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OBJECTIVE@#To study the chemical constituents of the roots of Angelica dahurica, a well-known Chinese herbal medicine named Baizhi in Chinese.@*METHODS@#Compounds were separated by various chromatographies, and the structures of new compounds were elucidated based on the analysis of their spectroscopic and spectrometric data (1D, 2D NMR, HRESI MS, IR, and UV). The absolute configurations of new compounds were determined by the calculated electronic circular dichroism and chemical derivatization. The inhibitory activities of all isolates against nitric oxide (NO) production were evaluated using lipopolysaccharide-activated RAW 264.7 macrophage cells.@*RESULTS@#Seven new 3,4-dihydro-furanocoumarin derivatives ( 1a/ 1b, 2a/ 2b, 3a/ 3b, 4) together with a known furanocoumarin ( 5) were isolated from the roots of A. dahurica. The new compounds included three pairs of enantiomers, (4S, 2''R)-angelicadin A ( 1a)/(4R, 2''S)-angelicadin A ( 1b), (4S, 2''S)-angelicadin A ( 2a)/(4R, 2''R)-angelicadin A ( 2b), and (4S, 2''S)-secoangelicadin A ( 3a)/(4R, 2''R)-secoangelicadin A ( 3b), together with (4R, 2''R)-secoangelicadin A methyl ester ( 4). The known xanthotoxol ( 5) inhibited the NO production with the half-maximal inhibitory concentration (IC50) value of (32.8 ± 0.8) µmol/L, but all the new compounds showed no inhibitory activities at the concentration of 100 µmol/L.@*CONCLUSION@#This is the first report of the discovery of 3,4-dihydro-furanocoumarins from A. dahurica. The results are not only meaningful for the understanding of the chemical constituents of A. dahurica, but also enrich the reservoir of natural products.
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Polysaccharide of Balanophora involucrata Hook. f. (BPS), the major component of Balanophora involucrata Hook. f., was confirmed the protective effect on liver injury in our previous study. This research aimed to investigate the protective mechanism of BPS on experimental liver injury by attenuating cell ferroptosis through modulating solute carrier family 7 member 11/glutathione peroxidase 4 (SLC7A11/GPX4) pathway. The animal experiment was approved by the Experimental Animal Ethical Committee of Hubei Minzu University and all rats had received human care in compliance with the institutional animal care guidelines. Rats were given intraperitoneal injection of (D-galactosamine, D-GalN) solution (800 mg·kg-1) one time to establish the acute liver injury model. The results showed aspartate amino transferase (AST), alanine aminotransferase (ALT) and 4-hydroxynonenal (4-HNE) levels in serum were decreased, and the contents of reactive oxygen species (ROS), Fe2+, malondialdehyde (MDA) and lipid peroxide (LPO) in liver tissues also decreased and glutathione (GSH) level increased after BPS administration with 200 mg·kg-1. Besides, BPS reduced iron deposition and increased the expression of SLC7A11 and GPX4 proteins in liver tissue. In conclusion, BPS ameliorated experimental liver injury by alleviating cell ferroptosis through SLC7A11/GPX4 pathway. The present study pointed to the possibility of utilizing BPS for protection against liver injury in clinic.
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To explore the mechanism of ovarian toxicity of Hook. F. (TwHF) by network pharmacology and molecular docking. The candidate toxic compounds and targets of TwHF were collected by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Comparative Toxicogenomics Database (CTD). Then, the potential ovarian toxic targets were obtained from CTD, and the target genes of ovarian toxicity of TwHF were analyzed using the STRING database. The protein-protein interaction (PPI) network was established by Cytoscape and analyzed by the cytoHubba plug-in to identify hub genes. Additionally, the target genes of ovarian toxicity of TwHF were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses by using the R software. Finally, Discovery Studio software was used for molecular docking verification of the core toxic compounds and the hub genes. Nine candidate toxic compounds of TwHF and 56 potential ovarian toxic targets were identified in this study. Further network analysis showed that the core ovarian toxic compounds of TwHF were triptolide, kaempferol and tripterine, and the hub ovarian toxic genes included , , , , , , , , and . Besides, the GO and KEGG analysis indicated that TwHF caused ovarian toxicity through oxidative stress, reproductive system development and function, regulation of cell cycle, response to endogenous hormones and exogenous stimuli, apoptosis regulation and aging. The docking studies suggested that 3 core ovarian toxic compounds of TwHF were able to fit in the binding pocket of the 10 hub genes. TwHF may cause ovarian toxicity by acting on 10 hub genes and 140 signaling pathways.
