Antiinflammatory effect of tetramethylpyrazine and ferulic acid.

Tetramethylpyrazine (TMP) is one of the alkaloids contained in Ligusticum wallichii Franch (L. wallichii). Ferulic acid (FA) is a phenolic compound contained in L. wallichii and Angelica sinensis (Oliv.) Diels (A. sinensis). The present study was carried out to examine the antiinflammatory effect and to elucidate the mode of the effect of TMP and FA. Both compounds significantly inhibited the edema induced by carrageenin, the increase of the dye leakage induced by acetic acid and the granuloma formation induced by cotton pellet. And also, TMP and FA inhibited the number of writhes induced by acetic acid. From these results, it is suggested that both compounds have the antiinflammatory effect and the analgesic effect, and both compounds exert an antiinflammatory effect at the early and the late stages of processes in the inflammatory pathology.     

Different effects of ferulic acid and tetramethylpyrazine on the production of superoxide anion and nitric oxide in murine macrophages

The effects of ferulic acid and tetramethylpyrazine, two active ingredients of the Chinese herbal medicineLigusticum wallichii Franchat, on the generation of superoxide anion and nitric oxide in macrophages were studied. Ferulic acid, but not tetramethylpyrazine, scavenges superoxide anion dose-dependently. Tetramethylpyrazine inhibits the expression of the iNOS gene, and consequently decreases the formation of nitric oxide. However, ferulic acid shows no effect on iNOS expression and NO production. The results suggest that the protective effects of extracts ofLigusticum wallichi Franchat against ischemic injury might be due to the scavenging of superoxide anion and the regulation of NO production.     

川芎嗪芳酸衍生物的合成及抗血小板聚集活性

以具有活血化淤作用的中药有效成分川芎嗪、阿魏酸为先导物, 按药物化学拼合原理, 设计合成了6个全新结构的川芎嗪芳酸衍生物, 其结构经IR, 1H NMR, 13C NMR及MS确证. 体外药效筛选结果显示, 部分川芎嗪芳酸衍生物对二磷酸腺苷(ADP)诱导的血小板聚集具有较好的抑制活性, 其中川芎嗪阿魏酸拼合物(1a)的抑制活性是奥扎格雷的5.7倍.     

Separation and determination of three phenylpropanoids in the traditional Chinese medicine and its preparations by capillary electrophoresis

Three phenylpropanoids (ferulic acid, chlorogenic acid, and caffeic acid) are simultaneously separated and determined within 13 min by a new capillary electrophoresis method using 15 mmol/L sodium borate (pH 8.71) as run buffer. The optimum conditions for the separation as well as the analytical characteristics, such as the calibration graph and limit of detection (LOD) for the determination of these three compounds, are studied. The linear range for the determination of ferulic, chlorogenic, and caffeic acid is 5.0 approximately 70.0, 8.0 approximately 112.0, and 9.0 approximately 64.0 microg/mL, with the LOD as 1.5, 2.25, and 6.0 microg/mL, respectively. The method, which is very simple, rapid, and of requisite sensitivity and reproduction, is satisfactorily used for the separation and determination not only of ferulic, chlorogenic, and caffeic acid in Cimicifuga foelida Li and its preparation (Yin-huang-han-pian), but also of ferulic acid and chlorogenic acid in Ligusticum chuanxiong hort. and Angelica sinensis (Oliv.) Diels.     

Content of Phenolic Compounds in Meadow Vegetation and Soil Depending on the Isolation Method

The aim of this paper was to determine the effect of the hydrolysis method on the amounts of phenolic compounds in the plant material in soil and, as a consequence, on the parameters to determine the degree of lignins transformation in soils. The study included the plant material (hay, sward, and roots) and soil—Albic Brunic Arenosol (horizon A, AE, and Bsv) samples. Phenolic compounds were isolated at two stages by applying acid hydrolysis followed by alkaline re-hydrolysis. The quantitative and qualitative analysis of phenolic compounds was performed with high-performance liquid chromatography with a DAD. The content of phenolic compounds in the extracts depended on the hydrolysis method and it was determined by the type of the research material. The amounts of phenolic compounds contained in the alkaline hydrolysates accounted for 55.7% (soil, horizon Bsv)—454% (roots) of their content in acid hydrolysates. In the extracts from acid hydrolysates, chlorogenic and p-hydroxybenzoic acids were dominant. In the alkaline extracts from the plant material, the highest content was recorded for p-coumaric and ferulic acids, and in the extracts from soil, ferulic and chlorogenic acids. A combination of acid and alkaline hydrolysis ensures the best extraction efficiency of insoluble-bound forms of polyphenols from plant and soil material.     

