Background:The outcomes of pediatric patients with acute lymphoblastic leukemia(ALL)remain far less than favorable.While apigenin is an anti-cancer agent,studies on the mechanism by which it regulates ALL cell cycle p...Background:The outcomes of pediatric patients with acute lymphoblastic leukemia(ALL)remain far less than favorable.While apigenin is an anti-cancer agent,studies on the mechanism by which it regulates ALL cell cycle progression are inadequate.Ferroptosis and AMP-activated protein kinase(AMPK)signaling are important processes for ALL patients.However,it remains unclear whether apigenin works by affecting AMPK and apoptosis.Materials and Methods:SUP-B15 and T-cell Jurkat ALL cells were treated with apigenin,and cell viability and apoptosis were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assays,respectively.The thiobarbituric acid-reactive substances(TBARS)assay was used to evaluate lipid peroxidation.Intracellular Fe2+levels were measured using a commercial kit.Corresponding proteins were detected by western blotting.Results:Results showed that apigenin reduced cell viability and the levels of Ki67 and proliferating cell nuclear antigen(PCNA)expression in a concentration-dependent manner in both types of ALL cells.Apigenin also exerted anti-apoptotic effects on SUP-B15 and Jurkat cells.Apigenin activated AMP-activated protein kinase(AMPK)signaling and induced ferroptosis,and those effects were attenuated by inhibition of AMPK.Eventually,the reduced cell proliferation and increased cell apoptosis caused by apigenin in ALL cells were partly abolished by AMPK inhibition.Conclusion:In summary,apigenin exerted anti-leukemia activity in ALL cells,and that effect was partially achieved by activation of AMPK signaling.Our findings suggest apigenin as a potential drug for treatment of ALL.展开更多
To investigate the mechanisms of apigenin(API)and proanthocyanidins(PC)in soothing sensitive skin(SS),a mast cell degranulation model was established by stimulating RBL-2H3 cells with the calcium ionophore A23187.Base...To investigate the mechanisms of apigenin(API)and proanthocyanidins(PC)in soothing sensitive skin(SS),a mast cell degranulation model was established by stimulating RBL-2H3 cells with the calcium ionophore A23187.Based on the combinatorial experiments,it was found that when API and PC were combined at the molar ratios of 4∶1 and 2∶1,they exhibited the antagonistic effects on histamine release(combination index CI>1);when they are combined at the molar ratios of 1∶1,1∶2 or 1∶4,they showed the synergistic effects on histamine release(CI<1).Among them,the combination of API and PC at a molar ratio of 1∶1 showed the better potent synergistic antihistamine release effect(CI=0.70).Histamine is a hallmark of the mast cell degranulation,consequently,the combination of API and PC at a molar ratio of 1∶1 yields the better efficiency in inhibiting the mast cell degranulation with the lowest IC_(50)value.Compared to the utilization of API or PC alone,the IC_(50)value was reduced by 11.150 and 6.503μmol/L,respectively.Compared to the positive control paeonol(PA),the treatment with the combination significantly reduced theβ-hex secretion,decreased the F-actin cytoskeleton rearrangement,and markedly suppressed the release of TNF-α,IL-4,and MCP-1.Further studies on the signaling pathways related to the mast cell degranulation indicated that the combination effectively inhibited the intracellular Ca^(2+)influx and significantly suppressed the phosphorylation of calmodulin-dependent protein kinase(CaMK)and phospholipase C/protein kinase C(PLC/PKC).In summary,the combination of API and PC at a molar ratio of 1∶1 exhibited the better synergistic antagonistic effect on the histamine release,inhibited the mast cell degranulation model activation by reducing Ca^(2+)influx and inhibiting the activation of Ca^(2+)/CaMK and PLC/PKC pathways,stabilized the cell membranes,regulated the inflammatory factor secretion,and exerted an effect in alleviating sensitive skin.展开更多
Objective:To investigate the effect of apigenin on carbon tetrachloride(CCl_(4))-induced liver fibrosis and elucidate the underlying mechanisms.Methods:A mouse model of CCl_(4)-induced liver fibrosis was used to evalu...Objective:To investigate the effect of apigenin on carbon tetrachloride(CCl_(4))-induced liver fibrosis and elucidate the underlying mechanisms.Methods:A mouse model of CCl_(4)-induced liver fibrosis was used to evaluate the effects of apigenin.Liver function was assessed using biochemical tests,and inflammation-associated markers,including interleukin-1 beta(IL-1β),IL-6,IL-10,and tumor necrosis factor-alpha(TNF-α),were determined by enzyme-linked immunosorbent assay(ELISA).H&E staining,Sirius Red staining,and collagen immunohistochemistry were also conducted.In addition,antioxidant enzyme activity and the underlying mechanisms of hepatoprotective effects of apigenin were examined.Results:CCl_(4)administration induced hepatic stellate cell activation and liver fibrogenesis in mice.Apigenin treatment markedly decreased liver injury markers,inflammation,oxidative stress,and collagen deposition,mitigating CCl_(4)-induced liver fibrosis.Furthermore,it significantly suppressed the activation of the phosphoinositide 3-kinase/protein kinase B/glycogen synthase kinase 3 beta(PI3K/AKT/GSK3β)pathway by reducing the ratios of p-PI3K/PI3K,p-AKT/AKT,and p-GSK3β/GSK3βin liver tissue.Conclusions:Apigenin ameliorates CCl_(4)-induced liver fibrosis in mice,likely through the inhibition of the PI3K/AKT/GSK3βsignaling pathway.These findings suggest that apigenin may have therapeutic potential for treating liver fibrosis.展开更多
Psoriasis is a chronic autoimmune disease featured by patches on the skin.It is caused by malfunction of immune cells and keratinocytes with inflammation as one of its key features.Apigenin(API)is a natural flavonoid ...Psoriasis is a chronic autoimmune disease featured by patches on the skin.It is caused by malfunction of immune cells and keratinocytes with inflammation as one of its key features.Apigenin(API)is a natural flavonoid with anti-inflammatory and immunoregulatory properties.Therefore,we speculated that API can ameliorate psoriasis,and determined its effect on the development of psoriasis by using imiquimod(IMQ)-induced psoriasis mouse model.Our results showed that API attenuated IMQ-induced phenotypic changes,such as erythema,scaling and epidermal thickening,and improved splenic hyperplasia.Abnormal differentiation of immune cells was restored in API-treated mice.Mechanistically,we revealed that API is a key regulator of signal transducer activator of transcription 3(STAT3).API regulated immune responses by reducing interleukin-23(IL-23)/STAT3/IL-17A axis.Moreover,it suppressed IMQ-caused cell hyperproliferation by inactivating STAT3 through regulation of extracellular signal-regulated kinase 1/2 and nuclear factor-κB(NF-κB)pathway.Furthermore,API reduced expression of inflammatory cytokines through inactivation of NF-κB.Taken together,our study demonstrates that API can ameliorate psoriasis and may be considered as a strategy for psoriasis treatment.展开更多
