ligustilide and butylidenephthalide

Abnormal lipid metabolism, such as increased fatty acid uptake and esterification, is associated with nonalcoholic fatty liver disease (NAFLD). The aqueous extract of the aerial part of

Topics: 4-Butyrolactone; Angelica; Animals; Diet, High-Fat; Drug Evaluation, Preclinical; Gene Expression Regulation; Hep G2 Cells; Humans; Lipid Metabolism; Lipogenesis; Male; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Oleic Acid; Phthalic Anhydrides; Plant Components, Aerial; Plant Extracts; Sterol Regulatory Element Binding Protein 1

The acaricidal activity of a methanolic extract and fractions from the rhizome of Cnidium officinale against Dermanyssus gallinae adults was investigated. The C. officinale methanolic extract exhibited 100% acaricidal activity after 48 h of treatment at a dose of 4000 ppm. The acaricidal constituents of the plant were sequentially partitioned with several solvents and then purified using silica gel column chromatography and high-performance liquid chromatography. Gas chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy revealed (Z)-ligustilide as a constituent of C. officinale. Acaricidal activity was examined in three experimental tests (spray, fumigation and contact), with the spraying method being the most effective. The methanolic extract of C. officinale showed both contact and fumigant activities, though only fumigant activity was observed with (Z)-ligustilide. The fumigant effects of the methanolic extract and (Z)-ligustilide caused 86.5 and 62.6% mortality, respectively, of D. gallinae adults at 48 h. Among (Z)-ligustilide, acaricides (bifenthrin, cypermethrin and spinosad) and butylidenephthalide, bifenthrin displayed the highest acaricidal activity, and the activity of butylidenephthalide was 2.3-fold higher than that of (Z)-ligustilide. These results suggest that C. officinale-derived material can be used for the development of a control agent for D. gallinae.

Topics: 4-Butyrolactone; Acaricides; Animals; Cnidium; Female; Male; Mites; Phthalic Anhydrides; Plant Extracts; Rhizome

To identify Chuanxiong Rhizoma,Angelicae Sinensis Radix and Ligustici Rhizoma et Radix by establishing the HPLC specific chromatograms of their volatile oil and to compare their specific peaks.. The HPLC method used methanol-water as mobile phase. Their specific peaks were analysed by HPLC-MS.. Under the selected spectrum condition, their HPLC specific chromatograms were established. Senkyunolide A, butylphalide, coniferylferulate, E-ligustilide, Z-ligustilide, neocnidilide and E-butylidenephthalide were identified as specific peaks in chromatograms based on their MS data.. This method is simple, accurate and available to identify Chuanxiong Rhizoma, Angelicae Sinensis Radix and Ligustici Rhizoma et Radix. It provides reference for quality control of their medicinal materials and Chinese Patent Medicine.

Topics: 4-Butyrolactone; Angelica sinensis; Benzofurans; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Ligusticum; Oils, Volatile; Phthalic Anhydrides; Plant Oils; Plant Roots; Rhizome

To investigate the establishment and application methods of entropy-weight TOPSIS model in synthetical quality evaluation of traditional Chinese medicine with Angelica sinensis growing in Gansu Province as an example.. The contents of ferulic acid, 3-butylphthalide, Z-butylidenephthalide, Z-ligustilide, linolic acid, volatile oil, and ethanol soluble extractive were used as an evaluation index set. The weights of each evaluation index were determined by information entropy method. The entropyweight TOPSIS model was established to synthetically evaluate the quality of Angelica sinensis growing in Gansu Province by Euclid closeness degree.. The results based on established model were in line with the daodi meaning and the knowledge of clinical experience.. The established model was simple in calculation, objective, reliable, and can be applied to synthetical quality evaluation of traditional Chinese medicine.

