Inhibitory effects of chlorogenic acid and its related compounds on the invasion of hepatoma cells in culture

Actions of chlorogenic acid, a major component of coffee, andits constituents, caffeic and quinic acids, on theproliferation and invasion of AH109A, a rat ascites hepatomacell line, were investigated using in vitro assay systems. Allthree components suppressed the AH109A invasion atconcentrations of 5–40 M without altering the cellproliferation. At the concentration of 10 M, chlorogenic,caffeic and quinic acids significantly (P < 0.05) suppressedthe invasion by 68%, 36% and 31%, respectively, implying thatthe suppressive effect of chlorogenic acid on the AH109Ainvasion might result from the additive effects of itsconstituents, caffeic and quinic acids. At the concentrationof 10 M, cinnamic acid and p-coumaric acid (4-hydroxycinnamicacid) exerted no or little influence on the invasion, whereascaffeic acid (3,4-dihydroxycinnamic acid) significantly (P <0.05) suppressed it, suggesting the possible involvement ofthe 3,4-dihydroxy group of caffeic acid in the suppression.Chlorogenic acid was thus demonstrated to be one of thechemical entities in coffee suppressing the hepatoma invasionin vitro, and both of its constituents, caffeic and quinicacids, to be responsible for the anti-invasive activity. Theseresults suggest the existence of nutritionally andpharmacologically important substances in coffee which controltumor cell invasion.     

Changes in the amounts of chlorogenic and caffeic acids during tobacco seed maturation

During maturation of tobacco seed, the amount of chlorogenic acid rapidly increased between days 7 and 11 after anthesis and then decreased until day 15. Chlorogenic acid was not detected in fully mature seed. On the other hand, caffeic acid appeared from day 15, reached a maximum at day 21, and rapidly disappeared by day 25 although the amount was always low in comparison with that of chlorogenic acid. Changes in dry wt, water content, testa color and germination of tobacco seeds during maturation were also investigated. The results suggested that there were rapid biochemical changes in seed between days 11 and 15 after anthesis.     

Effects of chlorogenic and caffeic acids on IAA oxidase preparations from sweet potato roots

IAA oxidase preparations from sweet potato (Ipomoea batatas) roots oxidised IAA in the absence of added phenolics. Activity was optimal around pH 6·8 and a minor pH optimum occurred around pH 4·3. Both chlorogenic and caffeic acids inhibited IAA oxidase activity at high concentrations (0·6–5·7 nmol/ml) but stimulated enzyme activity at low concentrations (0·10-0·55 nmol/ml); these effects were dependent on IAA and enzyme concentration and on pH. The activities of both substances are compared with those of other phenolics known to stimulate and inhibit plant IAA oxidases.     

Antistaphylococcal and biofilm inhibitory activities of gallic,caffeic, and chlorogenic acids

Staphylococcus aureus is a Gram-positive pathogen which is able to form biofilms, exhibiting a more pronounced resistance to antibiotics and disinfectants. The?hurdles posed in eradicating biofilms?have driven the search for new compounds able to fight these structures. Phenolic compounds constitute one of the most numerous and ubiquitous group of plant secondary metabolites with many biological activities. The aim of the present work was to study the potential antimicrobial and antibiofilm properties of gallic, caffeic, and chlorogenic acids against S. aureus as well to elucidate its mechanism of action. It was concluded that the phenolic acids studied in this work?have antistaphylococcal properties. For instance, gallic acid is able to influence the adhesion properties of S. aureus. The phenolic acids tested were also able to inhibit the production of α-hemolysin by this microorganism, with the exception of chlorogenic acid. Regarding its mechanism of action, caffeic acid interferes with the stability of the cell membrane and with the metabolic activity of the cells of S. aureus.     

