RESUMEN
Seventeen undescribed iridoid derivatives (1-17) and four known compounds (18-21) were isolated from the whole plant of Hedyotis diffusa Willd. Their structures were elucidated based on unambiguous spectroscopic data (UV, IR, HRESIMS, CD, and 1D and 2D NMR). It is noteworthy that compounds 1-8, which possess unique long-chain aliphatic acid moiety, were reported for the first time among the iridoid natural products. All compounds were evaluated for their anti-inflammatory activities in lipopolysaccharide-induced RAW 264.7 cells. Compounds 2, 4, and 6 showed significant suppression effects on nitric oxide production, with IC50 values of 5.69, 6.16, and 6.84 µM, respectively. The structure-activity relationships of these compounds indicated that long-chain aliphatic moieties at C-10 might be the key group for their anti-inflammatory activities. The therapeutic properties of these iridoid derivatives could give an insight into utilizing H. diffusa as a natural source of anti-inflammatory agents.
Asunto(s)
Hedyotis , Iridoides , Iridoides/farmacología , Iridoides/química , Hedyotis/química , Extractos Vegetales/química , Relación Estructura-Actividad , Antiinflamatorios/farmacología , Antiinflamatorios/químicaRESUMEN
Six undescribed lavandulylated flavonoids (1-6) were isolated from the roots of Sophora flavescens. Remarkably, compounds 1 and 2, which were composed of a flavane unit and a phloroglucinol unit, were the first reported dimers. Compounds 3 and 4 were the first reported neoflavonoids with lavandulyl units. Compounds 5 and 6 were chalcone with oxidized lavandulyl units. Their structures were fully characterized by cumulative analyses of UV, IR, HRESIMS, NMR and ECD spectroscopic data, along with computational calculations through density functional theory. Compounds 1 and 2 showed significant protein tyrosine phosphatase-1B inhibitory activities with IC50 values of 2.669 and 3.596 µM, respectively.
Asunto(s)
Flavonoides , Sophora , Flavonoides/química , Sophora flavescens , Sophora/química , Extractos Vegetales/química , Raíces de Plantas/químicaRESUMEN
A series of 4-thiosubstituted flavan derivatives (1-44) were designed and synthesized. The target compounds were assayed for inhibitory activity against α-glucosidase in vitro, and the results indicated that all compounds displayed significant effects in the range of IC50 = 1.03-7.48 µM compared to that of acarbose, the positive control drug. Structure-activity relationship (SAR) studies indicated that the hydroxyl groups in the flavan B ring, the electron withdrawing groups, and the length of the alkyl chains are important for this biological activity. In addition, some compounds were tested for their tolerance to sucrose in mice, and compound 44 exhibited activity comparable to that of acarbose. Docking analysis indicated that compound 44 binds to the enzyme in a pocket close to the catalytic site, similar to acarbose.
Asunto(s)
Acarbosa , Inhibidores de Glicósido Hidrolasas , Acarbosa/farmacología , Animales , Inhibidores de Glicósido Hidrolasas/farmacología , Hipoglucemiantes/farmacología , Ratones , Simulación del Acoplamiento Molecular , Estructura Molecular , Relación Estructura-Actividad , alfa-Glucosidasas/metabolismoRESUMEN
Seven new phenolic acids, 7, 8-epiblechnic acid (1), 8-epiblechnic acid 9-ehthyl-9'-methyl ester (2), 9'-ehyl-isolithospermate (3), 9''-methyl-isolithospermate (4), 9'-ethyl-9''-methyl-isolithospermate (5), 9', 9''-dimethyl-isolithospermate (6), sebesteniod E (7), were isolated from the roots of Salvia miltiorrhiza. Their structures were elucidated by detailed spectroscopic means including UV, IR, HRESIMS, and NMR data spectra. The bioactive assays of compounds 1-7 against neuroprotection activities were determined. The results suggested that compound 4 exhibited a moderate glutamate-induced neuroprotective activity and the cell survival rate was 24.0% (10-5 mol/L), while compound 2 showed weak activity (survival rate: 7.58%, 10-5 mol/L), using PHPB (survival rate: 7.56%, 10-5 mol/L) as positive control.
