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.
Animals ; Antineoplastic Agents, Phytogenic ; chemistry ; pharmacology ; Apigenin ; chemistry ; pharmacology ; Apoptosis ; drug effects ; Autophagy ; drug effects ; Humans ; Neoplasms ; drug therapy ; genetics ; metabolism ; physiopathology ; Phytochemicals ; chemistry ; pharmacology

OBJECTIVETo study chemical constituents of Incarvillea arguta and their accelerating PC-12 cell differentiation.

METHODThe constituents were isolated and repeatedly purified on silica gel column chromatography, and were identified on the basis of physicochemical and spectroscopic analysis. The neurotrophic activity of different portion and all purified compounds from I. arguta was determined on the model of PC-12 cell.

RESULTFive compounds were isolated from BuOH portion of alcohol extraction of I. arguta. Their structures were identified as plantarenaloside (I), 5-hydroxy-4', 6 7-trimethoxy-flavone (II), 4', 5-dihydroxy-6, 7-dimethoxyflavone (III), 4', 5-dihydroxy-7-methoxyflavone (IV), 5-dydroxy-4', 7-dimethoxyflavone (V).

CONCLUSIONCompound I is isolated from the plant for the first time and it has neurotrophic activity for PC-12 cell. Compounds II approximately V are isolated from the genus Incarvillea for the first time.

Animals ; Apigenin ; isolation & purification ; pharmacology ; Bignoniaceae ; chemistry ; Cell Transformation, Neoplastic ; drug effects ; Flavones ; isolation & purification ; pharmacology ; PC12 Cells ; Rats

OBJECTIVETo study on the chemical constituents of Lobelia chinensis.

METHODThe coloumn chromatographic techniques were applied to isolate constituents, and their structures were elucidated by means of spectral data analysis.

RESULTSixteen compounds were isolated and identified as daucosterol (1), diosmetin (2), apigenin (3), chrysoeriol (4), loteolin (5), hesperidin (6), loteolin-7-O-beta-D-glucoside (7), apigenin-7-O-beta-D-glucoside (8), linarin (9), diosmin(10), 5,7-dimethoxy-8- hydroxycoumarin (11), palmitinic acid (12), lacceroic acid (13), stearic acid (14), beta-sitosterol (15), daucosterol (16).

CONCLUSIONAll of these compouds were obtained from L. chinensis for the first time.

Apigenin ; analysis ; Cholestenones ; analysis ; Flavones ; Flavonoids ; analysis ; Glycosides ; analysis ; Hesperidin ; analysis ; Lobelia ; chemistry ; Plant Extracts ; pharmacology ; Sitosterols ; analysis

This study aimed to evaluate the biological effect and mechanism of Vernonia anthelmintica Injection(VAI) on melanin accumulation. The in vivo depigmentation model was induced by propylthiouracil(PTU) in zebrafish, and the effect of VAI on melanin accumulation was evaluated based on the in vitro B16F10 cell model. The chemical composition of VAI was identified according to the high-performance liquid chromatography quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS). Network pharmaco-logy was applied to predict potential targets and pathways of VAI. A "VAI component-target-pathway" network was established, and the pharmacodynamic molecules were screened out based on the topological characteristics of the network. The binding of active molecules to key targets was verified by molecular docking. The results showed that VAI promoted tyrosinase activity and melanin production in B16F10 cells in a dose-and time-dependent manner and could restore the melanin in the body of the zebrafish model. Fifty-six compounds were identified from VAI, including flavonoids(15/56), terpenoids(10/56), phenolic acids(9/56), fatty acids(9/56), steroids(6/56), and others(7/56). Network pharmacological analysis screened four potential quality markers, including apigenin, chrysoeriol, syringaresinol, and butein, involving 61 targets and 65 pathways, and molecular docking verified their binding to TYR, NFE2L2, CASP3, MAPK1, MAPK8, and MAPK14. It was found that the mRNA expression of MITF, TYR, TYRP1, and DCT in B16F10 cells was promoted. By UPLC-Q-TOF-MS and network pharmacology, this study determined the material basis of VAI against vitiligo, screened apigenin, chrysoeriol, syringaresinol, and butein as the quality markers of VAI, and verified the efficacy and internal mechanism of melanogenesis, providing a basis for quality control and further clinical research.
Animals ; Vernonia/chemistry* ; Melanins/metabolism* ; Zebrafish/metabolism* ; Network Pharmacology ; Molecular Docking Simulation ; Apigenin/pharmacology* ; Drugs, Chinese Herbal/pharmacology* ; Chromatography, High Pressure Liquid

