RESUMEN
Phytochemical investigation of the 70% ethanol extract of Isodon henryi Kudô afforded fifteen ent-kaurane diterpenoids, including nine previously undescribed compounds, named isohenolides C-K (1-9). Compounds 1-6 featured an unusual 6,7;8,15-diseco-7,20-olide ent-kaurane diterpenoid scaffold, in which 1 also possessed an 11,15-lactone ring while 2-6 all contained a free α-methylene-γ-carboxylic acid. Compound 6 was also a rare 6,8-cyclo-7,20-olide ent-kauranoid. Their structures were elucidated primarily by HRESIMS, 1D and 2D NMR spectroscopy, electronic circular dichroism and X-ray diffraction (Cu Kα) methods. Additionally, most compounds were also screened for anti-inflammatory actions against lipopolysaccharide-induced RAW 264.7 cells, and compounds 9 and 13 exhibited stronger nitric oxide inhibition, with IC50 values of 15.99 ± 0.75 and 18.19 ± 0.42 µM, respectively.
RESUMEN
Corni fructus (CF) is always subjected to wine processing before prescription in clinic, for an enhancing effect of nourishing liver and kidney. While, the underlying mechanism for this processing on CF remains obscure. In this study, a sensitive ultra-high-performance liquid chromatography mass spectrometry (UPLC-MS/MS) method combined multi-dimensional analyses was established to monitor chemical characterizations of raw and wine-processed CF (WCF) and hence reveal the effects and underlying mechanism of wine processing on CF. As indicated, a total of 216 compounds were tentatively identified, including 98 structurally complex and variable home/hetero-polymers, that were composed of iridoid glucosides, gallic acids, caffeic acid and/or 5-HMF. Interestingly, 53 of these compounds probably characterized potential novel, including 35 iridoid glucosides or their dimers, 9 iridoid glucoside-gallic acid dimers, 7 gallic acids derivatives and 2 gallic acid-caffeic acid dimers, which provides ideas for natural product researchers. Meanwhile, the multi-dimensional analyses including principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and linear regression analysis were used to explore the differences between CF and WCF. The results showed that 23 compounds as chemical markers greatly contributing to the distinction were screened out, and 3 of which (7α/ß-O-ethyl-morroniside, gallic acid and 5-HMF) in WCF indicated an increasing trend in intensities in relative to those in CF. Additionally, linear regression analysis showed that in WCF 53 compounds exhibited an increasing in intensities, while 132 ones did a decreasing trend, compared with those in CF. As our investigation demonstrated, acetal reaction of morroniside, ester hydrolysis in different organic acid derivatives as well as glycoside bond cleavage during wine processing probably resulted in the distinctions. The findings of this study provide a further understanding of the effect and mechanism of wine processing on CF.
Asunto(s)
Cornus , Análisis de Componente Principal , Espectrometría de Masas en Tándem , Vino , Vino/análisis , Cromatografía Líquida de Alta Presión/métodos , Cornus/química , Espectrometría de Masas en Tándem/métodos , Ácidos Cafeicos/análisis , Ácidos Cafeicos/química , Ácido Gálico/química , Ácido Gálico/análisis , Frutas/química , Análisis de los Mínimos CuadradosRESUMEN
A group of previously undescribed diarylheptanoids with mono/di-glucose substitution, diodiarylheptosides A-F (1-6), together with six known diarylheptanoids (7-12) were isolated from the rhizomes of Dioscorea nipponica. Their structures were established by comprehensive UV, IR, HR-ESI-MS and NMR analyses, and their absolute configurations were determined by a comparison of calculated and experimental ECD, some with optical rotations, after acid-hydrolysis. Moreover, bioassay results showed that compounds 3 and 11 exhibited stronger NO inhibitions on lipopolysaccharides-induced RAW 264.7 cells, with the IC50 values of 14.91 ± 0.62 and 12.78 ± 1.12 µM.
