RESUMEN
The column chromatography with silica gel, reversed-phase C_(18), and Sephadex LH-20 was employed to separate the methanol extract of the aerial parts of Hypericum elatoides. The compounds were identified by the comprehensive analysis of IR, NMR, and MS data as methyl 8-O-ß-D-glucopyranosyl-(Z)-5-octenoate(1), methyl 3-O-ß-D-glucopyranosyl-4-methylhexanoate(2), byzantionoside B(3), 9-epi-blumenol C glucoside(4), corchoionoside C(5),(6S,9R)-roseoside(6), cis-p-coumaric acid 4-O-ß-D-glucopyranoside(7), trans-p-coumaric acid 4-O-ß-D-glucopyranoside(8), methyl 3-(4-hydroxyphenyl)propanoate(9),(E)-chlorogenic acid methyl ester(10), quercetin-3-O-ß-D-glucopyranoside(11), ß-sitosterol(12), stigmasterol(13), stigmast-4-en-3-one(14), ß-amyrin(15), daucosterol(16), sitoindoside â (17), oleic acid(18), methyl α-linolenate(19), trilinolein(20), and cassipourol(21). Among them, compounds 1 and 2 were identified as new glycosides and named hyperelatosides G and H. Compounds 3-5, 7-9, 17, and 20-21 were isolated from the genus Hypericum for the first time. The remaining compounds were isolated from H. elatoides for the first time. The results of biological assays revealed that compound 11 exhibited significant anti-neuroinflammatory activity, and compounds 1, 3, and 19 displayed certain neuroprotective effects.
Asunto(s)
Glicósidos , Hypericum , Hypericum/química , Glicósidos/química , Glicósidos/aislamiento & purificación , Estructura Molecular , Medicamentos Herbarios Chinos/química , Espectroscopía de Resonancia MagnéticaRESUMEN
Nine new sesquiterpenes, hyperhubeins A-I (1-9), and 14 known analogues (10-23) were isolated from the aerial portions of Hypericum hubeiense. Their structures and absolute configurations were determined unambiguously via spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Compounds 1-3 possess an unprecedented sesquiterpene carbon skeleton. Further, a plausible biosynthetic pathway from farnesyl diphosphate (FPP) is proposed. The isolated phytochemicals were evaluated for neuroprotective and anti-neuroinflammatory properties in vitro. Compounds 1, 2, 5-8, 14, and 21 displayed notable neuroprotective activity against hydrogen peroxide (H2O2)-induced lesions in PC-12 cells at 10 µM. Additionally, compounds 1, 2, 12, and 13 exhibited inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV-2 microglial cells, with their IC50 values ranging from 4.92 to 6.81 µM. Possible interactions between these bioactive compounds and inducible nitric oxide synthase (iNOS) were predicted via molecular docking. Moreover, Western blotting indicated that compound 12 exerted anti-neuroinflammatory activity by suppressing LPS-stimulated expression of toll-like receptor-4 (TLR-4) and inhibiting consequent activation of nuclear factor-kappa-B (NF-κB) signaling.
Asunto(s)
Hypericum , Sesquiterpenos , Antiinflamatorios/química , Lipopolisacáridos/farmacología , Lipopolisacáridos/metabolismo , Peróxido de Hidrógeno , Simulación del Acoplamiento Molecular , FN-kappa B/metabolismo , Microglía/metabolismo , Dicroismo Circular , Óxido Nítrico , Óxido Nítrico Sintasa de Tipo II/metabolismoRESUMEN
Four new δ- and γ-lactone derivatives, hyperelatolides A-D (1-4, respectively), were discovered from the aerial portions of Hypericum elatoides R. Keller. Their structures were elucidated by analysis of NMR spectra, HRESIMS, quantum chemical calculations of NMR and ECD spectra, and X-ray crystallographic data. Hyperelatolides A (1) and B (2) represent the first examples of δ-lactone derivatives characterized by a (Z)-(5,5-dimethyl-2-(2-oxopropyl)cyclohexylidene)methyl moiety and a benzoyloxy group attached to the ß- and γ-positions of the δ-lactone core, respectively, while hyperelatolides C (3) and D (4) are unprecedented γ-lactone derivatives featuring substituents similar to those of 1 and 2. All compounds were tested for their inhibitory effects on NO production in LPS-activated BV-2 cells. Lactones 1 and 2 exhibited considerable antineuroinflammatory activity, with IC50 values of 5.74 ± 0.27 and 7.35 ± 0.26 µM, respectively. Moreover, the mechanistic study revealed that lactone 1 significantly suppressed nuclear factor kappa B signaling and downregulated the expression of inducible nitric oxide synthase and cyclooxygenase-2 in LPS-induced cells, which may contribute to its antineuroinflammatory activity.