To design and synthesize a series of novel scutellarein 4'-L-amino acid prodrugs with more potent anti-oxidative activity and improved physicochemical properties. Scutellarein was used as lead compound, according to successful experience of improving bioavailability of oral administration drugs by active transport mechanism, principle of hybridization was used to introducing L-amino acid structural fragments at 4'-position of scutellarein to design and synthesize target scutellarein 4'-L-amino acid prodrugs. The synthetic compounds were tested on their physicochemical properties and in vitro anti-oxidative activity against H202 induced oxidative damage in PC12 cells. Five compounds were found to have more potent anti-oxidative activity than positive control VE. Moreover the physicochemical properties of synthesized compounds were evaluated, and the results revealed that L-amino acid ether derivatives are more stable (t1/2 9-92 h) than their corresponding ester derivatives (t1/2 0.5 h). Water solubility of scutellarein 4'-L-amino acid ester and ether derivatives were 1 796-4 100 microg.mL-1 and 27.7-81.1 microg.mL-1 respectively, in comparison with scutellarin, the solubility of compounds 18, 19 and 22, 24-27 increased about 120-280 fold and 2-6 fold respectively. All these results suggested that L-amino acid prodrug strategy has significant potential in scutellarein prodrug design.
Amino Acids ; chemistry ; Animals ; Antioxidants ; chemical synthesis ; chemistry ; pharmacokinetics ; pharmacology ; Apigenin ; chemical synthesis ; chemistry ; pharmacokinetics ; pharmacology ; Biological Availability ; Drug Design ; L-Lactate Dehydrogenase ; metabolism ; PC12 Cells ; Prodrugs ; chemical synthesis ; chemistry ; pharmacokinetics ; pharmacology ; Rats

OBJECTIVETo study the effect of water stress on the content of scutellarin and caffeate in Erigeron breviscaps.

METHODFv/Fm, N content, as well as the content of scutellarin and caffeate under three water grads were measured.

RESULT AND CONCLUSIONFv/Fm of the plant decreased significantly in 8% and 23% water treatment, that proved drought and waterlogging occurred. Under the two conditions, the contents of N were lower but the contents of active constituents were higher than those under 15% treatment. The results support the carbon-nutrient balance hypothesis and the "stress effect hypothesis" for the formation of geo-herbs.

Apigenin ; metabolism ; therapeutic use ; Caffeine ; pharmacology ; Dehydration ; drug therapy ; therapy ; Droughts ; Erigeron ; chemistry ; growth & development ; metabolism ; Gene Expression Regulation, Plant ; Glucuronates ; metabolism ; therapeutic use ; Plant Preparations ; therapeutic use ; Plant Transpiration ; drug effects ; Plants, Medicinal ; chemistry ; Temperature ; Water ; physiology

The investigation on the herbal of Euphorbia humifusa Wild. was carried out in order to find its anti-HBV constituents. The isolation and purification were performed by chromatography such as Sephadex LH-20, MCI GEL CHP 20P, etc. Based on the spectral analysis, five apigenin glycosides were identified as apigenin-7-O-(6"-O-galloyl)-beta-D-glucopyranoside (1), apigenin-7-O-beta-D-apiofuranosyl (1-->2)-beta-D-glucopyranoside (2), apigenin-7-O-beta-D-lutinoside (3), apigenin-7-O-beta-D-glucopyranside (4) and apigenin (5). Among them, compound 1 is a new compound, compound 2 and 3 were isolated from this plant for the first time.
Antiviral Agents ; chemistry ; isolation & purification ; pharmacology ; Apigenin ; chemistry ; isolation & purification ; pharmacology ; Cell Survival ; drug effects ; Euphorbia ; chemistry ; Glucosides ; chemistry ; isolation & purification ; pharmacology ; Glycosides ; Hep G2 Cells ; Hepatitis B Surface Antigens ; metabolism ; Hepatitis B e Antigens ; metabolism ; Humans ; Molecular Structure ; Plants, Medicinal ; chemistry