Exploratory analysis of chromatographic fingerprints to distinguish rhizoma Chuanxiong and rhizoma Ligustici

Identification and quality control of products of natural origin, used for preventive and therapeutical goals, is required by regulating authorities, as the World Health Organization. This study focuses on the identification and distinction of the rhizomes from two Chinese herbs, rhizoma Chuanxiong (from Ligusticum chuanxiong Hort.) and rhizoma Ligustici (from Ligusticum jeholense Nakai et Kitag), by chromatographic fingerprints. A second goal is using the fingerprints to assay ferulic acid, as its concentration provides an additional differentiation feature. Several extraction methods were tested, to obtain the highest number of peaks in the fingerprints. The best results were found using 76:19:5 (v/v/v) methanol/water/formic acid as solvent and extracting the pulverized material on a shaking bath for 15 min. Then fingerprint optimization was done. Most information about the herbs, i.e. the highest number of peaks, was observed on a Hypersil ODS column (250 mm × 4.6 mm ID, 5 μm), 1.0% acetic acid in the mobile phase and employing within 50 min linear gradient elution from 5:95 (v/v) to 95:5 (v/v) acetonitrile/water. The final fingerprints were able to distinguish rhizoma Chuanxiong and Ligustici, based on correlation coefficients combined with exploratory data analysis. The distinction was visualized using Principal Component Analysis, Projection Pursuit and Hierarchical Clustering Analysis techniques. Quantification of ferulic acid was possible in the fingerprints of both rhizomes. The time-different intermediate precisions of the fingerprints and of the ferulic acid quantification were shown to be acceptable.     

Antidiarrhoeal and bronchodilatory potential of Valeriana wallichii

This study describes the antidiarrhoeal and bronchodilatory activities of Valeriana wallichii D.C. (Valerianaceae). The crude extract of V. wallichii (Vw.Cr) caused inhibition of castor oil-induced diarrhoea in mice at 300-600?mg?kg?1. In guinea-pig trachea, Vw.Cr concentration dependently (0.03-3.0?mg?mL?1) relaxed the low K+ (25?mM)-induced contractions, with a mild effect on the contractions induced by high K+ (80?mM). In the presence of glibenclamide, the relaxation of low K+-induced contractions was prevented. Similarly, cromakalim caused glibenclamide-sensitive inhibition of low K+, without any effect on high K+. These results indicate that V. wallichii exhibits antidiarrhoeal and bronchodilatory activities, possibly through K+ channel activation, and thus reveal its medicinal usefulness in hyperactive gut and airway disorders such as diarrhoea and asthma.     

Release of Polyphenols Is the Major Factor Influencing the Bioconversion of Rice Straw to Lactic Acid

In this study, we found that p-coumaric acid (p-CA), ferulic acid (FA), and condensed tannins were released from rice straw during saccharification. The presence of polyphenols prolonged the lag phase and lowered the productivity of lactic acid. p-CA was identified as a key inhibitor. Tannins had a lower inhibitory effect than p-CA; FA had little inhibitory effect. Acid, alkaline, and ball milling pretreatments elicited different levels of polyphenol release from rice straw. Due to the different levels of polyphenol release in the pretreatment step, the enzymatic hydrolysates contained different concentrations of polyphenols. Compared with fermentation with a synthetic medium, fermentation with the hydrolysates of ball-milled rice straw provided much lower productivity and yield of lactic acid due to the presence of polyphenols. Removal of these compounds played an important role in lactic acid fermentation. When rice straw was alkaline pretreated, the hydrolysates contained few phenolic compounds, resulting in high productivity and yield of lactic acid (1.8 g/L/h and 26.7 g/100 g straw), which were comparable to those in a synthetic medium. This indicates that there is a correlation between removal of phenolic compounds and efficiency in lactic acid fermentation.     