Loss of susceptibility to anoikis signals is a crucial step in metastasis.Anoikis resistance therefore represents a promising adjuvant therapeutic target for cancer management.In this study,we have conducted a rationa...Loss of susceptibility to anoikis signals is a crucial step in metastasis.Anoikis resistance therefore represents a promising adjuvant therapeutic target for cancer management.In this study,we have conducted a rationalized screening to search for novel leading anoikis sensitizer from daily foods.Among 19 tested dietary phytochemicals,the best results were obtained with apigenin,a natural component of celery.Phenotypically,apigenin sensitized breast cancer cells to anoikis,lowered the number of circulating tumor cells,and protected against breast cancer metastasis to lung in mice.Mechanistically,we demonstrated that the thromboxane A_(2)(TXA_(2))-TXA_(2)receptor(TP)axis has a critical role in acquired anoikis resistance by activating PI3K-Akt signaling pathway.Blockage of TXA_(2)signaling up-regulated p53 as well as its target gene p21,caused a G1 phase arrest,and finally led to apoptosis in breast cancer cells.TXA_(2)level was positively correlated with breast cancer cell anoikis rate,and apigenin significantly inhibited TXA_(2)biosynthesis in vitro and in vivo.Collectively,we identified apigenin as a potent anoikis sensitizer with anti-metastatic properties in a mouse model of breast cancer,and these findings might provide a rationale for introducing apigenin supplementation to breast cancer patients.展开更多
Apigenin （4＇,5,7-trihydroxyflavone） is a member of the flavone subclass of flavonoids present in fruits and vegetables. The involvement of autophagy in the apigenin-induced apoptotic death of human breast cancer ce...Apigenin （4＇,5,7-trihydroxyflavone） is a member of the flavone subclass of flavonoids present in fruits and vegetables. The involvement of autophagy in the apigenin-induced apoptotic death of human breast cancer cells was investigated. Cell proliferation and viability were assessed by 3-（4,5-dimethylthiazol- 2-yl）-2,5-diphenyltetrazolium bromide （MTT） and clonogenic assays. Flow cytometry, fluorescent staining and Western blot analysis were employed to detect apoptosis and autophagy, and the role of autophagy was assessed using autophagy inhibitors. Apigenin dose- and time-dependently repressed the proliferation and clonogenic survival of the human breast cancer T47D and MDA-MB-231 cell lines. The death of T47D and MDA-MB-231 cells was due to apoptosis associated with increased levels of Caspase3, PARP cleavage and Bax/Bcl-2 ratios. The results from flow cytometry and fluorescent staining also verified the occurrence of apoptosis. In addition, the apigenin-treated cells exhibited autophagy, as characterized by the appearance of autophagosomes under fluorescence microscopy and the accumulation of acidic vesicular organelles （AVOs） by flow cytometry. Furthermore, the results of the Western blot analysis revealed that the level of LC3-Ⅱ, the processed form of LC3-Ⅰ, was increased. Treatment with the autophagy inhibitor, 3-methyladenine （3-MA）, significantly enhanced the apoptosis induced by apigenin, which was accompanied by an increase in the level of PARP cleavage. Similar results were also confirmed by flow cytometry and fluorescence microscopy. These results indicate that apigenin has apoptosis- and autophagy-inducing effects in breast cancer cells. Autophagy plays a cyto-protective role in apigenin-induced apoptosis, and the combination of apigenin and an autophagy inhibitor may be a promising strategy for breast cancer control.展开更多
Objective:To obtain Iuteolin and apigenin rich fraction from the ethanolic extract of Cynodon dactylon(L.)(C.dactylon) Pers and evaluate the fraction's cytotoxicity and anti-Chikungunya potential using Vero cells....Objective:To obtain Iuteolin and apigenin rich fraction from the ethanolic extract of Cynodon dactylon(L.)(C.dactylon) Pers and evaluate the fraction's cytotoxicity and anti-Chikungunya potential using Vero cells.Methods:The ethanolic extract of C.dactylon was subjected to silica gel column chromatography to obtain anti-chikungunya virus(CHIKV) fraction.Reverse phase-HPLC and GC-MS studies were carried out to identily the major phytochemicals in the fraction using phylochemical standards.Cytotoxicity and the potential of the fraction against CHIKV were evaluated in vitro using Vero cells.Reduction in viral replication was assessed by reverse transcriptase-polymerase chain reaction(RT-PCR) after treating the viral infected Vero cells with the fraction.Results:Reverse Phase-HPLC and GC-MS studies confirmed the presence of flavonoids,luteolin and apigenin as major phytochemicals in the anti-CHIKV ethanolic fraction of C.dactylon- The fraction was found to exhibit potent viral inhibitory activity(about 98%) at the concentration of 50 μg/mL as observed by reduction in cytopathic effect,and the cytotoxic concentration of the fraction was found to be 250 μg/mL.RT-PCR analyses indicated that the reduction in viral mRNA synthesis in fraction treated infected cells was much higher than the viral infected control cells.Conclusions:Luteolin and apigenin rich ethanolic fraction from C.dactylon can be utilized as a potential therapeutic agent against CHIKV infection as the fraction does not show cytotoxicity while inhibiting the virus.展开更多
