Compounds Apigenin Research Articles

DFT calculations and POM analyses of cytotoxicity of some flavonoids from aerial parts of Cupressus sempervirens: Docking and identification of pharmacophore sites.

Two known polyphenols named apigenin 7-O-β-d-glucopyranoside (S1) and querctine-3-O-glucoside (S2), along with another two new compounds apigenin 4'-geranyl-8-glucopyranosyl-7-O-α-glucopyranoside (S3) and apigenin 4'-pernyl-8-glucopyranosyl -7-O-α-glucopyranoside (S4), were isolated from the leaves of Cupressus sempervirens. Structure elucidation of the isolated polyphenols was established on the basis of detailed spectroscopic analysis like 1D and 2D NMR analyses including 1H NMR, 13C NMR, COSY, DEPT, HMQC, UV, and Electron Spray Ionization Mass Spectroscopy (ESI-MS). Density Functional Theory (DFT) of computational, Petra/Osiris/Molinspiration (POM), and docking analyses methods were applied in the structural validation of new isolated compounds. The isolated compounds S1-S4 showed significant cytotoxicity against human hepatocellular liver carcinoma HepG2 cells, MCF-7, HC116 and A549.

Inhibition of fungal endo-1,3-B-glucanase by phenols isolated from Turnera diffusa: an alternative for conventional antifungals

La enzima endo-(1,3)-B-glucanasa tiene una función fisiológica en los procesos morfogenéticos durante el desarrollo y diferenciación en algunos hongos. Adicionalmente, esta enzima ha sido implicada durante el ataque de hongo en la interacción hongo fitopatógeno-planta. Por lo que la endo-(1,3)-B-glucanasa fúngica, se ha utilizado como sitio-objetivo para la búsqueda dirigida de antifúngicos. Utilizando un aislamiento bio-dirigido de compuestos bioactivos, se aislaron dos ácidos fenólicos de tallos de <em>Turnera diffusa</em>, los cuales inhiben la actividad de endo-(1,3)-B-glucanasa fúngica. Los compuestos identificados como apigenina y luteolina inhiben la actividad del enzima en 90 y 60%, respectivamente. Consistente con el efecto de la inhibición de la enzima fúngica, la apigenina a concentracion milimolar, fue capaz de inhibir completamente la germinación de esporas de <em>Botrytis cinerea</em>. Con estos resultados se infiere que la acción antifúngica de la apigenina es una consecuencia de su capacidad para inhibir la enzima endo-(1,3)-B-glucanasa.

Neuroprotective effect of Salvia splendens extract and its constituents against AlCl3-induced Alzheimer’s disease in rats

Salvia splendens is a species of the genus Salvia that is known for its neuro-therapeutic properties. The present study aimed to investigate the effect of two fractions from the methanolic extract of the aerial parts of S. splendens cultivated in Egypt, the petroleum ether-soluble (PES) and n-butanol-soluble (BS) fractions, against AlCl3-induced Alzheimer’s disease (AD) in rats. Rats treated with AlCl3 (100 mg/kg b.wt. p.o.) for 4 weeks developed behavioral, biochemical and histological changes similar to that of AD. Behavioral deficits were assessed by T-maze test and percentage changes in oxidative stress and AD markers in brain. Extent of DNA damage and histopathological changes were also evaluated. Results revealed that both fractions; PES and BS (at dose of 500 mg/kg b.wt), significantly attenuated AlCl3-induced behavioral impairment in rats. This effect was accompanied by acetylcholinesterase (AChE) activity inhibition (53.18% and 68.66%, respectively), and Aβ deposition reduction (33.3% and 34.3%, respectively). Both fractions markedly decreased oxidative stress markers level (lipid peroxide, protein carbonyl, reduced glutathione and nitric oxide), and inhibited catalase and caspase-3 activities. Also, the content of noradrenaline, adrenaline, 5-HT and dopamine were significantly increased. The fractions preserved the histo-architecture pattern of the hippocampus and cortex from the AlCl3-induced damage. Bioactivity-guided fractionation led to the isolation of two sterols; β-sitosterol and β-sitosterolpalmitate from PES fraction, and 6 phenolic compounds (acacetin, chrysoeriol, apigenin, luteolin, rosmarinic acid and caffeic acid) from BS fraction. Rosmarinic acid and caffeic acid significantly inhibited AChE in vitro (IC50 values of 0.398 mg/mL and 0.327 mg/mL, respectively) compared to physostigmine (IC50 0.227 mg/mL). The BS fraction is standardized (HPLC–DAD) to contain not less than 0.0254% (w/w)of rosmarinic acid and 0.0129% (w/w) of caffeic acid. These findings suggest that S. splendens is beneficial in attenuating AlCl3-induced neurotoxicity in rats.

