The combination of metabolome and transcriptome clarifies the inhibition of the Alternaria toxin accumulation by methyl ferulate.

As one of the most typical pathogens in fruit postharvest diseases, Alternaria alternata (A. alternata) can produce Alternaria toxins (ATs) aggravating fruit decay and harming human health. In this study, ATs (tenuazonic acid, alternariol monomethyl ether, and alternariol) production was inhibited effectively by 200 and 8000 mg/L MF (methyl ferulate) in vitro and in vivo. 1-Octen-3-ol and 3-octanol were the potential iconic volatile organic compounds of ATs (R2 > 0.99). MF induced oxidative stress, resulting in physiological and metabolic disorders, membrane lipid oxidation and cell damage. It decreased precursors and energy supply by disturbing amino acid metabolism, ABC transporters, citrate cycle, pentose and glucuronate interconversions to regulate ATs synthesis. MF down-regulated the genes related to ATs synthesis (PksJ, AaTAS1, and OmtI), transport (AaMFS1 and MFS), and pathogenicity to affect ATs production and virulence. This study provided a theoretical basis for the control of ATs production.

Effects of Microencapsulated Ferulic Acid or Its Prodrug Methyl Ferulate on Neuroinflammation Induced by Muramyl Dipeptide.

Ferulic acid (Fer) is known for its antioxidant and anti-inflammatory activities, which are possibly useful against neurodegenerative diseases. Despite the ability of Fer to permeate the brain, its fast elimination from the body does not allow its therapeutic use to be optimized. The present study proposes the preparation and characterization of tristearin- or stearic acid-based solid lipid microparticles (SLMs) as sustained delivery and targeting systems for Fer. The microparticles were produced by conventional hot emulsion techniques. The synthesis of the methyl ester of Fer (Fer-Me) allowed its encapsulation in the SLMs to increase. Fer-Me was hydrolyzed to Fer in rat whole blood and liver homogenate, evidencing its prodrug behavior. Furthermore, Fer-Me displayed antioxidant and anti-inflammatory properties. The amount of encapsulated Fer-Me was 0.719 ± 0.005% or 1.507 ± 0.014% in tristearin or stearic acid SLMs, respectively. The tristearin SLMs were able to control the prodrug release, while the stearic acid SLMs induced a significant increase of its dissolution rate in water. Jointly, the present results suggest that the tristearin SLMs loaded with Fer-Me could be a potential formulation against peripheral neuropathic pain; conversely, the stearic acid SLMs could be useful for Fer-Me uptake in the brain after nasal administration of the formulation.

Study on protective effects of methyl ferulate on mitochondria of H 9c2 cardiomyocytes injured by hypoxia / 中国药房

OBJECTIVE To investigate the e ffects of methyl ferulate （MF） on the mitochondrial function of H 9c2 cardiomyocytes after hypoxia-induced injury. METHODS H9c2 cardiomyocytes were divided into normal group （no administration，no modeling ），hypoxia model group （modeling alone ），MF high-dose ，medium-dose and low-dose groups （40， 20，10 μmol/L）and positive control drug group （cyclosporin A ，1 μmol/L）. After drug pretreatment and inducing hypoxia-induced injury，the levels of lactate dehydrogenase （LDH），malondialdehyde（MDA），creatine kinase （CK）and adenosine triphosphate （ATP）were tested. The intracellular reactive oxygen species （ROS），mitochondrial membrane potential （MMP），the opening of mitochondrial membrane permeability transition pore （mPTP） were detected with flow cytometry. RESULTS Compared with hypoxia model group ，the levels of LDH ，MDA，CK and ROS fluorescence intensity were decreased significantly in MF high-dose，medium-dose and low-dose groups ，while the level of ATP was increased significantly （P＜0.01 or P＜0.05）. The red/ green fluorescence intensity ratio of MMP and the green fluorescence intensity of mPTP were increased significantly （P＜0.01 or P＜0.05）. CONCLUSIONS MF can reverse the levels of biochemical indexes in H 9c2 cardiomyocyte after hypoxia-induced injury，keep MMP stable ，reduce the opening of mPTP ，and has an obvious protective effect on the mitochondrial function of H9c2 cardiomyocytes injured by hypoxia ，and this protective effect is dose-dependent.

α-Glucosidase inhibitors from brown rice bound phenolics extracts (BRBPE): Identification and mechanism.

