Showing papers on "Acacetin published in 2020"

Doxorubicin cardiomyopathy is ameliorated by acacetin via Sirt1-mediated activation of AMPK/Nrf2 signal molecules.

Abstract: Doxorubicin cardiotoxicity is frequently reported in patients undergoing chemotherapy. The present study investigates whether cardiomyopathy induced by doxorubicin can be improved by the natural flavone acacetin in a mouse model and uncovers the potential molecular mechanism using cultured rat cardiomyoblasts. It was found that the cardiac dysfunction and myocardial fibrosis induced by doxorubicin were significantly improved by acacetin in mice with impaired Nrf2/HO-1 and Sirt1/pAMPK molecules, which is reversed by acacetin treatment. Doxorubicin decreased cell viability and increased ROS production in rat cardiomyoblasts; these effects are significantly countered by acacetin (0.3-3 μM) in a concentration-dependent manner via activating Sirt1/pAMPK signals and enhancing antioxidation (Nrf2/HO-1 and SOD1/SOD2) and anti-apoptosis. These protective effects were abolished in cells with silencing Sirt1. The results demonstrate for the first time that doxorubicin cardiotoxicity is antagonized by acacetin via Sirt1-mediated activation of AMPK/Nrf2 signal molecules, indicating that acacetin may be a drug candidate used clinically for protecting against doxorubicin cardiomyopathy.

Acacetin Protects Against High Glucose-Induced Endothelial Cells Injury by Preserving Mitochondrial Function via Activating Sirt1/Sirt3/AMPK Signals.

Abstract: The strategy of decreasing atherosclerotic cardiovascular disorder is imperative for re-ducing premature death and improving quality of life in patients with diabetes mellitus. The aim of this study was to investigate whether the natural flavone acacetin could protect against endothelial injury induced by high glucose and attenuate diabetes-accelerated atherosclerosis in streptozotocin- (STZ) induced diabetic ApoE-/- mice model. It was found that in human umbilical vein endothelial cells (HUVECs) cultured with normal 5.5 mM or high 33 mM glucose, acacetin (0.3-3 uM) exerted strong cyto-protective effects by reversing high glucose-induced viability reduction and reducing apoptosis and excess production of intracellular reactive oxygen species (ROS) and malondialdehyde in a concentration-dependent manner. Acacetin countered high glucose-induced depolarization of mitochondrial membrane potential and reduction of ATP product and mitoBcl-2/mitoBax ratio. Silencing Sirt3 abolished the beneficial effects of acacetin. Further analysis revealed that these effects of acacetin rely on Sirt1 activation by increasing NAD+ followed by increasing Sirt3, pAMPK and PGC-1α. In STZ-diabetic mice, acacetin significantly upregulated the decreased signaling mole-cules (i.e. SOD, Bcl-2, PGC-1α, pAMPK, Sirt3 and Sirt1) in aorta tissue and attenuated atherosclerosis. These results indicate that vascular endothelial protection of acacetin by activating Sirt1/Sirt3/AMPK signals is likely involved in alleviating diabetes-accelerated atherosclerosis by preserving mitochondrial function, which suggests that acacetin may be a drug candidate for treating cardiovascular disorder in patients with diabetes.

Acacetin suppresses the electrocardiographic and arrhythmic manifestations of the J wave syndromes

Abstract: Background J wave syndromes (JWS), including Brugada (BrS) and early repolarization syndromes (ERS), are associated with increased risk for life-threatening ventricular arrhythmias. Pharmacologic approaches to therapy are currently very limited. Here, we evaluate the effects of the natural flavone acacetin. Methods The effects of acacetin on action potential (AP) morphology and transient outward current (Ito) were first studied in isolated canine RV epicardial myocytes using whole-cell patch clamp techniques. Acacetin’s effects on transmembrane APs, unipolar electrograms and transmural ECGs were then studied in isolated coronary-perfused canine RV and LV wedge preparations as well as in whole-heart, Langendorff-perfused preparations from which we recorded a 12 lead ECG and unipolar electrograms. Using floating glass microelectrodes we also recorded transmembrane APs from the RVOT of the whole-heart model. The Ito agonist NS5806, sodium channel blocker ajmaline, calcium channel blocker verapamil or hypothermia (32°C) were used to pharmacologically mimic the genetic defects and conditions associated with JWS, thus eliciting prominent J waves and provoking VT/VF. Results Acacetin (5–10 μM) reduced Ito density, AP notch and J wave area and totally suppressed the electrocardiographic and arrhythmic manifestation of both BrS and ERS, regardless of the experimental model used. In wedge and whole-heart models of JWS, increasing Ito with NS5806, decreasing INa or ICa (with ajmaline or verapamil) or hypothermia all resulted in accentuation of epicardial AP notch and ECG J waves, resulting in characteristic BrS and ERS phenotypes. Phase 2-reentrant extrasystoles originating from the RVOT triggered VT/VF. The J waves in leads V1 and V2 were never associated with a delay of RVOT activation and always coincided with the appearance of the AP notch recorded from RVOT epicardium. All repolarization defects giving rise to VT/VF in the BrS and ERS models were reversed by acacetin, resulting in total suppression of VT/VF. Conclusions We present experimental models of BrS and ERS capable of recapitulating all of the ECG and arrhythmic manifestations of the JWS. Our findings provide definitive support for the repolarization but not the depolarization hypothesis proposed to underlie BrS and point to acacetin as a promising new pharmacologic treatment for JWS.