Food-Derived Compounds Apigenin and Luteolin Modulate mRNA Splicing of Introns with Weak Splice Sites

SummaryCancer cells often exhibit extreme sensitivity to splicing inhibitors. We identified food-derived flavonoids, apigenin and luteolin, as compounds that modulate mRNA splicing at the genome-wide level, followed by proliferation inhibition. They bind to mRNA splicing-related proteins to induce a widespread change of splicing patterns in treated cells. Their inhibitory activity on splicing is relatively moderate, and introns with weak splice sites tend to be sensitive to them. Such introns remain unspliced, and the resulting intron-containing mRNAs are retained in the nucleus, resulting in the nuclear accumulation of poly(A)+ RNAs in these flavonoid-treated cells. Tumorigenic cells are more susceptible to these flavonoids than nontumorigenic cells, both for the nuclear poly(A)+ RNA-accumulating phenotype and cell viability. This study illustrates the possible mechanism of these flavonoids to suppress tumor progression in vivo that were demonstrated by previous studies and provides the potential of daily intake of moderate splicing inhibitors to prevent cancer development.

Apigenin inhibits growth and migration of fibroblasts by suppressing FAK signaling.

The naturally occurring compound apigenin has many biological effects, including anti-inflammatory, antioxidative and anticancer effects. Although hypertrophic scar formation is a common surgical complication, there is still no good treatment for it. In the present study, we examined the effect of apigenin on hypertrophic scar. After isolating fibroblasts from human hypertrophic scars, we assess the effects of apigenin on fibroblast cell survival, apoptosis and migration. The results showed that apigenin dose-dependently inhibited the growth and migration of hypertrophic scar fibroblasts. By inhibiting FAK kinase activity and FAK phosphorylation, apigenin also inhibited activation of the FAK signaling pathway. Apigenin thus appears to inhibit the growth and migration of hypertrophic scar fibroblasts by inhibiting FAK signaling. This suggests apigenin could potentially provide a new option for the treatment of hypertrophic scars.

Photoprotective and Antigenotoxic Effects of the Flavonoids Apigenin, Naringenin and Pinocembrin.

This work evaluated the photoprotective and antigenotoxic effects against ultraviolet B (UVB) radiation of flavonoid compounds apigenin, naringenin and pinocembrin. The photoprotective efficacy of these compounds was estimated using in vitro photoprotection indices, and the antigenotoxicity against UVB radiation was evaluated using the SOS chromotest and an enzymatic (proteinase K/T4 endonuclease V enzyme) comet assay in UV-treated Escherichia coli and human (HEK-293) cells, respectively. Naringenin and pinocembrin showed maximum UV-absorption peak in UVC and UVB zones, while apigenin showed UV-absorption capability from UVC to UVA range. These compounds acted as UV filters reducing UV-induced genotoxicity, both in bacteria and in human cells. The enzymatic comet assay resulted highly sensitive for detection of UVB-induced DNA damage in HEK-293 cells. In this work, the photoprotective potential of these flavonoids was widely discussed.