Asunto(s)
Diarilheptanoides , Dioscorea , Glicósidos , Fitoquímicos , Rizoma , Dioscorea/química , Rizoma/química , Diarilheptanoides/aislamiento & purificación , Diarilheptanoides/química , Diarilheptanoides/farmacología , Ratones , Células RAW 264.7 , Estructura Molecular , Animales , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Fitoquímicos/química , Glicósidos/aislamiento & purificación , Glicósidos/química , Glicósidos/farmacología , Óxido Nítrico/metabolismo , ChinaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Atherosclerosis (AS), a lipid-induced inflammatory condition of the arteries, is a primary contributor to atherosclerotic cardiovascular diseases including stroke. Arctium lappa L. leaf (ALL), an edible and medicinal herb in China, has been documented and commonly used for treating stroke since the ancient times. However, the elucidations on its anti-AS effects and molecular mechanism remain insufficient. AIM OF THE STUDY: To investigate the AS-ameliorating effects and the underlying mechanism of action of an ethanolic extract of leaves of Arctium lappa L. (ALLE). MATERIALS AND METHODS: ALLE was reflux extracted using with 70% ethanol. An HPLC method was established to monitor the quality of ALLE. High fat diet (HFD) and vitamin D3-induced experimental AS in rats were used to determine the in vivo effects; and oxidized low-density lipoprotein-induced RAW264.7 macrophage foam cells were used for in vitro assays. Simvatatin was used as positive control. Biochemical assays were implemented to ascertain the secretions of lipids and pro-inflammatory mediators. Haematoxylin-eosin (H&E) and Oil red O stains were employed to assess histopathological alterations and lipid accumulation conditions, respectively. CCK-8 assays were used to measure cytotoxicity. Immunoblotting assay was conducted to measure protein levels. RESULTS: ALLE treatment significantly ameliorated lipid deposition and histological abnormalities of aortas and livers in AS rats; improved the imbalances of serum lipids including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C); notably attenuated serum concentrations of inflammation-associated cytokines/molecules including TNF-α, IL-6, IL-1ß, VCAM-1, ICAM-1and MMP-9. Mechanistic studies demonstrated that ALLE suppressed the phosphorylation/activation of PI3K, Akt and NF-κB in AS rat aortas and in cultured foam cells. Additionally, the PI3K agonist 740Y-P notably reversed the in vitro inhibitory effects of ALLE on lipid deposition, productions of TC, TNF-α and IL-6, and protein levels of molecules of PI3K/Akt and NF-κB singnaling pathways. CONCLUSIONS: ALLE ameliorates HFD- and vitamin D3-induced experimental AS by modulating lipid metabolism and inflammatory responses, and underlying mechanisms involves inhibition of the PI3K/Akt and NF-κB singnaling pathways. The findings of this study provide scientific justifications for the traditional application of ALL in managing atherosclerotic diseases.
Asunto(s)
Arctium , Aterosclerosis , Fragmentos de Péptidos , Receptores del Factor de Crecimiento Derivado de Plaquetas , Accidente Cerebrovascular , Ratas , Animales , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Fosfatidilinositol 3-Quinasas/metabolismo , Metabolismo de los Lípidos , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Aterosclerosis/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Extractos Vegetales/química , Lípidos , Colesterol/farmacología , Etanol/farmacología , Lipoproteínas LDL/metabolismo , Colecalciferol/farmacología , Colecalciferol/uso terapéuticoRESUMEN
Six compounds were isolated from aqueous extract of wine-processed Corni Fructus through silica gel, ODS column chromatography, Sephadex LH-20 gel column chromatography, reverse phase preparative HPLC and other chromatographic separation technologies. Their structures were identified with multiple spectroscopical methods including HR-ESI-MS, UV, IR, NMR and ECD and so on. Their structures were established as pinoresinoside B(1), cornusgallicacid A(2),(+)-isolariciresinol-9'-O-ß-glucopyranoside(3),(-)-isolariciresinol 3α-O-ß-D-glucopyranoside(4),(7R,8S)-dihydrodehydrodiconiferyl alcohol 9-O-ß-D-glucopyranoside(5), and(-)-seco isolariciresinol-9'-O-ß-D-glucopyranoside(6). Among them, compounds 1 and 2 were two new compounds. The biological activity evaluation results showed that compounds 2 and 6 had strong DPPH free radical scavenging ability, with EC_(50) values of(4.18±1.96) and(21.45±1.19) µmol·L~(-1), respectively. Compounds 1 and 2 had protective effects on H_2O_2-induced oxidative damage in NRK-52E cells in a dose-dependent manner, and the cell survival rate of compound 2 at 100 µmol·L~(-1) was 96.09%±1.77%.