Brown rice bound phenolics extracts (BRBPE) have been reported to possess α-glucosidase inhibitory effects, the specific enzyme inhibitors involved in this process were unknown. Here, α-glucosidase inhibitors in BRBPE were screened using bioaffinity ultrafiltration methods, and seven phenolic compounds - three monomers (p-coumaric acid, ferulic acid and methyl ferulate), three dimers (8-5', 5-5' and 8-O-4' diferulic acid) and a trimer (5-5'/8-O-4″ dehydrotriferulic acid) were identified as exact inhibitors, among which 5-5'/8-O-4″ dehydrotriferulic acid and 5-5'diferulic acid exhibited the best inhibitory activity. Enzyme kinetic analysis suggested that the inhibitory mechanism of these seven inhibitors including competitive, noncompetitive, uncompetitive and mixed manner. Molecular docking analysis revealed that the seven inhibitors bind with α-glucosidase mainly by hydrogen bonding interaction, hydrophobic force and ionic bond. Molecular dynamics simulation further explored the structure and molecular property of phenolic-glucosidase complex. This work provided a deep insight into brown rice bound phenolics acting as potent α-glucosidase inhibitors.

Antibacterial Properties of Coaxial Spinning Membrane of Methyl ferulate/zein and Its Preservation Effect on Sea Bass.

Methyl ferulate is a new natural antibacterial agent with strong activity and low toxicity. It has good application prospects in food preservation. In this paper, the antibacterial activity of methyl ferulate against Shigella putrefaciens was verified, and it was embedded into zein by electrospinning technology to prepare fiber membranes. The addition of methyl ferulate could improve the tensile strength of zein fiber membrane and decrease the crystallinity of the membrane, which was mainly a physical combination. The fiber membrane improved the thermal stability of methyl ferulate. The water contact angle (WCA) decreased to 54.85°. The results showed that methyl ferulate in fiber membrane could be released slowly, gradually exerting its antibacterial activity. After coating perch with methyl ferulate/zein fiber membrane, the growth of microorganisms in perch meat was inhibited, and the pH value and total volatile basic nitrogen (TVB-N)content were effectively increased. In a word, methyl ferulate had antibacterial activity in the fiber film, which was able to achieve a sustained release effect in the process of fish packaging, prolonging its antibacterial activity, and having preservation effect on sea bass; thus, it could be used in food packaging.

Synthesis of trans- methyl ferulate bearing an oxadiazole ether as potential activators for controlling plant virus.

A series of new ferulic acid derivatives bearing an oxadiazole ether was synthesized by introducing a structure of oxadiazole into trans-ferulic acid via an ether linkage. The synthesized target compounds were evaluated in vivo for their anti-TMV (tobacco mosaic virus) activity, which indicated that some synthesized compounds displayed strong activity for controlling TMV. For protective activity, compounds 6f and 6h had the most activities of 65% and 69.8% at 500 mg L-1, respectively. Compounds 6a, 6b, 6e, 6f and 6h showed > 60% curative activities at 500 mg L-1. Preliminary proteomics analysis showed that compound 6h could regulate the phenylpropanoid biosynthesis pathway and chloroplast function. These results indicated that synthesized novel ferulic acid derivatives could be used for controlling TMV.

Structural elucidation, distribution and antioxidant activity of bound phenolics from whole grain brown rice.

Chemical profiles, distribution, and antioxidant activity of bound phenolics from brown rice were investigated. Four new dehydrodiferulic acid dimers (DFA) along with eighteen known phenolics were isolated from brown rice bound phenolic extracts and their structures were determined by multiple spectroscopic methods. Among them, ferulic acid and 8-5' DFA were the most abundant monomeric and dimeric bound phenolics in brown rice, rice bran and polished rice. In whole brown rice, polished rice contributed more than 50% of three phenolic monomers and six phenolic dimers, while rice bran contributed more than half of the other thirteen phenolics including eight monomers, four dimers, and one trimer. All the isolated compounds exhibited oxygen radical absorbance capacity. Thomasidioic acid, caffeic acid, methyl caffeate, and 8-5' DC DFA displayed potent peroxyl radical scavenging capacity, and the last three compounds also showed moderate cellular antioxidant activity.