Asunto(s)
Hypericum , Hypericum/química , Lipopolisacáridos/farmacología , Espectroscopía de Resonancia Magnética , Lactonas/farmacología , Lactonas/química , Transducción de Señal , Estructura Molecular , Óxido NítricoRESUMEN
Our primary focus in this research was to identify and characterize its bioactive compounds for potential therapeutic use. Twenty-seven metabolites of Polygonum orientale were identified using LC-QTOF tandem mass spectrometry. Interestingly, P. orientale extracts included several highly oxygenated flavonoids were isolated from P. orientale by column chromatography. 13C NMR data of highly oxygenated flavonoids (1-7) are reported here for the first time. In addition, nitric oxide, 1,1-diphenyl-2-picrylhydrazyl, and water-soluble tetrazolium salt assays were carried out on the isolated compounds to investigate their anti-inflammatory, anti-oxidant, and neuroprotective activities, respectively. Compounds 1, 2, 3, 5, 7, and 8 significantly attenuated lipopolysaccharide-stimulated NO production in BV2 cells without affecting cell viability. Compounds 9-12 exhibited significant antioxidant activity, while compounds 8, 9, and 12 exhibited protective effects against glutamate-induced neurotoxicity in HT22 cells. Our results indicate that P. orientale is a promising source of natural agents for the potential treatment of inflammation and neurodegenerative diseases.
Asunto(s)
Medicamentos Herbarios Chinos/química , Polygonum/química , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Línea Celular Tumoral , Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/farmacología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacología , Espectrometría de Masas en Tándem/métodosRESUMEN
Hericium erinaceus is a culinary-medicinal mushroom used traditionally in Eastern Asia to improve memory. In this work, we investigated the neuroprotective and neuritogenic effects of the secondary metabolites isolated from the MeOH extract of cultured mycelium of H. erinaceus and the primary mechanisms involved. One new dihydropyridine compound (6) and one new natural product (2) together with five known compounds (1,3-5,7) were obtained and their structures were elucidated by spectroscopic analysis, including 2D NMR and HRMS. The cell-based screening for bioactivity showed that 4-chloro-3,5-dimethoxybenzoic methyl ester (1) and a cyathane diterpenoid, erincine A (3), not only potentiated NGF-induced neurite outgrowth but also protected neuronally-differentiated cells against deprivation of NGF in PC12 pheochromocytoma cells. Additionally, compound 3 induced neuritogenesis in primary rat cortex neurons. Furthermore, our results revealed that TrkA-mediated and Erk1/2-dependant pathways could be involved in 1 and 3-promoted NGF-induced neurite outgrowth in PC12 cells.