Asunto(s)
Cornus , Vino , Naftoles , LigninaRESUMEN
Chemical constituents were isolated and purified from ethyl acetate fraction of Arctium lappa leaves by silica gel, ODS, MCI, and Sephadex LH-20 column chromatography. Their structures were identified with multiple spectroscopical methods including NMR, MS, IR, UV, and X-ray diffraction combined with literature data. Twenty compounds(1-20) were identified and their structures were determined as arctanol(1), citroside A(2), melitensin 15-O-ß-D-glucoside(3), 11ß,13-dihydroonopordopicrin(4), 11ß,13-dihydrosalonitenolide(5), 8α-hydroxy-ß-eudesmol(6), syringin(7), dihydrosyringin(8), 3,4,3',4'-tetrahydroxy-δ-truxinate(9),(+)-pinoresinol(10), phillygenin(11), syringaresinol(12), kaeperferol(13), quercetin(14), luteolin(15), hyperin(16), 4,5-O-dicaffeoylquinic acid(17), 1H-indole-3-carboxaldehyde(18), benzyl-ß-D-glucopyranoside(19), and N-(2'-phenylethyl) isobutyramide(20). Among them, compound 1 is a new norsesquiterpenoid, and compounds 2-5, 7-8, and 18-20 are isolated from this plant for the first time.
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Arctium , Arctium/química , Espectroscopía de Resonancia Magnética , Luteolina/análisis , Hojas de la Planta/químicaRESUMEN
Cinnamomi ramulus (CR) and Cinnamomi cortex (CC), both sourced from Cinnamomum cassia Presl, are commonly used Chinese medicines in the Chinese Pharmacopeia. However, while CR functions to dissipate cold and to resolve external problems of the body, CC functions to warm the internal organs. To clarify the material basis of these different functions and clinical effects, a simple and reliable UPLC-Orbitrap-Exploris-120-MS/MS method combined with multivariate statistical analyses was established in this study with the aim of exploring the difference in chemical compositions of aqueous extracts of CR and CC. As the results indicated, a total of 58 compounds was identified, including nine flavonoids, 23 phenylpropanoids and phenolic acids, two coumarins, four lignans, four terpenoids, 11 organic acids and five other components. Of these compounds, 26 significant differential compounds were identified statistically including six unique components in CR and four unique components in CC. Additionally, a robust HPLC method combined with hierarchical clustering analysis (HCA) was developed to simultaneously determine the concentrations and differentiating capacities of five major active ingredients in CR and CC: coumarin, cinnamyl alcohol, cinnamic acid, 2-methoxycinnamic acid and cinnamaldehyde. The HCA results showed that these five components could be used as markers for successfully distinguishing CR and CC. Finally, molecular docking analyses were conducted to obtain the affinities between each of the abovementioned 26 differential components, focusing on targets involved in diabetes peripheral neuropathy (DPN). The results indicated that the special and high-concentration components in CR showed high docking scores of affinities with targets such as HbA1c and proteins in the AMPK-PGC1-SIRT3 signaling pathway, suggesting that CR has greater potential than CC for treating DPN.
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Medicamentos Herbarios Chinos , Espectrometría de Masas en Tándem , Simulación del Acoplamiento Molecular , Medicamentos Herbarios Chinos/química , Cinnamomum zeylanicumRESUMEN
BACKGROUND: As an autoimmune systemic disorder, rheumatoid arthritis (RA) features chronic inflammation as well as synovial infiltration of immune cells. This study was designed with the purpose of discussing the hidden mechanism of SPTBN1 and exploring favorable molecular-targeted therapies. METHODS: With the application of RT-qPCR and western blot, the expressions of SPTBN1 and PIK3R2 before or after transfection were estimated. Besides, Cell Counting Kit-8, Edu, wound healing, transwell, enzyme-linked immunosorbent assay, and TUNEL were adopted for the evaluation of the viability, proliferation, migration, invasion, inflammatory response, and apoptosis of fibroblast-like synoviocyte (FLS). In addition, the interaction of SPTBN1 and PIK3R2 was testified by applying immunoprecipitation (IP) and western blot was utilized for the assessment of migration-, apoptosis-, and PI3K/AKT signal-related proteins. RESULTS: It was discovered that SPTBN1 declined in RA synovial cells and its overexpression repressed the proliferation, migration, invasion, and inflammation of RA-FLSs but promoted apoptosis. IP confirmed that SPTBN1 could bind to PIK3R2 in FLSs. To further figure out the hidden mechanism of SPTBN1 in RA, a series of functional experiments were carried out and the results demonstrated that the reduced expressions of MMP2, MMP9, IL-8, IL-1ß, IL-6, and Bcl2 as well as increased levels of Bax and cleaved caspase3 in SPTBN1-overexpressed RA-FLSs were reversed by PIK3R2 depletion, revealing that SPTBN1 repressed the migration and inflammation and promoted the apoptosis of RA-FLSs via binding to PIK3R2. Results obtained from western blot also revealed that PIK3R2 interference ascended the contents of p-PI3K and p-AKT in SPTBN1-overexpressed RA-FLSs, implying that SPTBN1 repressed PI3K/AKT signal in RA via PIK3R2. DISCUSSION: SPTBN1 alleviated the proliferation, migration, invasion, and inflammation in RA via interacting with PIK3R2.