AIM： To explore the growth inhibition and apoptosisinducing effect of apigenin on human gastric carcinoma SGC-7901 cells. METHODS： The effects of apigenin on the growth, clone formation and proliferation of human ga...AIM： To explore the growth inhibition and apoptosisinducing effect of apigenin on human gastric carcinoma SGC-7901 cells. METHODS： The effects of apigenin on the growth, clone formation and proliferation of human gastric carcinoma SGC-7901 cells were observed by N-rr, done-forming assay, and morphological observation. Fluorescent staining and flow cytometry analysis were used to detect apoptosis of cells. RESULTS： Apigenin obviously inhibited the growth, clone formation and proliferation of SGC-7901 cells in a dosedependent manner. Inhibition of growth was observed on d 1 at the concentration of 80 μmol/L, while after 4 d, the inhibition rate （IR） was 90%. The growth IRs at the concentration of 20, 40, and 80 μmol/L were 38%, 71%, and 99% respedJvely on the 7^th d. After the cells were treated with apigenin for 48 h, the number of clone-forming in control, 20, 40, and 80 μmol/L groups was 217±16.9, 170±11.1 （P〈0.05）, 98±11.1 （P〈0.05）, and 25±3.5 （P〈0.05） respectively. Typical morphological changes of apoptosis was found by fluorescent staining. The cell nuclei had lost its smooth boundaries, chromatin was condensed, and cell nuclei were broken. Flow cytometry detected typical apoptosis peak. After the cells were treated with apigenin for 48 h, the apoptosis rates were 5.76%, 19.17%, and 29.30% respectively in 20, 40, and 80 μmol/L groups. CONCLUSION： Apigenin shows obvious inhibition on the growth and clone formation of SGC-7901 cells by inducing apoptosis.展开更多
Cancer is a major health concern and leading burden on economy worldwide. An increasing effort is devoted to isolation and development of plant-derived dietary components as effective chemo-preventive products. Phytoc...Cancer is a major health concern and leading burden on economy worldwide. An increasing effort is devoted to isolation and development of plant-derived dietary components as effective chemo-preventive products. Phytochemical compounds from natural resources such as fruits and vegetables are responsible for decreasing the risk of certain cancers among the consuming populations. Apigenin, a flavonoid phytochemical found in many kinds of fruits and vegetables, has been shown to exert significant biological effects, such as anti-oxidant, anti-inflammatory and most particularly anti-neoplastic properties. This review is intended to summarize the most recent advances in the anti-proliferative and chemo-preventive effects of apigenin in different cancer models. Analysis of the data from the studied cancer models has revealed that apigenin exerts its anti-proliferative effects through multiple and complex pathways. This guided us to discover some controversial results about the exact role of certain molecular pathways such as autophagy in the anticancer effects of apigenin. Further, there were cumulative positive evidences supporting the involvement of certain pathways such as apoptosis, ROS and DNA damage and repair. Apigenin possesses a high potential to be used as a chemosensitizing agent through the up-regulation of DR5 pathway. According to these preclinical findings we recommend that further robust unbiased studies should consider the possible interactions between different molecular pathways.展开更多
Apigenin,a natural flavonoid has been reported against a variety of cancer types.However,it is unclear whether apigenin can promote autophagy and ferroptosis in Ishikawa cells.There are few reports on the mechanism of...Apigenin,a natural flavonoid has been reported against a variety of cancer types.However,it is unclear whether apigenin can promote autophagy and ferroptosis in Ishikawa cells.There are few reports on the mechanism of apigenin on autophagy and ferroptosis of endometrial cancer Ishikawa cells.We found that iron accumulation,lipid peroxidation,glutathione consumption,p62,HMOX1,and ferritin were increased,while,solute carrier family 7 member 11 and glutathione peroxidase 4 were decreased.Ferrostatin-1,an iron-death inhibitor could reverse the effects of apigenin in Ishikawa cells.On the other hand,apigenin could promote autophagy via up-regulating Beclin 1,ULK1,ATG5,ATG13,and LC3B and down-regulating AMPK,mTOR,P70S6K,and ATG4.Furthermore,apigenin could inhibit tumor tissue proliferation and restrict tumor growth via ferroptosis in vivo.展开更多
Ixeris chinesis (Thunb.) Ankai has been used as a Chinese folk medicine, but only scanty information is available on the physiological and biochemical functions of the compounds extracted from I. chinesis. In the pre...Ixeris chinesis (Thunb.) Ankai has been used as a Chinese folk medicine, but only scanty information is available on the physiological and biochemical functions of the compounds extracted from I. chinesis. In the present study the effects of apigenin -7-glucoside (APIG) isolated from I. chinesis against liver injury caused by carbon tetrachloride (CCl4) were investigated. Methods The contents of malondialdehyde (MDA), glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), and reduced glutathione (GSH) were evaluated by spectrophotography. The content of 8-Hydroxydeoxyguanosine (8-OHdG) was measured with high-performance liquid chromatography (HPLC) equipped with electrochemical and UV detection methods. The antioxidant activity of APIG was evaluated using chemiluminescence single photon counting technology. Results CCl4 significantly increased the enzyme activities of GPT and GOT in blood serum, as well as the level of MDA and 8-OHdG in liver tissue, and decreased the levels of GSH. Pretreatment with APIG was able not only to suppress the elevation of GPT, GOT, MDA and 8-OHdG, and inhibit the reduction of GSH in a dose-dependent manner in vivo, but also to reduce the damage of hepatocytes in vitro. On the other hand, we also found that APIG had strong antioxidant activity against reactive oxygen species (ROS) in vitro in a concentration-dependent manner. Conclusion The hepatoprotective activity of APIG is possibly due to its antioxidant properties, acting as scavengers of ROS. These results obtained in vivo and in vitro suggest that APIG has protective effects against hepatic oxidative injury induced by chemicals. Further studies on the pharmaceutical functions and immunological responses of APIG may help its clinical application.展开更多
Objective： To study the effects of apigenin on vascular endothelial growth factor （VEGF） in human breast cancer cells （MDA-MB-231. Methods： MTT assay was used to detect the cell proliferation inhibitory effect of...Objective： To study the effects of apigenin on vascular endothelial growth factor （VEGF） in human breast cancer cells （MDA-MB-231. Methods： MTT assay was used to detect the cell proliferation inhibitory effect of apigenin on MDA-MB-231 cell. ELISA was used to determine the protein level of VEGF secreted by MDA-MB-231 cells. RT-PCR was used to detect mRNA levels of VEGF in MDA-MB-231 cells. The protein levels of HIF-1α, p-AKT, p-ERK1/2, and p53 were detected by Western Blotting. Results： Apigenin did not inhibit the cell viability of MDA-MB-231 cell. Apigenin reduced the secretion and mRNA levels of VEGF in MDA-MB-231 cells. Additionally, apigenin decreased the expressions of HIF-1α, p-AKT and p-ERK1/2, but induced the expression of p53. Conclusion： Apigenin can inhibit VEGF expression in human breast cancer cells, and this may be achieved through decreasing HIF-1α.展开更多