Topics: 4-Butyrolactone; Angelica sinensis; Coumaric Acids; Drugs, Chinese Herbal; Entropy; Medicine, Chinese Traditional; Oils, Volatile; Phthalic Anhydrides

The root of Angelica sinensis (Oliv.) Diels (abbreviated as AS) (Danggui) has a long history in Asian herbal medicine. Recently, it was demonstrated that AS possesses anti-cancer and anti-oxidant activities. Because the transcription factor Nrf2 mediates the expression of many cellular anti-oxidative stress genes, including genes that are involved in phase II drug metabolism and anti-oxidative stress, this study sought to investigate whether pure compounds from AS or an AS extract could activate antioxidant response element (ARE)-mediated gene expression and induce anti-inflammatory activities. Z-Ligustilide (Ligu), 3-butylidenephthalide (Buty) and CO2 supercritical fluid-extracted lipophilic AS extract (SFE) were tested in HepG2-C8 cells stabilized with ARE luciferase reporter gene. Ligu and Buty caused significant toxicity only at 100 μm. All three samples induced ARE-luciferase activity; however, SFE at 8.5 µg/ml induced ARE-luciferase activity 2-3 fold more potently than did either of the pure compounds. SFE also significantly increased the endogenous mRNA of Nrf2 and the Nrf2 target anti-oxidative gene NAD(P)H dehydrogenase, quinone 1 (NQO1). The protein expression of NQO1 was also significantly induced by SFE. In RAW 264.7 cells, SFE suppressed lipopolysaccharide (LPS)-induced IL-1β and TNF-α expression about 2 fold stronger than sulforaphane, whereas both pure compounds and SFE suppressed inflammatory nitric oxide (NO) production. In summary, this study demonstrates that AS has anti-inflammatory effects and activates the Nrf2 pathway, which protects against oxidative stress.

Topics: 4-Butyrolactone; Angelica sinensis; Animals; Anti-Inflammatory Agents; Cell Line, Tumor; Gene Expression; Hep G2 Cells; Humans; Interleukin-1beta; Mice; NAD(P)H Dehydrogenase (Quinone); NF-E2-Related Factor 2; Nitric Oxide; Phthalic Anhydrides; Phytochemicals; Plant Extracts; RNA, Messenger; Superoxide Dismutase; Superoxide Dismutase-1; Tumor Necrosis Factor-alpha

To study the constituents of essential oil from Shunaoxin dropping pills by GC-MS.. The essential oil from Shunaoxin dropping pills were extracted by absolute alcohol and analyzed by GC-MS.. 15 components from the essential oil of Shunaoxin dropping pills were identified.. The main components in the essential oil of Shunaoxin dropping pills are lactones such as Z-ligustilide, senkyunolide A,3-butylphthalide and 3-butylidenephthalide, other components are organic acids such as ethyl linoleate, 9,12-octadecadienoic acid and ethyl palmitate.

Topics: 4-Butyrolactone; Angelica; Apiaceae; Benzofurans; Drugs, Chinese Herbal; Gas Chromatography-Mass Spectrometry; Lactones; Oils, Volatile; Phthalic Anhydrides

To study the variation of the biomass of the root and active components of Angelica sinensis during different growth periods.. 27 batches of Angelica sinensis were harvested from different growth periods, and the biomass of underground parts were determined; The Gas Chromatography-Mass Spectrometry (GC-MS) was used for determining the contents of Z-ligustilide and n-Butylidenephthalide in essential oil of Radix Angelicae Sinensis.. The average contents of n-Butylidenephthalide and Z-ligustilide were more than 1% and 40% in the total essential oil of Radix Angelicae sinensis respectively. Their contents showed larger difference during different growth period.. The contents of Z-ligustilide and n-Butylidenephthalide of Radix Angelicae Sinensis is closely related to their growth period.

Topics: 4-Butyrolactone; Angelica sinensis; Biomass; Gas Chromatography-Mass Spectrometry; Oils, Volatile; Phthalic Anhydrides; Plant Roots; Plants, Medicinal; Seasons

In natural product research, it is a common experience that fractionation of biologically-active crude extracts can lead to the loss of their original activity. This is attributed to synergistic effects, where two or more components are required to be present together for full activity of the sample. Our previous study showed that a volatile oil of Angelica sinensis radix (VOAS) inhibited endothelial cell proliferation in culture. Here we have used a bioactivity-guided fractionation method to preserve any synergistic effects of VOAS combining countercurrent chromatography (CCC), the MTS cell viability assay and gas chromatography (GC). Using a two-phase CCC solvent system (heptane-ethyl acetate-methanol-water at a volume ratio of 27:23:27:23%), forty-five fractions were isolated, nine of which exhibited anti-endothelial properties. GC analysis showed two bioactive alkylphthalides, Z-ligustilide and n-butylidenephthalide (BP) were the major compounds detected in the bioactive fractions, and were absent in non-bioactive fractions. Our results indicate that Z-ligustilide and BP are the main constituents responsible for the anti-endothelial properties of VOAS. This rapid and reliable approach in preserving sample activity while isolating and identifying its active compounds suggests that this protocol can be a powerful tool for drug discovery from natural products.