Food-Derived Compounds Apigenin and Luteolin Modulate mRNA Splicing of Introns with Weak Splice Sites

Cancer cells often exhibit an extreme sensitivity to splicing inhibitors. We identified food-derived flavonoids, apigenin and luteolin, as compounds that modulate mRNA splicing at the genome-wide level followed by proliferation inhibition. They bind to mRNA splicing-related proteins to induce widespread change of splicing patterns in treated cells. Their inhibitory activity on splicing is relatively moderate, and introns with weak splice sites tend to be sensitive to them. Such introns remain unspliced, and the resulting intron-containing mRNAs are retained in the nucleus, resulting in the nuclear accumulation of bulk poly(A)+ RNAs in these flavonoid-treated cells. Tumorigenic cells are more susceptible to these flavonoids than non-tumorigenic cells, both for the nuclear poly(A)+ RNA-accumulating phenotype and cell viability. This study illustrates the possible mechanism of these flavonoids to suppress tumor progression in vivo demonstrated in previous studies and provides the potential of daily intake of moderate splicing inhibitors to prevent cancer development.

A new glucosidic iridoid from Isodon rubescens

One new glucosidic iridoid, 6-O-veratroylbarlerin, was isolated from the chloroform/methanol extract of Isodon rubescens (Hemsl.) H.Hara, Lamiaceae aerial parts, along with the known compounds apigenin and caffeic acid. The structure of the new compound was elucidated on the basis of 1D and 2D NMR experiments and ESI-MS technique.

The flavonoid compound apigenin prevents colonic inflammation and motor dysfunctions associated with high fat diet-induced obesity.

Background and purposeApigenin can exert beneficial actions in the prevention of obesity. However, its putative action on obesity-associated bowel motor dysfunctions is unknown. This study examined the effects of apigenin on colonic inflammatory and motor abnormalities in a mouse model of diet-induced obesity.Experimental approachMale C57BL/6J mice were fed with standard diet (SD) or high-fat diet (HFD). SD or HFD mice were treated with apigenin (10 mg/Kg/day). After 8 weeks, body and epididymal fat weight, as well as cholesterol, triglycerides and glucose levels were evaluated. Malondialdehyde (MDA), IL-1β and IL-6 levels, and let-7f expression were also examined. Colonic infiltration by eosinophils, as well as substance P (SP) and inducible nitric oxide synthase (iNOS) expressions were evaluated. Motor responses elicited under blockade of NOS and tachykininergic contractions were recorded in vitro from colonic longitudinal muscle preparations.Key resultsWhen compared to SD mice, HFD animals displayed increased body weight, epididymal fat weight and metabolic indexes. HFD mice showed increments in colonic MDA, IL-1β and IL-6 levels, as well as a decrease in let-7f expression in both colonic and epididymal tissues. HFD mice displayed an increase in colonic eosinophil infiltration. Immunohistochemistry revealed an increase in SP and iNOS expression in myenteric ganglia of HFD mice. In preparations from HFD mice, electrically evoked contractions upon NOS blockade or mediated by tachykininergic stimulation were enhanced. In HFD mice, Apigenin counteracted the increase in body and epididymal fat weight, as well as the alterations of metabolic indexes. Apigenin reduced also MDA, IL-1β and IL-6 colonic levels as well as eosinophil infiltration, SP and iNOS expression, along with a normalization of electrically evoked tachykininergic and nitrergic contractions. In addition, apigenin normalized let-7f expression in epididymal fat tissues, but not in colonic specimens.Conclusions and implicationsApigenin prevents systemic metabolic alterations, counteracts enteric inflammation and normalizes colonic dysmotility associated with obesity.

Tuning phospholipid bilayer permeability by flavonoid apigenin: Electrochemical and atomic force microscopy study