This study aimed to characterize the effect of apigenin on the reproductive system in male mice. Adult male mice were treated with intraperitoneal injection of apigenin at the dose levels of 5, 10, 15, 20 and 25 mg/kg...This study aimed to characterize the effect of apigenin on the reproductive system in male mice. Adult male mice were treated with intraperitoneal injection of apigenin at the dose levels of 5, 10, 15, 20 and 25 mg/kg.bw, 0.05% DMSO and 0.9% normal saline daily for seven days. Then, testis and epididymis sperms in sperm motility, sperm morphology, the percentages of ploidy cells and seminiferous epithelium cells at the cell-circle phase, and the ratio of ploidy cells were evaluated. The results showed that sperm density significantly reduced in the 25 mg/kg group compared with the solvent control group. The abnormal sperms were mainly amorphous;non-hook sperms took the second largest group;and banana, double-tail and folded-tail sperms were rare. Abnormal sperms were mainly in the head sperm. Moreover, after intraperitoneal injection of 5 mg/kg apigenin, the percentage of 1C population increased, and the percentage of 4C declined, leading to a significant increase of the 1C:4C ratio, compared with the solvent and negative control groups. The percentage of seminiferous epithelium cells at the cell-circle phase of G0/G1 exhibited a significant increase in the 25 mg/kg group compared with the control groups. Taken together, that apigenin has adverse effects on the reproductive system in adult male mice is demonstrated.展开更多
Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in hig...Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in high-glucose and dexamethasone induced insulin-resistant(IR)HepG2 cells.All flavonoids improves the glucose consumption and glycogen synthesis abilities in IR-HepG2 cells via activating glucose transporter protein 4(GLUT4)and phosphor-glycogen synthase kinase(GSK-3β).These fl avonoids signifi cantly inhibited the production of reactive oxygen species(ROS)and advanced glycation end-products(AGEs),which were closely related to the suppression of the phosphorylation form of NF-κB and P65.The expression levels of insulin receptor substrate-1(IRS-1),insulin receptor substrate-2(IRS-2)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway in IR-HepG2 cells were all partially activated by the fl avonoids,with variable effects.Furthermore,the intracellular metabolic conditions of the fl avonoids were also evaluated.展开更多
In this work,apigenin was chosen as a raw material to synthesize a novel epoxy monomer(DGEA),while the bio-based epoxy resin was further obtained after curing with 4,4’-diaminodiphenylmethane(DDM).The control samples...In this work,apigenin was chosen as a raw material to synthesize a novel epoxy monomer(DGEA),while the bio-based epoxy resin was further obtained after curing with 4,4’-diaminodiphenylmethane(DDM).The control samples were prepared by curing diglycidyl ether of bisphenol A(DGEBA)with DDM.The non-isothermal differential scanning calorimeter(DSC)method was utilized to further investigate the curing behavior and curing kinetics of the DGEA/DDM system.Despite no flame retardant active elements,the DGEA/DDM thermoset still exhibited exceptional anti-flammability.Specifically,the DGEA/DDM thermoset reached a V-0 rating in the UL-94 test and owned a high limiting oxygen index(LOI)value of 37.0%,while DGEBA/DDM resins were consumed completely in the vertical combustion test with a low LOI of 23.0%.Furthermore,the microscale combustion calorimetry(MCC)results manifested that compared with DGEBA/DDM resins,both PHRR and THR values of the DGEA/DDM resins were dropped by 84.0%and 57.6%,respectively.Additionally,the DGEA/DDM resin also presented higher storage modulus and tensile strength compared with DGEBA/DDM one.Particularly,in contrast with that of the cured DGEBA/DDM one(156℃),the DGEA/DDM thermoset displayed an extremely high glass transition temperature(232℃).This study breaks new ground on how to produce biobased monomers with aromatic structures and achieve high-performance thermosetting polymers.展开更多
AIM:To investigate the retinoprotective role of Apigenin(Api)against high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs),and to explore its regulatory mechanism.METHODS:HRMECs were stimulate...AIM:To investigate the retinoprotective role of Apigenin(Api)against high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs),and to explore its regulatory mechanism.METHODS:HRMECs were stimulated by HG for 48h to establish the in vitro cell model.Different concentrations of Api(2.5,5,and 10μmol/L)were applied for treatment.Cell counting kit-8(CCK-8),Transwell,and tube formation assays were performed to examine the effects of Api on the viability,migration,and angiogenesis in HG-induced HRMECs.Vascular permeability was evaluated by Evans blue dye.The inflammatory cytokines and oxidative stress-related factors were measured using their commercial kits.Protein expression of nicotinamide adenine dinucleotide phosphate(NADPH)oxidase 4(NOX4)and p38 mitogen-activated protein kinase(MAPK)was measured by Western blot.RESULTS:Api prevented HG-induced HRMECs viability,migration,angiogenesis,and vascular permeability in a concentration-dependent manner.Meanwhile,Api also concentration-dependently inhibited inflammation and oxidative stress in HRMECs exposed to HG.In addition,HG caused an elevated expression of NOX4,which was retarded by Api treatment.HG stimulation facilitated the activation of p38 MAPK signaling in HRMECs,and Api could weaken this activation partly via downregulating NOX4 expression.Furthermore,overexpression of NOX4 or activation of p38 MAPK signaling greatly weakened the protective role of Api against HG-stimulated HRMECs.CONCLUSION:Api might exert a beneficial role in HGstimulated HRMECs through regulating NOX4/p38 MAPK pathway.展开更多
基金supported by The National Natural Science Foundation of China(No.31902283)Research Foundation for Master students at the Affiliated Hospital of Zunyi Medical College(No.22-2018).
