Wilforlide B

[Chemical constituents from Salacia polysperma].[Pubmed:38212027]

Zhongguo Zhong Yao Za Zhi. 2023 Dec;48(24):6676-6681.

Nine compounds were isolated from the 90% ethanol extract of Salacia polysperma by silica gel, Sephadex LH-20 column chromatography, together with preparative HPLC methods. Based on HR-ESI-MS, MS, 1D and 2D NMR spectral analyses, the structures of the nine compounds were identified as 28-hydroxy Wilforlide B(1), wilforlide A(2), 1beta,3beta-dihydroxyurs-9(11),12-diene(3),(-)-epicatechin(4),(+)-catechin(5),(-)-4'-O-methyl-ent-galloepicatechin(6), 3-hydroxy-1-(4-hydroxy-3-methoxy-phenyl)propan-1-one(7),(-)-(7S,8R)-4-hydroxy-3,3',5'-trimethoxy-8',9'-dinor-8,4'-oxyneoligna-7,9-diol-7'-aldehyde(8), and vanillic acid(9). Compound 1 is a new oleanane-type triterpene lactone. Compounds 1, 3, 4, 7-9 were isolated from the Salacia genus for the first time. All compounds were assayed for their alpha-glucosidase inhibitory activity. The results suggested that compound 8 exhibited moderate alpha-glucosidase inhibitory activity, with an IC_(50) value of 37.2 mumol.L~(-1), and the other compounds showed no alpha-glucosidase inhibitory activity.

Two new dihydro-beta-agarofuran sesquiterpenes from the roots of Celastrus angulatus.[Pubmed:36355831]

J Asian Nat Prod Res. 2023 Jul-Aug;25(8):748-755.

Two new dihydro-beta-agarofuran sesquiterpenes chiapen T (1) and chiapen U (2), along with chiapen A (3), 1beta-hydroxy-2beta,6alpha,12-triacetoxy-8beta-(beta-nicotinoyloxy)-9beta-(benzoyloxy)-beta-dihydroagarofuran (4), Wilforlide B (5), 3-hydroxy-2-oxo-3-friedelen-29-oic acid (6), epikatonic acid (7), 22-epi-maytenfolic acid (8), maytenoic acid (9), wilforic acid F (10), wilforic acid B (11), were reported for the first time from the Celastrus angulatus. The structures of all the compounds were elucidated by HR-ESI-MS, 1 D and 2 D NMR spectra, as well as single-crystal X-ray diffraction analyses. Compounds 1 and 2 were examined for anti-inflammatory activity, respectively. None of them showed potent activity.

Synchronous Investigation of the Mechanism and Substance Basis of Tripterygium Glycosides Tablets on Anti-rheumatoid Arthritis and Hepatotoxicity.[Pubmed:35763252]

Appl Biochem Biotechnol. 2022 Nov;194(11):5333-5352.

Tripterygium Glycosides Tablets (TGT) has shown obvious anti-rheumatoid arthritis (RA) effects accompanied by hepatotoxicity. Despite that many studies looked at TGT's anti-RA or hepatotoxic mechanism and substance basis, the results were still insufficient. Furthermore, the anti-RA and hepatotoxicity investigations of TGT were undertaken separately, neglecting the relationship between efficacy and toxicity. Herein, an integrated approach combining metabolomics, network pharmacology, serum pharmacochemistry, and molecular docking was adopted to elucidate the mechanism and substance basis of Tripterygium Glycosides Tablets (TGT) on anti-rheumatoid arthritis and hepatotoxicity simultaneously. The results showed that 33 components in TGT were absorbed into rat serum. Two toxic targets (PRKCA, FASN), three effective targets (PLA2G10, PTGES, PLA2G1B), and four effective and toxic targets (PTGS1, PTGS2, PLA2G2A, ALOX5) were obtained by metabolomics combined with network analysis and network pharmacology. A component-target-RA-hepatotoxicity network was constructed and five hepatotoxic components (1-desacetylwilforgine, wilfordconine, wilforgine, wilformine, wilfornine D), eight effective-toxic components (14-oxo-19-(4 --> 3) abeo-abieta-3,8,12-tetraen-19,18-olide, 7-oxo-18(4 --> 3) abeo-abieta-3,8,11,13-tetraen-18-oic acid, hypoglaulide, triptotriterpenic acid A, wilforol F, Wilforlide B, triptoquinone B, wilforlide A); and 23 non-effective and non-toxic components were acquired and validated by molecular docking. In addition, our research revealed that glycerophospholipid metabolism and ether lipid metabolism were correlated to both hepatotoxicity and anti-RA of TGT. While in sphingolipid metabolism, ceramidases regulated ceramide-sphingosine and phytoceramide-phytosphingosine reaction were found to be correlated to hepatotoxicity, sphinganine-1-phosphate lyase (SPL) regulated sphingosine 1-phosphate (S1P)-phosphoethanolamine and sphinganine 1-phosphate-phosphoethanolamine were found to be attributed to anti-RA effects.