The ability to tune the permeability of cell membranes might have significant implications in targeted drug delivery applications. In this work we employ electrochemical methods as well as nanolithography realized in the environment of in-situ atomic force microscopy (AFM) to demonstrate that bioactive compound apigenin is capable of altering the permeability of a model phospholipid dipalmitoylphosphatidylcholine bilayer supported by a gold surface. The electron transfer rate through the bilayer was investigated employing [Fe(CN)6]4−/[Fe(CN)6]3− redox couple as an electroactive probe. The value of the standard heterogeneous rate constant obtained in the absence of apigenin (k0 = 6.60∙10−5 cm·s−1) indicates that the electron transfer through the bilayer is rather sluggish confirming its compactness. The addition of apigenin to the system leads to a considerable increase of the electron transfer rate to k0 = 5.74∙10−3 cm·s−1 being virtually identical to the value obtained at the bare electrode/electrolyte interface (k0 = 2.24∙10−3 cm·s−1). This suggests that apigenin induces a significant rearrangement of the supported lipid bilayer increasing thus its permeability. The AFM nanolithography performed in-situ in the presence of apigenin confirmed that the supported lipid bilayer reorganizes itself to a monolayer of molecules laying parallel to the electrode surface.

Phenolic compounds apigenin, hesperidin and kaempferol reduce in vitro lipid accumulation in human adipocytes

BackgroundAdipocytes derived from human mesenchymal stem cells (MSCs) are widely used to investigate adipogenesis. Taking into account both the novelty of these MSCs and the scarcity of studies focused on the effects of phenolic compounds, the aim of the present study was to analyze the effect of apigenin, hesperidin and kaempferol on pre-adipocyte and mature adipocytes derived from this type of cells. In addition, the expression of genes involved in TG accumulation was also measured.MethodsPre-adipocytes were cultured from day 0 to day 8 and mature adipocytes for 48 h with the polyphenols at doses of 1, 10 and 25 µM.ResultsApigenin did not show an anti-adipogenic action. Pre-adipocytes treated with hesperidin and kaempferol showed reduced TG content at the three experimental doses. Apigenin did not modify the expression of the main adipogenic genes (c/ebpβ, c/ebpα, pparγ and srebp1c), hesperidin inhibited genes involved in the three phases of adipogenesis (c/ebpβ, srebp1c and perilipin) and kaempferol reduced c/ebpβ. In mature adipocytes, the three polyphenols reduced TG accumulation at the dose of 25 µM, but not at lower doses. All compounds increased mRNA levels of atgl. Apigenin and hesperidin decreased fasn expression. The present study shows the anti-adipogenic effect and delipidating effects of apigenin, hesperidin and kaempferol in human adipocytes derived from hMSCs. While hesperidin blocks all the stages of adipogenesis, kaempferol only inhibits the early stage. Regarding mature adipocytes, the three compounds reduce TG accumulation by activating, at least in part, lipolysis, and in the case of hesperidin and apigenin, also by reducing lipogenesis.ConclusionsThe present study shows for the first time the anti-adipogenic effect and delipidating effect of apigenin, hesperidin and kaempferol in human adipocytes derived from MSCs for the first time.

Effects of apigenin on lipopolysaccharide induced proliferation of rat aortic vascular smooth muscle cells

Objective: To investigate the effect of natural active compounds apigenin (API) on the proliferation of rat aortic vascular smooth muscle cells (VSMCs) induced by lipopolysaccharide (LPS) and related mechanisms. Methods: VSMCs of primary cultured SD rats were obtained and the cytotoxic effects of API (0, 10, 20, 40 and 80 μmol/L) was explored by CCK-8 method. Impact of LPS (0, 0.1, 1, 10 and 100 μg/ml) on VSMCs proliferation and the impact of API (0, 10, 20, 40 μmol/L) on LPS (10 μmol)-induced VSMCs proliferation by CCK-8 methods. Using EdU and FCM method, we observed the effect of API on proliferation of VSMCs induced by LPS. VSMCs proliferation and cell cycle were also assessed by EdU method and FACS in 10 μg/ml LPS, 10 μg/ml LPS+ 40 μmol/L API and equal volume DMSO treated VSMCs. Results: (1) CCK-8 cell vitality test showed that cell vitality was not affected by 0-40 μmol/L API, while cell vitality was significantly reduced by 80 μmol/L API (57%), which was significantly lower than in blank group (P<0.05). (2) VSMCs proliferation was significantly promoted by 0.1, 1 and 10 μg/ml LPS and peaked in 10 μg/ml LPS stimulated VSMCs group, while VSMCs proliferation was significantly reduced in 100 μg/ml LPS stimulated group (P<0.05 vs. blank group). (3) LPS (10 μm/ml) induced VSMCs proliferation was not affected by 10 μmol/L API, which was significantly inhibited by 20 and 40 μmol/L API (both P<0.05 vs. LPS). (4) VSMCs proliferation assessed by EdU was significantly higher in LPS group than in blank group (P<0.01), which could be significantly reduced by cotreatment with API (P<0.01). (5) FACS results showed that percent of VSMCs in G0/G1 stage was significantly lower in LPS group compared to blank group (P<0.05), which could be significantly increased post API treatment (P<0.05 vs. LPS), while percent of VSMCs in S stage was significantly lower post API treatment in comparison with LPS group. Conclusion: API can significantly inhibit LPS-induced proliferation of VSMCs, partly through inhibiting mitosis and inducing G0/G1 cell cycle arrest.

