ABSTRACT
Huangqi Guizhi Wuwu decoction (HGWWD) is a widely used traditional Chinese medicine (TCM) preparation for the treatment of ischemic stroke and diabetes peripheral neuropathy. However, the material basis for the efficacy of HGWWD remains unclear. In this study, a rapid, sensitive and selective ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) method was developed to separate and identify the absorbed components and metabolites of HGWWD in rat plasma after oral administration for the first time. By comparing the retention time, high-resolution mass spectrometry primary and secondary mass spectrometry data of blank plasma and drug-containing plasma, a total of 42 constituents, including 24 prototype compounds and 18 metabolites, were identified or tentatively characterized. The results indicated that monoterpenes, flavonoids, organic acids, amino acids, gingerols and alkaloids were main prototype compounds in rat plasma, and flavonoid-related metabolites, organic acid-related metabolites and gingerol-related metabolites were major metabolites. It is concluded the developed UHPLC-Q-TOF-MS method with high sensitivity and resolution is suitable for identifying and characterizing the absorbed components and metabolites of HGWWD, and the results will provide important data for further study on the relationship between the chemical constituents and pharmacological activities of HGWWD.
Subject(s)
Astragalus propinquus , Drugs, Chinese Herbal , Rats , Animals , Rats, Sprague-Dawley , Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal/chemistry , Mass Spectrometry/methods , Chromatography, Liquid , Flavonoids/analysisABSTRACT
Huangqi Guizhi Wuwu decoction (HGWWD) is a classic traditional Chinese medicine prescription for the treatment of ischemic stroke, etc. However, the material basis of its efficacy remains unclear, seriously affecting drug development and clinical applications. In the present study, an ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry method was developed to separate and identify the chemical components of HGWWD. A total of 81 compounds were identified and tentatively characterized. Eight compounds were accurately identified by comparing the retention time and mass spectrometry data with those of reference substances, the remaining compounds were characterized by comparing the mass spectrometry data and reference information. Based on the results of compound attribution, 35 compounds were from Astragali Radix, six compounds were from Cinnamomi Ramulus, 23 compounds were from Paeoniae Radix Alba, eight compounds were from Zingiberis Rhizoma Recens and nine compounds were from Jujubae Fructus. The results showed that monoterpenoids, flavonoids, organic acids, triterpenes, amino acids, gingerols, alkaloids, and glycosides were the main chemical components of HGWWD. This analytical method is suitable for characterizing the chemical constituents of HGWWD, and the results provide important information for elucidating its pharmacodynamic material basis and mechanism of action.
Subject(s)
Drugs, Chinese Herbal , Plant Extracts , Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal/analysis , Mass SpectrometryABSTRACT
Huangqi Guizhi Wuwu decoction (HGWD) is an effective traditional Chinese medicine prescription, which is used for treating blood arthralgia in the clinic. However, its material basis has not been studied yet. Herein, a new and highly sensitive ultra-high-performance liquid chromatography-quadrupole-time of flight-MS (UHPLC-Q-TOF-MS) technique is proposed and used for the high-resolution and accurate identification of the material basis of HGWD. Seventy-eight compounds have been identified in HGWD. The advantages of information-dependent acquisition (IDA), sequential window acquisition of all theoretical fragment-ion spectra (SWATH), and MSALL in the quantitative and qualitative analyses of compounds were compared. For the identification of compounds, the best mode with the highest accuracy is the IDA. For the quantification of compounds, MSALL shows the best repeatability and linearity. This research provides a theoretical basis for the study of quality control of traditional Chinese medicine preparations.
Subject(s)
Neuroprotective Agents , Chromatography, High Pressure Liquid , Medicine, Chinese Traditional , Quality Control , Tandem Mass SpectrometryABSTRACT
Seven flavonoids (1-7), two triterpenoids (8 and 9) and four steroids (10, 11, 12 and 13) were isolated from the whole plant of Tiarella polyphylla. Based on the physicochemical and spectroscopic analyses, their structures were identified as myricetin (1), astragalin (2), afzelin (3), quercitrin (4), myricitin (5), nicotiflorin (6), isoquercitrin (7), tiarellic acid (8), 3beta-hydroxy-20(29)lupen-27-oic acid (9), beta-sitosterol-3-O-beta-D-glucoside (10), stigmasterol-3-O-beta-D-glucoside (11), beta-sitosterol (12) and ergosterol endoperoxide (13). All 13 compounds, with the exception of tiarellic acid were isolated for the first time from T. polyphylla. In the anti-complementary assay, the steroids (12 and 13) exhibited potent activities; whereas, the flavonoids (1 to 7) showed weak or no activities, but even the triterpenoids (8 and 9) and steroidal saponins (10 and 11) evoked hemolysis.