Molecular mechanism of reproductive toxicity induced by Tripterygium Wilfordii based on network pharmacology.[Pubmed:34232166]

Medicine (Baltimore). 2021 Jul 9;100(27):e26197.

To explore the possible molecular mechanism of reproductive toxicity of Tripterygium wilfordii from the perspective of network pharmacology and bioinformatics.The compounds of T wilfordii were obtained by querying the relevant Chinese medicine database, the effective compounds were screened and the corresponding targets were obtained, and then compared with the reproductive toxicities related to disease targets obtained from the disease gene database to infer the potential toxic targets of reproductive toxicity of T wilfordii. Then, the key targets of reproductive toxicity of T wilfordii were screened using Search Tool for the Retrieval of Interacting Genes/Protein and Cytoscape. The gene ontology function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as module analysis, were performed on the key targets using Database for Annotation, Visualization, and Integrated Discovery and Cytoscape, respectively. Finally, the network between effective compounds-toxic targets was conducted to see how the compounds interacted.A total of 48 effective compounds and 482 potential toxic targets related to the reproductive toxicity of T wilfordii were screened. The enrichment analysis results showed that the key targets were mainly enriched in biological processes such as response to drug, ionotropic glutamate receptor signaling pathway, and KEGG pathways such as neuroactive ligand-receptor interaction, cAMP signaling pathway. In the protein-protein interaction network of potential toxic targets, there were 78 key targets such as TP53, INS, IL6, AGT, ADCY3, and so on. Enrichment analysis of the top module with 19 genes from module analysis indicated that T wilfordii might cause reproductive toxicity by gene ontology terms and KEGG pathways such as regulation of vasoconstriction, G-protein coupled receptor signaling pathway, inflammatory response, cAMP signaling pathway, and so on. In the network between effective compounds of T wilfordii and key targets, there were 5 compounds with high degree including Tingenone, Wilfordic Acid, Abruslactone A, Nobilin, and Wilforlide B.The complex molecular mechanism of reproductive toxicity of T wilfordii can be preliminarily elucidated with the help of the network pharmacology method, and the analysis results can provide some reference for the further mechanism research of reproductive toxicity of T wilfordii.

alpha-Glucosidase inhibitory triterpenoids from Euonymus fortunei.[Pubmed:34004587]

Bioorg Chem. 2021 Jun;111:104980.

alpha-Glucosidase plays an important role in catalyzing the hydrolytic cleavage of disaccharides into monosaccharides. In this study, a phytochemical investigation of the potential alpha-glucosidase inhibitory fraction from the aerial parts of Euonymus fortunei led to the isolation and identification of two new tetracyclic triterpenoids, fortunenones A and B (1-2), together with 11 known triterpenoids (3-13). Fortunenones A and B are rare C(32) triterpenoids possessing a 24,24-dimethyl group. The partial isolated compounds were evaluated their effects on alpha-glucosidase, of which echinochlorin D (5), lupenone (7), Wilforlide B (12), and wilforlide A (13) exhibited remarkable inhibitory effects with the half inhibitory concentration ranged from 207.2 x 10(-6) M to 388.3 x 10(-6) M compared with the positive control, acarbose. An enzyme kinetics analysis by Lineweaver-Burk plots revealed that the inhibition types of the four active compounds were all mixed inhibition. Molecular docking further revealed that hydrophobic interactions and hydrogen bonds play an important role in the inhibition of alpha-glucosidase activity. Our results demonstrate the potential of E. fortunei extract and its constituents to inhibit alpha-glucosidase.

Characterization of eight terpenoids from tissue cultures of the Chinese herbal plant, Tripterygium wilfordii, by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry.[Pubmed:25237706]

Biomed Chromatogr. 2014 Sep;28(9):1183-92.

In this study, a reliable method for analysis and identification of eight terpenoids in tissue cultures of Tripterygium wilfordii has been established using high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC-ESI-MS). Our study indicated that sterile seedlings, callus cultures and cell-suspension cultures can rapidly increase the amount of biological materials. HPLC-ESI-MS was used to identify terpenoids from the extracts of these tissue cultures. Triptolide, triptophenolide, celastrol and wilforlide A were unambiguously determined by comparing the retention times, UV spectral data, and mass fragmentation behaviors with those of the reference compounds. Another four compounds were tentatively identified as triptonoterpenol, triptonoterpene, 22beta-hydroxy-3-oxoolean-12-en-29-oic acid and Wilforlide B, based on their UV and mass spectrometry spectra. The quantitative analysis showed that all three materials contain triptolide, triptophenolide, celastrol, wilforlide A, and the contents of the four compounds in the cell-suspension cultures were 53.1, 240, 129 and 964 microg/g, respectively, which were at least 2.0-fold higher than these in the sterile seedlings and callus cultures. Considering the known pharmacological activity of triptolide and celastrol, we recommend the cell-suspension cultures as biological materials for future studies, such as clinical and toxicological studies. The developed method was validated by the evaluation of its precision, linearity, detection limits and recovery, and it was successfully used to identify and quantify the terpenoids in the tissue cultures.