Subject(s)
Drugs, Chinese Herbal/toxicity , Medicine, Chinese Traditional , Molecular Docking Simulation , Network Pharmacology , Protein Interaction MapsABSTRACT
Tripterygium wilfordii Hook F has significant anti-inflammatory and immunosuppressive properties and is widely used for treating autoimmune and inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, and kidney disease, especially in traditional Chinese medicine. The mechanisms underlying its effects may be diverse but they remain unclear, and its toxicity and side effects limit its wider clinical application. This review summarizes the clinical application of Tripterygium wilfordii Hook F in recent years, as well as the results of studies into its mechanisms and toxicity, to provide a reference for its future clinical application.
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Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovitis and destruction of articular cartilage and bone. With the aging of the population, the incidence of RA is increasing year by year and the burden of public health is becoming more and more serious. Tripterygium wilfordii has the effects of dispelling wind and dredging collaterals, dehumidifying and relieving pain, detoxification and insecticide. It is often used in the treatment of various autoimmune diseases, tumors and skin diseases in clinic, and the prominent effect is observed in the treatment of RA especially. This review systematically summarizes and discusses the latest research progress of T. wilfordii in the treatment of RA in the aspects of experimental pharmacology and clinical research, including its single application, the compatible application with other Chinese materia medica, and the combination of Western medicine, which is expected to promote the innovative drug development and more reasonable and effective clinical application of T. wilfordii in the treatment of RA.
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Objective: To study chemical constituents of Cephalotaxus fortunei. Methods: The chemical constituents were separated and purified by preparative thin-layer chromatography, silica gel, ODS, HP20 macroporous resin and Sephadex LH-20 gel column chromatography, and semi-preparative HPLC. Their structures were determined by NMR and ESI-MS spectroscopic techniques. Results: Seventeen lignans were isolated from the ethanol extracts of C. fortunei and their structures were identified as shonanin (1), arctigenin (2), α-conidendrin (3), matairesinol (4), nortrachelogenin (5), epinortrachelogenin (6), (7'S)- hydroxymatairesinol (7), (7'R)-hydroxymatairesanol (8), (7'S)-hydroxyarctigenin (9), secoisolariciresinol (10), 4,4'-di-O-methylcephafortin A (11), 5-(3″,4″-dimethoxyphenyl)-3-hydroxy-3-(4'-hydroxy-3'-methoxybenzyl)-4-hydroxymethyl-dihydrofuran-2-one (12), cephafortin B (13), dihydrodehydrodiconiferyl alcohol (14), 7R,8S-4,7,9,9'-tetrahydroxy-3,3'-dimethoxy-8-O-4'-neolignan (15), 7R,8R-4,7,9,9'- tetrahydroxy-3,3'-dimethoxy-8-O-4'-neolignan (16), and threo-1,2-bis-(4-hydroxy-3-methoxyphenyl)-1,3-propanediol (17). Conclusion: Compounds 3, 6, 10 and 17 were isolated from genus Cephalotaxus for the first time, and compounds 4, 5, 7-9, 12 and 14 were isolated from C. fortunei for the first time.
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Objective: To investigate the effect of Tripterygium wilfordii on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) mice, analyze its effects on its intestinal flora, and explore its mechanism. Methods: Animal models of UC mice induced by DSS were established and divided into control group (Con), model group (Mod), mesalazine group (Mes), low dose group of T. wilfordii (RT1) and high dose group of T. wilfordii (RT2). The disease activity index (DAI), colon length, colon thickness, colon lesion gross score, colon histopathology score, and TNF-α and IL-6 cytokine expression levels in the serum of the mice were determined. The changes of intestinal flora in mice were detected by high-throughput sequencing, and the mechanism of action of T. wilfordii on UC mice was discussed. Results: After administration of T. wilfordii, it effectively alleviated colonic inflammatory symptoms and reduced the expression of inflammatory factors in mice, and had a good therapeutic effect on UC mice. The sequencing results of the flora showed that the mice in the Mod group were more disordered than the Nor group, and the abundance of the bacteria was reduced. After treatment with T. wilfordii, the recovery rate of intestinal flora was accelerated. Compared with Mod group, the diversity of intestinal flora was significantly improved. The level of portal was mainly decreased by the proportion of Bacteroidetes, and the increase of Firmicutes. The genus was mainly characterized by a decrease in the genus Lachnospiraceae and Bacteroides. Conclusion: T. wilfordii can regulate the composition of UC mouse flora, accelerate the recovery of flora, and have a good therapeutic effect on UC mice.
