Acrolein, known as one of the most common reactive carbonyl species, is a toxic small molecule affecting human health in daily life. This study is focused on the scavenging abilities and mechanism of ferulic acid and some other phenolic acids against acrolein. Among the 13 phenolic compounds investigated, ferulic acid was found to have the highest efficiency in scavenging acrolein under physiological conditions. Ferulic acid remained at (3.04±1.89)% and acrolein remained at (29.51±4.44)% after being incubated with each other for 24 h. The molecular mechanism of the detoxifying process was also studied. Detoxifying products, namely 2-methoxy-4-vinylphenol (product 21) and 5-(4-hydroxy-3-methoxyphenyl)pent-4-enal (product 22), were identified though nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC-MS), after the scavenging process. Ferulic acid showed significant activity in scavenging acrolein under physiological conditions. This study indicates a new method for inhibiting damage from acrolein.
Acrolein/toxicity* ; Coumaric Acids/pharmacology* ; Glutathione/physiology* ; Hydroxybenzoates/pharmacology* ; Magnetic Resonance Spectroscopy ; Structure-Activity Relationship

OBJECTIVE: To investigate the effect of ferulic acid, a natural compound, on pancreatic beta cell viability, Ca²⁺ channels, and insulin secretion. METHODS: We studied the effects of ferulic acid on rat insulinoma cell line viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide viability assay. The whole-cell patch-clamp technique and enzyme-linked immunosorbent assay were also used to examine the action of ferulic acid on Ca²⁺ channels and insulin secretion, respectively. RESULTS: Ferulic acid did not affect cell viability during exposures up to 72 h. The electrophysiological study demonstrated that ferulic acid rapidly and concentration-dependently increased L-type Ca²⁺ channel current, shifting its activation curve in the hyperpolarizing direction with a decreased slope factor, while the voltage dependence of inactivation was not affected. On the other hand, ferulic acid have no effect on T-type Ca²⁺ channels. Furthermore, ferulic acid significantly increased insulin secretion, an effect inhibited by nifedipine and Ca²⁺-free extracellular fluid, confirming that ferulic acid-induced insulin secretion in these cells was mediated by augmenting Ca²⁺ influx through L-type Ca²⁺ channel. Our data also suggest that this may be a direct, nongenomic action. CONCLUSION This is the first electrophysiological demonstration that acute ferulic acid treatment could increase L-type Ca²⁺ channel current in pancreatic β cells by enhancing its voltage dependence of activation, leading to insulin secretion.
Rats ; Animals ; Insulin Secretion ; Insulin/pharmacology* ; Insulin-Secreting Cells/metabolism* ; Coumaric Acids/metabolism* ; Calcium/metabolism*

OBJECTIVETo investigate the renal protective effect of sodium ferulate magnetic nanoparticle targeting therapy in septic rats receives norepinephrine treatment.

METHODSFirst we constructed sodium ferulate magnetic nanoparticle, Wistar male rats were randomly divided into 4 groups (n = 6): control group, septic group, norepinephrine treatment group (NE treatment group) and NE plus sodium ferulate magnetic nanoparticle treatment group (NE + SF group), septic rat model was reproduced by intravenous injection of lipolysaccharide (IPS) in rats in NE treatment group norepinephrine were used to elevate the blood pressure of septic rats, in NE + SF group sodium ferulate magnetic nanoparticle was injected via tail vein, magnetic field was placed near renal region. Urinary concentration of N-acetyl-beta-D-glucosaminidase (NAG), kidney injury molecule (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), renal tissue concentration of malonaldehyde (MDA), superoxide dismutase (SOD), and serum concentration of blood urea nitrogen (BUN), creatinine (Cr), alanine aminotransferase (ALT), aspartate aminotransferase (AST) were measured 3 hours after treatment.