Topics: 4-Butyrolactone; Angelica sinensis; Cell Growth Processes; Cell Survival; Countercurrent Distribution; Drug Synergism; Human Umbilical Vein Endothelial Cells; Humans; Oils, Volatile; Phthalic Anhydrides; Plant Extracts; Plant Roots; Robotics

An extract from the roots of Ligusticum porteri, orally administered to groups of normal and diabetic mice, showed significant hypoglycemic and antihyperglycemic effects. Experimental type-II DM was achieved by treating mice with streptozotocin 15 min after an injection of β-nicotinamide adenine dinucleotide. (Z)-6,6',7,3'α-diligustilide (1), (Z)-ligustilide (2), 3-(Z)-butylidenephthalide (3), myristicin (4), and ferulic acid (5) were isolated from the active extract. When tested In Vivo, compounds 1-3 showed antihyperglycemic activity, with 3 being the most active. Compound 3 (56.2 mg/kg) decreased blood glucose levels in NAD-STZ-diabetic mice after an oral sucrose load, suggesting that its antihyperglycemic effect is due to inhibition of α-glucosidase at the intestinal level. Furthermore, 3 inhibited the activity of yeast-α-glucosidase (IC(50) 2.35 mM) in a noncompetitive fashion with a K(i) of 4.86 mM. Docking analysis predicted that 3 binds to the enzyme in a pocket close to the catalytic site, but different from that for acarbose, with a K(i) of 11.48 mM. Compounds 1 and 2 did not affect α-glucosidase In Vivo, but altered glucose absorption by a mechanism yet to be determined. The stimulatory effect of 5 on insulin secretion, present in high amounts in the extract, has been demonstrated in previous investigations. The present study provides scientific support of the use of L. porteri in Mexican folk medicine for the treatment of diabetes.

Topics: Acarbose; Administration, Oral; Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Glycoside Hydrolase Inhibitors; Hypoglycemic Agents; Insulin; Insulin Secretion; Ligusticum; Medicine, Traditional; Mexico; Mice; Phthalic Anhydrides; Stereoisomerism; Streptozocin

Monomeric phthalides such as Z-ligustilide (1) and Z-butylidenephthalide (2) are major constituents of medicinal plants of the Apiaceae family. While 1 has been associated with a variety of observed biological effects, it is also known for its instability and rapid chemical degradation. For the purpose of isolating pure 1 and 2, a gentle and rapid two-step countercurrent isolation procedure was developed. From a supercritical CO2 fluid extract of Angelica sinensis roots, the phthalides were isolated with high GC-MS purities of 99.4% for 1 and 98.9% for 2 and consistently lower qHNMR purities of 98.1% and 96.4%, respectively. Taking advantage of molarity-based qHNMR methodology, a time-resolved study of the dynamic changes and residual complexity of pure 1 was conducted. GC-MS and (qH)NMR analysis of artificially degraded 1 provided evidence for the phthalide degradation pathways and optimized storing conditions. Parallel qHNMR analysis led to the recognition of variations in time- and process-dependent sample purity and has impact on the overall assessment of time-dependent changes in complex natural products systems. The study underscores the importance of independent quantitative monitoring as a prerequisite for the biological evaluation of labile natural products such as monomeric phthalides.