Acacetin improves endothelial dysfunction and aortic fibrosis in insulin-resistant SHR rats by estrogen receptors

Abstract: The aim of the work was to investigate the effects of acacetin on endothelial dysfunction and aortic fibrosis in insulin-resistant SHR rats and explore its mechanism. Seven-week-old male spontaneously hypertensive rats (SHR) were selected to establish a rat model of hypertension with insulin resistance induced by 10% fructose. The nuclear factor kappa B p65 (NF-κB p65) and Collagen I were observed by Immunohistochemistry. Immunofluorescence was used to observe estrogen receptor-alpha (ERα), estrogen receptor-beta (ERβ), and G protein-coupled receptor 30 (GPR30). Western blotting was used to detect interleukin (IL-1β), Arginase 2 (ARG2), Nostrin, endothelial nitric oxide synthase (eNOS), TGF-β, Smad3, ERK pathway proteins such as p-c-Raf, p-MEK1/2, p-ERK, ERK, p-P90RSK and p-MSK1. We found that acacetin did have an improvement on endothelial dysfunction and fibrosis. Meanwhile, it was also found to have a significant effect on the level of estrogen in this model by accident. Then, the experiment of uterine weight gain in mice confirmed that acacetin had a certain estrogen-like effect in vivo and played its role through the estrogen receptors pathway. In vitro experience HUVEC cells were stimulated with 30 mM/L glucose and 100 mM/L NaCl for 24 h to establish the endothelial cell injury model. HUVEC cells were treated with 1 μM/L estrogen receptors antagonist (ICI 182780) for 30 min before administration. Cell experiments showed that acacetin could reduce the apoptosis of HUVEC cells, the levels of inflammatory cytokines and the expression of TGF-β, Collagen I and Smad3 in endothelial cell injury model. After treatment with ICI 182780, the improvement of acacetin was significantly reversed. The results showed that acacetin relieved endothelial dysfunction and reduced the aortic fibrosis in insulin-resistant SHR rats by reducing the release of inflammatory factors and improving vasodilatory function through estrogen signaling pathway.

Acacetin Alleviates Inflammation and Matrix Degradation in Nucleus Pulposus Cells and Ameliorates Intervertebral Disc Degeneration in vivo.

Abstract: Purpose Intervertebral disc degeneration (IDD) is one of the most prevalent musculoskeletal disorders. The nucleus pulposus is the major component of the intervertebral disc, and nucleus pulposus cells (NPCs) play a significant role in the normal functioning of the intervertebral disc. Reactive oxygen species (ROS) generation, inflammation and extracellular matrix degradation in NPCs contribute to the degeneration of intervertebral discs. Acacetin is a drug that exerts antioxidant and anti-inflammatory effects on many types of cells. However, whether acacetin can relieve the degeneration of NPCs remains unknown. Methods NPCs were extracted from rat intervertebral discs. The NPCs were treated with tert-butyl peroxide (TBHP) to simulate a high-ROS environment, and acacetin was subsequently added. The contents of ROS, inflammatory mediators (COX-2, iNOS) and extracellular matrix components (aggrecan, collagen II, MMP13, MMP9, MMP3) were measured. Components of related signaling pathways (Nrf2, MAPK) were also evaluated. To determine the effect of acacetin in vivo, we simulated disc degeneration via needle puncture. Acacetin was then applied intraperitoneally, and the degenerative status was evaluated using MRI and histopathological analysis. Results In vitro, acacetin alleviated TBHP-induced ROS generation and upregulated the expression of antioxidant proteins, including HO-1, NQO1, and SOD. In addition, acacetin relieved the TBHP-induced generation of inflammatory mediators (COX-2, iNOS) and degradation of the extracellular matrix (aggrecan, collagen II, MMP13, MMP9, and MMP3). Acacetin exerted its effect by activating the Nrf2 pathway and inhibiting p38, JNK and ERK1/2 phosphorylation. In vivo, acacetin ameliorated puncture-induced disc degeneration in a rat tail model, which was evaluated using MRI and histopathological analysis. Conclusion Acacetin alleviated IDD in vitro and in vivo and may have the potential to be developed as an effective treatment for IDD.