RESULTSAfter injected LPS via tail vein, systolic blood pressure, pH value, PaO2 and PaCO2 of arterial blood of septic rats decreased significantly. Systolic blood pressure, pH value, PaO2 and PaCO2 of arterial blood returned to baseline approximately after norepinephrine treatment, sodium ferulate magnetic nanoparticle targeting therapy did not change hemodynamic effects of norepinephrine. Compared with control group, urine NAG, KIM-1 and NGAL of sepsis group were increased significantly (P < 0.01), after treatment with norepinephrine, urine NAG, KIM-1 and NGAL of NE treatment group were elevated rapidly compared with those of sepsis group (P < 0.01), combined with sodium ferulate magnetic nanoparticles targeting treatment, urine NAG, KIM-1 and NGAL of NE + SF group were decreased significantly compared with those of sepsis group and NE treatment group (P < 0.01). Compared with control group, renal tissue MDA levels of septic rats increased significantly (P < 0.01), NE treatment could notably raise MDA levels compared with those of sepsis group (P < 0.01), renal tissue MDA levels of NE + SF group were decreased significantly compared with those of sepsis group and NE treatment group (P < 0.01). Compared with control group, renal tissue activities of SOD of sepsis group and NE treatment group were decreased significantly (P < 0.01), after targeted treatment with sodium ferulate magnetic nanoparticle, renal tissue SOD activities of NE + SF group increased significantly compared with those of sepsis group and NE treatment group (P < 0.01 vs sepsis group and NE treatment group). Serum BUN, Cr, ALT, AST levels did not significantly change in each groups.

CONCLUSIONSodium ferulate magnetic nanoparticle targeting therapy can effectively decrease urine NAG, KIM-1, NGAL and renal tissue MDA level, increase tissue SOD activity of sepsis group and NE treatment group rats, thus protect renal function of septic rats.

Animals ; Coumaric Acids ; administration & dosage ; pharmacology ; Kidney ; drug effects ; pathology ; Magnetics ; Male ; Nanoparticles ; Rats ; Rats, Sprague-Dawley ; Sepsis ; pathology ; urine

OBJECTIVETo assess and compare the in vitro anti-oxidative activities among Siwu Decoction Serial Recipes, their composed crude herbs, and main aromatic acids they contained.

METHODSTheir anti-oxidative activities (including Siwu Decoction and correlated recipes such as Taohong Siwu Decoction, Xiangfu Siwu Decoction, Shaofu Zhuyu Decoction, and Xiongqiong Decoction, 16 kinds of crude herbs, and main aromatic acids they contained) were determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical clearance method.

RESULTSThe selected five decoctions showed obvious activities of scavenging free radicals. Siwu Decoction was better than other decoctions in scavenging free radicals and Xiongqiong Decoction was the least. Among the 16 kinds of crude herbs, red peony root, white peony root, safflower, ligustici chuanxiong, common aucklandia root showed the strongest activities, while peach seed showed the poorest activities. Among aromatic acids, gallic acid, protocatechuic acid, vanillic acid, caffeic acid, chlorogenic acid, p-coumaric acid, and ferulic acid showed obvious anti-oxidative activities in scavenging free radicals, showing obvious dose-effect correlation. p-hydroxybenzoic acid, benzoic acid, and cinnamic acid showed no activities on scavenging free radicals (P > 0.05).

CONCLUSIONSiwu Decoction and aromatic acids contained in correlated decoctions played significant roles in anti-oxidative activities.

Antioxidants ; pharmacology ; Biphenyl Compounds ; Caffeic Acids ; pharmacology ; Chlorogenic Acid ; pharmacology ; Coumaric Acids ; pharmacology ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; pharmacology ; Free Radicals ; metabolism ; Gallic Acid ; pharmacology ; Hydroxybenzoates ; pharmacology ; Picrates