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Objective: To study the constituents of the leaves of Dysoxylum binectariferum. Methods: The chemical constituents were isolated by various column chromatographic methods, and their structures were identified on the basis of MS and NMR spectral analysis. Results: Five steroids were obtained and their structures were elucidated as stigmast-4(5)-en-3β,6β,22-triol (1), stigmast-5(6)-en-3β,21,22-triol (2), 2α,3β,4β-trihydroxypregnan-16-one (3), 2α,3β-dihydroxy-4β-acetoxypregnan-16-one (4) and 2α,3β-dihydroxypregnan-17(20)-en-16-one (5). Conclusion: Compound 1 is identified as a new compound and named dybinstigm A. Compounds 2-5 are obtained from D. binectariferum for the first time.
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Objective: To observe the effect of Tripterygium wilfordii processed by liquorice on the metabolites in the serum of mice, and to explore its possible metabolic pathways to reduce hepatotoxicity. Methods: C57BL/6 mice were randomly divided into control (Con) group, raw T. wilfordii (Raw) group, and T. wilfordii processed by liquorice (Pro) group. Liver histopathological sections and biochemical indexes of liver function and inflammatory factors were detected. LC-MS technology combined with metabolomics methods were used to characterize the differences in metabolism between each group. Results: Compared with Raw group, the liver injury of mice in Pro group was significantly improved, the levels of biochemical indicators and inflammatory factors were significantly decreased, which indicated that TwHF could reduce the hepatotoxicity of mice after processing by liquorice. Twelve potential biomarkers including hexadecanoic acid, phosphatidic acid, glyceride, lecithin and cholic acid were screened, mainly involved nine metabolic pathways including biosynthesis of unsaturated fatty acids, glycerophospholipid metabolism, arachidonic acid metabolism, etc. Conclusion: TwHF processed by liquorice could reduce the hepatotoxicity of mice and the mechanism may be related to the regulation of fatty acid metabolism, which provides a reference for clinical rational application.
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Objective: The present study was performed to evaluate the immunomodulatory, anticancer, and antioxidative properties of the fraction (CP_2) isolated from Cyclea peltata. Methods: Immunomodulation was evaluated in lymphocytes by lymphocyte proliferation assay and in THP-1 macrophage cell lines by MTT assay. The nitrite production by the macrophages was also measured by the nitrite assay using griess reagent. The anticancer activity of the fraction was determined by MTT assay. The antioxidant activity was evaluated by DPPH assay and total antioxidant assay by phosphomolybdenum method. It is expressed as number of gram equivalent of ascorbic acid. Results: The plant fraction showed the presence of flavonoids which induced lymphocyte proliferation rate of 4.29±0.007 at 100 μg/ml. It was not toxic to THP-1 macrophage cells and also could induce nitrite production at 1 mg/ml. It also exhibited good anticancer activity at 100 μg/ml after 48h of incubation. The DPPH activity was found to be low since 100 μg/ml showed only an inhibition rate of 22±0.026. The total antioxidant activity at 1000 μg/ml of CP_2 was found to be equivalent to 79±0.03 μg/ml of ascorbic acid exhibiting moderate antioxidant activity. Conclusion: The fraction CP_2 containing flavonoid, isolated from Cyclea peltata has good immunomodulatory, antioxidant and anticancerous property.
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As a major active component extracted from traditional Chinese herb Tripterygium wilfordii Hook F, triptolide exhibits multiple pharmacological effects. Autophagy is an evolutionary conserved intracellular catabolic process involved in cytoplasmic materials degradation. Autophagic dysfunction contributes to the pathologies of many human diseases, which makes it a promising therapeutic target. Recent studies have shown that triptolide exerts neuroprotection, anti-tumor activities, organ toxicity, and podocyte protection by modulating autophagy. This article highlights the current information on triptolide-modulated autophagy, analyzes the possible pathways involved, and describes the crosstalk between autophagy and apoptosis modulated by triptolide, in hope of providing implications for the roles of autophagy in pharmacological effects of triptolide and expanding its novel usage as an autophagy modulator.