Biotransformation and improved enzymatic extraction of chlorogenic acid from coffee pulp by filamentous fungi

The highest enzymatic extraction of covalent linked chlorogenic (36.1%) and caffeic (CA) (33%) acids from coffee pulp (CP) was achieved by solid‐state fermentation with a mixture of three enzymatic extracts produced by Aspergillus tamarii, Rhizomucor pusillus, and Trametes sp. Enzyme extracts were produced in a practical inexpensive way. Synergistic effects on the extraction yield were observed when more than one enzyme extract was used. In addition, biotransformation of chlorogenic acid (ChA) by Aspergillus niger C23308 was studied. Equimolar transformation of ChA into CA and quinic acids (QA) was observed during the first 36 h in submerged culture. Subsequently, after 36 h, equimolar transformation of CA into protocatechuic acid was observed; this pathway is being reported for the first time for A. niger. QA was used as a carbon source by A. niger C23308. This study presents the potential of using CP to produce enzymes and compounds such as ChA with biological activities. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29: 337–345, 2013     

绿原酸对美国白蛾幼虫生长发育和解毒相关蛋白活性的影响

【目的】明确植物次生代谢物质绿原酸对美国白蛾Hyphantria cunea幼虫生长发育和解毒相关蛋白活性的影响。【方法】将含不同浓度绿原酸(0, 0.125%, 0.250%, 0.500%, 1.000%和2.000%)的人工饲料饲养美国白蛾幼虫,测定各组中5龄幼虫6 d内的死亡率, 各组中5龄幼虫在取食48 h时的营养效应指标,0.500%绿原酸处理组中幼虫(3龄幼虫开始)的生长发育,以及在取食36 h时各组中5龄幼虫肠道中的解毒相关蛋白活性。【结果】绿原酸处理组中美国白蛾5龄幼虫6 d内的死亡率随着人工饲料中绿原酸浓度的增大而逐渐升高,且显著高于对照组(取食含10% DMSO人工饲料的)。绿原酸对美国白蛾5龄幼虫的营养效应指标有显著影响,各处理组幼虫的相对取食量和近似消化率显著高于对照组,食物转化率显著低于对照组,除0.125%绿原酸处理组外,其余处理组幼虫的食物利用率和相对生长速率也显著低于对照组。0.500%绿原酸处理使美国白蛾3-5龄幼虫发育历期比对照组显著延长28.24%(3.7 d),老熟幼虫(6-7龄幼虫)的发育历期缩短8.97%(0.7 d),且幼虫总成活率、化蛹率、羽化率、雌雄性比及产卵量等各项指标均显著低于对照组。不同浓度绿原酸处理对美国白蛾幼虫肠道中的细胞色素P450酶(CYP450)、谷胱甘肽S-转移酶(GSTs)、尿苷二磷酸葡萄糖醛酸转移酶(UGT)和ABC转运蛋白(ABC transporters)的活性具有显著影响,但对羧酸酯酶(CarE)活性未见显著影响。【结论】绿原酸可影响美国白蛾幼虫的存活率、食物利用效率、生长发育和繁殖,而美国白蛾幼虫可能通过调节食物利用率和诱导其解毒相关蛋白活性从而对食物中绿原酸产生适应性。     

Effects of caffeic acid phenethyl ester and alpha-tocopherol on reperfusion injury in rat brain

Oxygen-derived free radicals have been implicated in the pathogenesis of cerebral injury after ischaemia-reperfusion. Caffeic acid phenethyl ester (CAPE), an active component of propolis extract, exhibits antioxidant properties. The purpose of the present study was to investigate the effects of ischaemia and subsequent reperfusion on rat brain and to investigate the effects of two free radical scavengers, CAPE and alpha-tocopherol, on this in vivo model of cerebral injury. Ischaemia was induced by bilateral occlusion of the carotid arteries for 20 min and reperfusion was achieved by releasing the occlusion to restore the circulation for 20 min. Control rats underwent a sham operation. CAPE at 10 micromol kg(-1) or alpha-tocopherol at 25 micromol kg(-1) was administered intraperitoneally before reperfusion. Reperfusion led to significant increase in the activity of xanthine oxidase and higher malondialdehyde levels in the brain. Acute administration of both CAPE and alpha-tocopherol suppressed ischaemia-reperfusion-induced cerebral lipid peroxidation and injury, but CAPE seems to offer a better therapeutic advantage over alpha-tocopherol.     