A significant number of organic carboxylic acids have been shown to influence the absorption and distribution of drugs mediated by organic anion transporters (OATs). In this study, uptake experiments were performed to assess the inhibitory effects of cinnamic acid, ferulic acid, oleanolic acid, deoxycholic acid, and cynarin on hOAT1, hOAT3, hOATP1B1, and hOATP2B1. After a drug-drug interaction (DDI) investigation, cinnamic acid, ferulic acid, deoxycholic acid, and cynarin were found and validated to inhibit hOAT1 in a competitive manner, and deoxycholic acid was found to be an inhibitor of all four transporters. The apparent 50% inhibitory concentrations of cinnamic acid, ferulic acid, deoxycholic acid, and cynarin were estimated to be 133.87, 3.69, 90.03 and 6.03 μmol·L(-1) for hOAT1, respectively. The apparent 50% inhibitory concentrations of deoxycholic acid were estimated to be 9.57 μmol·L(-1) for hOAT3, 70.54 μmol·L(-1) for hOATP1B1, and 168.27 μmol·L(-1) for hOATP2B1. Because cinnamic acid, ferulic acid, and cynarin are ingredients of food or food additives, the present study suggests there are new food-drug interactions to be disclosed. In addition, deoxycholic acid may be used as a probe for studying the correlation of OATs and OATPs.
Carboxylic Acids ; pharmacology ; Cinnamates ; pharmacology ; Coumaric Acids ; pharmacology ; Deoxycholic Acid ; pharmacology ; Diet ; Drug Interactions ; HEK293 Cells ; Humans ; Organic Anion Transport Protein 1 ; antagonists & inhibitors ; Organic Anion Transporters ; antagonists & inhibitors ; Plant Extracts ; pharmacology ; Plants, Medicinal ; chemistry

Ferulic acid, an useful compound of Chinese traditional medicine, was used as leading compound. Six ferulic acid derivatives were designed and synthesized based on bioisosterism. Their structures were characterized by IR, 1H NMR, 13C NMR and mass spectra. In vivo experiment showed that ferulic acid derivatives had good inhibitory effects on adenosine diphosphate (ADP) induced platelet aggregation, which were significantly higher than that of Ozagrel.
Animals ; Coumaric Acids ; chemical synthesis ; chemistry ; pharmacology ; Male ; Platelet Aggregation ; drug effects ; Platelet Aggregation Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Rabbits ; Random Allocation ; Structure-Activity Relationship

Ferulic acid (FA) was loaded into liposomes via calcium acetate gradient with (80.2 +/- 5.2)% entrapment efficiency. The average sizes of blank liposome and FA liposome were about 155 nm and 154 nm, respectively. The zeta potential of blank liposome and FA liposome were (13.14 +/- 1.67) mV and (4.12 +/- 0.05) mV, respectively. Unilamellar vesicles were present in freeze-fracture electron microscopy. In the pharmacodynamic studies, the protective effect of liposomal ferulic acid on tBHP-challenged U937 cells was measured with the morphology of cell injury, mitochondrial transmembrane potential alternation and cell viability assay used as index. The results of MTT assay, microscopy indicated that FA liposomes exhibited greater antioxidant activity than FA solution on U937 cell.
Antioxidants ; administration & dosage ; pharmacology ; Cholesterol ; chemistry ; Coumaric Acids ; administration & dosage ; pharmacology ; Drug Carriers ; Humans ; Liposomes ; chemistry ; Membrane Potentials ; drug effects ; Mitochondria ; physiology ; Particle Size ; U937 Cells

The present study aims to predict the action targets of antidepressant active ingredients of Xiaoyaosan to understand the "multi-components, multi-targets and multi-pathways" mechanism. Using network pharmacology, the reported antidepressant active ingredients in Xiaoyaosan (saikosaponin A, saikosaponin C, saikosaponin D, ferulic acid, Z-ligustilide, atractylenolide I, atractylenolide II, atractylenolide III, paeoniflorin, albiflorin, liquiritin, glycyrrhizic acid and pachymic acid), were used to predict the targets of main active ingredients of Xiaoyaosan according to reversed pharmacophore matching method. The prediction was made via screening of the antidepressive drug targets approved by FDA in the DrugBank database and annotating the information of targets with the aid of MAS 3.0 biological molecular function software. The Cytoscape software was used to construct the Xiaoyaosan ingredients-targets-pathways network. The network analysis indicates that the active ingredients in Xiaoyaosan involve 25 targets in the energy metabolism-immune-signal transmutation relevant biological processes. The antidepressant effect of Xiaoyaosan reflects the features of traditional Chinese medicine in multi-components, multi-targets and multi-pathways. This research provides a scientific basis for elucidation of the antidepressant pharmacological mechanism of Xiaoyaosan.
Antidepressive Agents ; pharmacology ; Benzoates ; Bridged-Ring Compounds ; Coumaric Acids ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; pharmacology ; Flavanones ; Glucosides ; Glycyrrhizic Acid ; Lactones ; Medicine, Chinese Traditional ; Monoterpenes ; Sesquiterpenes ; Software