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Animals , Humans , Apoptosis , Autophagy , Diterpenes , Pharmacology , Epoxy Compounds , Pharmacology , Neoplasms , Drug Therapy , Pathology , Neuroprotective Agents , Pharmacology , Phenanthrenes , Pharmacology , PodocytesABSTRACT
Tripterygium wilfordii Hook F (TwHF) and its extracts have long been used for the treatment of rheumatoid arthritis, autoimmune diseases, and kidney disease due to their anti-inflammatory, immunoregulatory, and other pharmacological effects. However, the clinical immunoregulatory effects of TwHF and its extracts remain unclear, so we reviewed their effects for use in clinical practice. This review provides a comprehensive summary of the recent literature on the immunoregulatory effects of TwHF and its extracts in clinical studies. TwHF and its extracts affect the proliferation and activation of Tand B cells; ratio of Tcell subsets; inflammatory response of monocytes, macrophages, and immunoglobulins; and secretion of many cytokines. Together, these effects dictate immune function in a variety of diseases. TwHF and its extracts can be used alone or in combination with existing therapies against many immune disorders through immunomodulation.
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Objective To study the intestinal absorption kinetics of Tripterygium wilfordii (TW) solid dispersions and the effects of different intestinal segments, drug concentrations, pH value, and P-glycoprotein (P-gp) on intestinal absorption. Methods The absorption behavior was investigated in situ with a single-pass intestinal perfusion (SPIP) model in rats. The content of each index component was determined by HPLC. The gravimetric method was used to correct the data and calculate the absorption rate constant (Ka) and apparent permeability coefficient (Papp) of each index component. Results The index components of TW were absorbed in the whole intestine, and the absorption rate constant (Ka) of all the index components of TW solid dispersion was significantly increased than that of extract (P < 0.05), and had some differences among different segments. With the increase of drug concentration, the absorption of each index component had saturation phenomenon, which indicated that it may be carrier-mediated transport mechanism. Acidic environment (pH 5.4) was beneficial to the absorption of various index components, especially the acidic content celastrol. After adding P-gp inhibitor, the Ka and Papp of celastrol were significantly different from those without P-gp inhibitor (P < 0.05), which suggested that it may be the P-gp substrate. Conclusion All the index components of TW solid dispersion are absorbed in the whole intestine and have saturation phenomenon, which suggested the absorption may be carrier-mediated transport mechanism. Acidic environment is beneficial to the absorption of all components. The absorption process of celastrol is affected by drug concentration and P-gp inhibitor, which indicated that it may be P-gp substrate. The preparation of solid dispersing can significantly enhance the absorption of various components of TW, suggesting that all the index components are BCS II drugs, and the bioavailability of the preparation may be improved.
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Objective A rapid and efficient UPLC-ESI-HRMSn method was developed and applied to rapidly identify the components in Rheum nobile. Methods With 100% methanol as extract preparation for solution,the extract was separated on an ACQUITY UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 μm), and eluted with a gradient of methanol-water that containing 0.1% formic acid. Chemical constituents were separated and investigated by UPLC-ESI-HRMSn in both positive and negative ion modes. Combined with accurate mass characteristic fragments, retention time and previous literature database, the structures of compounds were identified or tentatively characterized. Results A total of 34 compounds including four anthraquinones, 15 phenolic acid derivatives, 11 tannin precursor and tannins and four organic acid were identified. Twenty-seven compounds were reported for the first time from R. nobile. Conclusion The analytical method of UPLC-ESI-HRMSn was valuable for rapid identification of unknown constituents of R. nobile, which supplies a clear material basis for further study.
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Objective: To study the chemical constituents in the whole herb of Balanophora involucrate. Methods: The compounds were isolated and purified using polyamide, silica gel colimu, ODS, MCI gel, and semi-preparative HPLC, and their structures were elucidated by means of physicochemical properties and spectroscopic analysis. The anti-inflammatory activities of all the isolated compounds were evaluated using Griess method and ELISA for the determination of LPS-induced NO and IL-6 releases in inflammation cell model induced by LPS. Results: Eleven lignans were isolated from 75% ethyl alcohol extract from the whole herb of B. involucrata and identified as (+)-pinoresinol (1), (+)-5’-hydroxypinoresinol (2), isolariciresinol 4-O-β-D-glucopyranoside (3), (+)-isolariciresinol (4), burselignan (5), (+)-9-acetoxyisolariciresinol (6), yunnanensin A (7), (-)-secoisolariciresinol-4-O-β-D- glucopyranoside (8), (-)-secoisolariciresinol (9), dihydrocubebin (10), and secoisolariciresinol-9’-acetate (11). Conclusion: Among them, compound 11 is a new natural product, and compound 2, 5, 7, 8, and 10 are isolated from the genus of Balanophora for the first time. All compounds showed strong anti-inflammatory activities.