Topics: 4-Butyrolactone; Angelica sinensis; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Phthalic Anhydrides; Plant Roots; Plants, Medicinal; Stereoisomerism

The antifungal activities of ligustilide and butylidene phthalide, which are major oil components comprising the essential oil of Ligusticum chuanxiong, in combination with antifungal drugs were evaluated. Checkerboard microtiter and microdilution tests were used to measure combined effects against Trichophyton species, T. erinacei, T. mentagrophytes, T. rubrum, T. schoenleinii, T. tonsurans and T. soudanense. Susceptibility of these Trichophyton species to L. chuanxiong essential oil differed distinctly. The fractional inhibitory concentrations (FICIs) against Trichophyton species ranged between 0.27 and 0.56 for ketoconazole combined with ligustilde or butylidene phthalide, indicating synergism or additive effects between the antibiotic and essential oil compounds. Testing by itraconazole instead of ketoconazole, similar combination effects were observed with FICIs from 0.31 to 0.63 against the tested strains of T. mentagrophytes, T. rubrum, T. schoenleinii, and T. soudanense. Thus, data reported here showed that Trichophyton susceptibility to ketoconazole and itraconazole could be notably improved by ligustilde and butylidene phthalide.

Topics: 4-Butyrolactone; Anti-Bacterial Agents; Antifungal Agents; Drug Synergism; Drugs, Chinese Herbal; Gas Chromatography-Mass Spectrometry; Itraconazole; Ketoconazole; Ligusticum; Microbial Sensitivity Tests; Oils, Volatile; Phthalic Anhydrides; Plant Oils; Plant Roots; Trichophyton

Pressurized liquid extraction, one of the most promising and recent sample preparation techniques, offers the advantages of reducing solvent consumption and allowing for automated sample handling. It is being exploited in diverse areas because of its distinct advantages. However, because the extraction is performed at elevated temperatures using PLE, thermal degradation could be a concern. Z-ligustilide, one of the biologically active components in Angelica sinensis, is an unstable compound, which decomposes rapidly at high temperature. In this study, we carried out a comparative study to evaluate PLE as a possible alternative to current extraction methods like Soxhlet and sonication for simultaneous extraction of Z-ligustilide, Z-butylidenephthalide and ferulic acid in A. sinensis. The operating parameters for PLE including extraction solvent, particle size, pressure, temperature, static extraction time, flush volume and numbers of extraction were optimized by using univariate approach coupled with central composite design (CCD) in order to obtain the highest extraction efficiency. Determination of Z-ligustilide, Z-butylidenephthalide and ferulic acid were carried out by means of high performance liquid chromatography with diode-array detector. The results showed that PLE was a simple, high efficient and automated method with lower solvent consumption compared to conventional extraction methods such as Soxhlet and sonication. PLE could be used for simultaneous extraction of Z-ligustilide, Z-butylidenephthalide and ferulic acid in A. sinensis.

Topics: 4-Butyrolactone; Algorithms; Angelica sinensis; Chromatography, High Pressure Liquid; Coumaric Acids; Particle Size; Phthalic Anhydrides; Pressure; Solvents; Temperature; Ultrasonics

To investigate the bio-affinities of ligustilide and butylidenephthalide to rat aortic smooth muscle cells and the inhibitory effects of them on bFGF-stimulated proliferation of rat vascular smooth muscle cell (VSMC).. VSMCs were cultured from rat aorta pectoralis and identified by an immunohistochemical method. The bio-affinities between solute (ligustilide or butylidenephthalide) and cell membrane were measured by rat aortic cell membrane chromatography (CMC). The inhibitory effects of ligustilide and butylidenephthalide on bFGF-stimulated VSMC proliferation were evaluated by MIT colorimetric method.. Both ligustilide and butylidenephthalide had selective affinities to rat aortic smooth muscle cell as the same as verapamil, one of the calcium ion antagonists. They could potently inhibit the bFGF-stimulated VSMC proliferation at the concentrations of 5.5 and 11.1 micromol x L(-1), separately (P < 0.05), but had no effects on the normal VSMC growth.. Both ligustilide and butylidenephthalide can inhibit the abnormal proliferation of VSMC induced by bFGF.