Asunto(s)
Basidiomycota/química , Mezclas Complejas/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Neuritas/metabolismo , Receptor trkA/metabolismo , Animales , Supervivencia Celular , Mezclas Complejas/química , Células PC12 , RatasRESUMEN
The phytochemical investigation of the roots of Rhus trichocarpa led to this isolation of five new alkyl phloroglucinol derivatives, characterized as (Z)-15-hydroxy-1-(2,4,6-trihydroxyphenyl)-9-octadecen-1-one (named trichocarpol A, 1), (Z)-15-hydroxy-1-(2,6-dihydroxy-4-methoxyphenyl)-9-octadecen-1-one (named trichocarpol B, 2), (Z)-17-hydroxy-1-(2,4,6-trihydroxyphenyl)-9-octadecen-1-one (named trichocarpol C, 3), (Z)-18-hydroxy-1-(2,4,6-trihydroxyphenyl)-9-octadecen-1-one (named trichocarpol D, 4), and (9Z,12Z)-18-hydroxy-1-(2,4,6-trihydroxyphenyl)-9,12-octadecadien-1-one (named trichocarpol E, 5), together with a known compound, 4-(2,6-dihydroxy-4-methoxyphenyl)-4-oxobutanoic acid (6). In vitro cytotoxic activity of compounds 1-6 was evaluated in the human gastric adenocarcinoma AGS cell line and compounds 1-5 showed significant cytotoxicity. Our results indicate that R. trichocarpa, especially the alkyl phloroglucinol derivatives in it, is a good source of promising natural agents for the treatment of gastric cancer.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antineoplásicos Fitogénicos/aislamiento & purificación , Floroglucinol/análogos & derivados , Extractos Vegetales/farmacología , Rhus/química , Neoplasias Gástricas/tratamiento farmacológico , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Humanos , Espectroscopía de Resonancia Magnética , Estructura Molecular , Extractos Vegetales/aislamiento & purificación , Raíces de Plantas/químicaRESUMEN
Continuous efforts to identify sEH inhibitors using activity-guided fractionation have revealed 12 known compounds, 2-13, from Rheum undulatum. Compounds 2-13 and 1, which was obtained from the in-house library, were tested for inhibitory activity against sEH. Compounds 1-9, 11, and 12 were shown to have inhibitory activity, with IC50 values ranging from 2.5 ± 0.5 to 53.2 ± 4.4 µM. They were subjected to enzyme kinetic studies to explore the binding mode between the ligand and receptor. Based on our results, compounds 1, 2, 5-9, and 11 (mixed type) and compounds 3 and 12 (noncompetitive type) had a preferred allosteric site. Compound 4 was identified as a competitive-type interaction in the active site. Molecular docking studies revealed the interacting residues and binding energy between sEH and inhibitors. Additionally, molecular dynamics provided detailed information on the interaction between the ligand and receptor.
Asunto(s)
Inhibidores Enzimáticos/farmacología , Epóxido Hidrolasas/antagonistas & inhibidores , Extractos Vegetales/farmacología , Estructuras de las Plantas/química , Rheum/química , Dominio Catalítico/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Epóxido Hidrolasas/metabolismo , Humanos , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Solubilidad , Relación Estructura-ActividadRESUMEN
Aloe is a short-stemmed succulent herb widely used in traditional medicine to treat various diseases and as raw material in cosmetics and heath foods. In this study, we isolated and identified two new anthraquinone derivatives, aloinoside C (6) and aloinoside D (7), together with six known compounds from an aqueous dissolved Aloe exudate. Their structures were identified by spectroscopic analysis. The inhibitory effects of the isolated compounds on soluble epoxide hydrolase (sEH) were evaluated. Compounds 1-8 inhibited sEH activity potently, with IC50 values ranging from 4.1±0.6 to 41.1±4.2 µM. A kinetic analysis of compounds 1-8 revealed that the inhibitory actions of compounds 1, 6 and 8 were non-competitive, whereas those of compounds 2-5 and 7 were the mixed-type. Molecular docking increases our understanding of receptor-ligand binding of all compounds. These results demonstrate that compounds 1-8 from Aloe are potential sEH inhibitors.