Asunto(s)
Salvia miltiorrhiza , Hidroxibenzoatos/farmacología , Estructura Molecular , Raíces de Plantas , Salvia miltiorrhiza/químicaRESUMEN
A phytochemistry of the whole plant of Agrimonia pilosa led to the discovery of two new nortriterpenoids, agrimonorterpenes A and B (1 and 2), together with one known triterpenoid fupenzic acid (3) and seven known sesquiterpenoids (4-10). The new structures were determined as 19α-hydroxy-2-oxo-nor-A (3)-urs-11,12-dien-28-oic acid (1) and 2, 19ß-dihydroxy-3-oxo-23-noroleana-1, 4, 12-trien-28-oic acid (2) by the spectroscopic data of UV, IR, HR-ESI-MS, and NMR. Notably, the structure of 1 possessed a rare five-membered A- ring. And this is the first time to discover the sesquiterpenoids (4-10) from A. pilosa. Compound 3 displayed the selective cytotoxicity against HCT116, BGC823, and HepG2 cell lines with the IC50 values of 16.31 µM, 21.94 µM, and 23.40 µM, respectively.
Asunto(s)
Agrimonia/química , Sesquiterpenos/aislamiento & purificación , Triterpenos/aislamiento & purificación , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Inhibidores de Glicósido Hidrolasas/toxicidad , Espectroscopía de Resonancia Magnética , Rotación Óptica , Sesquiterpenos/química , Sesquiterpenos/toxicidad , Espectrofotometría Infrarroja , Espectrofotometría Ultravioleta , Triterpenos/química , Triterpenos/toxicidadRESUMEN
One pair of new amides enantiomers (1a and 1b) and two known amides were isolated from the rhizomes of Polygonum cuspidatum. Their structures were established using UV, IR, HRESIMS, and NMR data. Notably, compound 1 possesses unique C-C connection between feruloyltyramine and resveratrol. Their absolute configurations were determined by the ECD method. All compounds were evaluated for their α-glucosidase inhibitory activity and compounds 2 and 3 showed significant inhibitory activity with IC50 values of 2.82 and 13.06 µmol/L, respectively (positive control acarbose, IC50 385 µmol/L).
Asunto(s)
Fallopia japonica , Polygonum , Amidas/farmacología , Estructura Molecular , Extractos Vegetales , RizomaRESUMEN
Phytochemical investigation of the rhizome of Ligusticum chuanxiong Hort led to the isolation and identification of three new compounds, chuanxiongoside A, (2E,4E)-8-(6-O-inositolyl)-8-oxo-2,7-dimethyl-octadienoic acid (2), chuanxiongoside C (3). The structures of these compounds were unambiguously established by HR-ESI-MS, UV, IR, CD, NMR spectral data and comparison to reported data. All the isolated compounds (1-3) were investigated for their inhibitory effects on nitric oxide (NO) production in LPS-induced RAW 264.7 cells. All compounds showed excellent inhibition of NO production stronger than curcumin. [Formula: see text].
Asunto(s)
Medicamentos Herbarios Chinos , Ligusticum , Humanos , Inflamación , Estructura Molecular , RizomaRESUMEN
Four new compounds including two new phenylpropanoid esters of sucrose, polygonusucroside A (1) and B (2); two new anthraquinones, 8-O-ß-d-(6'-galloyl)-glucopyranoside (3) and polyanthraquinoside A (4), together with six known compounds were isolated from Polygonum cuspidatum. Their structures were established using UV, IR, HRESIMS, and NMR data. All compounds were evaluated for their α-glucosidase inhibitory activities and neuroprotective effects. Compounds 5, 7 and 9 showed significant α-glucosidase inhibitory activities with IC50 values of 27.30, 5.51, and 1.09 µmol/L, respectively (acarbose as positive control, IC50 = 6.17 µmol/L). In addition, the assessment of neuroprotective effect showed that compound 3 exhibited remarkable effect against PC12 cells injured by serum-deprivation and compounds 2, 7, and 9 exhibited moderate effects against PC12 cells injured by rotenone.
Asunto(s)
Antraquinonas/farmacología , Ésteres/farmacología , Fallopia japonica/química , Fármacos Neuroprotectores/farmacología , Animales , Antraquinonas/aislamiento & purificación , China , Ésteres/aislamiento & purificación , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Inhibidores de Glicósido Hidrolasas/farmacología , Estructura Molecular , Fármacos Neuroprotectores/aislamiento & purificación , Células PC12 , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Ratas , Rotenona , Sacarosa , alfa-GlucosidasasRESUMEN
Two new lignans, wikstronoside B (1) and forsysesquinorlignan (2), were isolated from the fruits of Forsythia suspensa, along with two known sesquineolignans, hedyotol A and hedyotol C (3 and 4). The structures of new compounds were established via extensive spectroscopy techniques, including UV, IR, HRESIMS, NMR, and ECD. Compounds 3 and 4 were isolated from this plant for the first time. Their anti-inflammatory effects were evaluated via a detection model with LPS-induced murine macrophage RAW264.7 cells, and compound 3 showed a moderate activity.