Apigenin, a modulator of PPARγ, attenuates HFD-induced NAFLD by regulating hepatocyte lipid metabolism and oxidative stress via Nrf2 activation

Lipid metabolic disorders and oxidative stress in the liver are key steps in the progression of nonalcoholic fatty liver disease (NAFLD), which is a major risk factor for the development of metabolic syndrome. To date, no pharmacological treatment for this condition has been approved. Our previous study has found that the food-derived compound apigenin (Api) significantly attenuates obesity-induced metabolic syndrome by acting as a peroxisome proliferator-activated receptor gamma modulator (PPARM). Herein, a high fat diet (HFD) induced NAFLD model was used to dig out whether Api had the effect on NAFLD. The results showed that Api had obvious effect in restraining NAFLD progression, including attenuating HFD induced lipid accumulation and oxidative stress in vivo. As a PPARM, although Api did significantly inhibit the expression of PPARγ target genes encoding the protein associated with lipid metabolism, it had no obvious activating effect on PPARγ. Interestingly, we found that Api promoted Nrf2 into the nucleus, thereby markedly activating Nrf2 to inhibit the lipid metabolism related genes and increase the oxidative stress related genes. Further Nrf2 knockdown/knockout and overexpression experiments showed that Api regulating PPARγ target genes was dependent on Nrf2 activation and the activation of Nrf2 counteracted the activation effect of PPARγ by Api. Importantly, we also found that Api might bind with Nrf2 via auto dock and ITC assay. Therefore, our results indicate that Api ameliorates NAFLD by a novel regulating mode of Nrf2 and PPARγ in inhibiting lipid metabolism and oxidative stress abnormity.

Chemical Composition and Antioxidant Activity of Cirsium vulgare Inflorescences

The chemical composition of Cirsium vulgare flower heads was examined. Petrol and chloroform extracts of this plant material were analyzed by GC-MS for the presence of fatty acids, phytosterols, and triterpenes. Diethyl ether, ethyl acetate, and butanol fractions of the methanolic extract were subjected to multistep - chromatographic separations, and as a result, fourteen flavonoids were obtained (1-14). All compounds were isolated from this morphological part for the first time and eleven from the plant. Among the identified components were four aglycones, eight glycosides, and two glycoside esters, derivatives of apigenin, luteolin, kaemferol, and quercetin. One of them was a rarely occurring compound apigenin 7-0-p-(6"-butyl)-glucuronide) (14). Total flavonoid content and antioxidant activity were determined in the various fractions of methanolic extract.