Asunto(s)
Artritis Reumatoide , Enfermedades Autoinmunes , Humanos , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Factores de Transcripción , Inflamación , Proliferación Celular , EspectrinaRESUMEN
A new iridoid glycoside, cornushmf A(1) and nine known iridoids(2-10) were isolated from the water extract of the wine-processed Corni Fructus by various column chromatographies. Their chemical structures were identified by comprehensive spectroscopic methods as 7ß-O-(2â³-formylfuran-5â³-methylene)-morroniside(1), 7-dehydrologanin(2), sweroside(3), 7ß-O-methylmorroniside(4), 7α-O-methylmorroniside(5), 7ß-O-ethylmorroniside(6), 7α-O-ethylmorroniside(7), cornuside(8), sarracenin(9), and loganin(10).
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Cornus , Medicamentos Herbarios Chinos , Vino , Cornus/química , Medicamentos Herbarios Chinos/química , IridoidesRESUMEN
In view of the current inadequate standards for Gleditsiae Spina in the Chinese Pharmacopoeia, this study put forward some new items of the quality standards of Gleditsiae Spina. Thin-layer chromatography(TLC) was performed for identification with the reference substance of taxifolin and the reference material of Gleditsiae Spina as the control. According to the general principles of the Chinese Pharmacopoeia(2020 edition, Vol. 4), the moisture, total ash content, and alcohol-soluble extract of medicinal materials and decoction pieces of Gleditsiae Spina were determined. The content determination method for medicinal materials and decoction pieces of Gleditsiae Spina was established using high-performance liquid chromatography(HPLC), with taxifolin as the quality control index. Based on the determination results of 30 batches of samples of Gleditsiae Spina from different habitats, the draft quality standards of Gleditsiae Spina were developed, which provided suggestions for the revision of the quality standards of Gleditsiae Spina in the Chinese Pharmacopoeia.
Asunto(s)
Medicamentos Herbarios Chinos , Cromatografía Líquida de Alta Presión , Control de Calidad , Estándares de ReferenciaRESUMEN
Reverse prediction and molecular docking techniques were employed to evaluate the feasibility of reniformin A(RA) as an anti-tumor leading compound. Based on the reverse prediction, network pharmacology was used to construct a "disease-compound-target-pathway" network. Thirty-nine tumor-related targets of RA were predicted, which participated in the regulation of multiple cellular activities such as apoptosis, cell cycle, and tumor metastasis, and regulated estrogen signal transduction and inflammatory response. Discovery Studio 2020 was adopted for molecular docking and toxicity prediction(TOPKAT). As revealed by the results, the binding affinity of RA with the tumor-related targets ABL1, ESR1, SRC and BCL-XL was stronger than that of oridonin(OD), while its mutagenicity, rodent carcinogenesis, and oral LD_(50) in rats were all inferior to that of OD. Furthermore, in vitro experiments were performed to confirm the anti-tumor activity of RA, and the mechanism was preliminarily discussed. The results demonstrated that RA was superior to OD in cytotoxicity, inhibition of cell colony formation, and induction of apoptosis. RA, possessing potent anti-tumor activity, is expected to be a new anti-tumor leading compound.
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Medicamentos Herbarios Chinos , Neoplasias , Animales , Medicamentos Herbarios Chinos/farmacología , Plomo , Simulación del Acoplamiento Molecular , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Ratas , Transducción de SeñalRESUMEN
Over-expression of the pathway specific positive regulator gene is an effective way to activate silent gene cluster. In the curret study, the SARP family regulatory gene, vasR2, was over-expressed in strain Verrucosispora sp. NS0172 and the cryptic gene cluster responsible for the biosynthesis of pentaketide ansamycin was partially activated. Two tetraketides (1 and 2) and a triketide (3) ansamycins, together with five known compounds (4-8), were isolated and elucidated from strain NS0172OEvasR2. Their NMR data were completely assigned by analysis of their HR-ESI-MS and 1H, 13C NMR, HMQC, HMBC and 1H-1H COSY spectra.