Comparison of the Antihypertensive Activity of Phenolic Acids

Phenolic acids, found in cereals, legumes, vegetables, and fruits, have various biological functions. We aimed to compare the antihypertensive potential of different phenolic acids by evaluating their ACE inhibitory activity and cytoprotective capacity in EA.hy 926 endothelial cells. In addition, we explored the mechanism underlying the antihypertensive activity of sinapic acid. Of all the phenolic acids studied, sinapic acid, caffeic acid, coumaric acid, and ferulic acid significantly inhibited ACE activity. Moreover, gallic acid, sinapic acid, and ferulic acid significantly enhanced intracellular NO production. Based on the results of GSH depletion, ROS production, and MDA level analyses, sinapic acid was selected to study the mechanism underlying the antihypertensive effect. Sinapic acid decreases endothelial dysfunction by enhancing the expression of antioxidant-related proteins. Sinapic acid increased phosphorylation of eNOS and Akt in a dose-dependent manner. These findings indicate the potential of sinapic acid as a treatment for hypertension.     

Phthalides and other constituents from Ligusticum porteri; sedative and spasmolytic activities of some natural products and derivatives

The chemical constituents of the organic extracts from the rhizomes of Ligusticum porteri were isolated, characterised and identified as Z-ligustilide, Z-butylidenephthalide, diligustilide, tokinolide B, riligustilide, senkyunolides F and I, ferulic acid, among other known compounds. The preparation of 4,5-dehydrotokinolide B from tokinolide B is reported, and its structure confirmed by X-ray analysis. The sedative and spasmolytic activities of some of these natural products and derivatives were evaluated by applying them to in?vivo and in?vitro models. Several of these dimeric phthalides displayed sedative and spasmolytic properties that may correlate with some popular uses of L. porteri.     

Medicinal foodstuffs. XX. Vasorelaxant active constituents from the roots of Angelica furcijuga Kitagawa: structures of hyuganins A, B, C, and D

From the methanolic extract with vasorelaxant activity obtained from Angelica furcijuga Kitagawa, four new khellactone-type coumarins, hyuganins A, B, C, and D, were isolated together with twelve known coumarins, two known acetylenic compounds, and a known lignan. The structures of hyuganins A, B, C, and D were determined on the basis of chemical and physicochemical evidence. Nine principal coumarins (hyuganin A, anomalin, pteryxin, isopteryxin, isoepoxypteryxin, praerosides II and IV, apiosylskimmin, (R)-peucedanol 7-O-beta-D-glucopyranoside), two acetylenic compounds [(-)-falcarinol and falcarindioll, and related compounds were examined for inhibitory activities on high concentration of K+ (High K+)- and dl-norepinephrine (NE)-induced contractions. The results indicate that the 3'- and 4'-acyl groups of khellactone-type coumarins are essential for the inhibitory activity on the contractions by High K+. Hyuganin A and anomalin showed inhibitory effects on High K+-induced contraction, but not on NE-induced contraction. Other active coumarins (pteryxin, isopteryxin, isoepoxypteryxin) and an acetylenic compound (falcarindiol) non-selectively inhibited both contractions by High K+ and NE.     

Simultaneous determination of ferulic acid and gastrodin of Tianshu Capsule in rat plasma by ultra‐fast liquid chromatography with tandem mass spectrometry and its application to a comparative pharmacokinetic study in normal and migraine rats

Tianshu Capsule, consisting of Ligusticum chuanxiong Hort and Gastrodia elata Blume, is a widely used Traditional Chinese Medicine preparation for the treatment of migraine. Ferulic acid and gastrodin are main active constituents in Ligusticum chuanxiong Hort and Gastrodia elata Blume, and have been used as marker components for quality control of Tianshu Capsule. In this study, a selective, sensitive, and reliable ultra‐fast liquid chromatography with tandem mass spectrometry method was developed for simultaneous determination of ferulic acid and gastrodin in rat plasma using geniposide as internal standard. The plasma samples were extracted by protein precipitation with methanol after acidification and separated on a Shim‐Pack XR‐ODS C₁₈ column (75 × 3.0 mm, 2.2 μm) using gradient elution with a mobile phase consisting of water (containing 0.1% formic acid) and acetonitrile at a flow rate of 0.6 mL/min. Detection was performed on 3200 QTRAP mass spectrometry equipped with turbo ion spray source in negative ionization mode. Validation parameters were within acceptable ranges. The validated method was applied to compare the pharmacokinetic profiles of ferulic acid and gastrodin in normal and migraine rats. Our results showed that there were remarkable differences in the pharmacokinetic properties of the analytes between the normal and migraine groups.     