Optimizing the Electrical Conductivity of a Nutrient Solution for Plant Growth and Bioactive Compounds of Agastache rugosa in a Plant Factory

Abstract: The objective of this study was to determine the proper electrical conductivity (EC) of a nutrient solution (NS) for accumulating bioactive compounds of Agastache rugosa without decreasing plant growth. Six-week-old seedlings were transplanted in a deep flow technique system with Hoagland NS with a 2.0 dS·m−1 EC for the initial week. From eight days after transplanting, the plants were treated with six EC treatments of 0.5, 1.0, 2.0, 4.0, 6.0, and 8.0 dS·m−1 for three weeks. Plant growth parameters, leaf gas exchange parameters, the relative chlorophyll value, and the ratio of variable to maximum fluorescence (Fv/Fm) were measured, and the rosmarinic acid (RA), tilianin, and acacetin concentrations were analyzed at 28 days after transplanting. The results showed that almost all plant growth parameters were maximized at 2.0 and 4.0 dS·m−1 and minimized at 8.0 dS·m−1 compared with the other EC treatments. The relative chlorophyll and Fv/Fm values were maximized at 2.0 and 4.0 dS·m−1. Similarly, leaf gas exchange parameters were increased at 2.0 and 4.0 dS·m−1. The RA content exhibited significantly higher values at 0.5, 1.0, 2.0, and 4.0 dS·m−1 compared with other treatments. The tilianin and acacetin contents exhibited the significantly highest values at 4.0 and 0.5 dS·m−1, respectively. These results suggest optimal EC treatment at 4.0 dS·m−1 for increasing bioactive compounds in A. rugosa plants without decreasing plant growth. Excessively high or low EC induced salinity stress or nutrient deficiency, respectively. Furthermore, among the plant organs, the roots of A. rugosa contained the highest RA concentration and the flowers contained the highest tilianin and acacetin concentrations, which revealed a higher utilization potential of the roots and flowers for bioactive compounds.

Acacetin and Pinostrobin Inhibit Malignant Breast Epithelial Cell Adhesion and Focal Adhesion Formation to Attenuate Cell Migration.

Abstract: Naturally occurring flavonoids, such as acacetin and pinostrobin, disrupt a wide range of processes during tumor progression, such as cell proliferation, apoptosis, and angiogenesis. Although the antiproliferative and antiapoptotic effects of acacetin and pinostrobin have been studied using various cell lines, relatively little is known about the effects of acacetin and pinostrobin on cancer cell migration and metastasis. For instance, it is unclear whether acacetin or pinostrobin have any effect on breast cancer cell migration or adhesion. In this study, we assessed the effects of acacetin and pinostrobin on malignant MDA-MB-231 and T47D breast epithelial cells and non-tumorigenic MCF10A breast epithelial cells. Our results demonstrate that both acacetin and pinostrobin selectively inhibit the migration of both MDA-MB-231 and T47D cells in a dose-dependent manner while exhibiting blunted effects on MCF10A cells. Interestingly, neither compound had an effect on cell proliferation in any of the 3 cell lines. Furthermore, both acacetin and pinostrobin inhibit MDA-MB-231 and T47D cell adhesion, cell spreading, and focal adhesion formation, but have no significant effect on MCF10A cells. Collectively, these results suggest that both acacetin and pinostrobin selectively inhibit malignant breast epithelial cell migration through attenuation of cell adhesion and focal adhesion formation. These findings indicate that both acacetin and pinostrobin may serve as potential therapeutic options to target breast tumor cell migration during late-stage tumor progression.

