RESUMO
The phytochemical investigation of the fruits of Cornus officinalis yielded a new phenolic acid derivative, neophenolic acid A (1), and a novel flavonoid glycoside, (2R)-naringenin-7-O-ß-(6''-galloyl-glucopyranoside) (2 a), along with six known flavonoid glycosides (2 b-7). Their structures were determined by 1D, 2D NMR and HRESIMS data. The absolute configuration of 1 was established by ECD analysis. Compoundsâ 1-â7 were evaluated for their neuroprotective activities against corticosterone (CORT)-induced injury in PC-12â cells. Compoundsâ 1, 2 a, 2 b, 5, and 6 exhibited neuroprotective activities against CORT-induced neurotoxicity in PC-12â cells. The underlying mechanism study suggested that compoundsâ 1, 2 a, 2 b, 5, and 6 were able to attenuate CORT-induced apoptosis and damage, increase the levels of MMP and decrease Ca2+ inward flow in PC-12â cells.
Assuntos
Apoptose , Cornus , Frutas , Fármacos Neuroprotetores , Cornus/química , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Animais , Frutas/química , Ratos , Células PC12 , Apoptose/efeitos dos fármacos , Corticosterona/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Estrutura Molecular , Flavonoides/farmacologia , Flavonoides/isolamento & purificação , Flavonoides/química , Relação Estrutura-Atividade , Cálcio/metabolismoRESUMO
Two previously undescribed flavonoid thioglucosides lepidiumflavonosides A and B (1-2) and two known megastigmane compounds (7E,9S)-9-hydroxy-5,7-megastigmadien-4-one 9-O-ß-D-glucopyranoside (3) and (9S)-4-oxo-ß-inol ß-D-glucopyranoside (4) were isolated from the water extract of the seeds of Lepidium apetalum Willd. The structural elucidation of isolated compounds was unambiguously determined based on extensive 1D and 2D NMR spectroscopic analyses. All compounds were evaluated for their estrogen-like effects on MCF-7 cells in vitro. The results showed that compounds 1-4 significantly promoted the proliferation of MCF-7 cells, and the proliferation was antagonized by the specific ER antagonist ICI182,780, suggesting that compounds 1-4 might have the estrogen-like effect in vitro potentially.
Assuntos
Flavonoides , Lepidium , Flavonoides/farmacologia , Flavonoides/química , Tioglucosídeos/análise , Lepidium/química , Estrogênios/farmacologia , Sementes/químicaRESUMO
Two new cyclotrypyamine alkaloids equisetinines A and B, as well as three known alkaloids (3-5) were isolated from the stems of Ephedra equisetina Bunge. Their structures were characterized by spectroscopic methods, and the absolute configurations of the new compounds were determined by interpretation of their electronic circular dichroism. Anti-asthmatic activities of compounds were evaluated by releasing ß-Hex in C48/80-induced RBL-2H3 cells, and compound 5 exhibited significant anti-asthmatic activities.
RESUMO
An outbreak of African swine fever (ASF) in China in 2018 caused substantial economic losses to the swine industry. To accurately diagnose clinical infection with ASF virus (ASFV), we developed a TaqMan probe-based duplex real-time PCR that simultaneously detected two discontinuous genes in the virus genome, thereby preventing the inaccurate results obtained with only one reaction. Two sets of ASFV gene-specific primers, along with two fluorescent TaqMan probes were designed to target conserved regions of the B646L and B438L genes. This method had high sensitivity and specificity, with a limit of detection of 10 copies/µL, and it did not cross-react with the genomes of other viral pathogens that affect pigs (i.e., CSFV, PRRSV, PEDV, PRV, PPV and PCV2). Overall, 180 clinical samples from ASFV-infected pig farms were used to compare this method with a commercial kit, which yielded excellent consistency (98.3%). This new diagnostic method should greatly improve the efficiency of ASFV surveillance and reduce economic losses, providing benefits for both animal and public health.
Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Febre Suína Africana/diagnóstico , Vírus da Febre Suína Africana/genética , Animais , DNA Viral , Genoma Viral/genética , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade , SuínosRESUMO
Six new iridal-type triterpenoids containing an unprecedented cyclopentane ring, polycycloiridals E-J (1-6), were isolated from a large-scale re-extraction of Iris tectorum. A possible biosynthesis pathway is postulated. The known spirioiridotectal D (7) was also obtained in the current investigation, and its structure was unequivocally defined using X-ray diffraction data. Compound 7 suppressed LPS-activated NO production in the BV2 cell line with an IC50 value of 0.54 µM.
Assuntos
Ciclopentanos/isolamento & purificação , Gênero Iris/química , Rizoma/química , Triterpenos/isolamento & purificação , Ciclopentanos/química , Ciclopentanos/farmacologia , Estrutura Molecular , Extratos Vegetais/química , Triterpenos/química , Triterpenos/farmacologia , Difração de Raios XRESUMO
Objective: To investigate the chemical constituents from the barks of Eucommia ulmoides. Methods: After the reflux extraction of the barks of Eucommia ulmoides with 95% ethanol, and the ethyl acetate part was separated and purified by chromatographic methods, such as silica gel, Sephadex LH-20, and ODS C18. The structures of isolated compounds were elucidated with modern spectral methods. Results: Five lignanoids and three phenylpropanoids were isolated from Eucommia ulmoieds, which were confirmed as cycloolivil (1), (7R, 8S, 8'R)-4, 9, 4', 8'-tetrahydroxy-3, 3'-dimethyoxyl-7, 9'-monoepoxy lignan (2), erythro-guaiacyl-glycerol-ß-coniferyl aldehyde ether (3), pinonesinol (4), 8-hydroxypinoresinol (5), C-veratroylglycol (6), ß-hydroxyl-3-methoxyl-4-hydroxyacetophenone (7) and 3-hydroxy-4-methoxycinnamaladehyde (8). Conclusion: Compounds 58 are isolated from this plant for the first time.
Assuntos
Eucommiaceae , Medicamentos de Ervas Chinesas , Lignanas , FenóisRESUMO
Eleven flavonol glycosides were isolated from the ethanol extract of Lysimachia clethroides by a combination of various chromatographic techniques including column chromatography over silica gel, Sephadex LH-20, and reversed-phase HPLC. Their structures were identified as astragalin (1), isoquercitrin (2), isorhamnetin-3-O-ß-D-glucopyranoside (3), quercetin-3-O-ß-D-6"-acetylglucopyranoside (4), quercetin-7-O-ß-D-glucopyranoside (5), prunin (6), 2-hydroxynaringin-5-O-ß-D-glucopyranoside (7), kaempferol-3-O-rutinonoside (8), kaempferol-3-O-robinobioside (9), rutin (10) and kaempferol-3,7-di-O-ß-D-glucopyranoside (11). Among them, compounds 4, 7 and 11 were obtained from the Lysimachia genus for the first time, while compounds 3, 5 and 9 were firstly reported from this plant. In the preliminary assays, compounds 2, 6 and 8 possessed significant inhibition against aldose reduc- tase, with IC50 values of 2.69, 1.00, 1.80 µmol · L(-1), respectively; none of compounds 1-11 exhibited obvious cytotoxic activity (IC50 > 10 µmol · L(-1)).
Assuntos
Medicamentos de Ervas Chinesas/química , Flavonóis/química , Glicosídeos/química , Primulaceae/química , Estrutura Molecular , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
Seven new triterpenoid saponins, schekwangsiensides A-G (1-7), and a new triterpenoid, schekwangsienin (8), together with nine known triterpenoids and saponins (9-17), were isolated from the aerial parts of Schefflera kwangsiensis. The structures of these compounds were elucidated on the basis of spectroscopic data analysis and chemical evidence. Furthermore, in in vitro assays, compounds 4, 8, 9, and 15 (10 µM) exhibited moderate hepatoprotective activities against D-galactosamine-induced HL-7702 cell damage.
Assuntos
Araliaceae/química , Substâncias Protetoras/farmacologia , Saponinas/farmacologia , Triterpenos/farmacologia , Linhagem Celular , Galactosamina/toxicidade , Fígado/efeitos dos fármacos , Ressonância Magnética Nuclear Biomolecular , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Saponinas/química , Saponinas/isolamento & purificação , Triterpenos/química , Triterpenos/isolamento & purificaçãoRESUMO
Four new ionone and ionone glycosides (1-4), and a new monoterpene (5), together with 10 known analogues (6-15), were isolated from the air-dried roots of Rehmannia glutinosa. The structures of these compounds were elucidated on the basis of spectroscopic data analysis. Furthermore, in in vitro assays, compound 3 (10 µM) exhibited moderate hepatoprotective activities against d-galactosamine-induced HL-7702 cell damage.