An HPLC/MS method for identifying major constituents in the hypocholesterolemic extracts of Chinese medicine formula 'Xue-Fu-Zhu-Yu decoction'

In this paper, HPLC-ESI-MS technique was used to analyze the hypocholesterolemic extracts of 'Xue-Fu-Zhu-Yu decoction', a traditional Chinese medicine consisting of six crude drugs (i.e. Paeonia lactiflora, Ligusticum chuanxiong, Citrus aurantium, Carthamus tinctorius, Prunus persica and Bupleurum falcatum). A total of 17 compounds were identified and their plant derivations were also distinguished. Nine compounds among them were unambiguously determined as oxypaeoniflorin, amygdalin, albiflorin, paeoniflorin, ferulic acid, naringin, hesperidin, senkyunolide I and neohesperidin by comparing the retention times (tR), UV spectra and m/z values with those of the reference compounds. The other eight compounds were tentatively identified as prunasin, 6-hydroxy-kaempferol 3,6-diglucoside, 6-hydroxykaempferol 3-rutinoside-6-glucoside, galloylpaeoniflorin, 6-hydroxy-kaempferol 3-glucoside, anhydrosafflor yellow B, narirutin and kaempferol 3-rutinoside by MS2 spectra and the comparison of their UV spectra and MS spectra with literature data.     

(Z)-3-丁烯基-5-羟基苯酞的合成

以对羟基苯甲酸为原料,首次合成(Z)-3-丁烯基-5-羟基苯酞．发现芳环上的甲胺甲酸基中氮原子的诱导作用是关键步骤,使甲胺甲酸基邻位选择性理化,从而在芳环上定向引入甲酸基．     

Comparison of phenolic content and antioxidant activity of Actaea racemosa L. and Actaea cordifolia DC

Actaea racemosa L. is used as a component of drugs or dietary supplements to alleviate the menopause symptoms. Its biological activity is associated with the presence of phenolic compounds. In our work, the analysis of isoflavones and phenolic acids – caffeic acid (CA), ferulic acid and isoferulic acid (iFA) – both free and bonded in two species of Actaea, was conducted using HPLC-PAD technique. Moreover, the antioxidant effect of extracts from different parts of the investigated plants was determined on the basis of DPPH assay. Significant variation of CA and iFA content was observed. The highest content of CA was found in A. racemosa, while Actaea cordifolia contained the highest amount of iFA. Isoflavones were not found in the investigated plants. The antioxidant activity assay showed the high free radical-scavenging ability of the extracts obtained from different parts of the plant.     

Inhibitory Effect of Salvia miltiorrhiza Extract and Its Active Components on Cervical Intraepithelial Neoplastic Cells

The effective treatment of cervical intraepithelial neoplasia (CIN) can prevent cervical cancer. Salvia miltiorrhiza is a medicinal and health-promoting plant. To identify a potential treatment for CIN, the effect of S. miltiorrhiza extract and its active components on immortalized cervical epithelial cells was studied in vitro. The H8 cell was used as a CIN model. We found that S. miltiorrhiza extract effectively inhibited H8 cells through the CCK8 method. An HPLC–MS analysis revealed that S. miltiorrhiza extract contained salvianolic acid H, salvianolic acid A, salvianolic acid B, monomethyl lithospermate, 9‴-methyl lithospermate B, and 9‴-methyl lithospermate B/isomer. Salvianolic acid A had the best inhibitory effect on H8 cells with an IC₅₀ value of 5.74 ± 0.63 μM. We also found that the combination of salvianolic acid A and oxysophoridine had a synergistic inhibitory effect on H8 cells at molar ratios of 4:1, 2:1, 1:1, 1:2, and 1:4, with salvianolic acid A/oxysophoridine = 1:2 having the best synergistic effect. Using Hoechst33342, flow cytometry, and Western blotting analysis, we found that the combination of salvianolic acid A and oxysophoridine can induce programmed apoptosis of H8 cells and block the cell cycle in the G2/M phase, which was correlated with decreased cyclinB1 and CDK1 protein levels. In conclusion, S. miltiorrhiza extract can inhibit the growth of H8 cells, and the combination of salvianolic acid A (its active component) and oxysophoridine has a synergistic inhibitory effect on H8 cells and may be a potential treatment for cervical intraepithelial neoplasia.     