Asunto(s)
Aloe/química , Antraquinonas/farmacología , Inhibidores Enzimáticos/farmacología , Epóxido Hidrolasas/antagonistas & inhibidores , Antraquinonas/síntesis química , Antraquinonas/química , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Epóxido Hidrolasas/metabolismo , Estructura Molecular , Solubilidad , Relación Estructura-ActividadRESUMEN
This Letter describes the identification of potent antioxidant and anti-osteoporosis agents from the fruits of Prunus mume. From the methanol extract, a novel flavan dimer, characterized as 2ß,3ß-epoxy-5,7,4'-trihydroxyflavan-(4αâ8)-epicatechin (1), was isolated along with five known flavonoids (2-6). Their structures were determined based on extensive spectroscopic analysis, including IR, HRESIMS, 1D- and 2D-NMR, and CD spectra. The antioxidant activities of compounds 1-6 were evaluated in terms of their peroxyl radical-scavenging (Trolox equivalent) and reducing capacities. All isolates showed potent peroxyl radical-scavenging and reducing activities at concentrations of 1-10 µM. Among them, compounds 1 and 2 were the most active at 1 µM. Anti-osteoporosis activities were investigated using both murine osteoblastic MC3T3-E1 cells and osteoclastic RAW 264.7 cells. Compounds 2, 3, and 6 significantly stimulated the differentiation of osteoblastic MC3T3-E1 cells to increase collagen synthesis or mineralization functions of osteoblasts. Compounds 1, 3, 4, and 6 significantly suppressed tartrate-resistant acid phosphatase (TRAP) activity in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastic RAW 264.7 macrophage cells.
Asunto(s)
Antioxidantes/química , Flavonoides/química , Flavonoides/farmacología , Prunus/química , Fosfatasa Ácida/metabolismo , Animales , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Diferenciación Celular/efectos de los fármacos , Línea Celular , Colágeno/biosíntesis , Flavonoides/aislamiento & purificación , Radicales Libres/química , Frutas/química , Frutas/metabolismo , Isoenzimas/metabolismo , Espectroscopía de Resonancia Magnética , Ratones , Conformación Molecular , Prunus/metabolismo , Ligando RANK/farmacología , Fosfatasa Ácida TartratorresistenteRESUMEN
Two novel phenolic glucosides (1-2), as well as seven known compounds (3-9), were isolated from the stem of Acanthopanax koreanum; their chemical structures were determined by chemical and spectroscopic methods and subsequently compared with previously reported data. Their inhibition of nuclear factor kappa B (NF-κB) was measured in human embryonic kidney (293T) cells by using an NF-κB luciferase assay.
Asunto(s)
Eleutherococcus/química , Expresión Génica/efectos de los fármacos , FN-kappa B/biosíntesis , Fenoles/administración & dosificación , Células HEK293 , Humanos , Fenoles/química , Fenoles/aislamiento & purificación , Tallos de la Planta/químicaRESUMEN
Zanthoxylum schinifolium is an aromatic shrub, the pericarp and leaves of which are widely used in culinary applications in East Asian countries. In the present study, one new neolignan glycoside, zanthoxyloside A (1) together with 16 known glycosides (2-12) and alkaloids (13-17), were isolated from methanol extract of the stems of Z. schinifolium. The absolute configuration of one known monoterpenoid glycoside (2) was determined. The structures of the isolated compounds were established by one dimensional (1D), 2D NMR and mass spectrometry. The nuclear factor-κB (NF-κB) inhibitory activities of the isolated compounds stimulated with tumor necrosis factor alpha (TNFα) were measured using a luciferase reporter system. Compounds 1, 5, 16, and 17 exhibited significant inhibition of NF-κB activation in a dose-dependent manner. Furthermore, compounds 1, 5, 16, and 17 inhibited TNFα-induced expression of inducible nitric oxide synthase (iNOS) and intercellular adhesion molecule-1 (ICAM-1) mRNA and dose-dependent inhibition of iNOS promoter activity.