In vitro-assessment of putative antiprogestin activities of phytochemicals and synthetic UV absorbers in human endometrial Ishikawa cells

Critical steps of embryo implantation are controlled by progesterone. These processes can be interrupted by progesterone receptor (PR) antagonists, e.g. drugs used for abortion. Antiprogestin effects induced by natural compounds and environmental chemicals have been rarely addressed. In our in vitro study, we investigated putative antiprogestin activities of the plant compounds apigenin (API) and trans-ferulic acid (t-FA) as well as the UV absorbers octyl methoxycinnamate (OMC) and 4-methylbenzylidene camphor (4-MBC). They were compared with the selective progesterone receptor modulators (SPRMs) mifepristone (RU486) and ulipristal acetate (UPA) as well as the full PR-antagonist ZK137316. Effects of test compounds in combination with progesterone on the progesterone-sensitive target gene estrogen sulfotransferase (SULT1E1) were characterized by sigmoidal concentration–response curves obtained by RT-qPCR. The agonistic effect of progesterone on SULT1E1 mRNA levels was concentration-dependently antagonized by RU486, UPA and ZK137316 as well as, with lower potency, apigenin. t-FA, OMC and 4-MBC had no effect on SULT1E1 mRNA levels. We demonstrated that apigenin, although at higher concentrations, exerts a similar effect as the well-characterized SPRMs RU486 and UPA or the progesterone antagonist ZK137316 in this model. Our endometrium-specific Ishikawa cell assay is a useful complement to artificial transactivation assays for the identification of environmental substances with antiprogestin activities.

Abstract A58: Characterized herbal extract of Wedelia chinensis suppresses prostate cancer growth and metastasis by targeting multiple intrinsic pathways and modulating immune cells

Abstract We previously demonstrated that the principal active compounds (wedelolectone, luteolin, and apigenin) in the ethanol extract of Wedelia chinensis synergistically inhibit human prostate carcinoma 22Rv1 cell growth and that this extract therefore has potential for use as a prostate cancer (PCa) therapy. Here, we developed a standardized preparation for a W. chinensis ethanol extract that is enriched in the principal active compounds. A comparison of the effect of herbal treatment, androgen ablation therapy, and a combination of the two on the development of androgen-dependent LNCaP tumors in a mouse model showed that the herbal extract alone decreased androgen-induced tumor growth and when in combination with androgen ablation therapy, resulted in more potent inhibition of both tumor growth and cancer metastasis. Our study demonstrated this herbal remedy simultaneously inhibited androgen receptor, NFκB and HER2/3-AKT signaling pathways to induce cell apoptosis. Importantly, our herbal remedy diminished androgen receptor overexpression and AKT activation induced by androgen ablation thus preventing castration-resistant PCa development. Moreover, the herbal remedy standing-alone curbed chemokine expression from hormone-refractory PC-3 tumor and consequently restrained the mobilization of CD11b+Gr1+ myeloid cells in tumor-bearing mice, which effectively inhibited PCa growth and metastasis. In conclusion, this standardized preparation of W. chinensis ethanol extract improved the outcome of PCa therapy either as an add-on to hormonal therapy for androgen-dependent disease or as a monotherapy for hormone-refractory disease. Citation Format: Chin-Hsien Tsai, Sheue-Fen Tzeng, Pei-Wen Hsiao. Characterized herbal extract of Wedelia chinensis suppresses prostate cancer growth and metastasis by targeting multiple intrinsic pathways and modulating immune cells. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr A58. doi:10.1158/1538-7445.CHTME14-A58

Apigenin protects endothelial cells from lipopolysaccharide (LPS)-induced inflammation by decreasing caspase-3 activation and modulating mitochondrial function.

Acute and chronic inflammation is characterized by increased reactive oxygen species (ROS) production, dysregulation of mitochondrial metabolism and abnormal immune function contributing to cardiovascular diseases and sepsis. Clinical and epidemiological studies suggest potential beneficial effects of dietary interventions in inflammatory diseases but understanding of how nutrients work remains insufficient. In the present study, we evaluated the effects of apigenin, an anti-inflammatory flavonoid abundantly found in our diet, in endothelial cells during inflammation. Here, we show that apigenin reduced lipopolysaccharide (LPS)-induced apoptosis by decreasing ROS production and the activity of caspase-3 in endothelial cells. Apigenin conferred protection against LPS-induced mitochondrial dysfunction and reestablished normal mitochondrial complex I activity, a major site of electron leakage and superoxide production, suggesting its ability to modulate endothelial cell metabolic function during inflammation. Collectively, these findings indicate that the dietary compound apigenin stabilizes mitochondrial function during inflammation preventing endothelial cell damage and thus provide new translational opportunities for the use of dietary components in the prevention and treatment of inflammatory diseases.