Asunto(s)
Forsythia , Lignanos , Animales , Frutas , Ratones , Estructura Molecular , Extractos VegetalesRESUMEN
Five new phenylpropanoid glycosides, susaroysides A-E (1-5) were isolated from the fruits of Forsythia suspensa. Their structures were elucidated by comprehensive spectroscopic data analysis. The absolute configurations of their sugars were determined by GC analysis. Notably, susaroysides A-D possessed a sugar with an unsubstituted anomeric carbon, which is relatively rare in natural sources. Compound 1 exhibited significant anti-inflammatory activity against the lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α expression in macrophage cells with the IC50 value of 1.053⯵M.
Asunto(s)
Antiinflamatorios/farmacología , Forsythia/química , Frutas/química , Glicósidos/farmacología , Macrófagos/efectos de los fármacos , Extractos Vegetales/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Humanos , Lipopolisacáridos/farmacología , Macrófagos/citología , Macrófagos/inmunología , Macrófagos/metabolismo , Fenoles/química , Propanoles/químicaRESUMEN
In the course of studying the components from the roots of Sophora flavescens, eight new unusual biflavonoids consisting of a flavanone fused with a dihydrochalcone skeleton were isolated. These new chemical structures were elucidated by means of UV, IR, HRESIMS, NMR and ECD spectroscopic data and a comparison of experimental ECD spectra with calculated ECD spectra. Some compounds were subjected to an antidiabetic bioassay on human recombinant PTP1B inhibition, and showed strong inhibitory activity.
Asunto(s)
Monoterpenos Acíclicos/farmacología , Biflavonoides/farmacología , Inhibidores Enzimáticos/farmacología , Extractos Vegetales/farmacología , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Sophora/química , Monoterpenos Acíclicos/química , Monoterpenos Acíclicos/aislamiento & purificación , Biflavonoides/química , Biflavonoides/aislamiento & purificación , Chalconas/química , Chalconas/aislamiento & purificación , Chalconas/farmacología , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Humanos , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Raíces de Plantas/química , Proteína Tirosina Fosfatasa no Receptora Tipo 1/metabolismo , Proteínas Recombinantes/metabolismo , Relación Estructura-ActividadRESUMEN
Eight new triterpenoid saponins (1-8), were isolated from the roots of Glycyrrhiza uralensis Fisch., together with 10 known triterpenoid saponins (9-18). Their structures were determined by analysis of their spectroscopic data and comparison with the reference. All of the compounds were evaluated for their antioxidant effects in the in vitro assay. Compounds 2 and 8 showed significant antioxidant activities against Fe2+/cysteine-induced liver microsomal lipid peroxidation at 0.1 µM.
Asunto(s)
Antioxidantes/farmacología , Glycyrrhiza uralensis/química , Saponinas/farmacología , Triterpenos/farmacología , Antioxidantes/aislamiento & purificación , China , Peroxidación de Lípido , Microsomas Hepáticos/efectos de los fármacos , Estructura Molecular , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Raíces de Plantas/química , Saponinas/aislamiento & purificación , Triterpenos/aislamiento & purificaciónRESUMEN
Flower of Chrysanthemum morifolium is widely used in China and Japan as a folk medicine in treatment of many diseases. However, its active compounds remain largely unknown. In the present work, we have isolated, purified and characterized six new compounds (1-6), including two new arylnaphthalene lignans and four new phenolic glycosides, together with eight known compounds (7-14), from the flower of C. morifolium. Their structures and absolute configurations were elucidated in detail using 1D and 2D NMR, UV, IR, ORD, HRESIMS and ECD spectrometric data. In addition, compounds 1-3 possessed the significant neuroprotective activity against hydrogen peroxide-induced neurotoxicity in human neuroblastoma SH-SY5Y cells.