Safflower Seed Oil and Its Active Compound Acacetin Inhibit UVB-Induced Skin Photoaging

Abstract: Ultraviolet (UV) is one of the major factors harmful to skin health. Irradiation with ultraviolet accelerates the decline of skin function, causing the skin to have deep wrinkles, dryness, decreased procollagen production, and degradation of collagen. Novel materials are needed to prevent the aging of the skin by blocking the effects of UV. Safflower seed oil (Charthamus tinctorius L., SSO) contains significantly high levels of unsaturated fatty acids and phytochemicals. SSO has been traditionally used in China, Japan, and Korea to improve skin and hair. Our objective in this study was to determine the effect of SSO and its active compound acacetin on UVB-induced skin photoaging in HaCaT cells and human dermal fibroblasts (HDF). SSO inhibited UVB-induced matrix metalloproteinase-1 (MMP-1) at both protein and mRNA levels in HaCaT cells and HDF. MMP-1 is known to play important roles in collagen degradation and wrinkle formation. Acacetin, a type of flavonoid, is present in SSO. Similar to SSO, acacetin also inhibited UVB-induced MMP-1 protein and mRNA levels in HaCaT cells and HDF. MMP-1 mRNA is primarily regulated by the mitogen-activated kinase (MAPK) signaling pathway. Acacetin regulated the phosphorylation of JNK1/2 and c-jun, but did not inhibit the phosphorylation of ERK1/2, p38 and AKT. Taken together, these results indicate that SSO and its active compound acacetin can prevent UVB-induced MMP-1 expression, which leads to skin photoaging, and may therefore have therapeutic potential as an anti-wrinkle agent to improve skin health.

Acacetin inhibits Streptococcus pneumoniae virulence by targeting pneumolysin.

Abstract: Objectives Streptococcus pneumoniae (S. pneumoniae) is an important commensal and pathogenic bacterium responsible for pneumonia, meningitis and other invasive diseases. Pneumolysin (PLY) is the major virulence factor that contributes significantly to the interaction between S. pneumoniae and the host. Key findings In this study, the results of antibacterial analysis, the haemolysis test and the Western blotting assay showed that acacetin inhibited PLY-mediated pore-forming activity caused by S. pneumoniae culture precipitates and purified PLY without anti-S. pneumoniae activity. In addition, acacetin treatment inhibited PLY oligomerization without affecting the expression of PLY in S. pneumoniae culture supernatants. Live/dead cells and cytotoxicity assays suggested that acacetin significantly enhanced the survival rate of injured cells by inhibiting the biological toxicity of PLY without cytotoxicity in the coculture system. The in vivo mouse model of S. pneumoniae infection further demonstrated that acacetin treatment could significantly reduce the levels of inflammatory factors (INF-γ and IL-β) in bronchoalveolar lavage fluid (BALF) and alleviate the pathological damage of lung injury. Conclusions Taken together, the results presented in this study indicated that acacetin inhibited the pore-forming activity of PLY and reduced the virulence of S. pneumoniae in vivo and in vitro, which may provide a leading compound for the treatment of S. pneumoniae infection.

Acacetin Induces Apoptosis in Human Osteosarcoma Cells by Modulation of ROS/JNK Activation.

Abstract: Purpose The long-term survival rate of osteosarcoma, which is the most common type of primary malignant bone tumor, has stagnated in past decades. Acacetin is a natural flavonoid compound that has antioxidative and anti-inflammatory effects and exhibits extensive therapeutic effects on various cancers. In this study, the anticancer potential of acacetin and the underlying molecular mechanisms were examined in human osteosarcoma cells (SJSA and HOS). Materials and methods HOS and SJSA cell lines were exposed to different concentrations of acacetin. Cell proliferation and viability were assessed by CCK-8 and colony-formation assays. Hoechst 33258 fluorescent staining was employed to detect apoptosis. Cell apoptosis was measured by an annexin V-FITC/PI assay by flow cytometry. The alteration in the mitochondrial membrane potential was detected by a JC-1 Assay Kit. Apoptosis-related protein expression was determined by Western blotting. Intracellular reactive oxygen species (ROS) production was detected by fluorescence microscopy and flow cytometry. Subsequently, the activation of the ROS/JNK signaling pathway was investigated. Results Acacetin could inhibit proliferation and induce apoptosis in SJSA and HOS cells. The acacetin treatment resulted in the activation of caspase-3, -8, and -9 and cleaved PARP. Further studies showed that acacetin-induced apoptosis was attributed to ROS. In addition, we found that acacetin induced the activation of the downstream c-Jun N-terminal kinase (JNK) signaling pathway. Subsequently, after treatment with the ROS scavenger GSH and the JNK inhibitor SP600125, the apoptosis-inducing effect triggered by acacetin was significantly attenuated. Conclusion The results of the present study indicate that acacetin may induce apoptosis to inhibit cell growth by activating the ROS/JNK signaling pathway in SJSA and HOS cells, suggesting that acacetin may be a promising candidate for the management of osteosarcomas.