Simple method for determination of five terpenoids from different parts of Tripterygium wilfordii and its preparations by HPLC coupled with evaporative light scattering detection.[Pubmed:17623469]

J Sep Sci. 2007 Jun;30(9):1284-91.

By optimizing the extraction, separation, and analytical conditions, a reliable and accurate high-performance liquid chromatography method coupled with evaporative light scattering detection (ELSD) was developed for simultaneous determination of five terpenoids, i.e., triptolide, tripchlorolide, demethylzelastral, Wilforlide B, and wilforlide A, in root, stem, leaves, root bark, twig, and root without bark of Tripterygium wilfordii Hook. f and six of its herbal preparations. This approach would thus provide a more accurate and general method for evaluating the quality of the herb and its preparations. Separation of these five terpenoids was achieved on a ZORBAX Eclipse XDB-C8 column with gradient elution using water and acetonitrile as solvents, both containing 0.05% formic acid, at a temperature of 30 degrees C and a flow rate of 0.8 mL/min. The drift tube temperature of ELSD was set at 100 degrees C, and the nitrogen flow rate at 1.5 L/min. Good linear relationships were obtained with correlation coefficients for the analytes exceeding 0.992, and the LOD and LOQ were less than 0.149 microg and 0.297 microg on column, respectively. Intra-day and inter-day precision of the analytes were less than 1.25% and 5.97%, respectively, and the average recovery rates obtained were in the range of 95.9 +/- 3.7% to 100.4 +/- 5.0% for all terpenoids with RSDs below 4.99%. Quantitative analysis of the five terpenoids in different parts of Tripterygium wilfordii and its six preparations showed that the contents of the terpenoids varied significantly. The tender root contained higher concentrations of triptolide, tripchlorolide, demethylzelastral, and Wilforlide B than any other part of the herb. Correspondingly, the root bark contained the greatest concentration of wilforlide A, and the stem and twig came in second and third. This suggested that we could infer whether the medicinal materials were absolute roots without bark or not from the comparative contents of these terpenoids in the tablets in view of the fact that only the roots without bark are the valid officinal part of the plant. This method and the quantitation results obtained can provide a scientific and general as well as simple and convenient approach for the product manufacturers to set up quality control standards and for informing the public about the quality and safety of the preparations.

Triterpenes from Tripterygium wilfordii Hook.[Pubmed:16864458]

J Asian Nat Prod Res. 2006 Jul-Aug;8(5):425-9.

Two new friedelane-type triterpenes, tripterfrielanons A (1) and B (2), along with six known triterpenoids, friedelin (3), canophyllal (4), canophyllalic acid (5), 3-oxo-29-hydroxyfriedelane (6), wilforlide A (7), Wilforlide B (8), have been isolated from the EtOH extract of the roots of Tripterygiumwilfordii Hook.f. Compounds 4, 5, 6 were isolated for the first time from this plant. The new triterpenes 1 and 2 exhibited mild cytotoxic activity against human Hela cell lines in vitro. The assay showed the IC50 of 1 and 2 were 8.5 and 25 microg/mL, respectively.

[Studies on triterpenoids of total glucosides of tripterygium wilfordii].[Pubmed:7720147]

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 1994 Dec;16(6):466-8.

Three more triterpenoids were isolated from total glucosides of tripterygium wilfordii (T1). T16 and T17 were identified as salaspermic acid and as Wilforlide B. T18 was a new compound. The structure of T18 was determined, as 3-oxo-22 alpha-hydroxy-delta 12-oleanen-29-oic acid by detail spectroscopic and chemical analysis, and named triptotriterpenonic acid A.

[Studies on the chemical constituents of Euonymus mupinensis].[Pubmed:8010015]

Yao Xue Xue Bao. 1993;28(9):684-9.

Eight compounds have been isolated from Euonymus mupinensis. Their structures were identified by means of physico-chemical and spectral analysis. They are wilforlide A (I), Wilforlide B (II), olean-12-en-3,29-diol (III), olean-3-oxo-29-ol (IV), stigmastan-3-one (V), stigmastan-3,6-dione (VI), beta-sistosterol (VII) and beta-sistosterol-3-O-beta-D-glucopyranoside (VIII). Compound IV is a new compound, named as mupinensisone. Compounds I-VIII were isolated for the first time from this plant. 13C-NMR chemical shifts of compounds V and VI were assigned for the first time.