Asunto(s)
Alcaloides/farmacología , Antiinflamatorios/farmacología , Glicósidos/farmacología , FN-kappa B/antagonistas & inhibidores , Extractos Vegetales/farmacología , Zanthoxylum/química , Alcaloides/química , Alcaloides/aislamiento & purificación , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Línea Celular , Regulación de la Expresión Génica/efectos de los fármacos , Glicósidos/química , Glicósidos/aislamiento & purificación , Humanos , Molécula 1 de Adhesión Intercelular/genética , FN-kappa B/inmunología , Óxido Nítrico Sintasa de Tipo II/genética , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Tallos de la Planta/química , ARN Mensajero/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
The search for lead compounds with anti-neuroinflammatory activity from structurally 'optimized' natural products is a crucial and promising strategy in the quest to discover safe and efficacious agents for treating neurodegenerative diseases. A phytochemical investigation on the aerial portions of Hypericum elatoides led to the isolation of five nitrogenous polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperelanitriles A-D (1-4) and hyperelamine A (5). Their structures were determined by spectroscopic analysis, ECD and NMR calculations, and X-ray crystallography. To the best of our knowledge, compounds 1-4 represent the first examples of acylphloroglucinols featuring an α-aminonitrile moiety, while 5 is a rare enamine-containing PPAP. Further, the synthesis of these naturally occurring PPAP-based nitriles or amines was accomplished. Compound 5 exhibited inhibitory activity against LPS-activated NO production in BV-2 cells, potentially through the suppression of TLR-4/NF-κB signaling. Here we show the isolation, structural elucidation, synthesis, and bioactive evaluation of compounds 1-5.
RESUMEN
Two new compounds, gallic acid ester of torachrysone-8-O-ß-D-glucoside (1) and (E)-2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-xyloside (4), along with eight known compounds (2, 3, 5-10) were isolated from a 70% ethanol extract of Polygonum multiflorum roots. The structures were determined by (1)H and (13)C NMR, HMQC, and HMBC spectrometry. Extracts of P. multiflorum have been reported to promote hair growth in vivo. This study was carried out to evaluate the effects of isolated compounds from P. multiflorum on promoting hair growth using dermal papilla cells (DPCs), which play an important role in hair growth. When DPCs were treated with compounds (1-10) from P. multiflorum, compounds 1, 2, 3, 6, and 10 increased the proliferation of DPCs compared with the control. Specifically, compound 2 (10 and 20 µM) induced a greater increase in the proliferation of DPCs than minoxidil (10 µM). Additionally, treatment of vibrissa follicles with compound 2 for 21 days increased hair-fiber length significantly. On the basis of this result, further investigation and optimization of these derivatives might help in the development of therapeutic agents for the treatment of alopecia.
Asunto(s)
Glucósidos/farmacología , Glicósidos/farmacología , Cabello/efectos de los fármacos , Cabello/crecimiento & desarrollo , Extractos Vegetales/farmacología , Polygonum/química , Animales , Proliferación Celular/efectos de los fármacos , Dermis/citología , Dermis/efectos de los fármacos , Glucósidos/química , Glucósidos/aislamiento & purificación , Glicósidos/química , Glicósidos/aislamiento & purificación , Cabello/citología , Folículo Piloso/citología , Folículo Piloso/efectos de los fármacos , Folículo Piloso/crecimiento & desarrollo , Humanos , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Raíces de Plantas/química , Ratas , Ratas WistarRESUMEN
Artemisia iwayomogi has been used as a folk medicine for treating various diseases including inflammatory and immune-related diseases. Scopoletin (1) and scopolin (2) were isolated from this species. Scopoletin (1) showed more potent peroxyl radical-scavenging capacity, reducing capacity, and cellular antioxidant capacity compared to scopolin (2). The inhibitory effect of 1 on the receptor activator of nuclear factor κB ligand-induced osteoclastic differentiation of RAW 264.7 macrophage cells was also more potent than that of 2. The production of general reactive oxygen species (ROS) and superoxide anions during differentiation of preosteoclastic RAW 264.7 cells into osteoclasts was attenuated by compounds 1 and 2. These findings indicate that the suppressive effects of 1 and 2 on the differentiation of preosteoclastic RAW 264.7 cells is partially due to their intracellular antioxidant capacity, as they can scavenge ROS and play an important signaling role in the differentiation process.