Asunto(s)
Catecoles/farmacología , Chrysanthemum/química , Flores/química , Glucósidos/farmacología , Lignanos/farmacología , Fármacos Neuroprotectores/farmacología , Animales , Catecoles/química , Catecoles/aislamiento & purificación , Línea Celular Tumoral , Glucósidos/química , Glucósidos/aislamiento & purificación , Humanos , Peróxido de Hidrógeno/efectos adversos , Lignanos/química , Lignanos/aislamiento & purificación , Ratones , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/aislamiento & purificación , Estrés Oxidativo/efectos de los fármacos , Células RAW 264.7RESUMEN
Four new ferulic acid derivatives ligusticumacid A-C (1-3) and ligusticumaldehyde A (4), one new dimer ligusticumacid D (5), and two novel 8-8' lignans ligusticumacid E-F (6-7) were isolated from the rhizome of Ligusticum chuanxiong Hort. In particular, compounds 1-2, 5 were rarely phenylpropanoid phenolic acid dimers through different polymerization action in natural products. Their structures were established using UV, IR, HRESIMS, NMR data. The absolute configurations of 3 was determined by quantum ECD calculation and 4, 6-7 were determined by the ECD exciton chirality method. In addition, all compounds were evaluated for their neuroprotective effects on human neuroblastoma SH-SY5Y cell injury induced by H2O2. Compound 2 had a moderate neuroprotective activity and 7 had a weak neuroprotective activity on human neuroblastoma SH-SY5Y cell injury induced by H2O2 respectively.
Asunto(s)
Ácidos Cumáricos/química , Ligusticum/química , Fármacos Neuroprotectores/química , Línea Celular Tumoral , China , Ácidos Cumáricos/aislamiento & purificación , Humanos , Estructura Molecular , Fármacos Neuroprotectores/aislamiento & purificación , Rizoma/químicaRESUMEN
In our study to investigate components with hepatoprotective activities, eight new phenylethanoid glycoside derivatives (1-8) were isolated from the 75% EtOH-H2O extract of the fruits of Forsythia suspensa along with six known compounds (9-14). These new structures were elucidated through HRESIMS and extensive NMR spectroscopic techniques. The absolute configurations of their sugars were determined by GC analysis. The pharmacological assay showed that compounds 2, 3, and 9-11 displayed remarkable hepatoprotective activities against N-acetyl-p-aminophenol (APAP)-induced HepG2 cell damage at the concentration of 10µM (Bicyclol as positive contrast).
Asunto(s)
Forsythia/química , Glicósidos/farmacología , Acetaminofén , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Frutas/química , Glicósidos/aislamiento & purificación , Células Hep G2/efectos de los fármacos , Humanos , Estructura MolecularRESUMEN
Three new caffeoylquinic acid derivatives, chrysanthemorimic acids A-C (1-3), and 11 known compounds (4-14) were isolated and characterized from the flowers of Chrysanthemum morifolium. Their structures were confirmed by spectroscopic data as well as by comparison of the experimental and calculated electronic circular dichroism spectra. Chrysanthemorimic acids A-C possess a rare 8-oxa-bicyclo[3.2.1]oct-3-en-2-one ring that is formed through a [5+2] cycloaddition of caffeoylquinic acid with a d-glucose derivative. Compounds 1-3, 6-8, 12, and 13 displayed significant effects against hydrogen peroxide-induced neurotoxicity in SH-SY5Y cells at 10 µM.
Asunto(s)
Ácido Clorogénico/aislamiento & purificación , Ácido Clorogénico/farmacología , Chrysanthemum/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Flores/química , Fármacos Neuroprotectores/aislamiento & purificación , Fármacos Neuroprotectores/farmacología , Ácido Clorogénico/análogos & derivados , Ácido Clorogénico/química , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/química , Flavonoides/química , Glucosa/análisis , Peróxido de Hidrógeno/análisis , Estructura Molecular , Fármacos Neuroprotectores/química , Resonancia Magnética Nuclear BiomolecularRESUMEN
Phytochemical and pharmacological study on the rhizomes of Atractylodes lancea led to the identification of twenty-one compounds: six new eudesmane-type sesquiterpenoids (1-6), two new eremophilane-type sesquiterpenoids (7, 8), and thirteen known compounds (9-21). These new compounds were elucidated using extensive spectroscopic analyses with experimental and calculated electronic circular dichroism (ECD) for the configurational assignments. Notably, this study was the first report on the isolation of two eremophilane-type sesquiterpenoids (7, 8) from the genus Atractylodes. Compounds 5, 7, and 16 showed potent hepatoprotective activities against N-acetyl-p-aminophenol (APAP)-induced HepG2 cell injury at a concentration of 10µM (bicyclol as the positive drug).