Topics: 4-Butyrolactone; Animals; Aorta, Thoracic; Cell Proliferation; Cells, Cultured; Female; Fibroblast Growth Factor 2; Ligusticum; Male; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Phthalic Anhydrides; Plants, Medicinal; Rats; Rats, Sprague-Dawley

To analyze the chemical components in Danggui (the roots of Angelica sinensis (Oliv.) Diel).. HPLC-MS/MS was used to identify the main components in Danggui. Furthermore, the MS fragmentation regularity of the phthalides was proposed. The mobile phase of HPLC consisted of 0.5% acetic acid in water and 0.5% acetic acid in acetonitrile, analytical column was Hypersil ODS2 (250 mm x 4.6 mm, 5 microm), flow rate 1.0 mL x min(-1), injected volume 2 microL. The ionization source was ESI in positive ion mode.. Ferulic acid, nine known phthalides and one unknown phthalide derivative were tentatively identified in chromatograms based on their MS data and the comparison of their UV spectra with those published in the literatures.. The structural information of phthalides was obtained via HPLC-MS/MS, which provides an accurate and fast method to identify the phthalides and provides more scientific information for quality control of Danggui.

Topics: 4-Butyrolactone; Angelica sinensis; Benzofurans; Chromatography, High Pressure Liquid; Coumaric Acids; Molecular Structure; Phthalic Anhydrides; Plant Roots; Plants, Medicinal; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization

A valid chromatographic fingerprint method using liquid chromatography-diode array detection-atmospheric pressure chemical ionization mass spectrometry in negative mode (LC-DAD-APCI-MS) is proposed for studying the absorption and metabolites of a traditional Chinese medicine (TCM) Angelica sinensis (danggui) in rabbit plasma, after the rabbit is administered with danggui oral solution (DOS). More than thirty-two common components were detected in both DOS and rabbit plasma, which shows that the components in the DOS were absorbed into the body of the rabbit. Of these, senkyunolide I, senkyunolide H, Z-6,7-epoxyligustilide, 3-butylidene-7-hydroxyphthalide, Z-ligustilide, Z-butylidenephthalide, Diels-Alder dimers of ligustilide, linolenic acid, linoleic acid and falcarindiol were tentatively identified from their MS, UV spectra and retention behavior by comparing the results with the published literature. At least ten components were found in rabbit plasma but not in DOS, indicating that these components must be metabolites of some of the components in the original extract. The results prove that the proposed method can be used to rapidly analyze multiple constituents in TCMs, and to screen for bioactive compounds by comparing and contrasting the chromatographic fingerprints of DOS and plasma samples.

Topics: 4-Butyrolactone; Absorption; Administration, Oral; Aldehydes; alpha-Linolenic Acid; Angelica sinensis; Animals; Benzofurans; Diynes; Drugs, Chinese Herbal; Fatty Alcohols; Linoleic Acid; Mass Spectrometry; Phthalic Anhydrides; Plant Extracts; Rabbits

Effective components, ligustilide and butylidenephthalide, from Ligusticum Chuanxiong (Ligusticum wallichii Franchat, Umbelliferae) were screened and identified by using a cell membrane chromatography (CMC) and a gas chromatography/mass spectrometry (GC/MS). The components showed the effects of inhibiting vasoconstriction in vitro on rat abdominal aorta segments. The screening procedure was performed in a rat artery CMC column (50 mm x 2.0 mm I.D.) with a sodium phosphate buffer (pH 7.4) as mobile phase at 37 degrees C. The identification was accomplished by a DB-5MS 30 m capillary column (0.25 mm I.D., 0.25 microm film thickness) with helium as carrier gas operating under program control temperature and electron impact ionization mass spectrometer in a scan mode. Results demonstrated that ligustilide and butylidenephthalide can act on rat artery cell membrane similar to verapamil in CMC system. They significantly inhibited the vasoconstrictions induced by norepinephrine bitartrate (NE) and calcium chloride (CaCl2). The relaxing effect of ligustilide on the NE- and CaCl2-induced constrictions is more potent than that of butylidenephthalide. Ligustilide and butylidenephthalide seem to be the two main effective components of Ligusticum Chuanxiong as a traditional Chinese medicine for treating blood vessel diseases.