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Micromonosporaceae , Policétidos , Rifabutina/metabolismo , Micromonosporaceae/genética , Micromonosporaceae/metabolismo , Familia de Multigenes , Policétidos/metabolismoRESUMEN
Four new gallate derivatives-ornusgallate A, ent-cornusgallate A, cornusgallate B and C (1a, 1b, 2, 3)-were isolated from the wine-processed fruit of Cornus officinalis. Among them, 1a and 1b are new natural compounds with novel skeletons. Their chemical structures were elucidated by comprehensive spectroscopy methods including NMR, IR, HRESIMS, UV, ECD spectra and single-crystal X-ray diffraction analysis. The in vitro anti-inflammatory activities of all compounds were assayed in RAW 264.7 cells by assessing LPS-induced NO production. As the result, all compounds exhibited anti-inflammatory activities at attested concentrations. Among the tested compounds, compound 2 exhibited the strongest anti- inflammatory activity.
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Antiinflamatorios , Cornus/química , Frutas/química , Ácido Gálico , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Ácido Gálico/análogos & derivados , Ácido Gálico/química , Ácido Gálico/aislamiento & purificación , Ácido Gálico/farmacología , Lipopolisacáridos/toxicidad , Ratones , Óxido Nítrico/metabolismo , Células RAW 264.7RESUMEN
One new ent-Kaurane diterpenoid (1) was isolated from the ethyl acetate fraction of Isodon henryi. Along with ten diterpenoids (2-11) were isolated from this plant for the first time, including six 7,20-epoxy diterpenoids, three enmenol-type diterpenoids and one 6,7-seco-ent-kaurene diterpenoid. Their structures were elucidated by 1 D and 2 D NMR, confirmed by HRESIMS and electronic circular dichroism analyses. Furthermore, the cytotoxicities of twelve compounds were investigated in five human cancer cell lines, including A2780, BGC-823, HCT-116, HepG2 and HeLa. And the IC50 values of these diterpenoids ranged from 2.1 to 88.8 µM in the tested cell lines. Based on the molecular structures of 12 compounds and the bioassay results, it suggests that α,ß-unsaturated pentanone is the cytotoxic active site of 7,20 epoxy ent-kaurane diterpenoid, but it does not contribute much to enmenol-type diterpenoid.Supplemental data for this article can be accessed at https://doi.org/10.1080/14786419.2019.1675067.
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Diterpenos de Tipo Kaurano/aislamiento & purificación , Isodon/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Espectroscopía de Resonancia Magnética con Carbono-13 , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Diterpenos de Tipo Kaurano/química , Humanos , Concentración 50 Inhibidora , Espectroscopía de Protones por Resonancia Magnética , Relación Estructura-ActividadRESUMEN
Constitutively expression of the pathway-specific activators is an effective method to activate silent gene clusters and improve natural product production. In this study, nine shunt products of aminoansamycins (1-9) were identified from a recombinant mutant strain S35-LAL by overexpressed the large-ATP-binding regulator of the LuxR family (LAL) gene aas1 in Streptomyces sp. S35. All the compounds showed no anti-microbial, anti-T3SS and cytotoxic activities.
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Productos Biológicos/metabolismo , Lactamas Macrocíclicas/metabolismo , Familia de Multigenes , Streptomyces/genética , Organismos Modificados Genéticamente , Streptomyces/metabolismoRESUMEN
One new bisesquiterpenoid, biepiasreorlid II (1), three new sesquiterpene lactones 8α-methoxy-epiasterolid (4), 3ß-acetoxyl-8-epiasterolid (5), and 3ß-acetoxyl-atractylenolide I (6), along with five known analogues (2-3 and 7-9), were obtained from rhizome of Atractylodes macrocephala Koidz. All structures were assigned on the basis of detailed spectroscopic analyses. The absolute configuration of 1 was established by the analysis of single-crystal X-ray diffraction with Ga Kα radiation, and 4-6 were elucidated by TDDFT-ECD calculations. The CREB agonistic activity was investigated in HEK293T cells using dual luciferase reporter assay. Compounds 1, 2, 5, and 7-9 exhibited strong to agonistic activities on CREB.