Fluorescence spectroscopy and molecular simulation on the interaction of caffeic acid with human serum albumin

Fluorescence spectroscopy and molecular simulation were explored to study the interaction between caffeic acid and human serum albumin (HSA). The experimental results indicated that the fluorescence quenching mechanism between caffeic acid and HSA is a static quenching, which was proved again by the analysis of fluorescence lifetime by time‐correlated single photon counting. The binding process is spontaneous and the hydrophobic force is the main force between caffeic acid and HSA. In addition, the binding of caffeic acid to HSA was modeled by molecular dynamics simulations. The root mean square deviations, root mean square fluctuations, radius of gyration and the number of hydrogen bonds of the molecular dynamic (MD) simulation process were analyzed. Both experimental and modeling results demonstrated strong binding between HSA and caffeic acid. HSA had a slight conformational change when it binds with caffeic acid. The obtained information is useful for HSA drug design. Copyright © 2016 John Wiley & Sons, Ltd.     

链霉菌对烟草中烟碱与绿原酸的降解作用研究

为了研究对烟草中烟碱与绿原酸的快速生物降解,筛选了能有效降解烟草中烟碱与绿原酸的链霉菌Z6菌株与Z8菌株,考察了Z6和Z8菌株在不同培养基上的培养特征,探讨了所选菌株对烟碱与绿原酸的降解特性。实验结果表明,Z8链霉菌在烟草固体培养基中培养48h后,对培养基中烟碱的降解率达到83.9%;培养72h后,对烟碱的降解率可达到93.7%,此时烟草中的烟碱含量降低到0.38mg/g,达到了欧盟条例的无害化标准。Z6菌对绿原酸的降解程度较高,培养48h后,对绿原酸的降解率为57.1%;培养72h后,降解率可达到67.5%.     

Effect of repeated harvesting on the content of caffeic acid and seven species of caffeoylquinic acids in sweet potato leaves

The purpose of this study was to investigate the effect of repeated harvesting on the content of caffeic acid (CA) and seven species of caffeoylquinic acids (CQAs) in sweet potato leaves using a newly developed high-performance liquid chromatography method. Six cultivars and two breeding lines were used in this study. Leaves were collected at monthly intervals from 1st harvest (May) to 4th harvest (August) in 2011 and 2012. ANOVA analysis revealed that the contents of CQAs were significantly different among all cultivars and breeding lines, but no significant differences were found for CA. No annual variation was confirmed in CA and CQAs. Repeated harvest of sweet potato leaves affected the content of only 4-CQA and 5-CQA. Post-hoc comparisons using Tukey’s method indicated that the contents of 4-CQA and 5-CQA in sweet potato leaves harvested at first time were significantly higher compared to those at the other harvest times.     

绿原酸对凡纳滨对虾抗氧化系统及抗低盐度胁迫的影响

对绿原酸调节凡纳滨对虾(Litopenaeus vannamei)血淋巴抗氧化系统功能及抗低盐度胁迫的效果进行了评价。360尾凡纳滨对虾随机分为4组,分别投喂含有0、100、200和400 mg/kg绿原酸的饲料28 d,随后将对虾从盐度为32的天然海水直接转入至盐度为10的水中胁迫72 h。结果表明,在正常养殖条件下,绿原酸对凡纳滨对虾的成活率、血淋巴总抗氧化能力(Total antioxidative capacity, T-AOC)、超氧化物歧化酶(Superoxide dismutase, SOD)及过氧化氢酶(Catalase, CAT)活力均无明显影响,然而投喂含有绿原酸的饲料14 d,对虾血淋巴谷胱甘肽过氧化物酶(Glutathione peroxidase, GPx)活性和血淋巴细胞GPx和CAT基因表达水平均显著高于对照组(P<0.05);低盐度胁迫24 h,绿原酸组凡纳滨对虾的存活率较对照组提高10%,但各组之间无显著性差异(P>0.05);低盐度胁迫24 h,各组凡纳滨对虾血淋巴T-AOC、SOD和GPx活性与胁迫前相比均显著增加,说明低盐度胁迫条件下机体产生了抗氧化胁迫反应,同时绿原酸组对虾血淋巴GPx、CAT活性均显著高于对照组(P<0.05);低盐度胁迫72 h,绿原酸组对虾血淋巴T-AOC、GPx和CAT活性和血淋巴细胞GPx和CAT基因表达水平均明显高于对照组。上述结果表明绿原酸可有效调节凡纳滨对虾的抗氧化系统功能,增强对虾对于低盐度胁迫下的适应能力。     

Effects of caffeic acid phenethyl ester on matrix molecules and angiogenetic and anti-angiogenetic factors in gastric cancer cells cultured on different substrates