Induction of growth cessation by acacetin via β-catenin pathway and apoptosis by apoptosis inducing factor activation in colorectal carcinoma cells.

Abstract: Acacetin, a bioflavanoid, contains anti-inflammatory and anti-cancer activities as shown in different experimental models. However, its anticancer potential and mechanism of action against colorectal cancer cells is largely unknown. Here, we have investigated the efficacy of acacetin using two colorectal adenocarcinoma SW480 and HCT-116 cell lines. Cell survival was examined by Trypan-blue exclusion and MTT assays, cell cycle analysis by FACS, apoptosis was assessed using Annexin V FITC assay and nuclear condensation by Hoechst staining, ROS level by DCFDA and Mitosox, and protein expression level by Western blotting. Acacetin reduced the cell survival and proliferation of both types of cells, and induced S- and G2-M phase arrest and also reduced the levels of β-catenin and its downstream target c-myc. Further, acacetin induced apoptosis as examined by Annexin-V FITC and nuclear condensation. It increased intracellular ROS production, especially mitochondrial ROS. Acacetin increased mitochondrial membrane potential depolarization and Bax:Bcl-2 ratio. Although significant changes in caspases -8 and -9 and PARP level was not observed, acacetin could induce the truncation and subsequent translocation of activated AIF from mitochondria to cytosol, which could further induce chromosomal breakage leading to apoptosis. In conclusion, Acacetin induces mitochondrial ROS-mediated cell death in a caspase-independent manner in SW480 and HCT-116 colon carcinoma cells by inducing apoptosis inducing factor (AIF), which may potentiate its anticancer and chemotherapeutic prospects against colorectal carcinoma.

Evaluating the effects of acacetin versus a low dose of cisplatin drug on male reproductive system and kidney in mice: With emphasis on inflammation process.

Abstract: This study aimed to compare acacetin adverse effect besides a cisplatin low dose on male reproductive and urinary systems on mice. In this study, 36 male Balb/c mice were received Dimethyl sulfoxide, cisplatin (1 mg/kg) or acacetin (10, 25, 50 mg/kg) for 3 days, while the sixth group, treated with acacetin (50 mg/kg) for 10 days. All treatments were done consequence daily and intraperitoneally. Histological and biochemical factors to male reproductive and urinary systems were assayed. Only in cisplatin exposed group, significant differences were seen with the others. So that, some reproductive criteria were significantly decreased; serum levels of follicle-stimulating hormone, luteinizing hormone, testosterone, sperm parameters, the diameters of seminiferous tubules, Johnsen's score and from the urinary system; renal corpuscles' space, Mg2+ concentration (p < .01). Moreover, significant increases were seen in serum levels of tumour necrosis factor-alpha, Blood urea nitrogen, creatinine, testis myeloperoxidase activity and tumour necrosis factor-alpha expression, kidney histological damage and renal corpuscle diameter (p < .01). Cisplatin exposure disrupts histological and functional characteristics of either male reproductive or urinary systems, suggesting by inflammation-promoting. Acacetin does not induce any harmful impact on these two systems and could be considered as a safe flavonoid by high dose and prolonged usage.

Flavonoids from Herb of Monarda fistulosa

Abstract: Monardoside (apigenin 5-O-rutinoside), which was a new natural compound, isorhoifolin (apigenin 7-O-rutinoside), linarin (acacetin 7-O-rutinoside), and didymin (isosacuranetin 7-O-rutinoside) were isolated and characterized from the herb of Monarda fistulosa L. using PMR, 13C NMR, and UV spectroscopy, mass spectrometry, and chemical transformations.

Constructing E. coli Co-Cultures for De Novo Biosynthesis of Natural Product Acacetin.

Abstract: Modular co-culture engineering is an emerging approach for biosynthesis of complex natural products In this study, microbial co-cultures composed of two and three Escherichia coli strains, respectively, are constructed for de novo biosynthesis of flavonoid acacetin, a value-added natural compound possessing numerous demonstrated biological activities, from simple carbon substrate glucose To this end, the heterologous biosynthetic pathway is divided into different modules, each of which is accommodated in a dedicated E coli strain for functional expression After the optimization of the inoculation ratio between the constituent strains, the engineered co-cultures show a 483-fold improvement in production comparing to the mono-culture controls Importantly, cultivation of the three-strain co-culture in shake flasks result in the production of 203 mg L-1 acacetin after 48 h To the authors' knowledge, this is the first report on acacetin de novo biosynthesis in a heterologous microbial host The results of this work confirm the effectiveness of modular co-culture engineering for complex flavonoid biosynthesis

Inhibitory Effect of Lygodium Root on the Cytochrome P450 3A Enzyme in vitro and in vivo.

