signaling pathways in human umbilical vein endothelial cells (HUVECs)

Glycidol is a well-known food contaminant mainly formed in refined edible oils and various thermally processed foods. Here, we studied the toxicity effects and related mechanism of glycidol on Human umbilical vein endothelial cells (HUVECs). Glycidol was found to induce Gap period 2 (G2)/Mitosis (M) phase cell cycle arrest, apoptosis, and autophagy in HUVECs. Inhibition of autophagy by 3-methyladenine (3-MA) attenuated glycidol-induced cell death, suggesting that glycidol-induced apoptosis was autophagy-dependent. Moreover, glycidol treatment induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal protein kinase (JNK), and p38. Inhibition of ERK, JNK, and p38 phosphorylation by the inhibitors U0126, SP600125, and SB203580 attenuated glycidol-induced autophagy and prevented glycidol-mediated reduction in cell viability, demonstrating that glycidol inhibited HUVECs growth by inducing autophagic-dependent apoptosis through activation of the ERK, JNK and p38 signaling pathways. In addition, apigenin (API) and its octoic acid diester apigenin-7 (API-C8), 4′-O-dioctanoate were found to significantly attenuate glycidol-induced cell growth inhibition by inhibiting the above signaling pathways. Collectively, glycidol induces autophagic-dependent apoptosis via activating the ERK/JNK/p38 signaling pathways in HUVECs and API-C8 could attenuate the toxicity effects.

Effect of apigenin on tryptophan metabolic key enzymes expression in lipopolysaccharide-induced microglial cells and its mechanism

[Aims] Flavonoid apigenin (API) has a wide range of biological functions, particularly anti-inflammation. Indoleamine 2,3-dioxygenase (IDO) and 2-Amino-3-carboxymuconate-6-semialdehyde decarboxylase (ACMSD) are important tryptophan metabolic enzymes that play pivotal roles in the production of toxic metabolite quinolinic acid. However, the relationship between inflammation and ACMSD remains unclear. The present study investigated the relationship between inflammation and tryptophan metabolic key enzymes. Similarly, the anti-inflammatory effect of API on important tryptophan metabolic enzymes was examined in lipopolysaccharide (LPS)-treated microglial cells.[Main methods] MG6 cells were exposed to LPS with or without API treatment for 24–48 h. IDO and ACMSD mRNA expression and production of inflammatory mediators were analyzed. Activation of inflammatory signaling pathways, such as mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB), was also examined to study the mechanism of API in the inflammatory state.[Key findings] LPS suppressed ACMSD expression and enhanced IDO expression. However, API elevated ACMSD mRNA expression and suppressed IDO mRNA expression in LPS-treated MG6 cells. Furthermore, API suppressed interleukin-6 and nitric oxide production, whereas overproduction of inflammatory mediators enhanced IDO expression and assisted tryptophan degradation. API also inhibited activation of extracellular signal-regulated kinase (Erk) and jun N-terminal kinase (JNK) MAPK, and degradation of IκBα.[Significance] These results indicate alteration of ACMSD expression under inflammatory conditions. Moreover, API recovers expression of tryptophan metabolic key enzymes, which may be mediated by inhibition of proinflammatory mediator production via inactivation of Erk, JNK MAPK, and NF-κB pathways in LPS-stimulated microglial cells.

The Preparation of Apigenin Nanoparticles and the Study of Their Anti-Inflammatory and Anti-Tumor Activities In Vitro

Apigenin (API) has many biological activities, but its poor solubility limits its clinical application. In this research, API nanoparticles were prepared by the liquid antisolvent precipitation (LAP) technique, which effectively improved the solubility and bioavailability of API. Through the design of a single-factor test, the effects of the type and dosage of surfactants, API concentration, the antisolvent to solvent volume ratio, the speed and time of stirring, the temperature of precipitation, and the dropping speed on the MPS (mean particle size) of API nanosuspension were carried out. The optimum technological conditions were determined as follows: 5 mg/mL of tween 80 as a surfactant, 20 mg/mL of API, an antisolvent/solvent volume ratio of 10, a 1200 r/min stirring speed for 5 min, a 45 °C precipitation temperature, and a 1 mL/min dropping speed. Under the optimum conditions, we obtained API nanosuspension with 170.5 nm MPS and then it was freeze-dried to obtain the API nanoparticles. Moreover, we characterized the API nanoparticles by SEM, FTIR, XRD, DSC, and TG. Results showed that although API nanoparticles transformed into an amorphous form, their internal chemical structure had not been changed and had a higher solubility. Finally, API nanoparticles’ anti-inflammatory activities were evaluated by observing the effect of API on nitric oxide (NO) production and IL-10 production toward RAW264.7 cells induced by lipopolysaccharide (LPS). Moreover, the anti-tumor effect of API was determined by testing cell viability and apoptosis. The results suggested that API nanoparticles exhibited much better anti-inflammatory and anti-tumor activities compared to raw API.