Asunto(s)
Artemisia/química , Cumarinas/farmacología , Glucósidos/farmacología , Macrófagos/efectos de los fármacos , Osteoclastos/efectos de los fármacos , Especies Reactivas de Oxígeno/farmacología , Escopoletina/farmacología , Animales , Antioxidantes/farmacología , Diferenciación Celular , Cumarinas/química , Glucósidos/química , Peróxido de Hidrógeno/análisis , Corea (Geográfico) , Ratones , Estructura Molecular , Especies Reactivas de Oxígeno/análisis , Escopoletina/químicaRESUMEN
In the present study, a new oleanane-type triterpenoid saponin, pulsatilloside F (1), along with 21 known compounds (2-22), were isolated from the root of Pulsatilla koreana. Their chemical structures were elucidated by mass, (1)H-, (13)C-NMR, correlation spectroscopy (COSY), heteronuclear multiple quantum coherence (HMQC) and heteronuclear multiple bond connectivity (HMBC) spectroscopy. Anti-inflammatory effects of the compounds were evaluated in terms of inhibitory of tumor necrosis factor α (TNF-α) secretion in the lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophage cell line. Compounds 19 and 20 exhibited particularly inhibitory effects with respective IC50 values of 0.32 and 0.65 µm. Compounds 1-4, 7 and 10-13 exhibited inhibitory effects with inhibition rates up to 41.55-73.76% at a concentration of 5 µm, respectively.
Asunto(s)
Antiinflamatorios/química , Pulsatilla/química , Saponinas/química , Triterpenos/química , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Línea Celular Tumoral , Lipopolisacáridos/toxicidad , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Espectroscopía de Resonancia Magnética , Ratones , Conformación Molecular , Raíces de Plantas/química , Saponinas/aislamiento & purificación , Saponinas/farmacología , Triterpenos/aislamiento & purificación , Triterpenos/farmacología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
Pulsatilla koreana, a species endemic to Korea, is an important herb used in traditional medicine to treat amoebic dysentery and malaria. In the present study, 23 oleanane-type triterpenoid saponins 1-23 and eight lupane-type triterpenoid saponins 24-31 were isolated from the roots of P. koreana. Their structures were elucidated on the basis of spectroscopic data. The methanol extract and isolated compounds were next assessed for nematicidal activity against the root-knot nematode (Meloidogyne incognita). The methanol extract showed strong nematicidal activity after 48 h, with a LC50 value of 92.8 µg/mL. Compounds 2, 5, 9, 20, and 21 showed significant effects, with LC50 values ranging from 70.1 to 94.7 µg/mL after 48 h. These results suggest that triterpenoid saponins from P. koreana should be explored as potential natural nematicides for developing new agents to control root-knot nematode disease.
Asunto(s)
Antinematodos , Raíces de Plantas/química , Pulsatilla/química , Saponinas , Triterpenos , Tylenchoidea , Animales , Antinematodos/química , Antinematodos/aislamiento & purificación , Antinematodos/farmacología , Humanos , Corea (Geográfico) , Saponinas/química , Saponinas/aislamiento & purificación , Saponinas/farmacología , Triterpenos/química , Triterpenos/aislamiento & purificación , Triterpenos/farmacologíaRESUMEN
Plants of the genus Hypericum contain various types of secondary metabolites that exhibited extensive biological activities. In the ongoing efforts to discover natural neuroinflammatory inhibitors with the potential to develop into therapeutic agents for neurodegenerative diseases, two new benzophenone glycosides, hyperewalones A and B (1 and 2), along with eight known compounds (3-10), were isolated from the aerial parts of Hypericum przewalskii. Their structures were elucidated by comprehensive analysis of IR, HRESIMS, 1D and 2D NMR spectra, and chemical derivatization. The anti-neuroinflammatory activity of compounds 1-10 was evaluated by determining their ability to inhibit the production of nitric oxide (NO) in lipopolysaccharide (LPS)-activated BV-2 microglial cells. Compounds 2, 4, 6-8 exhibited significant anti-neuroinflammatory activity with IC50 values of 0.61-4.90 µM. These findings suggest that the benzophenone, ionone, and flavonoid glycosides isolated from H. przewalskii are promising anti-neuroinflammatory compounds worthy of further investigations.