Topics: 4-Butyrolactone; Animals; Aorta, Abdominal; Calcium Chloride; Gas Chromatography-Mass Spectrometry; In Vitro Techniques; Ligusticum; Muscle, Smooth, Vascular; Norepinephrine; Parasympatholytics; Phthalic Anhydrides; Plant Extracts; Plant Oils; Rats; Rats, Sprague-Dawley; Vasoconstriction; Vasodilation

We previously showed that the extract of Japanese angelica root (JAR-E) reversed the decrease in pentobarbital (PB) sleep induced by isolation stress and yohimbine and methoxamine, stimulants of central noradrenergic systems, in mice. Here, we tested the effects of several fractions from JAR-E and ligustilide and butylidenephthalide, phthalide components of JAR-E, on PB sleep in isolated mice to elucidate the mechanism of the action of JAR-E. Methanol-soluble (Met-S) and -insoluble (Met-IS) fractions were obtained from JAR-E. Methylenechloride-soluble (MC-S) and -insoluble fractions (MC-IS) were prepared from Met-S. MC-S (11.4-76 mg/kg, p.o.) reversed the isolation stress-induced decrease in PB sleep, but neither Met-IS (0.8-2.4 g/kg, p.o.) nor MC-IS (0.7-2 g/kg, p.o.) had the same effect. The i.p. administration of MC-S exhibited a similar activity to that observed after the p.o. administration of the same fraction. Ligustilide (5-20 mg/kg, i.p.) and butylidenephthalide (10-30 mg/kg, i.p.) reversed PB sleep decrease in isolated mice. Both components (20 mg/kg, i.p.) attenuated the suppressive effects of yohimbine (30 nmol, i.c.v.), methoxamine (200 nmol, i.c.v.) and a benzodiazepine inverse agonist FG7142 (10 mg/kg, i.p.) on PB sleep in group-housed mice. These results suggest the contribution of ligustilide and butylidenephthalide to the effect of JAR-E on PB sleep in isolated mice, and implicate central noradrenergic and/or GABA(A) systems in the effects of these components.

Topics: 4-Butyrolactone; Animals; Brain; Carbolines; Diazepam; Dose-Response Relationship, Drug; Injections, Intraventricular; Male; Methoxamine; Methylene Chloride; Mice; Parasympatholytics; Pentobarbital; Phthalic Anhydrides; Plant Extracts; Plant Roots; Plants, Medicinal; Sleep; Social Isolation; Yohimbine

Six compounds were isolated from Radix Angelicae Sinensis and identified as (E)-ligustilide, (Z)-ligustilide, (Z)-n-butylidene phthalide, palmitic acid, beta-sitosterol and ferulic acid.

Topics: 4-Butyrolactone; Angelica sinensis; Apiaceae; Drugs, Chinese Herbal; Palmitic Acid; Phthalic Anhydrides; Plants, Medicinal

Inhibitory effects of cnidium rhizome-derived phthalides on competence and progression phases of fetal bovine serum (10%)-induced proliferation were compared in primary cultures of mouse aorta smooth muscle cells (SMC). Their potencies for the competence inhibition were in the order of senkyunolide L ((Z)-6-hydroxy-7-chloro-6,7-dihydroligustilide) > senkyunolide H ((Z)-6,7-dihydroxy-6,7-dihydroligustilide) > senkyunolide J ((3S)-(E)-6,7-dihydroxy-3,6,7,8-tetrahydroligustilide) > senkyunolide I ((E)-6,7-dihydroxy-6,7-dihydroligustilide) > ligustilide = senkyunolide A ((3S)-3,8-dihydroligustilide) > butylidenephthalide. The order of their potencies for the progression inhibition was parallel with that for the competence inhibition. Senkyunolide L is considered to have been formed during the extraction of cnidium. These results demonstrate that the (Z)-6,7-dihydroxy isomer of the dihydroligustilide derivatives is essential for the anti-competent effect on proliferation of the SMC in primary culture. Senkyunolide H in cnidium rhizome may be a prototype for a new anti-atherosclerotic drug.

Topics: 4-Butyrolactone; Analysis of Variance; Animals; Aorta, Thoracic; Benzofurans; Cell Division; Cells, Cultured; Drugs, Chinese Herbal; Male; Mice; Muscle, Smooth, Vascular; Phthalic Anhydrides; Structure-Activity Relationship

Topics: 4-Butyrolactone; Bicyclic Monoterpenes; Drugs, Chinese Herbal; Monoterpenes; Oils, Volatile; Phthalic Anhydrides; Terpenes