Subject(s)
Saxifragaceae/chemistry , Chemical Phenomena , Chemistry, Physical , Complement Inactivating Agents/chemistry , Complement Inactivating Agents/isolation & purification , Complement Inactivating Agents/pharmacology , Complement Pathway, Classical/drug effects , Flavonoids/chemistry , Flavonoids/isolation & purification , Flavonoids/pharmacology , Hemolysis/drug effects , Humans , Magnetic Resonance Spectroscopy , Plant Extracts/chemistry , Saponins/chemistry , Saponins/isolation & purification , Saponins/pharmacology , Spectrometry, Mass, Electrospray Ionization , Structure-Activity Relationship , Triterpenes/chemistry , Triterpenes/isolation & purification , Triterpenes/pharmacologyABSTRACT
A new biflavonol glycoside named as solanoflavone (1) was isolated from aerial part of Solanum melongena. The chemical structure was elucidated as isorhamnetin-3-O-beta-D-glucopyranoside-(4'-->O-->4''')-galangin-3''-O-beta-D-glucopyranoside on the basis of physicochemical and spectroscopic methods, including 2D NMR spectral techniques.
Subject(s)
Flavonols/isolation & purification , Glycosides/isolation & purification , Solanum melongena/chemistry , Anti-Inflammatory Agents/isolation & purification , Flavonols/chemistry , Glycosides/chemistry , Magnetic Resonance Spectroscopy/methods , Molecular Structure , Spectrum AnalysisABSTRACT
Three lignans isolated from the roots of A. koreanum (Araliaceae), namely eleutheroside E (1), tortoside A (2), and hemiariensin (4), were evaluated for their ability to inhibit NFAT transcription factor. Of these compounds, compound 4, possessing a diarylbutane skeleton, exhibited potent inhibitory activity against NFAT transcription factor (IC50: 36.3 +/- 2.5 microM). However, the activities of 1 (IC50: > 500 microM) and 2 (IC50: 136.1 +/- 9.4 microM), which possess bisaryldioxabicyclooctane skeletons, were lower. As the lignan derivatives of the same skeletons, hinokinin (5) and (-)-yatein (6) with diarylbutane skeletons and (+)-syringaresinol (3) with a bisaryldioxabicyclooctane skeleton were also studied for their inhibitory effects on NFAT transcription factor.
Subject(s)
DNA-Binding Proteins/genetics , Eleutherococcus/chemistry , Nuclear Proteins/genetics , Transcription Factors/genetics , Buffers , Chromatography, High Pressure Liquid , Chromatography, Thin Layer , Humans , Indicators and Reagents , Jurkat Cells , Lignans , Magnetic Resonance Spectroscopy , NFATC Transcription Factors , Spectrophotometry, Ultraviolet , Transcription, Genetic/drug effectsABSTRACT
Two triterpenoids (1,4) and two triterpenoid glycosides (2,3) were isolated from the root of Acanthopanax koreanum (Araliaceae). Their structures were identified as impressic acid (1), acankoreoside A (2), 3-epi-betulinic acid 28-O-[alpha-L-rhamnopyranosyl(1 --> 4)-beta-D-glucopyranosyl(1 --> 6)]-beta-D-glucopyranosyl] ester (3), and ursolic acid (4) by physicochemical and spectroscopic methods. Of these compounds, impressic acid (1) exhibited a potent inhibitory activity against NFAT transcription factor (IC50: 12.65 microM).