Asunto(s)
Atractylodes/química , Sesquiterpenos de Eudesmano/química , Sesquiterpenos/química , Acetaminofén/efectos adversos , Células Hep G2 , Humanos , Estructura Molecular , Sesquiterpenos Policíclicos , Rizoma/química , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos de Eudesmano/aislamiento & purificaciónRESUMEN
Phytochemical investigation of the extract of Arctii Fructus led to the isolation and characterization of two new compounds, named arctiisesquineolignan B (1) and arctiiphenolglycoside A (2). Their structures were elucidated by means of spectroscopic methods (UV, IR, HR-ESI-MS, 1D and 2D NMR) and chemical evidence, as well as by comparison with known analogs in the literature. Compound 2 exhibited stronger antioxidant activity than the positive control ascorbic acid at a concentration of 10 µM.
Asunto(s)
Antioxidantes/aislamiento & purificación , Arctium/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Frutas/química , Lignanos/aislamiento & purificación , Algoritmos , Antioxidantes/química , Antioxidantes/farmacología , Ácido Ascórbico/farmacología , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Glicósidos/química , Lignanos/química , Lignanos/farmacología , Estructura Molecular , Resonancia Magnética Nuclear BiomolecularRESUMEN
Lyciumsterols A-K (1-11), 11 new octahydroxylated C21 steroids, were isolated from the root bark of Lycium chinense, along with 15 known compounds. Characterization of these C21 steroids showed the presence of eight hydroxy groups on the C21 steroid skeleton with a (2E,4E)-5-phenyl-2,4-pentadienoate group at C-12 or C-20 and various 2,6-deoxy sugar residues at C-3. The structures of these compounds were elucidated using spectroscopic data interpretation. Compounds 2, 3, and 7 exhibited dose-dependent protective effects on pancreatic islet cells and may help to improve cell viability. In addition, it was found that compounds 7, 8, 9, and 11 exhibited autophagy activation.
Asunto(s)
Lycium/química , Pregnanos/aislamiento & purificación , Pregnanos/farmacología , Autofagia/efectos de los fármacos , Humanos , Estructura Molecular , Corteza de la Planta/química , Extractos Vegetales/química , Raíces de Plantas/química , Pregnanos/químicaRESUMEN
Based on the theory of traditional Chinese medicine, modern methods for drug investigation such as molecular targets in vitro and effects in vivo were used to study the prescription of Jingdan Yimin(JD), including selection of raw materials, composition, proportion, and effective dose of the compounds for treatment of metabolic syndrome. The IRF mice models, characterized by insulin resistance and hypercholesterolemia, were induced by high fat diet. The insulin sensitivity was estimated with insulin tolerance test(ITT) and glucose tolerance test(GTT); the levels of blood glucose and total cholesterol(TC), and the activities of α-glucosidase, protein tyrosine phosphatase 1B(PTP1B), and fructose phosphate amide transferase(GFAT)were measured with biochemical methods, respectively. The sample H13(h) extracted from Rhodiola crenulata, Y12(y) from Cordyceps militaris, and D(d) from Rheum palmatum were selected according to the inhibition activity on both PTP1B and α-glucosidase in vitro, regulation on hypercholesterolemia in IRF mice, and effects on GFAT activity, respectively; their synergistic effects on the treatment of metabolic syndrome were determined in IRF mice; composition proportion of hâ¶yâ¶d was measured in accordance with the results of L8(27) orthogonal experiments targeting on the inhibition of both PTP1B and α-glucosidase; finally, the effective dose was assessed based on the effects on IGT and hypercholesterolemia, respectively, in IRF mice. In conclusion, the prescription JD is composed by R. crenulata, C. militaris, and R. palmatum with the rate of 20â¶1â¶1, and its effective oral dose is 200 mgâ¢kg⻹ for treatment of metabolic syndrome; its main mechanism is to inhibit the targets PTP1B and α-glucosidase. Monarch drug, R. crenulata, can clear away the lung-heat, tonify Qi, resolve stasis and nourish the heart. Adjuvant drug, C. militaris, can tonify the lung Qi and the kidney essence, strengthen waist and knee, accompanied with R. crenulata to enhance the function of invigorating lung and kidney. Assistant drug, rhubarb, can clear heat, detoxify, and remove blood stasis. These three herbs are compatible to show the effects of tonifying Qi, nourishing essence, clearing heat, reducing phlegm and resolving masses for the treatment of metabolic syndrome.