The traditional uses, phytochemistry, and pharmacology of Stemona species: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants of genus Stemona (Stemonaceae) have been long used locally and traditionally in many South and East Asian counties to relieve cough, dispel phlegm, prevent asthma, control pests, diminish inflammation, decrease pain, and treat some cutaneous diseases. AIM OF STUDY: This review provided comprehensive and up-to-date information about botanic characterization and distribution, ethnopharmacology, secondary metabolites, pharmacological activities, and toxicology of plants of genus Stemona to explore the scientific potential and future therapeutic potential of the plants. MATERIALS AND METHODS: This article conducted a literature review on information about the Stemona species in multiple electronic databases, including PubMed, Web of Science, Wiley, Science Direct, Elsevier, Google Scholar, ACS publications, SpringerLink, and China National Knowledge Internet. Information was also derived from other literature sources (e.g. Chinese Pharmacopoeia, 2015 edition, Chinese herbal classic books, PhD and MSc thesis). Plant names were validated by "The Plant List" (www.theplantlist.org). All studies of the genus Stemona were included in this review until March 2020. RESULTS: Our comprehensive analysis of the scientific literatures indicated that many Stemona species are popular and valuable herbal medicines with therapeutic potentials to treat various ailments. Phytochemical analyses identified alkaloids and stilbenoids as the major bioactive substances of Stemona species. Numerous studies have shown that the extracts and secondary metabolites isolated from these plants have a wide range of pharmacological activities, including insecticidal and antifeedant, antitussive, anti-inflammatory, anticancer, antimicrobial, and antivirus activities. CONCLUSION: Though plants of genus Stemona have been put to enormous traditional uses, the pharmacological studies conducted were insufficient. Therefore, more secondary metabolites need to be studied for more detailed pharmacological studies. Further studies are also required to establish the mechanisms which mediate the plants' bioactivities in relation to the medicinal uses as well as investigate any potential toxicity for future clinical studies.

Feruloyl esterase activity and its role in regulating the feruloylation of maize cell walls.

Cell walls of grasses have ferulic acid (FA) ester-linked to the arabinosyl substitutions of arabinoxylan (AX). Feruloyl esterases (FAE) are carboxylic acid esterases that release FA from cell walls and synthetic substrates. Despite the importance of FA for cell wall recalcitrance and in response to biotic and abiotic stresses, the physiological function of plant FAEs remains unclear. Here, we developed a simple method for the determination of FAE activity (ZmFAE) in maize using the total protein extract and investigated its role in regulating the feruloylation of cell wall. The method includes a single protein extraction and enzymatic reaction with protein concentration as low as 65 µg at 35 °C for 30 min, using methyl ferulate as the substrate. The methodology allowed the determination of the apparent Km (392.82 µM) and Vmax (79.15 pkat mg-1 protein). We also found that ZmFAE activity was correlated (r = 0.829) with the levels of FA in seedling roots, plant roots and leaves of maize. Furthermore, the exposure to osmotic stress resulted in a 50% increase in ZmFAE activity in seedling roots. These data suggest that FAE-catalyzed reaction is important for cell wall feruloylation during plant development and in response to abiotic stress. We conclude proposing a model for the feruloylation and deferuloylation of AX, which explains the role of FAE in regulating the levels of ester-linked FA. Our model might orient further studies investigating the role of plant FAEs and assist strategies for genetic engineering of grasses to obtain plants with reduced biomass recalcitrance.

Study on a Fermented Whole Wheat: Phenolic Content, Activity on PTP1B Enzyme and In Vitro Prebiotic Properties.

Fermented cereals, staple foods in Asia and Africa, are recently receiving a growing interest in Western countries. The object of this work is the characterization of a fermented wheat used as a food ingredient and dietary supplement. To this aim, the phenolic composition, the activity on protein tyrosine phosphatase 1B (PTP1B), an enzyme overexpressed in type-II diabetes, the in vitro prebiotic properties on Lactobacillus reuteri and the microbial composition were investigated. Basic and acidic hydrolysis were tested for an exhaustive recovery of bound phenols: the acidic hydrolysis gave best yields. Methyl ferulate and neocarlinoside were identified for the first time in wheat. The inhibitory power of the extracts of several batches were investigated on PTP1B enzyme. The product was not able to inhibit the enzyme, otherwise, for the first time, a complete inhibition was observed for schaftoside, a major C-flavonoid of wheat. The microbial composition was assessed identifying Lactobacillus, Enterococcus, and Pediococcus as the main bacterial species. The fermented wheat was a suitable substrate for the grown of L. reuteri, recognized for its health properties in the human gut. The proposed method for phenols is easier compared to those based on strong basic hydrolysis; our results assessed the bound phenols as the major fraction, differently from that suggested by the literature for fermented cereals.