Abstract: Purpose The aim of the present study was to investigate the interactions of the main components of Lygodium root (ie, p-coumaric acid, acacetin, apigenin, buddleoside and Diosmetin-7-O-β-D-glucopyranoside) with cytochrome P450 3A enzyme activity both in vitro and in vivo. Methods In vitro inhibition of drugs was assessed by incubating rat liver microsomes (RLMs) with a typical P450 3A enzyme substrate, midazolam, to determine their 50% inhibitory concentration (IC50) values. For the in vivo study, healthy male Sprague Dawley rats were consecutively administered acacetin or apigenin for 7 days at the dosage of 5 mg/kg after being randomly divided into 3 groups: Group A (control group), Group B (acacetin group) and Group C (apigenin group). Results Among the five main components of Lygodium root, only acacetin and apigenin showed inhibitory effects on the cytochrome P450 3A enzyme in vitro. The IC50 values of acacetin and apigenin were 58.46 μM and 8.20 μM, respectively. Additionally, the in vivo analysis results revealed that acacetin and apigenin could systemically inhibit midazolam metabolism in rats. The Tmax, AUC(0-t) and Cmax of midazolam in group B and group C were significantly increased (P<0.05), accompanied by a significant decrease in Vz/F and CLz/F (P<0.05). Conclusion Acacetin and apigenin could inhibit the activity of the cytochrome P450 3A enzyme in vitro and in vivo, indicating that herbal drug interactions might occur when taking Lygodium root and midazolam synchronously.

Acacetin Suppresses IL-1β-Induced Expression of Matrix Metalloproteinases in Chondrocytes and Protects against Osteoarthritis in a Mouse Model by Inhibiting NF-κB Signaling Pathways

Abstract: Osteoarthritis (OA) is a very common chronic joint dysfunction, and there is currently a poor understanding of its etiology and pathogenesis. Therefore, there are no active disease-modifying drugs currently available for clinical treatment. Several natural compounds have been shown to play a role in inhibiting OA progression. The present study is aimed at investigating the curative effects of acacetin, a natural flavonoid compound, against OA. Our results demonstrated that MMP-1, MMP-3, and MMP-13 were highly expressed in OA specimens. Acacetin inhibited the interleukin-1β- (IL-1β-) induced expression of MMP-1, MMP-3, and MMP-13in chondrocytes by blocking nuclear factor-κB (NF-κB) signaling pathways. Furthermore, we found that acacetin suppressed OA progression and inhibited the expression of MMP-1, MMP-3, and MMP-13 in ACLT-induced OA mice. Taken together, our study revealed that acacetin may serve as a potential drug for treating OA.

Chemical Composition and Biological Activities of Red beetroot (Beta Vulgaris Linnaeus) Roots

Abstract: Plants have been used for many years as a source of traditional medicine to treat various diseases and conditions. Beta Vulgaris Linnaeus ranks among the 10 most powerful vegetables as excellent sources for phytochemicals, which showed potent antioxidant and anticancer activities. The aim of this study is to characterize the chemical composition and determine the cytotoxicity and antibacterial activity of B.Vulgaris roots extract. The results of GC-Ms analysis of the unsaponifiable matter of B.Vulgaris roots showed the presence of 18 components. The undecane is the major hydrocarbon compound and α-citronellol is the major oxygenated compound. The methanolic extract of B.Vulgaris roots were enriched with a complicated mixture of phenolic acids and flavoniod which elucidated for the first time from this plant , including polyphenolic acid; ellagic acid (1); pyrogallol(2); salicylic(3); catechol(4); benzoic(5); protocatchuic (6); chlorogenic(7); p-hydroxy benzoic acids (8) . The molecular components of a flavoniod fraction, obtained from liquid chromatography extract, were identified using HPLC -ESI -MS. The major components were vitexin -2" -O-rhamnoside (1); demethylated -2"-xylosylvitexin (2); isorhamnetin -3-gentiobioside (3); rutin(4); beside minor components , luteolin-6-arabinose-8-glucose(1); hesperidin (2); acacetin (3); kaempferol-3-(2 -p -comaroyl) glucose (4); apigenin 6 -arabinose -8-glactose (5); quercetin (6); naringin (7). The structures of all isolated compounds were elucidated by conventional methods, spectroscopic analysis alongside their mass spectrometric investigations. The search for new, potentially biologically active extract becomes much more efficient after identification of all compounds in that mixture. The cytotoxic activity of methanolic extract was evaluated against pancreatic carcinoma (PANC-1) , hepatocellular carcinoma cell line HEPG-2 and , Lung carcinoma (A549) using MTT assay and vinblastine as a reference drug. methanolic extract showed higher activity with (IC50=3.69 µg/ml), mild cytotoxic activity against HepG2 with (IC50=4.43 µg/ml) ,Lung carcinoma (A549) with (IC50=4.9 µg/ml) and a weak activity against prostate carcinoma PC-3 with (IC50=6.1 µg/ml). The antimicrobial activity of B.Vulgaris roots methanolic extract was evaluated using agar well diffusion method towards two representatives for each of Gram positive and Gram negative bacteria. The extract demonstrated inhibitory effect against pathogenic microorganisms: Staphylococcus aureus, ATCC 29213; (ZI=24mm) strains and Pseudomonas aerogenasa ATCC 27853); (ZI=19.3 mm) at 100 µL concentration.