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Tripterygium wilfordii, a traditional Chinese herbal medicine with multiaspect pharmacological activities, contains abundant chemical constituents. Based on the new concept of quality markers (Q-markers) of traditional Chinese medicine put forward by Academician Chang-xiao Liu, this paper systematically reviewed the chemical constituents and pharmacological activities of T. wilfordii, the Q-markers of T. wilfordii were predicted and analyzed according to the definition of quality markers and the research of its traditional efficacy, traditional medicinal properties, new clinical use, measurable composition, plasma composition, and compatibility, in order to provide reference for further study on the quality of T. wilfordii.
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This work was conducted to evaluate the pharmacognostic and phytochemical study of varieties of Nagakesara. When it is further studied, it is observed that Nagakesara available in the markets of different areas is from different source plants. There are nearly 5 drugs sold in the market with the same name, the common floral parts available in the markets are commonly from Nagakesara (Mesua ferrea Linn.), Surapunnaga (Ochrocarpus longifolius Benth and Hook f.), Tamalpatra (Cinnamomum tamala Nees and Ebern.), Punnaga (Calophyllum inophyllum Linn.), Dillenia pentagyna Roxb. Hence a comparative study of these two samples 1) Nagakesara (Mesua ferrea), and 2) Tamalpatra (Cinnamomum tamala) has been carried out. The phytochemical study shows the presence of tannins, steroids and carbohydrates in almost all varieties of Nagakesara. Flower buds of Nagakesara plant of different species available in the market was taken up for the study. CONCLUSION: A detailed Pharamcognostic and Phytochemical review was done through which it was concluded that Mesua ferrea Linn. belonging to family Guttiferae may be the exact source of Nagakesara. The flower buds of Cinnamomum tamala Nees and Ebern. which is known as black variety in the markets according to our study,.
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The quality control of herbal crude drugs and their bio constituents is of paramount importance in justifying their acceptability. The crude drugs can be identified systematically on the basis of their morphological, histological, chemical, physical and biological studies. Cyclea peltata (Lam) Hook. f. Thoms belonging to the family Menispermaceae is a common plant seen in South India. It is mentioned in Ayurvedic classics by the name Rajapatha and is one of the important drugs used in Ayurveda therapeutics and is used widely in different formulations in medical practice. The aim of the study is to evaluate the preliminary pharmacognostical and phytochemical characters of Cyclea peltata (Lam) Hook. f. Thoms. Pharmacognostical evaluation of the plant Cyclea peltata (Lam) Hook. f. Thoms. was done by studying the macroscopic and microscopic features of leaf and root of the plant. The physical parameters studied included foreign matter, moisture content, volatile oil, total ash, acid insoluble ash, water soluble extractive, alcohol soluble extractive, fibre content and sugar content. The preliminary phytochemical analysis included qualitative chemical analysis, Thin Layer Chromatography, High Performance Thin Layer Chromatography and Atomic Absorption Spectroscopy. Various pharmacognostic and preliminary phytochemical characters observed in this may help in standardization, identification and carrying out further research in Cyclea peltata (Lam) Hook. f. Thoms.
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Objective: To investigate the chemical constituents from the roots of Angelica dahurica. Methods: The chemical constituents were isolated and purified by AB-8 macroporous adsorption resin and Sephadex LH-20 column as well as semi-preparative reversed phase HPLC. The chemical structures were identified by spectral data. Results: Ten compounds were isolated and identified as xanthoarnol-3′-O-β-D-glucopyranoside (1), angedahuricoside A (2), angedahuricoside B (3), isofraxidin-7-O-β-D-glucopyranoside (4), fraxidin-8-O-β-D-glucopyranoside (5), (-)-marmesinin (6), (2′S,3′R)-3′-hydroxymarmesinin (7), hyuganoside V (8), daucosterol (9), and sucrose (10). Conclusion: Compounds 1–3 are new ones and compounds 4–6 and 8 are obtained from title plant for the first time.
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Objective To improve the dissolution in vitro, thereby to prepare the solid dispersion (SD) from the extract of Tripterygium wilfordii (ETW). Methods Polyethylene glycol 6000 (PEG 6000) and poloxamer 188 (F68) were used as carrier to prepare ETW-SD by solvent-melting method. The triptolide, triptonide, wilforine, tripterine and wilforlide were used as the evaluation indexes to characterize the optimal prescription of ETW-SD by dissolution in vitro, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). Results The optimal formulation for ETW-SD composed of ETW-PEG 6000-F68 (1∶2∶1). Compared with the raw materials, the dissolution of triptonide, triptolide and wilforine increased by a factor of 3.32, and wilforine by 2 times, while the dissolution of tripterine and wilforlide reached more than 83% within 60 min.