Chemical constituents from plant of Fritillaria palldiflora / 中草药

Objective: To study the chemical constituents from Fritillaria pallidiflora. Methods: The constituents were isolated from F. pallidiflora and purified by column chromatography, and the structures were identified by spectra analysis and chemical methods. Results: Sixteen compounds were isolated from F. pallidiflora, including phenolic acids, esters, alkaloids, and the structures were identified as 1,4-diphenylbutane (1), cis-cinnamic acid (2), 4-hydroxy-3-methoxybenzaldehyde (3), acetovanillone (4), 9-octadecenoicacidmethylester (5), methyl ferulate (6), 1-O-feruloylglycerol (7), trans-isoferulic acid (8), syringaresinol (9), pinoresinol (10), 2,3-O-diferuloylglycerol (11), 1,3-O-diferuloyl-glycerol (12), cyclo (L-Pro-L-Ala) (13), cyclo (L-Leu-L-Val) (14), bis (diethylene glycol)phthalate (15), and cyclo-(Phe-Val) (16). Conclusion: All compounds are isolated from F. pallidiflora for the first time, and componds 1, 3-8, 10-13, 15, and 16 are isolated from the genus of Fritillaria for the first time.

Synthesis and cytotoxic activity of 4-O-ß-D-galactopyranosyl derivatives of phenolic acids esters.

The glycosylation of naturally occurring phenolic acids has a significant impact on their solubility, stability and physiochemical properties. D-Galactose residue was found to form a part of glycoconjugates in several tissues and involved in a variety of physiological process. To the best of our knowledge, we have noticed a little information about the glycosylation of the phenolic acids with galactose residue. In this work, we describe the glycosylation of methyl vanillate and methyl ferulate with peracetylated-ß-D-galactopyranose in the presence of BF3·OEt2. The coupling reaction yielded efficiently and selectively only the acetylated ß-D-galactopyranosides 3 and 6. Removal of the acetyl groups using sodium methoxide afforded the corresponding ß-D-galactopyranosides 4 and 7 in good yields. Anticancer activity in vitro was evaluated against two human cancer cell lines (MCF-7 breast cancer cell lines and PC-3 prostate cancer cell lines). ß-D-galactopyranosides 4 and 7 demonstrated improved cytotoxic activity compared to the parental esters.

Caffeoyl and coumaroyl derivatives from Acacia cochliacantha exhibit ovicidal activity against Haemonchus contortus.

ETHNOPHARMACOLOGY RELEVANCE: Acacia cochliacantha is a small tree whose foliage is traditionally used in Mexico for treatment of kidney pain, gastrointestinal illnesses and to kill intestinal parasites. In recent decades, the study of vegetal extracts has offered other possible alternatives for the control of Haemonchus contortus. Considering that this nematode affects dramatically the health and productivity of small ruminants, the aim of this study was to identify the anthelmintic compounds from A. cochliacantha hydro-alcoholic extract (HA-E) through an ovicidal test. MATERIAL AND METHODS: In vitro egg hatch assay was conducted to determinate the anthelmintic effects of a HA-E (60g). Liquid-liquid ethyl acetate/water extraction gave two fractions (EtOAc-F, 1.92g; Aq-F; 58.1g). The less polar compounds from ethyl acetate fraction were extracted by addition of dichloromethane offering a precipitate phase (Mt-F, 1.25g) and a soluble mixture (DCMt-F 1.15g). All fractions were evaluated for ovicidal activity obtaining the egg hatching inhibition (EHI, 0.07-25mg/mL). Ivermectin (0.5mg/mL) was used as a reference drug (positive control), and distilled water, 2.5% DMSO and 2% methanol were used as negative controls. The isolated compounds from the most active fractions were subjected to spectroscopic (1H NMR) Spectrometric (MS) and UV HPLC analysis in order to identify the bioactive compounds. RESULTS: The less polar treatments (AcOEt-F, DCMt-F, DCMt-P) showed the highest ovicidal activities (98-100% EHI; at 0.62-1.56mg/mL) and the major compounds found in these fractions were identified as caffeoyl and coumaroyl derivatives, including caffeic acid (1), p-coumaric acid (2), ferulic acid (3), methyl caffeate (4), methyl-p-coumarate (5), methyl ferulate (6) and quercetin. In case of the less active fractions (Aq-F, Mt-F) were constituted principally by glycosylated flavonoids. CONCLUSION: These results show that caffeoyl and coumaroyl derivatives from Acacia cochliacantha leaves had promising anthelmintic activity against Haemonchus contortus. This leguminous may offer an alternative source for the control of gastrointestinal nematodes of small ruminants.