RESUMO
Alkaloids are important active ingredients occurring in many traditional Chinese medicines, and alkaloid glycosides are one of their existence forms. The introduction of saccharide units improves the water solubility of alkaloid glycosides thus presenting better biological activity.Because of the low content in plants, alkaloid glycosides have been not comprehensively studied. In this study, ultrahigh performance liquid chromatography-quadrupole time of flight-tandem mass spectrometry(UPLC-QTOF-MS/MS) was employed to identify and analyze the alkaloid glycosides in Coptis chinensis, Phellodendron chinense, Menispermum dauricum, Sinomenium acutum, Tinospora sagittata and Stephania tetrandra. The results showed that except Tinospora sagittata, the other five herbal medicines contained alkaloid glycosides. Furthermore, the alkaloid glycosides in each herbal medicine were identified based on UV absorption spectra, quasimolecular ion peaks in MS, fragment ions information in the MS/MS, and previous literature reports. A total of 42 alkaloid glycosides were identified. More alkaloid glycosides were identified in C. chinensis and Menispermum dauricum, and eleven in C. chinensis were potential new compounds. Furthermore, the alkaloid glycosides in the water extract of C. chinensis were coarsely se-parated by macroporous adsorption resin, purified by column chromatography with D151 cation exchange resin, ODS and MCI, combined with semi-preparative high performance liquid chromatography. Two new alkaloid glycosides were obtained, and their structures were identified by mass spectrometry and NMR data as(S)-7-hydroxy-1-(p-hydroxybenzyl)-2,2-N,N-dimethyl-1,2,3,4-tetrahydroisoquinoline-6-O-ß-D-glucopyranoside and(S)-N-methyltetrahydropalmatubine-9-O-ß-D-glucopyranoside, respectively. This study is of great significance for enriching the information about the chemical composition and the in-depth development of C. chinensis. Meanwhile, it can provide a reference for rapid identification and isolation of alkaloid glycosides from other Chinese herbal medicines.
Assuntos
Alcaloides , Antineoplásicos , Coptis , Medicamentos de Ervas Chinesas , Plantas Medicinais , Glicosídeos/química , Medicina Tradicional Chinesa , Espectrometria de Massas em Tandem/métodos , Coptis chinensis , Medicamentos de Ervas Chinesas/química , Alcaloides/análise , Extratos Vegetais/química , Plantas Medicinais/química , Água , Cromatografia Líquida de Alta Pressão/métodos , Coptis/químicaRESUMO
Thirteen cinnamic acid derivatives (1-13), including six formerly unreported hybrids incorporating different short-chain fatty acid esters (1-6), have been obtained and structurally elucidated from an ethnological herb Tinospora sagittata. The structures of them have been established by spectroscopic data analyses and NMR comparison with known analogs, while those of 1, 2, 4 and 6 have been further supported by total synthesis, and it is the first report of this type of metabolites from the title species. All the isolates have been assessed in an array of bioassays encompassing cytotoxic, antibacterial, anti-inflammatory, antioxidant, as well as α-glucosidase and HDAC1 inhibitory models. Compound 7 showed significant inhibitory activity against α-glucosidase, and half of the isolates also displayed moderate antiradical effect.