Asunto(s)
Hypericum , Benzofenonas/química , Benzofenonas/farmacología , Glicósidos/química , Hypericum/química , Estructura Molecular , Óxido Nítrico , Componentes Aéreos de las Plantas/químicaRESUMEN
Five terpenoids, including two new cyathane diterpenoids neocyathin S (1) and neocyathin T (2), together with three drimane sesquiterpenoids, one known 3ß,6ß-dihydroxycinnamolide (3), two new ones 3ß,6α-dihydroxycinnamolide (4) and 2-keto-3ß,6ß-dihydroxycinnamolide (5), were isolated from the cultures of the basidiomycete Cyathus africanus. Their structures were established based on extensive spectroscopic methods including 2D NMR (HSQC, 1Hâ1H-COSY, HMBC, ROESY) and HRESIMS experiments. The absolute configurations of two pairs of epimers, 1 and 2 as well as 3 and 4, were determined by ECD quantum chemical calculation. All the five compounds enhanced nerve growth factor (NGF)-mediated neurite outgrowth using rat pheochromocytoma (PC12) cells at concentration 10 µM.
Asunto(s)
Cyathus/metabolismo , Diterpenos/farmacología , Fármacos Neuroprotectores/farmacología , Sesquiterpenos/farmacología , Animales , Medios de Cultivo/química , Cyathus/crecimiento & desarrollo , Diterpenos/química , Diterpenos/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Estructura Molecular , Neuronas/efectos de los fármacos , Neuronas/fisiología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/aislamiento & purificación , Células PC12 , Sesquiterpenos Policíclicos , Ratas , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
A phytochemical study on the aerial parts of Hypericum elatoides led to the isolation of a previously undescribed polycyclic polyprenylated acylphloroglucinol derivative, hyperelatone A, seven previously undescribed phenolic metabolites, hyperelatones B-H, along with ten known analogues. The structures of hyperelatones A-H were elucidated by 1D and 2D NMR spectroscopy, HRESIMS experiment, single-crystal X-ray diffraction and comparison of experimental and calculated ECD spectra, as well as chemical derivatization. All compounds were evaluated for their neuroprotective activity against hydrogen peroxide (H2O2)-induced cell injury in rat pheochromocytoma PC-12â¯cells and inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV-2 microglial cells. Hyperelatones B-D and H, cinchonain Ib, and tenuiside A showed noticeable neuroprotection at concentrations of 1.0-100.0⯵M. Hyperelatones D, G, and H, (-)-epicatechin, tenuiside A, and (Z)-3-hexenyl-ß-D-glucopyranoside exhibited significant anti-neuroinflammatory activity with IC50 values ranging from 0.75⯱â¯0.02 to 5.83⯱â¯0.23⯵M.
Asunto(s)
Antiinflamatorios/farmacología , Hypericum/química , Fármacos Neuroprotectores/farmacología , Fenoles/metabolismo , Floroglucinol/análogos & derivados , Floroglucinol/farmacología , Componentes Aéreos de las Plantas/química , Compuestos Policíclicos/química , Animales , Antiinflamatorios/química , Línea Celular , Cristalografía por Rayos X , Peróxido de Hidrógeno/metabolismo , Concentración 50 Inhibidora , Lipopolisacáridos/farmacología , Microglía/citología , Microglía/efectos de los fármacos , Microglía/metabolismo , Estructura Molecular , Fármacos Neuroprotectores/química , Óxido Nítrico/biosíntesis , Células PC12 , Floroglucinol/química , Floroglucinol/aislamiento & purificación , Prenilación , Ratas , Análisis Espectral/métodosRESUMEN
Five new biphenyl ether glycosides, hyperelatosides A-E (1-5), one new benzoate glycoside, hyperelatoside F (6), along with nine known phenolic compounds (7-15), were isolated from the aerial parts of Hypericum elatoides. Their structures were elucidated by 1D and 2D NMR spectroscopy and HRESIMS, as well as chemical derivatization. This is the first report of the identification of biphenyl ether glycosides as plant metabolites and their possible biosynthetic pathway is proposed. Except for 3, the new phenolic metabolites exhibited significant neurotrophic activities to enhance nerve growth factor-induced neurite outgrowth in PC12 cells. In addition, the anti-neuroinflammatory and antioxidant activities of compounds 1-15 were preliminarily evaluated in vitro.