An assessment of the interaction for three Chrysanthemum indicum flavonoids and α-amylase by surface plasmon resonance.

Abstract: This study evaluated the interaction of Chrysanthemum indicum (CI) flavonoids (luteolin, acacetin, and buddleoside) with α-amylase. Surface plasmon resonance (SPR) assay showed their equilibrium dissociation constants (KD ) are 1.9695 ± 0.12, 2.9240 ± 0.20, and 3.2966 ± 0.08 mM at pH 6.0, respectively. Furthermore, their binding affinities were influenced by KCl, MgCl2, and CaCl2. Enzymatic kinetic studies revealed that three flavonoids exhibited noncompetitive α-amylase inhibitory activity. The inhibitory sequence is luteolin > acacetin > buddleoside, which was in accordance with the results of binding affinity from SPR. 1,1-diphenyl-2-picryl hydrazyl radical assay demonstrated that antioxidant activities of three flavonoids were inhibited significantly with α-amylase. Meanwhile, the study reveals that hydroxyl on C'-4, C'-5, and C-7 of flavonoids play an important role on the interaction of three flavonoids with α-amylase. Also, SPR could be used as sensor for rapid screening inhibitors of α-amylase and provide useful information for the application of C. indicum flavonoids in food and pharmaceutical area.

Flavonoids Distinctly Stabilize Lymph Endothelial- or Blood Endothelial Disintegration Induced by Colon Cancer Spheroids SW620.

Abstract: The health effects of plant phenolics in vegetables and other food and the increasing evidence of the preventive potential of flavonoids in "Western Diseases" such as cancer, neurodegenerative diseases and others, have gained enormous interest. This prompted us to investigate the effects of 20 different flavonoids of the groups of flavones, flavonols and flavanones in 3D in vitro systems to determine their ability to inhibit the formation of circular chemorepellent induced defects (CCIDs) in monolayers of lymph- or blood-endothelial cells (LECs, BECs; respectively) by 12(S)-HETE, which is secreted by SW620 colon cancer spheroids. Several compounds reduced the spheroid-induced defects of the endothelial barriers. In the SW620/LEC model, apigenin and luteolin were most active and acacetin, nepetin, wogonin, pinocembrin, chrysin and hispidulin showed weak effects. In the SW620/BEC model acacetin, apigenin, luteolin, wogonin, hispidulin and chrysin exhibited weak activity.

Protective effect of acacetin in human periodontal ligament cells via regulation of autophagy and inflammation.

Abstract: Our study investigated the effects of acacetin, a natural flavonoid compound, on the survival and expression of inflammatory related cytokines in lipopolysaccharide (LPS)-stimulated human periodontal ligament (PDL) cells. Treatment with acacetin significantly promoted survival and suppressed apoptosis in LPS-stimulated PDL cells in a dose-dependent manner, as shown by CCK-8 and flow cytometry assays, respectively. Moreover, ELISA assay showed that acacetin dose-dependently attenuated LPS-induced increases of TNF-α, IL-6 and IL-1β in PDL cells. Western blot analysis showed that administration of acacetin dose-dependently increased the ratio of LC3II/LC3I, as well as the expression of beclin-1, as compared to LPS-stimulated PDL cells. Inhibition of autophagy by rapamycin, an autophagy inhibitor, increased the production of pro-inflammatory cytokines and decreased survival, abolishing the beneficial role of acacetin in LPS-stimulated PDL cells. In addition, the expression of GSK-3β, a regulator of autophagy, was suppressed by administration with acacetin in a dose-dependent manner. Acacetin treatment promotes survival and suppresses inflammation in LPS-stimulated PDL cells via regulating autophagy and GSK-3β signal in PDL cells, suggesting that acacetin may be a potential novel agent for the treatment of chronic periodontitis.