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Atractylodes/química , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/antagonistas & inhibidores , Lactonas/farmacología , Sesquiterpenos/farmacología , China , Células HEK293 , Humanos , Lactonas/aislamiento & purificación , Estructura Molecular , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Rizoma/química , Sesquiterpenos/aislamiento & purificaciónRESUMEN
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMEN
Discovering anticancer drugs that do not have adverse side effects has been a developing research field worldwide in recent decades. In this work, four previously undescribed cytotoxic diterpenoids were isolated from the aerial parts of Isodon excisoides. Interestingly, these four diterpenoids were two pairs of tautomers that were first reported in plants. Their structures were further elucidated using various spectroscopic methods. The tautomerization phenomenon and mechanism for these two pairs of tautomers were emphatically described. The theoretical simulation results indicated that the diterpene tautomerization is greatly related to certain factors, including the existence of a transition state, the change of bond length and the level of conversion energy; the tautomerization for the two pairs of tautomers is mainly caused by proton transfer. For bioassays, the cytotoxicities of the tautomers against five human cancer cell lines were also investigated. The results indicated that each of the four diterpenoids showed significant cytotoxicity in at least three cell lines and could serve as potential anticancer agents for further investigation.
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Antineoplásicos/química , Neoplasias del Colon/tratamiento farmacológico , Alcaloides Diterpénicos/química , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Apoptosis , Alcaloides Diterpénicos/aislamiento & purificación , Alcaloides Diterpénicos/farmacología , Descubrimiento de Drogas , Células HCT116 , Humanos , Isodon , Estructura Molecular , Análisis EspectralRESUMEN
To obtain diterpene glycosides from an aqueous extract of the aerial parts of Isodon henryi and further investigate their cytotoxicities, in this study, a total of seven compounds were isolated, including six ent-kaurane diterpene glycosides (1-6) and one diterpene aglycon (7). Among the seven ent-kaurane diterpenes obtained, four were novel compounds, including ent-7,20-epoxy- kaur-16-en-1α,6ß,7ß,15ß-tetrahydroxyl-11-O-ß-d-glucopyranoside (1), ent-7,20-epoxy-kaur-16-en- 6ß,7ß,14ß,15ß-tetrahydroxyl-1-O-ß-d-glucopyranoside (2), ent-7,20-epoxy-kaur-16-en-6ß,7ß,15ß- trihydroxyl-1-O-ß-d-glucopyranoside (3), and ent-7,20-epoxy-kaur-16-en-7ß,11ß,14α,15ß-tetrahydr- oxyl-6-O-ß-d-glucopyranoside (4), and three were isolated from this plant for the first time (5-7). Their structures were elucidated by utilizing spectroscopic methods and electronic circular dichroism analyses. Furthermore, the cytotoxicities of all seven compounds were investigated in four human cancer cell lines, including A2780, BGC-823, HCT-116, and HepG2. The IC50 values of these diterpenes ranged from 0.18 to 2.44 mM in the tested cell lines. In addition, the structure-cytotoxicity relationship of diterpene glycosides was also evaluated to study the effect of glycosylation on the cytotoxicity of diterpene compounds.
Asunto(s)
Diterpenos de Tipo Kaurano/química , Diterpenos de Tipo Kaurano/farmacología , Glicósidos/química , Glicósidos/farmacología , Isodon/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Modelos Moleculares , Estructura Molecular , Análisis Espectral , Relación Estructura-ActividadRESUMEN
The chemical constituents of the water extraction of the aerial parts of Isodon henryi were investigated by various chromatographic methods including D-101 macroporous adsorptive resins,silica gel,sephadex LH-20,and semi-preparative HPLC. As a result,ten compounds were separated and purified. By analyses of the UV,IR,MS,NMR spectra,their structures were determined as rabdosinate( 1),lasiokaurin( 2),epinodosinol( 3),rabdosichuanin C( 4),epinodosin( 5),hebeirubescensin k( 6),rubescensin C( 7),enmenol( 8),oridonin( 9),and enmenol-1-ß-glucoside( 10). Compounds 1-8 and 10 were isolated from I. henryi for the first time. Compounds 2 and 9 showed inhibitory effects against four tumor cells,with IC50 values of 2. 25-9. 32 µmol·L-1.