Exploration of binding mechanism of apigenin to pepsin: Spectroscopic analysis, molecular docking, enzyme activity and antioxidant assays

Pepsin plays an important role in nutrient metabolism. Apigenin (AP) is a beneficial polyphenol to human health. To enhance the bioavailability of AP and elucidate the inhibitory effect of AP on pepsin, the interaction mechanism of AP with pepsin was investigated using spectroscopic analysis and molecular docking, and the activity of pepsin and antioxidant activity of AP was also evaluated. Specifically, AP performed static quenching of pepsin and had only one binding site on pepsin. More interestingly, the interaction between AP and pepsin was spontaneous, while hydrogen bonds and van der Waals forces were the main binding forces. Generally, synchronous and three-dimensional fluorescence confirmed that AP induced the conformational changes of pepsin, and molecular docking proved the above results and illustrated the specific binding patterns. Specifically, AP inhibited the activity of pepsin, while pepsin decreased the antioxidant activity of AP. These results provided useful information for elucidating the interactions between AP and pepsin.

Highly Biocompatible Apigenin-Loaded Silk Fibroin Nanospheres: Preparation, Characterization, and Anti-Breast-Cancer Activity

Breast cancer is among the most common fatal diseases among women. Low-toxicity apigenin (AGN) is of interest due to its good antitumor activity, but its clinical application is severely limited due to its poor water solubility and low bioavailability. An effective strategy to enhance the anti-breast-cancer activity of AGN is to develop it as a nanodelivery system. Silk fibroin (SF) is an ideal drug carrier with good biocompatibility, biodegradability, and a simple extraction process. This paper develops a novel and efficient apigenin-loaded silk fibroin nanodelivery system (SF-AGN) by nanoprecipitation with SF as a carrier. The system was characterized in terms of morphology, zeta potential, particle size, ultraviolet (UV), infrared (IR), and synchronous thermal analyses (TG-DSC), and the in vitro cytotoxicity and in vivo pharmacokinetics were examined. Finally, the chronic toxicity of SF-AGN in mice was studied. The SF-AGN nanodelivery system has good dispersibility, a hydrated particle size of 163.35 nm, a zeta potential of -18.5 mV, an average drug loading of 6.20%, and good thermal stability. MTT studies showed that SF-AGN significantly enhanced the inhibitory effect of AGN on 4T1 and MDA-MB-231 cells. Pharmacokinetic studies have demonstrated that SF-AGN can dramatically improve the bioavailability of AGN. The results of toxicity experiments showed that SF-AGN is biocompatible and does not alter normal tissues or organs. In sum, the SF-AGN nanodelivery system is a promising drug-delivery system for the clinical treatment of breast cancer.

Apigenin restores memory function in stressed mice

AbstractBackgroundStress, a known cause of neuropsychiatric disorders, is associated with cognitve dysfunction, neuroendocrine systems breakdown and altered brain oxidative status and proteins (Roozendaal, 2002; Radecki et al., 2005; Lupien et al., 2007). Apigenin (API), a natural flavonoid, with diverse biological activity, is thought to possess neuroprotective potentials (Li et al., 2015). This study investigated whether API administration abrogates chronic unpredictable mild stress (CUMS)‐induced cognitive impairment, as well as exploring its probable underlying mechanisms.MethodSwiss male mice (n = 10) were treated with API (12.5 ‐ 25 mg/kg, intraperitoneally) 30 min before exposure to CUMS daily for 14 days, thereafter tested for memory function using the Y‐maze and novel object recognition (NOR) tests. Levels of malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), and corticosterone levels were assessed using enzyme‐linked immunosorbent assay. The expressions of brain derived neurotrophic factor (BDNF), phosphorylated extracellular signal‐regulated kinase (pERK), and cAMP response element‐binding protein (pCREB) were assessed using immunohistochemistry.ResultCUMS produced cognitive impairment in mice as shown in the Y‐maze and NOR tests. CUMS significantly elevated MDA, and serum corticosterone levels, including reducing GSH and SOD levels, decreasing BDNF, pERK, and pCREB levels in the prefrontal cortex and hippocampus. However, chronic administration of API significantly prevented all these CUMS‐induced behavioral and biochemical alterations.ConclusionAPI may be a potential therapeutic agent for cognitive disturbances as seen within the stress model and its neuroprotective effect was partly mediated by restoring oxidative status, serum corticosterone levels, up‐regulating BDNF, pCREB and pERK levels.

Engineering of QbD driven and ultrasonically shaped lyotropic liquid crystalline nanoparticles for Apigenin in the management of skin cancer

Treatment of skin cancer demands targeted delivery without minimal systemic circulation for maximum therapeutic window. Dermal delivery with nano-formulation offers such advantages. Therefore, present study aims to formulate Lyotropic liquid crystalline nanoparticles (LLC NPs) loaded with Apigenin (API) for dermal delivery using quality by design (QbD) approach for effective permeation resulting in improved bioavailability. Apigenin loaded LLC NPs (API-LLC NPs) were formulated and optimized by applying risk assessment and design of experiments (Box-Behnken Design). The optimized API-LLC NPs showed particle size, PdI and entrapment efficiency of 287.7 ± 9.53 nm, 0.152 ± 0.051 and 80 ± 2.2 % respectively. The optimized API-LLC NPs were characterized for morphology and crystallinity using optical microscopy, TEM, DSC and PXRD. In vitro and ex vivo studies showed sustained release and better permeation profile. CLSM study presented better penetration of API-LLC NPs which were quantitatively confirmed with dermatokinetics. Cytotoxic efficacy assessed on B16F10 cell lines showed a dose-dependent efficacy of API-LLC NPs with an IC50 of 45.74 ± 0.05. In a nutshell, the developed API-LLC NPs exhibit excellent potential for targeting deeper skin layers thereby can be considered a promising topical drug delivery nanocarrier in the treatment and management of skin cancer.