Agents for the treatment of overactive detrusor. II. Synthesis and inhibitory activity on detrusor contraction of 1,1'-biphenyl-2,6-dicarboxylic acid diesters with an aminoalkyl group in the ester function.

A series of 1,1'-biphenyl-2,6-dicarboxylic acid diesters with an aminoalkyl group in the ester function were synthesized and examined for their inhibitory activity on detrusor contraction in vitro and in vivo. In the in vivo test, arrhythmia was observed as a side effect. Among those compounds synthesized, 2-methyl 6-[4-(1-methylpiperidinyl)] 3-hydroxy-5-methyl-2'-nitro-1,1'-biphenyl-2,6-dicarboxylate (18) showed strong inhibitory activity on detrusor contractions in vivo (ED50 = 0.54 mg/kg i.v., ED50 = 7.2mg/kg i.d.) and good separation from the side effect. Compound 18 was chosen for further pharmacological evaluation as an agent for the treatment of overactive detrusor.     

川芎中微量元素的初级形态分析

中药川芎是伞形科藁木属川芎的干燥根茎,用于活血化瘀,治疗缺血性心、脑血管疾病及慢性心衰、肾衰,疗效良好。目前对于川芎及其提取物的药理作用、临床应用及其化学成分的研究较多,     

Regulation of melanin synthesis by selenium-containing carbohydrates

This study reports depigmenting potency of selenium-containing carbohydrates, which would be based upon the finding of direct inhibition to mushroom tyrosinase. Two selenoglycosiede, SG-3 (bis(2,3,4-tri-O-acetyl-beta-D-arabinopyranosyl) selenide) and SG-8 (4'-methylbenzoyl 2,3,4,6-tetra-O-acetyl-D-selenomanopyranoside) among eleven selenium-containing compounds examined, were discovered to be effective depigmenting compounds on a mushroom tyrosinase inhibitory assay. SG-3 exhibited a competitive inhibition effect that was similar to kojic acid, well-known tyrosinase inhibitor. At 100 microM and 150 microM, SG-8 had an uncompetitive inhibitory effect that was higher than kojic acid. A study of a melan-a cell originated-tyrosinase inhibition assay showed that SG-8 had a lower inhibitory effect than kojic acid. SG-3 showed a similar inhibition effect to kojic acid on the melan-a cell-originated tyrosinase inhibitory assay. SG-8 showed dose-dependently cytotoxicity in a study of inhibition melanin synthesis by melan-a cells. Most melan-a cells did not survive after being treated with 20 microM of SG-8. At 10 microM, SG-3 inhibited melanin synthesis in the melan-a cells, and the effect was similar to phenylthiourea, which is a well-known inhibitor of melanin synthesis. Therefore, SG-3 is a new candidate for depigmenting reagents.     

Simultaneous determination of six index constituents and comparative analysis of four ethnomedicines from genus Gentiana using a UPLC‐UV‐MS method

Many species from genus Gentiana (Gentianaceae) have a long history of applications as folk medicines in the world. A simple rapid UPLC‐UV‐MS/MS method has been developed and validated for the simultaneous determination of six index constituents (gentiopicroside, swertiamarin, loganic acid, sweroside, mangiferin and ferulic acid) from the four ethnomedicines (G. rigescens Franch. ex Hemsl., G. rhodantha Franch. ex Hemsl., G. scabra Bunge and G. farreri Balf. f.). The UPLC analysis was performed on Shim‐Pack XR‐ODS III (150 × 2.0 mm, 2.2 µm). The mobile phase was consisted of acetonitrile–0.1% formic acid water using gradient elution. The wavelength 242 nm was chose for the four iridoids as well as mangiferin and 320 nm was set for ferulic acid. Mass spectrometry was applied for identification and quantification for analytes with low concentration. All the regression equations revealed a good linear relationship (R² > 0.9993). Accuracy and precision were all within the required limits. The chromatogram fingerprints analysis combined with principal component analysis showed the similarity values of the four species were <0.788 while the similarity values of G. scabra Bunge and G. rigescens Franch. ex Hemsl. were >0.993, which provided reasonable foundation for utilization and clinical application of the four ethnomedicines. This developed method appears to be a useful tool for quality control of the four ethnomedicines. Copyright © 2014 John Wiley & Sons, Ltd.