Assuntos
Antineoplásicos , Tinospora , Tinospora/química , alfa-Glucosidases , Cinamatos/farmacologia , Cinamatos/química , Estrutura MolecularRESUMO
BACKGROUND: Tinospora sagittata (Oliv.) Gagnep. var. craveniana (S.Y.Hu) Lo (TSG) is a traditional Chinese herb that has been used for the treatment of upper respiratory tract infection and has anti-bacterial and anti-ulcer activity. Our study investigated the bactericidal effects of TSG and its major component, palmatine, against a Helicobacter pylori (H. pylori) strain isolated from pig and the standard strain H. pylori SS1 in vitro and in vivo. METHODS: H. pylori was isolated from pig and named H. pylori SCYA201401. For in vitro experiments, the inhibitory activity of TSG and palmatine against H. pylori SCYA201401 and H. pylori SS1 were tested by use of the agar cup diffusion technique. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were determined from the absence of H. pylori colonies on agar plates. Time-kill curves were used to evaluate bactericidal activity; the average number of colonies was calculated at 0 to 48 h after liquid incubation, with concentrations of drugs at 0.5, 1, and 2 × MIC. For in vivo experiments, H. pylori SCYA201401-infected mice were randomly divided into TSG, palmatine, triple therapy (omeprazole, clarithromycin, and amoxicillin), blank control, and model groups. The eradication ratios were determined by use of rapid urease tests and bacterial culture. RESULTS: In vitro, the MIC and MBC of TSG against H. pylori SCYA201401 and SS1 were both 6250 µg/mL, whereas palmatine against H. pylori SCYA201401 was 6.25 µg/mL and against H. pylori SS1 was 3.12 µg/mL. The time-kill curves showed a dose-dependent, progressive decline in the numbers of viable bacteria up to 40 h. In vivo, the eradication ratios in the TSG and palmatine groups of mice were 80 and 50 % compared with 70 % in the triple-therapy group. CONCLUSION: TSG and its major component, palmatine, have bactericidal activity against H. pylori in vitro and in vivo. The possibility that TSG or palmatine can be effective in the treatment of human and animals H. pylori infection deserves investigation.
Assuntos
Antibacterianos/farmacologia , Alcaloides de Berberina/farmacologia , Helicobacter pylori/efeitos dos fármacos , Extratos Vegetais/farmacologia , Tinospora/química , Animais , Antibacterianos/química , Alcaloides de Berberina/química , Infecções por Helicobacter/microbiologia , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , SuínosRESUMO
Two new clerodane-type diterpenes, tinosporins C (1) and tinosporins D (2) were isolated from the stems of Tinospora sagittata (Oliv.), together with three known ones, columbin (3), tinophylloloside (4), and tinospinoside D (5). The structures of these compounds were determined on the basis of spectroscopic data interpretation, with that of the absolute configuration of compound 1 was assigned by experimental and calculated ECD spectra. The cytotoxicity and α-glucosidase inhibitory activities of isolated compounds were evaluated in vitro.
RESUMO
Twenty-six clerodane diterpenoids have been isolated from T. sagittata, a plant species of traditional Chinese medicine Radix Tinosporae, also named as "Jin Guo Lan". Among them, there are eight previously undescribed clerodane diterpenoids (tinotanoids A-H: 1-8), and 18 known diterpenoids (9-26). The absolute configurations of compounds 1, 2, 5, 8, 13, 17 and 20 were determined by single-crystal X-ray diffraction. Compound 1 is the first example of rotameric clerodane diterpenoid with a γ-lactone ring which is constructed between C-11 and C-17; meanwhile, compounds 3 and 4 are two pairs of inseparable epimers. Compounds 2, 12 and 17 demonstrated excellent inhibitory activity on NO production against LPS-stimulated BV-2 cells with IC50 values of 9.56 ± 0.69, 9.11 ± 0.53 and 11.12 ± 0.70 µM, respectively. These activities were significantly higher than that of the positive control minocycline (IC50 = 23.57 ± 0.92 µM). Moreover, compounds 2, 12 and 17 dramatically reduced the LPS-induced upregulation of iNOS and COX-2 expression. Compounds 2 and 12 significantly inhibited the levels of pro-inflammatory cytokines TNF-α, IL-1ß and IL-6 that were increased by LPS stimulation.