文摘Background:The outcomes of pediatric patients with acute lymphoblastic leukemia(ALL)remain far less than favorable.While apigenin is an anti-cancer agent,studies on the mechanism by which it regulates ALL cell cycle progression are inadequate.Ferroptosis and AMP-activated protein kinase(AMPK)signaling are important processes for ALL patients.However,it remains unclear whether apigenin works by affecting AMPK and apoptosis.Materials and Methods:SUP-B15 and T-cell Jurkat ALL cells were treated with apigenin,and cell viability and apoptosis were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assays,respectively.The thiobarbituric acid-reactive substances(TBARS)assay was used to evaluate lipid peroxidation.Intracellular Fe2+levels were measured using a commercial kit.Corresponding proteins were detected by western blotting.Results:Results showed that apigenin reduced cell viability and the levels of Ki67 and proliferating cell nuclear antigen(PCNA)expression in a concentration-dependent manner in both types of ALL cells.Apigenin also exerted anti-apoptotic effects on SUP-B15 and Jurkat cells.Apigenin activated AMP-activated protein kinase(AMPK)signaling and induced ferroptosis,and those effects were attenuated by inhibition of AMPK.Eventually,the reduced cell proliferation and increased cell apoptosis caused by apigenin in ALL cells were partly abolished by AMPK inhibition.Conclusion:In summary,apigenin exerted anti-leukemia activity in ALL cells,and that effect was partially achieved by activation of AMPK signaling.Our findings suggest apigenin as a potential drug for treatment of ALL.
文摘To investigate the mechanisms of apigenin(API)and proanthocyanidins(PC)in soothing sensitive skin(SS),a mast cell degranulation model was established by stimulating RBL-2H3 cells with the calcium ionophore A23187.Based on the combinatorial experiments,it was found that when API and PC were combined at the molar ratios of 4∶1 and 2∶1,they exhibited the antagonistic effects on histamine release(combination index CI>1);when they are combined at the molar ratios of 1∶1,1∶2 or 1∶4,they showed the synergistic effects on histamine release(CI<1).Among them,the combination of API and PC at a molar ratio of 1∶1 showed the better potent synergistic antihistamine release effect(CI=0.70).Histamine is a hallmark of the mast cell degranulation,consequently,the combination of API and PC at a molar ratio of 1∶1 yields the better efficiency in inhibiting the mast cell degranulation with the lowest IC_(50)value.Compared to the utilization of API or PC alone,the IC_(50)value was reduced by 11.150 and 6.503μmol/L,respectively.Compared to the positive control paeonol(PA),the treatment with the combination significantly reduced theβ-hex secretion,decreased the F-actin cytoskeleton rearrangement,and markedly suppressed the release of TNF-α,IL-4,and MCP-1.Further studies on the signaling pathways related to the mast cell degranulation indicated that the combination effectively inhibited the intracellular Ca^(2+)influx and significantly suppressed the phosphorylation of calmodulin-dependent protein kinase(CaMK)and phospholipase C/protein kinase C(PLC/PKC).In summary,the combination of API and PC at a molar ratio of 1∶1 exhibited the better synergistic antagonistic effect on the histamine release,inhibited the mast cell degranulation model activation by reducing Ca^(2+)influx and inhibiting the activation of Ca^(2+)/CaMK and PLC/PKC pathways,stabilized the cell membranes,regulated the inflammatory factor secretion,and exerted an effect in alleviating sensitive skin.
基金supported by the grant from Henan Province Science and Technology Research Project(Project No:242102310250,222102310373)Key Research Project Program of Higher Education Institutions in Henan Province(NO 24A32006,22B360003)Medical Science and Technology Tackling Program of Henan Province(NO LHGJ20230677).
文摘Objective:To investigate the effect of apigenin on carbon tetrachloride(CCl_(4))-induced liver fibrosis and elucidate the underlying mechanisms.Methods:A mouse model of CCl_(4)-induced liver fibrosis was used to evaluate the effects of apigenin.Liver function was assessed using biochemical tests,and inflammation-associated markers,including interleukin-1 beta(IL-1β),IL-6,IL-10,and tumor necrosis factor-alpha(TNF-α),were determined by enzyme-linked immunosorbent assay(ELISA).H&E staining,Sirius Red staining,and collagen immunohistochemistry were also conducted.In addition,antioxidant enzyme activity and the underlying mechanisms of hepatoprotective effects of apigenin were examined.Results:CCl_(4)administration induced hepatic stellate cell activation and liver fibrogenesis in mice.Apigenin treatment markedly decreased liver injury markers,inflammation,oxidative stress,and collagen deposition,mitigating CCl_(4)-induced liver fibrosis.Furthermore,it significantly suppressed the activation of the phosphoinositide 3-kinase/protein kinase B/glycogen synthase kinase 3 beta(PI3K/AKT/GSK3β)pathway by reducing the ratios of p-PI3K/PI3K,p-AKT/AKT,and p-GSK3β/GSK3βin liver tissue.Conclusions:Apigenin ameliorates CCl_(4)-induced liver fibrosis in mice,likely through the inhibition of the PI3K/AKT/GSK3βsignaling pathway.These findings suggest that apigenin may have therapeutic potential for treating liver fibrosis.