Subject(s)
DNA-Binding Proteins/antagonists & inhibitors , Eleutherococcus , Nuclear Proteins/antagonists & inhibitors , Transcription Factors/antagonists & inhibitors , Triterpenes/isolation & purification , Triterpenes/pharmacology , DNA-Binding Proteins/metabolism , NFATC Transcription Factors , Nuclear Proteins/metabolism , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Plant Roots , Transcription Factors/metabolism , Triterpenes/chemistryABSTRACT
Five known kaurane type diterpenoids, 16alphaH,17-isovaleryloxy-ent-kauran-19-oic acid (1), 16alpha-hydroxy-17-isovaleryloxy-ent-kauran-19-oic acid (2), paniculoside-IV (3), 16alpha-hydroxy-ent-kauran-19-oic acid (4), and ent-kaur-16-en-19-oic acid (5) were isolated from the root of Acanthopanax koreanum by repeated column chromatography and reversed phase preparative HPLC. The structures of these compounds were established from physicochemical and spectral data. Among the isolated compounds 16alphaH,17-isovaleryloxy-ent-kauran-19-oic acid (1) showed potent inhibitory activity (IC50 value, 16.2 uM) on TNF-alpha secretion from HMC-1, a trypsin-stimulated human leukemic mast cell line.
Subject(s)
Diterpenes, Kaurane/chemistry , Diterpenes, Kaurane/pharmacology , Eleutherococcus/chemistry , Trypsin/pharmacology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/metabolism , Diterpenes, Kaurane/isolation & purification , Flavonoids/pharmacology , Humans , Korea , Leukemia, Mast-Cell/chemically induced , Leukemia, Mast-Cell/metabolism , Luteolin , Methanol , Plant Extracts/chemistry , Plant Roots/chemistry , Plants, Medicinal/chemistry , Tumor Cells, CulturedABSTRACT
In a search for inhibitory components from natural products against NFAT transcription factor, this study investigated the ethyl acetate extract of the fruits of Liquidambar formosana. Four oleanane triterpenoids were isolated and identified to be liquidambaric acid, oleanolic acid, 3alpha-acetoxy-25-hydroxy-olean-12-en-28-oic acid and lantanolic acid. Of these compounds, 3alpha-acetoxy-25-hydroxy-olean-12-en-28-oic acid (IC50: 4.63 microM) and lantanolic acid (IC50: 12.62 microM) exhibited strong inhibitory activity against the NFAT transcription factor.
Subject(s)
DNA-Binding Proteins/antagonists & inhibitors , Liquidambar/chemistry , Nuclear Proteins/antagonists & inhibitors , Oleanolic Acid/analogs & derivatives , Oleanolic Acid/pharmacology , Transcription Factors/antagonists & inhibitors , Triterpenes/pharmacology , Fruit/chemistry , Humans , Jurkat Cells , NFATC Transcription Factors , Oleanolic Acid/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Structure-Activity Relationship , Triterpenes/chemistryABSTRACT
Six diterpenoids and two diterpene glycosides were isolated from the dichloromethane and the water fractions of Acanthopanax koreanum roots, respectively. Of these compounds, 16alphaH, 17-isovaleryloxy-ent-kauran-19-oic acid containing an isovaleryloxy group at C-17 was found to exhibit the strongest inhibitory activity (IC(50), 6.7 microm) against NFAT transcription factor. However, sumogaside, 16alpha-hydroxy-ent-kauran-19-oic acid and paniculosides IV containing a hydroxy group at C-16 or a glycoside at C-4 carboxyl acid showed no activity.
Subject(s)
Eleutherococcus , Phytotherapy , Plant Extracts/pharmacology , Reverse Transcriptase Inhibitors/pharmacology , Transcription Factors/antagonists & inhibitors , Diterpenes/administration & dosage , Diterpenes/pharmacology , Diterpenes/therapeutic use , Humans , Inhibitory Concentration 50 , Plant Extracts/administration & dosage , Plant Extracts/therapeutic use , Plant Roots , Reverse Transcriptase Inhibitors/administration & dosage , Reverse Transcriptase Inhibitors/therapeutic useABSTRACT
A new pimarane-type diterpene compound, acanthokoreoic acid A together with three known compounds, acanthoic acid, acanthol, and sumogaside were isolated from a CH(2)Cl(2) fraction of Acanthopanax koreanum by repeated column chromatography and reversed phase preparative HPLC. Acanthoic acid was isolated in high yields and showed potent inhibitory activity on the IL-8 secretion of the TNF-alpha-stimulated human colon adenocarcinoma cell line HT-29 and on the TNF-alpha secretion of the trypsin-stimulated human leukemic mast cell line HMC-1.