Inhibitory effect of acacetin, apigenin, chrysin and pinocembrin on human cytochrome P450 3A4

Abstract: Cytochrome P450 3A4 is the most significant enzyme in metabolism of medications. Flavonoids are common secondary plant metabolites found in fruits and vegetables. Some flavonoids can interact with other drugs by inhibiting cytochrome P450 enzymes. Thus, the objective of this study was to determine inhibition kinetics of cytochrome P450 3A4 by flavonoids: acacetin, apigenin, chrysin and pinocembrin. For this purpose, testosterone was used as marker substrate, and generation of the 6β-hydroxy metabolite was monitored by high performance liquid chromatography coupled with diode array detector. IC50 values, inhibition constants, and rates of inhibition were determined. IC50 values ranged between 0.6 and 11.4 µM. The strongest inhibitor was chrysin (IC50 0.6 µM, inhibition constant 0.6 µM, inhibition rate constant 0.065 min–1, inhibition efficacy 0.108 min–1 µM–1). Compared to other flavonoids analyzed, chrysin’s inhibitory effect can be attributed to the hydrophobic nonsubstituted B ring, as well as rigidity of the structure. When foods rich in chrysin are consumed, e.g. honey and propolis, chrysin can cause food-drug interactions. Further in vitro studies are needed to determine the reactive intermediate responsible for inactivation of cytochrome P450 3A4 enzyme, as well as in vivo studies to determine possible clinical significance of this inhibition. This work is licensed under a Creative Commons Attribution 4.0 International License .

Atherosclerosis is attenuated by acacetin via Sirt1-mediated activation of AMPK/Sirt3 signals in diabetic ApoE-/- mice

Abstract: BackgroundThe strategy of decreasing atherosclerotic cardiovascular disorder is imperative to reduce premature death and improve quality of life in patients with diabetes mellitus. The present study was designed to investigate whether the natural flavone acacetin could improve diabetes- accelerated atherosclerotic lesions.MethodsDiabetic model was established in 7-week-old ApoE−/− mice by intraperitoneal injection of STZ (daily 50 mg/kg) for 5 days. Animals of control, control with acacetin treatment, STZ-diabetes, STZ-diabetes with acacetin treatment received acacetin prodrug subcutaneously (20 mg/kg, b.i.d.) or equivolume saline for 12 weeks, and the elasticity of carotid artery and the ability of vascular wall movement were determined with ultrasound and magnetic resonance imaging. Human umbilical vein endothelial cells (HUVECs) were cultured with medium containing 5.5 mM or 33 mM glucose and treated with acacetin or vehicle. Changes of related aortic lesions and signaling molecules were determined by biochemical and molecular approaches in animals and cultured HUVECs.ResultsIt was found that acacetin significantly suppressed atherosclerotic lesions and neointima hyperplasia, improved the elasticity of carotid artery and the ability of vascular wall movement without reducing blood glucose level and reversed the impaired signaling molecules (i.e. SOD, Bcl2, PGC-1α, pAMPK, Sirt3 and Sirt1) in artery tissues in diabetic mice. In cultured HUVECs, high glucose-induced cell viability reduction, ROS over-production, decrease of anti-oxidation, increase of apoptosis, and impairment of mitochondrial function were countered by acacetin (0.3-3 µM) in a concentration-dependent manner. Moreover, acacetin relies on Sirt1 activation by increasing NAMPT and NAD+ followed by Sirt3, pAMPK and PGC-1α activation. Silencing Sirt1 abolished acacetin-induced activation of Sirt3, pAMPK, and PGC-1α.ConclusionsThese results indicate that Sirt1-mediated activation of pAMPK/Sirt3 signals is involved in protective effects of acacetin against atherosclerosis in diabetes by preserving mitochondrial function via reducing mitochondrial apoptosis and ROS production and enhancing its biogenesis, which suggests that acacetin may be a drug candidate for reducing atherosclerotic cardiovascular disorder in patients with diabetes.

A New Flavonoid Glycoside from Scutellaria barbata

Abstract: A new flavonoid glycoside 1, together with nine known compounds, has been isolated from Scutellaria barbata D. Don. The structure of compound 1 was elucidated as acacetin 7-O-β-D-galactopyranosyl(1→2)-β-Dglucopyranoside by spectroscopic data (1D and 2D NMR methods) and chemical evidences. Additionally, compound 1 displayed potent inhibitory activity against α-glucosidase with an IC50 value of 8.9 μM in vitro.