基金supported by the National Natural Science Foundation of China(NSFC)(81973316,82173807)the China Postdoctoral Science Foundation(2020M681914)+1 种基金the Fund from Tianjin Municipal Health Commission(ZC200093)the Open Fund of Tianjin Central Hospital of Obstetrics and Gynecology/Tianjin Key Laboratory of human development and reproductive regulation(2021XHY01)。
文摘Psoriasis is a chronic autoimmune disease featured by patches on the skin.It is caused by malfunction of immune cells and keratinocytes with inflammation as one of its key features.Apigenin(API)is a natural flavonoid with anti-inflammatory and immunoregulatory properties.Therefore,we speculated that API can ameliorate psoriasis,and determined its effect on the development of psoriasis by using imiquimod(IMQ)-induced psoriasis mouse model.Our results showed that API attenuated IMQ-induced phenotypic changes,such as erythema,scaling and epidermal thickening,and improved splenic hyperplasia.Abnormal differentiation of immune cells was restored in API-treated mice.Mechanistically,we revealed that API is a key regulator of signal transducer activator of transcription 3(STAT3).API regulated immune responses by reducing interleukin-23(IL-23)/STAT3/IL-17A axis.Moreover,it suppressed IMQ-caused cell hyperproliferation by inactivating STAT3 through regulation of extracellular signal-regulated kinase 1/2 and nuclear factor-κB(NF-κB)pathway.Furthermore,API reduced expression of inflammatory cytokines through inactivation of NF-κB.Taken together,our study demonstrates that API can ameliorate psoriasis and may be considered as a strategy for psoriasis treatment.
基金supported by the National Natural Science Foundation of China (81773064,31972973,32021005)National Youth 1000 Talents Plan+2 种基金the Jiangsu Specially-Appointed Professor ProgramJiangsu Province Recruitment Plan for High-level,Innovative and Entrepreneurial Talents (Innovative Research Team)Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province
文摘Loss of susceptibility to anoikis signals is a crucial step in metastasis.Anoikis resistance therefore represents a promising adjuvant therapeutic target for cancer management.In this study,we have conducted a rationalized screening to search for novel leading anoikis sensitizer from daily foods.Among 19 tested dietary phytochemicals,the best results were obtained with apigenin,a natural component of celery.Phenotypically,apigenin sensitized breast cancer cells to anoikis,lowered the number of circulating tumor cells,and protected against breast cancer metastasis to lung in mice.Mechanistically,we demonstrated that the thromboxane A_(2)(TXA_(2))-TXA_(2)receptor(TP)axis has a critical role in acquired anoikis resistance by activating PI3K-Akt signaling pathway.Blockage of TXA_(2)signaling up-regulated p53 as well as its target gene p21,caused a G1 phase arrest,and finally led to apoptosis in breast cancer cells.TXA_(2)level was positively correlated with breast cancer cell anoikis rate,and apigenin significantly inhibited TXA_(2)biosynthesis in vitro and in vivo.Collectively,we identified apigenin as a potent anoikis sensitizer with anti-metastatic properties in a mouse model of breast cancer,and these findings might provide a rationale for introducing apigenin supplementation to breast cancer patients.
基金supported by the National Natural Science Foundation of China (Grant no. 81001186)the Tianjin Municipal Natural Science Foundation (Grant no. 10JCYBJ C14100,11JCZDJC28000,13JCYBJC21800)
文摘Apigenin （4＇,5,7-trihydroxyflavone） is a member of the flavone subclass of flavonoids present in fruits and vegetables. The involvement of autophagy in the apigenin-induced apoptotic death of human breast cancer cells was investigated. Cell proliferation and viability were assessed by 3-（4,5-dimethylthiazol- 2-yl）-2,5-diphenyltetrazolium bromide （MTT） and clonogenic assays. Flow cytometry, fluorescent staining and Western blot analysis were employed to detect apoptosis and autophagy, and the role of autophagy was assessed using autophagy inhibitors. Apigenin dose- and time-dependently repressed the proliferation and clonogenic survival of the human breast cancer T47D and MDA-MB-231 cell lines. The death of T47D and MDA-MB-231 cells was due to apoptosis associated with increased levels of Caspase3, PARP cleavage and Bax/Bcl-2 ratios. The results from flow cytometry and fluorescent staining also verified the occurrence of apoptosis. In addition, the apigenin-treated cells exhibited autophagy, as characterized by the appearance of autophagosomes under fluorescence microscopy and the accumulation of acidic vesicular organelles （AVOs） by flow cytometry. Furthermore, the results of the Western blot analysis revealed that the level of LC3-Ⅱ, the processed form of LC3-Ⅰ, was increased. Treatment with the autophagy inhibitor, 3-methyladenine （3-MA）, significantly enhanced the apoptosis induced by apigenin, which was accompanied by an increase in the level of PARP cleavage. Similar results were also confirmed by flow cytometry and fluorescence microscopy. These results indicate that apigenin has apoptosis- and autophagy-inducing effects in breast cancer cells. Autophagy plays a cyto-protective role in apigenin-induced apoptosis, and the combination of apigenin and an autophagy inhibitor may be a promising strategy for breast cancer control.
文摘Objective:To obtain Iuteolin and apigenin rich fraction from the ethanolic extract of Cynodon dactylon(L.)(C.dactylon) Pers and evaluate the fraction's cytotoxicity and anti-Chikungunya potential using Vero cells.Methods:The ethanolic extract of C.dactylon was subjected to silica gel column chromatography to obtain anti-chikungunya virus(CHIKV) fraction.Reverse phase-HPLC and GC-MS studies were carried out to identily the major phytochemicals in the fraction using phylochemical standards.Cytotoxicity and the potential of the fraction against CHIKV were evaluated in vitro using Vero cells.Reduction in viral replication was assessed by reverse transcriptase-polymerase chain reaction(RT-PCR) after treating the viral infected Vero cells with the fraction.Results:Reverse Phase-HPLC and GC-MS studies confirmed the presence of flavonoids,luteolin and apigenin as major phytochemicals in the anti-CHIKV ethanolic fraction of C.dactylon- The fraction was found to exhibit potent viral inhibitory activity(about 98%) at the concentration of 50 μg/mL as observed by reduction in cytopathic effect,and the cytotoxic concentration of the fraction was found to be 250 μg/mL.RT-PCR analyses indicated that the reduction in viral mRNA synthesis in fraction treated infected cells was much higher than the viral infected control cells.Conclusions:Luteolin and apigenin rich ethanolic fraction from C.dactylon can be utilized as a potential therapeutic agent against CHIKV infection as the fraction does not show cytotoxicity while inhibiting the virus.