Migration, invasion, metastasis and angiogenesis associated with cancer depend on the surrounding microenvironment. Angiogenesis, the growth of new capillaries, is a regulator of cancer growth and a useful target for cancer therapy. We examined matrix protein interactions in a gastric cancer cell culture that was treated with different doses of caffeic acid (3,4-dihydroxycinnamic acid) phenethyl ester (CAPE). We also investigated the relations among the levels of vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), endostatin (ES) and trombospondin-1 (TSP-1). Cytotoxity of CAPE was measured using the 3-(4,5-dmethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. We examined the behavior of cells on laminin and collagen I coated surfaces in response to the angiogenic effect of these matrix molecules. We examined the protein alterations of these matrix molecules immunohistochemically and measured the levels of VEGF, MMP-9, ES and TSP-1 using the ELISA test. We showed that application of CAPE to the gastric cancer cell line on tissue culture plastic, laminin and collagen I significantly decreased the VEGF and MMP-9 protein levels. We found that TSP-1 levels were increased significantly in the gastric cancer cells after application of CAPE. The protein levels of gastric cancer cells also were increased significantly when tissue was cultured on laminin and collagen I. Application of CAPE to cells on laminin or collagen I coated surfaces significantly increased all of the proteins except ES. ES levels were increased on the collagen I covered surfaces, but the laminin surface decreased the levels of ES significantly. We demonstrated the beneficial effect of CAPE on a gastric cancer cell line including inhibition of proliferation and induction of some proteins that might be related to decreased angiogenesis.     

Study on the binding of chlorogenic acid to pepsin by spectral and molecular docking

The interaction of pepsin with chlorogenic acid (CHA) was investigated using fluorescence, UV/vis spectroscopy and molecular modeling methods. Stern–Volmer analysis indicated that the fluorescence quenching of pepsin by CHA resulted from a static mechanism, and the binding constant was 1.1846 × 10⁵ and 1.1587 × 10⁵ L/mol at 288 and 310 K, respectively. The distance between donor (pepsin) and acceptor (CHA) was calculated to be 2.39 nm and the number of binding sites for CHA binding on pepsin was ~ 1. The results of synchronous fluorescence and three‐dimensional fluorescence showed that binding of CHA to pepsin could induce conformational changes in pepsin. Molecular docking experiments found that CHA bonded with pepsin in the area of the hydrophobic cavity with Van der Waals' forces or hydrogen bonding interaction, which were consistent with the results obtained from the thermodynamic parameter analysis. Furthermore, the binding of CHA can inhibit pepsin activity in vitro. Copyright © 2013 John Wiley & Sons, Ltd.     

Effects of Chlorogenic Acid and Its Metabolites on Spontaneous Locomotor Activity in Mice

Chlorogenic acid possessed a weak caffeine-like psychostimulant property when assessed for its effect on spontaneous locomotor activity in mice. In the evaluation of the effects for the major metabolites of chlorogenic acid which were detected upon incubation with rat feces and/or excreted in urine after oral administration to rats, caffeic and m-coumaric acids were found to be the principal active metabolites, while the others contributed little to this caffeine-like psychostimulant activity.     

The potential usage of caffeic acid phenethyl ester (CAPE) against chemotherapy‐induced and radiotherapy‐induced toxicity

Protection of the patients against the side effects of chemotherapy and radiotherapy regimens has attracted increasing interest of clinicians and practitioners. Caffeic acid phenethyl ester (CAPE), which is extracted from the propolis of honeybee hives as an active component, specifically inhibits nuclear factor κB at micromolar concentrations and show ability to stop 5‐lipoxygenase‐catalysed oxygenation of linoleic acid and arachidonic acid. CAPE has antiinflammatory, antiproliferative, antioxidant, cytostatic, antiviral, antibacterial, antifungal and antineoplastic properties. The purpose of this review is to summarize in vivo and in vitro usage of CAPE to prevent the chemotherapy‐induced and radiotherapy‐induced damages and side effects in experimental animals and to develop a new approach for the potential usage of CAPE in clinical trial as a protective agent during chemotherapy and radiotherapy regimens. Copyright © 2012 John Wiley & Sons, Ltd.     