Scutellarin is a flavonoid extracted from a traditional Chinese herb, Erigeron breviscapus. The present study investigated the effect of scutellarin on MUC5AC mucin production and the possible mechanism. Human bronchial epithelial 16 (HBE16) cells were pretreated with scutellarin for 60 min, and then exposed to human neutrophil elastase (HNE) or interleukin (IL)-13 for 12 hr. RT-PCR and ELISA were performed to measure the amount of MUC5AC mucin production. The results showed that scutellarin inhibited MUC5AC expression both in mRNA and protein level induced by HNE in a concentration-dependent manner. However, scutellarin failed to inhibit MUC5AC mucin production induced by IL-13. To investigate the intracellular mechanisms associated with the effect of scutellarin on MUC5AC mucin production, western blotting was carried out to examine the phosphorylation of protein kinase C (PKC), signal transducer and activator of transcription 6 (STAT6) and extracellular signal-regulated kinase 1/2 (ERK1/2). The phosphorylation of PKC and ERK1/2 was attenuated after treatment with scutellarin, whereas STAT6 was not significantly affected. Therefore, it is suggested that scutellarin down-regulates MUC5AC mucin production on HBE16 cells via ERK-dependent and PKC-dependent pathways.
Apigenin/chemistry/*pharmacology ; Cells, Cultured ; Dose-Response Relationship, Drug ; Down-Regulation ; Epithelial Cells/*drug effects/metabolism ; Erigeron/chemistry ; Glucuronic Acids/chemistry/*pharmacology ; Humans ; Interleukin-13/*pharmacology ; Leukocyte Elastase/*pharmacology ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Mucin 5AC/genetics/*metabolism ; Phosphorylation ; Protein Kinase C/metabolism ; Respiratory Mucosa/drug effects/*metabolism ; STAT6 Transcription Factor/metabolism ; Signal Transduction

OBJECTIVETo observe the effect of caffeic acid, seopoletin and scutellarin on rat retinal neurons in vitro and explore neuroprotection in glaucoma of Erigeron breviscapus.

METHODThe retinal of 18 post-natal 2-3 days Sprague-Dawley rats were dissociated into cell suspension with trypsin digestion. The cell suspension was implated in 96-well culture plates covered with hyaluronic acid and laminin in each well. After culturing for 3 days, caffeic acid, seopoletin and scutellarin were added to the cultures, continue to culture 2 days. Then, the A of living cells in each well was tested by MTT colorimetric microassay. Some of the 5-day culture cells were identified by Nissel technique.

RESULTMost of the living cells were retinal neurons by Nissel identification. The number of living cells increased significantly in high concentrations of caffeic acid, seopoletin and scutellarin compared with control group (P < 0.05, P < 0.01).

CONCLUSIONcaffeic acid, seopoletin and scutellarin can all promote retinal neurons to live in vitro, with caffeic acid being most effective.

Animals ; Animals, Newborn ; Apigenin ; isolation & purification ; pharmacology ; Caffeic Acids ; isolation & purification ; pharmacology ; Cell Survival ; drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Erigeron ; chemistry ; Glucuronates ; isolation & purification ; pharmacology ; Neurons ; drug effects ; Neuroprotective Agents ; isolation & purification ; pharmacology ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Retina ; cytology ; Scopoletin ; isolation & purification ; pharmacology

OBJECTIVE: To investigate the effect of purified vitexin compound 2 (VB2), a noval lignanoid from the acetoacetate extract of Vitex negundo seed on the proliferation and apoptosis as well as the expression of mTOR and 4E-BP1 mRNA signal pathway in human choriocarcinoma JEG-3 cell lines in vitro. METHODS: The inhibitory effect of different concentrations of VB2 on JEG-3 cells was examined by methyl thiazolyl tetrazolium (MTT) assay. Flow cytormetry was used to analyze the apoptosis after using different concentrations of VB2, and the expression of mTOR and 4E-BP1 mRNA was determined by RT-PCR. RESULTS: The inhibitory rate of JEG-3 cell growth which was cultured with different concentrations of VB2 (2.5, 5.0, 10.0, 20.0, 40.0, 80.0, and 160.0 μmol/L) for 24, 48, or 72 hours increased from (6.34±0.41)% to (85.89±0.81)%, and it was positively correlated with the dose and time of culture (P<0.05). VB2 at 5.0, 10.0, or 20.0 μmol/L increased the rate of JEG-3 cell apoptosis in vitro from (9.26±1.02)% to (35.55±1.24)% after 48 hour culture, which was in a dose dependent manner (P<0.05), while 5.0, 10.0, or 20.0 μmol/L of VB2 down-regulated the mRNA levels of mTOR and 4E-BP1 after 48 hour culture, which presented a significant negative correlation between VB2 and the mRNA levels of mTOR and 4E-BP1(P<0.05). CONCLUSION VB2 can restrain the proliferation of choriocarcinoma cell JEG-3 and induce its apoptosis. This effect may be related to the inhibition of VB2 on the mRNA expression of JEG-3 cell mTOR and 4E-BP1.
Adaptor Proteins, Signal Transducing ; metabolism ; Antineoplastic Agents, Phytogenic ; chemistry ; isolation & purification ; pharmacology ; Apigenin ; isolation & purification ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Choriocarcinoma ; pathology ; Female ; Humans ; Phosphoproteins ; metabolism ; Signal Transduction ; drug effects ; TOR Serine-Threonine Kinases ; metabolism ; Uterine Neoplasms ; pathology ; Vitex ; chemistry