文摘AIM： To explore the growth inhibition and apoptosisinducing effect of apigenin on human gastric carcinoma SGC-7901 cells. METHODS： The effects of apigenin on the growth, clone formation and proliferation of human gastric carcinoma SGC-7901 cells were observed by N-rr, done-forming assay, and morphological observation. Fluorescent staining and flow cytometry analysis were used to detect apoptosis of cells. RESULTS： Apigenin obviously inhibited the growth, clone formation and proliferation of SGC-7901 cells in a dosedependent manner. Inhibition of growth was observed on d 1 at the concentration of 80 μmol/L, while after 4 d, the inhibition rate （IR） was 90%. The growth IRs at the concentration of 20, 40, and 80 μmol/L were 38%, 71%, and 99% respedJvely on the 7^th d. After the cells were treated with apigenin for 48 h, the number of clone-forming in control, 20, 40, and 80 μmol/L groups was 217±16.9, 170±11.1 （P〈0.05）, 98±11.1 （P〈0.05）, and 25±3.5 （P〈0.05） respectively. Typical morphological changes of apoptosis was found by fluorescent staining. The cell nuclei had lost its smooth boundaries, chromatin was condensed, and cell nuclei were broken. Flow cytometry detected typical apoptosis peak. After the cells were treated with apigenin for 48 h, the apoptosis rates were 5.76%, 19.17%, and 29.30% respectively in 20, 40, and 80 μmol/L groups. CONCLUSION： Apigenin shows obvious inhibition on the growth and clone formation of SGC-7901 cells by inducing apoptosis.
基金supported by the key medical project of Jiangsu province(No.BL2014078)the key discipline of Jiangsu province(2011-2015)
文摘Cancer is a major health concern and leading burden on economy worldwide. An increasing effort is devoted to isolation and development of plant-derived dietary components as effective chemo-preventive products. Phytochemical compounds from natural resources such as fruits and vegetables are responsible for decreasing the risk of certain cancers among the consuming populations. Apigenin, a flavonoid phytochemical found in many kinds of fruits and vegetables, has been shown to exert significant biological effects, such as anti-oxidant, anti-inflammatory and most particularly anti-neoplastic properties. This review is intended to summarize the most recent advances in the anti-proliferative and chemo-preventive effects of apigenin in different cancer models. Analysis of the data from the studied cancer models has revealed that apigenin exerts its anti-proliferative effects through multiple and complex pathways. This guided us to discover some controversial results about the exact role of certain molecular pathways such as autophagy in the anticancer effects of apigenin. Further, there were cumulative positive evidences supporting the involvement of certain pathways such as apoptosis, ROS and DNA damage and repair. Apigenin possesses a high potential to be used as a chemosensitizing agent through the up-regulation of DR5 pathway. According to these preclinical findings we recommend that further robust unbiased studies should consider the possible interactions between different molecular pathways.
基金the National Key Research&Development Program of China(2022YFF1100305)the National Natural Science Foundation of Ningxia Province(2021AAC02019)the Major Projects of Science and Technology in Anhui Province(201903a06020021,201904a06020008,202004a06020042,202004a06020052).
文摘Apigenin,a natural flavonoid has been reported against a variety of cancer types.However,it is unclear whether apigenin can promote autophagy and ferroptosis in Ishikawa cells.There are few reports on the mechanism of apigenin on autophagy and ferroptosis of endometrial cancer Ishikawa cells.We found that iron accumulation,lipid peroxidation,glutathione consumption,p62,HMOX1,and ferritin were increased,while,solute carrier family 7 member 11 and glutathione peroxidase 4 were decreased.Ferrostatin-1,an iron-death inhibitor could reverse the effects of apigenin in Ishikawa cells.On the other hand,apigenin could promote autophagy via up-regulating Beclin 1,ULK1,ATG5,ATG13,and LC3B and down-regulating AMPK,mTOR,P70S6K,and ATG4.Furthermore,apigenin could inhibit tumor tissue proliferation and restrict tumor growth via ferroptosis in vivo.
基金This work was supported by the Key Grant Project of the Ministry of Education of China (No.03076).
文摘Ixeris chinesis (Thunb.) Ankai has been used as a Chinese folk medicine, but only scanty information is available on the physiological and biochemical functions of the compounds extracted from I. chinesis. In the present study the effects of apigenin -7-glucoside (APIG) isolated from I. chinesis against liver injury caused by carbon tetrachloride (CCl4) were investigated. Methods The contents of malondialdehyde (MDA), glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), and reduced glutathione (GSH) were evaluated by spectrophotography. The content of 8-Hydroxydeoxyguanosine (8-OHdG) was measured with high-performance liquid chromatography (HPLC) equipped with electrochemical and UV detection methods. The antioxidant activity of APIG was evaluated using chemiluminescence single photon counting technology. Results CCl4 significantly increased the enzyme activities of GPT and GOT in blood serum, as well as the level of MDA and 8-OHdG in liver tissue, and decreased the levels of GSH. Pretreatment with APIG was able not only to suppress the elevation of GPT, GOT, MDA and 8-OHdG, and inhibit the reduction of GSH in a dose-dependent manner in vivo, but also to reduce the damage of hepatocytes in vitro. On the other hand, we also found that APIG had strong antioxidant activity against reactive oxygen species (ROS) in vitro in a concentration-dependent manner. Conclusion The hepatoprotective activity of APIG is possibly due to its antioxidant properties, acting as scavengers of ROS. These results obtained in vivo and in vitro suggest that APIG has protective effects against hepatic oxidative injury induced by chemicals. Further studies on the pharmaceutical functions and immunological responses of APIG may help its clinical application.
文摘Objective： To study the effects of apigenin on vascular endothelial growth factor （VEGF） in human breast cancer cells （MDA-MB-231. Methods： MTT assay was used to detect the cell proliferation inhibitory effect of apigenin on MDA-MB-231 cell. ELISA was used to determine the protein level of VEGF secreted by MDA-MB-231 cells. RT-PCR was used to detect mRNA levels of VEGF in MDA-MB-231 cells. The protein levels of HIF-1α, p-AKT, p-ERK1/2, and p53 were detected by Western Blotting. Results： Apigenin did not inhibit the cell viability of MDA-MB-231 cell. Apigenin reduced the secretion and mRNA levels of VEGF in MDA-MB-231 cells. Additionally, apigenin decreased the expressions of HIF-1α, p-AKT and p-ERK1/2, but induced the expression of p53. Conclusion： Apigenin can inhibit VEGF expression in human breast cancer cells, and this may be achieved through decreasing HIF-1α.