Study on the influence of caffeic acid against sodium valproate–induced nephrotoxicity in rats

Renal injury is a hallmark adverse reaction to sodium valproate (SVP), and caffeic acid (CAFF) is a phenolic compound that has anti‐inflammatory and antioxsidant properties. So, this investigation was assessed to evaluate the nephrotoxic potential of SVP and the defensive impact of CAFF against SVP nephrotoxicity. SVP was given at a dose of 500 mg/kg (i.p.) once daily for 2 weeks, while CAFF was given at a dose of 50 mg/kg (orally), simultaneously with SVP. Concurrent treatment with CAFF reduced urea and creatinine, lipid peroxidation (malondialdehyde), tumor necrosis factor alpha (TNF‐α), interferon gamma (IFN‐γ), nuclear factor kappa B (NF‐κB/p65), and transforming growth factor β (TGF‐β) levels. However, with increased glutathione content, CAFF also halted the activated Notch signaling cascade. Furthermore, CAFF suppressed caspase‐3 and inducible nitric oxide synthase expressions. To conclude, on the basis of the results obtained, CAFF proved to protect against SVP‐induced nephrotoxicity via its antioxidant, anti‐inflammatory, and antiapoptotic properties.     

Molecular mechanism of action of chlorogenic acid on erythrocyte and lipid membranes

Abstract

The high antioxidant capacity of chlorogenic acid (CGA) in respect to biological systems is commonly known, though the molecular mechanism underlying that activity is not known. The aim of the study was to determine that mechanism at the molecular and cell level, in particular with regard to the erythrocyte and the lipid phase of its membrane. The effect of CGA on erythrocytes and lipid membranes was studied using microscopic, spectrophotometric and electric methods. The biological activity of the acid was determined on the basis of changes in the physical parameters of the membrane, in particular its osmotic resistance and shapes of erythrocytes, polar head packing order and fluidity of erythrocyte membrane as well as capacity and resistivity of black lipid membrane (BLM). The study showed that CGA becomes localized mainly in the outer part of membrane, does not induce hemolysis or change the osmotic resistance of erythrocytes, and induces formation of echinocytes. The values of generalized polarization and fluorescence anisotropy indicate that CGA alters the hydrophilic region of the membrane, practically without changing the fluidity in the hydrophobic region. The assay of electric parameters showed that CGA causes decreased capacity and resistivity of black lipid membranes. The overall result is that CGA takes position mainly in the hydrophilic region of the membrane, modifying its properties. Such localization allows the acid to reduce free radicals in the immediate vicinity of the cell and hinders their diffusion into the membrane interior.     

Mechanism and stoichiometry of the redox reaction between iron(III) and caffeic acid

The stoichiometry of the redox reaction of caffeic acid with iron(III) was determined at pH 2.5. A linear increase in the yield of iron(II) was found with increasing iron(III) concentration until reached constant values when iron(III)/caffeic acid molar ratios were higher than 9. The reaction proceeds through two steps each having different rates, and involving intermediates with different redox activities. A mechanism of the redox reaction consistent with our results is proposed.     

Binding mechanism of caffeic acid and simvastatin to the integrin linked kinase for therapeutic implications: a comparative docking and MD simulation studies

Abstract

Integrin linked kinase (ILK) is a Ser/Thr kinase, which regulates various integrin mediated signaling pathways, and is involved in cell adhesion, migration and differentiation. Alteration in the ILK is responsible for abnormal functioning of the cell system, which may lead to the cancer progression and metastasis. Caffeic acid (CA) and simvastatin are used as antioxidant and possess anticancer properties. Thus, inhibiting the kinase activity of ILK by CA and simvastatin may be implicated in the cancer therapy. In this study, we have performed molecular docking followed by 100?ns MD simulations to understand the interaction mechanism of ILK protein with the CA and simvastatin. Average potential energy was found to be highest in case of ILK–CA complex (?770,949?kJ/mol). Binding free energy was found to be higher in case of simvastatin than CA. Our results indicate that simvastatin binds more effectively to the active pocket of ILK. We further performed MTT assay to understand its anticancer potential. Simvastatin shows the IC₅₀ values for HepG2 and MCF-7 as 19.18?±?0.12 and 13.84?±?0.22?µM, respectively. However, the IC₅₀ value of CA on HepG2 and MCF-7 was reported as 175.50?±?1.44 and 144.90?±?1.53?µM, respectively. Our study provides a deeper insight into the binding mechanism of simvastatin and CA to ILK, which further opens a promising channel for their implications in cancer therapy.