Effect of the phenolic compounds apigenin and carnosic acid on oral carcinogenesis in hamster induced by DMBA

To investigate oral carcinogenesis in hamster induced by the topical application of 7,12-dimethyl benzanthracene (DMBA) to evaluate the different lesions produced and the possible preventive effects of the phenolic compounds apigenin (flavone) and carnosic acid (diterpene). Thirty-two Syrian hamsters were divided into three groups: I: 0.5% DMBA (n = 12); II: 0.5% DMBA + potassium apigenin (n = 8); III: 0.5% DMBA + carnosic acid (n = 12). All the animals were sacrificed after 11 weeks, and a macroscopic and light microscopic study was made of the lesions. The largest number of neoplasms, showing the most aggressive biological behavior, corresponded to the control group. The group treated with potassium apigenin ranked second in tumor incidence, although the tumors were not very aggressive behavior. In the group treated with carnosic acid, only one malignancy was recorded, showing the smallest volume of all the recorded tumor lesions. Our findings indicate that both potassium apigenin and carnosic acid have chemoprotective effects against carcinogenesis induced by DMBA in hamster.

Aqueous extract of Anisomeles indica and its purified compound exerts anti-metastatic activity through inhibition of NF-κB/AP-1-dependent MMP-9 activation in human breast cancer MCF-7 cells

Anisomeles indica popularly known in Taiwan as ‘yu-chen-tsao’ has been traditionally used as an anticancer and anti-inflammatory agent; however, little is known about its anti-metastatic potential. Therefore, we attempted in this study to examine the anti-metastatic potential of A. indica aqueous extract (AI), its isolated compounds apigenin, ovatodiolide, β-sitosterol and acteoside in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced human breast adenocarcinoma MCF-7 cells. Among the test agents, crude extract AI and pure compound apigenin potently suppressed the TPA-induced MCF-7 cells migration and invasion. In addition, AI and apigenin time- and dose-dependently down regulated the matrix metalloproteinase (MMP)-9 enzymatic activities and its mRNA expression. Furthermore, AI and apigenin also down regulated the nuclear factor (NF)-κB subunit p65, and activator protein (AP)-1 subunit c-Fos proteins expression in nucleus and, transcriptional activity of NF-κB and AP-1. This is the first report on the anti-metastatic potential of A. indica that suppressed the cancer cell invasion through the inhibition of MMP-9 enzyme via NF-κB/AP-1 signaling. Taken together, our data indicate that A. indica can be considered as a source of new anti-metastatic agent for food and pharmaceutical industries.

Impact of different colored shade polyethylene and maturation on development of flavonoids and phenolic acids in flowers of Chrysanthemum indicum L.

Chrysanthemum indicum L. is a significant medicinal plant, which flowers (capitula) are usually used as Chinese medicine. The phytochemical test analyzed the regularity of biosynthesis and degradation of flavonoids and phenolic acids in flowers which grown under colored polyethylene and harvested from five flowering stages. Dry weight of one thousand buds or flower heads from different maturation stages and total number of flowers from individual plant were evaluated as biomass yield. The results indicated that the total number of buds and flower heads of individual plant grown under red polyethylene film was substantially higher than other treatments (P<0.01), as well as accumulated more quercetin, apigenin and chlorogenic acid, but gave poor content of luteolin and caffeic acid. Comparing with plants grown in open condition, blue polyethylene has the lowest mean weight of one thousand buds or flower heads from different harvesting stages, but it has potentials to increase the total number of buds and flower heads from individual plant and the yield ofbioactive compounds total flavonoids, quercetin, apigenin, acacetin, linarin, chlorogenic acid and caffeic acid, except luteolin. Key word: Chrysanthemum indicum L., colored polyethylene, maturation, flavonoids, phenolic acids.