文摘This study aimed to characterize the effect of apigenin on the reproductive system in male mice. Adult male mice were treated with intraperitoneal injection of apigenin at the dose levels of 5, 10, 15, 20 and 25 mg/kg.bw, 0.05% DMSO and 0.9% normal saline daily for seven days. Then, testis and epididymis sperms in sperm motility, sperm morphology, the percentages of ploidy cells and seminiferous epithelium cells at the cell-circle phase, and the ratio of ploidy cells were evaluated. The results showed that sperm density significantly reduced in the 25 mg/kg group compared with the solvent control group. The abnormal sperms were mainly amorphous;non-hook sperms took the second largest group;and banana, double-tail and folded-tail sperms were rare. Abnormal sperms were mainly in the head sperm. Moreover, after intraperitoneal injection of 5 mg/kg apigenin, the percentage of 1C population increased, and the percentage of 4C declined, leading to a significant increase of the 1C:4C ratio, compared with the solvent and negative control groups. The percentage of seminiferous epithelium cells at the cell-circle phase of G0/G1 exhibited a significant increase in the 25 mg/kg group compared with the control groups. Taken together, that apigenin has adverse effects on the reproductive system in adult male mice is demonstrated.
基金supported by National Natural Science Foundation of China(32072212)Multi-Year Research Grant of University of Macao(MYRG2018-00169-ICMS)+5 种基金Science and Technology Development Fund of Macao(FDCT)(0098/2020/A)MICINN supporting the Ramón y Cajal grant for M.A.Prieto(RYC-201722891)Jianbo Xiao(RYC2020-030365-I)Xunta de Galicia supporting the Axudas Conecta Peme,the IN852A 2018/58 Neuro Food Project,the program EXCELENCIA-ED431F 2020/12the pre-doctoral grants of P.García-Oliveira(ED481A-2019/295)to Ibero-American Program on Science and Technology(CYTED-AQUA-CIBUS,P317RT0003).
文摘Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in high-glucose and dexamethasone induced insulin-resistant(IR)HepG2 cells.All flavonoids improves the glucose consumption and glycogen synthesis abilities in IR-HepG2 cells via activating glucose transporter protein 4(GLUT4)and phosphor-glycogen synthase kinase(GSK-3β).These fl avonoids signifi cantly inhibited the production of reactive oxygen species(ROS)and advanced glycation end-products(AGEs),which were closely related to the suppression of the phosphorylation form of NF-κB and P65.The expression levels of insulin receptor substrate-1(IRS-1),insulin receptor substrate-2(IRS-2)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway in IR-HepG2 cells were all partially activated by the fl avonoids,with variable effects.Furthermore,the intracellular metabolic conditions of the fl avonoids were also evaluated.
基金financially supported by the National Natural Science Foundation of China(Nos.22075265 and 22050410269)the Youth Innovation Promotion Association of the Chinese Academy of Sciences(No.2021459)。
文摘In this work,apigenin was chosen as a raw material to synthesize a novel epoxy monomer(DGEA),while the bio-based epoxy resin was further obtained after curing with 4,4’-diaminodiphenylmethane(DDM).The control samples were prepared by curing diglycidyl ether of bisphenol A(DGEBA)with DDM.The non-isothermal differential scanning calorimeter(DSC)method was utilized to further investigate the curing behavior and curing kinetics of the DGEA/DDM system.Despite no flame retardant active elements,the DGEA/DDM thermoset still exhibited exceptional anti-flammability.Specifically,the DGEA/DDM thermoset reached a V-0 rating in the UL-94 test and owned a high limiting oxygen index(LOI)value of 37.0%,while DGEBA/DDM resins were consumed completely in the vertical combustion test with a low LOI of 23.0%.Furthermore,the microscale combustion calorimetry(MCC)results manifested that compared with DGEBA/DDM resins,both PHRR and THR values of the DGEA/DDM resins were dropped by 84.0%and 57.6%,respectively.Additionally,the DGEA/DDM resin also presented higher storage modulus and tensile strength compared with DGEBA/DDM one.Particularly,in contrast with that of the cured DGEBA/DDM one(156℃),the DGEA/DDM thermoset displayed an extremely high glass transition temperature(232℃).This study breaks new ground on how to produce biobased monomers with aromatic structures and achieve high-performance thermosetting polymers.
文摘AIM:To investigate the retinoprotective role of Apigenin(Api)against high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs),and to explore its regulatory mechanism.METHODS:HRMECs were stimulated by HG for 48h to establish the in vitro cell model.Different concentrations of Api(2.5,5,and 10μmol/L)were applied for treatment.Cell counting kit-8(CCK-8),Transwell,and tube formation assays were performed to examine the effects of Api on the viability,migration,and angiogenesis in HG-induced HRMECs.Vascular permeability was evaluated by Evans blue dye.The inflammatory cytokines and oxidative stress-related factors were measured using their commercial kits.Protein expression of nicotinamide adenine dinucleotide phosphate(NADPH)oxidase 4(NOX4)and p38 mitogen-activated protein kinase(MAPK)was measured by Western blot.RESULTS:Api prevented HG-induced HRMECs viability,migration,angiogenesis,and vascular permeability in a concentration-dependent manner.Meanwhile,Api also concentration-dependently inhibited inflammation and oxidative stress in HRMECs exposed to HG.In addition,HG caused an elevated expression of NOX4,which was retarded by Api treatment.HG stimulation facilitated the activation of p38 MAPK signaling in HRMECs,and Api could weaken this activation partly via downregulating NOX4 expression.Furthermore,overexpression of NOX4 or activation of p38 MAPK signaling greatly weakened the protective role of Api against HG-stimulated HRMECs.CONCLUSION:Api might exert a beneficial role in HGstimulated HRMECs through regulating NOX4/p38 MAPK pathway.