A study was made on the pharmacokinetic regularity of effective components salvianolic acid B and ferulic acid in Salviae Miltiorrhizae Radix et Rhizoma (SMRR) and Chuanxiong Rhizoma(CR) in rats, so as to discuss the compatibility mechanism of Salviae Miltiorrhizae Radix et Rhizoma and Chuanxiong Rhizoma. Rats were randomly divided into three groups and intravenously injected with 50 mg x kg(-1) salvianolic acid B for the single SMRR extracts group, 0.5 mg x kg(-1) ferulic acid for the single CR extracts group and 50 mg x kg(-1) salvianolic acid B + 0.5 mg x kg(-1) ferulic acid for the SMRR and CR combination group. The blood samples were collected at different time points and purified by liquid-liquid extraction with ethyl acetate. With chloramphenicol as internal standard (IS), UPLC was adopted to determine concentrations of salvianolic acid B and ferulic acid. The pharmacokinetic parameters of salvianolic acid B and ferulic acid were calculated with WinNonlin 6.2 software and analyzed by SPSS 19.0 statistical software. The UPLC analysis method was adopted to determine salvianolic acid B and ferulic acid in rat plasma, including linear equation, stability, repeatability, precision and recovery. The established sample processing and analysis methods were stable and reliable, with significant differences in major pharmacokinetic parameters, e.g., area under the curve (AUC), mean residence time (MRT) and terminal half-life (t(1/2)). According to the experimental results, the combined application of SMRR and CR can significantly impact the pharmacokinetic process of their effective components in rats and promote the wide distribution, shorten the action time and prolong the in vivo action time of salvianolic acid B and increase the blood drug concentration and accelerate the clearance of ferulic acid in vivo.
Animals ; Apiaceae ; chemistry ; Benzofurans ; blood ; pharmacokinetics ; Coumaric Acids ; blood ; pharmacology ; Drug Interactions ; Drugs, Chinese Herbal ; analysis ; pharmacokinetics ; Male ; Rats ; Rats, Sprague-Dawley ; Rhizome ; chemistry ; Salvia miltiorrhiza ; chemistry

AIMTo study the effects of ferulic acid (FA) on E-selectin expression in human umbilical vein endothelial cells (HUVECs) activated by lipopolysaccharide and leukocyte-endothelial cell adhesion.

METHODSThe effects of FA on E-selectin and E-selectin mRNA expression were determined by flow cytometry and reverse transcription polymerase chain reaction. The effect of FA on HL60-HUVEC adhesion was evaluated with the method of staining the cells by Rose Bengal.

RESULTSThe expression of E-selectin and E-selectin mRNA were down regulated by FA (0.62 and 0.41 mmol x L(-1), respectively). HL60 cells adhered to activated HUVECs were also reduced by FA (0.62 and 0.41 mmol x L(-1), respectively).

CONCLUSIONFA can inhibit the expression of E-selectin and E-selectin mRNA and HL60-HUVEC adhesion. This may contribute to its protective effect against ischemia-reperfusion injury.

Cell Adhesion ; drug effects ; Cells, Cultured ; Coumaric Acids ; pharmacology ; E-Selectin ; biosynthesis ; genetics ; Endothelial Cells ; metabolism ; HL-60 Cells ; physiology ; Humans ; RNA, Messenger ; biosynthesis ; genetics ; Umbilical Veins ; cytology