Assuntos
Diterpenos Clerodânicos , Menispermaceae , Tinospora , Diterpenos Clerodânicos/farmacologia , Diterpenos Clerodânicos/química , Tinospora/química , Lipopolissacarídeos/farmacologia , Raízes de Plantas/química , Estrutura MolecularRESUMO
ETHNOPHARMACOLOGY RELEVANCE: As a Yi medicine for eliminating wind to relieve pain, Tinospora sagittata var. yunnanensis (S. Y. Hu) H. S. Lo (TSY) is widely used to treat sore throat, stomach pain, bone and muscle injuries, and tumors; however, the material basis and mechanism of action remain unclear. AIM OF THE STUDY: This study aims to investigate the potential active compounds of TSY and related pharmacological mechanisms against gastric cancer using a multitarget strategy. MATERIALS AND METHODS: The main chemical components of TSY were collected through a literature review and database searches. The components were further screened for ADMET properties, and their targets were predicted using network pharmacology (admetSAR) and substructure-drug-target network-based inference (SDTNBI) approaches in silico. The pharmacological mechanism of action of TSY extract for pain relief, sedation, and anti-gastric cancer activities were identified via in vivo and in vitro biochemical analyses. RESULTS: Here, 28 chemical components were identified, 7 active compounds were selected, and 75 targets of TSY extract were predicted. A compound-target-disease network topological approach revealed that the predicted targets are highly related to the digestive system and nervous system. Network pharmacology results suggested that the anti-gastric cancer activity of TSY was highly correlated with its analgesic and sedative targets and MAPK. In vivo experiments confirmed that TSY extract not only reduced the number of voluntary activities in the mouse model but also exhibited a synergistic effect on sodium pentobarbital-induced sleep, reduced the number of mice exhibiting writhing responses to acetic acid, and increased the hot plate pain threshold of mice. Thus, TSY extract exhibits good analgesic and sedative effects. The TSY extract inhibited HGC-27 cell proliferation and induced apoptosis by regulating apoptotic proteins (BAX, BCL-2 and BCL-XL) in vitro. CONCLUSIONS: TSY exhibits combined analgesic, sedative, and anti-gastric cancer activities.
Assuntos
Neoplasias , Tinospora , Animais , Camundongos , Tinospora/química , Hipnóticos e Sedativos/uso terapêutico , Analgésicos/efeitos adversos , Dor/tratamento farmacológico , Ácido Acético/uso terapêutico , Extratos Vegetais/farmacologia , Neoplasias/tratamento farmacológicoRESUMO
Six undescribed low-polarity compounds including three rare 14-methylergostane steroids (1-3), one euphane triterpenoid (4) and two octadecanoic acid ethyl esters (5 and 6), along with ten previously reported terpenyl cometabolites (7-16), were isolated from the stems of Tinospora sagittata. Their structures were determined by detailed spectroscopic analyses and comparison with structurally related known compounds, and all of them have been reported from T. sagittata for the first time. Compounds 4-6 and 16 showed potent in vitro inhibitory activity against the diabetes target α-glucosidase, while compounds 10 and 14 displayed promising antibacterial effect toward Staphylococcus aureus ATCC 25923.
Assuntos
Antibacterianos/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Tinospora/química , Antibacterianos/isolamento & purificação , China , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Caules de Planta/química , Staphylococcus aureus/efeitos dos fármacosRESUMO
Tinospora sagittata is a perennial vine of the family Menispermaceae and distributed in Hunan, Hubei, Guangxi, and Sichuan province of P. R. China. It has been used in Chinese traditional medicine for centuries. The chloroplast (cp) genome of T. sagittata, characterized using Illumina technology, is 163,662 bp in size. There are a total of 130 genes, coding for 85 proteins, 37 tRNAs, and 8 rRNAs. Phylogenetic relationship analysis based on 16 complete cp genome sequences exhibited that T. sagittata was phylogenetically closer to Menispermum dauricum and Stephania japonica.
RESUMO
Three new clerodane type diterpenoids (2-4), together with one known analogues (1), were isolated from the tuberous roots of Tinospora sagittata (Oliv.) Gagnep. Compound 3 is an unusual clerodane diterpenoid with the carbonyl functionality at C-3, which represents the first example from this diterpenoid compounds class. The structures were established on the basis of spectroscopic data interpretation. The absolute configuration of 1 was determined for the first time by single-crystal X-ray diffraction analysis with CuKα irradiation. These isolates were evaluated for their cytotoxic activities against five human cancer cell lines and inhibitory activities on LPS-induced NO production in RAW264.7 cells.