Assuntos
Medicamentos de Ervas Chinesas/isolamento & purificação , Glicosídeos/isolamento & purificação , Hepatócitos/efeitos dos fármacos , Norisoprenoides/isolamento & purificação , Rehmannia/química , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Galactosamina/farmacologia , Glicosídeos/química , Glicosídeos/farmacologia , Humanos , Estrutura Molecular , Norisoprenoides/química , Norisoprenoides/farmacologia , Ressonância Magnética Nuclear Biomolecular , Raízes de Plantas/químicaRESUMO
OBJECTIVE: To investigate chemical constituents from the ripe fruit of Panax ginseng. METHODS: The compounds were isolated and purified by chromatographic methods such as macroporous resin, sephadex LH-20, Bio-gel P-2, ODS and silica gel. Their structures were identified by their physical and spectral data(ESI-MS, 1H-NMR and 13C-NMR). RESULTS: Eleven compounds were isola- ted and identified as arginyl-fructose (1), arginyl-fructosyl-glucose (2), L-pyroglutamic acid (3), p-hydroxybenzoic acid (4), 5-hydroxy-methylfuraldehyde (5), ginsenosides Rb1 (6), Re (7), Rg1 (8), Rb2 (9), Rc (10) and daucosterol (11). CONCLUSION: Compounds 1-5 were obtained from the fruit of Panax ginseng for the first time.
Assuntos
Frutas/química , Panax/química , GinsenosídeosRESUMO
Six new carboxylic acids (1-6), together with 11 known ones (7-17), were isolated from the aerial parts of Lysimachia clethroides. Their structures were elucidated on the basis of spectroscopic analysis and chemical evidence. Five new carboxylic acids (1 and 3-6) were evaluated for their in vitro inhibitory activity against aldose reductase.
Assuntos
Aldeído Redutase/antagonistas & inibidores , Ácidos Carboxílicos/isolamento & purificação , Ácidos Carboxílicos/farmacologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Primulaceae/química , Ácidos Carboxílicos/química , Medicamentos de Ervas Chinesas/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Relação Estrutura-AtividadeRESUMO
Fifteen previously undescribed minor iridoid glycosides, including four monomers and eleven dimers, were isolated from the fruits of Cornus officinalis Sieb. et Zucc. Their chemical structures were determined on the basis of spectroscopic data and chemical evidence. All of the isolated compounds were evaluated for their effects of the glucose consumption on the insulin resistant HepG2 cells, and four compounds, named cornuofficinalisides F, H, L, and O, increased the glucose consumption significantly at 10 µM, the EC50 values of them were determined to be 0.898, 1.625, 0.923, and 8.589 µM, respectively. Moreover, the four compounds could improve the ability of glucose uptake significantly in insulin resistant HepG2 cells.
Assuntos
Cornus , Glicosídeos Iridoides/farmacologia , Insulina , GlucoseRESUMO
Alzheimer's disease (AD) is a progressive neurodegenerative disease for which there is a lack of effective therapeutic drugs. There is great potential for natural products to be used in the development of anti-AD drugs. P-coumaric acid (PCA), a small molecule phenolic acid widely distributed in the plant kingdom, has pharmacological effects such as neuroprotection, but its anti-AD mechanism has not been fully elucidated. In the current study, we investigated the mechanism of PCA intervention in the Aß25-35-induced AD model using gut microbiomics and serum metabolomics combined with in vitro and in vivo pharmacological experiments. PCA was found to ameliorate cognitive dysfunction and neuronal cell damage in Aß25-35-injected mice as measured by behavioral, pathological and biochemical indicators. 16S rDNA sequencing and serum metabolomics showed that PCA reduced the abundance of pro-inflammatory-associated microbiota (morganella, holdemanella, fusicatenibacter and serratia) in the gut, which were closely associated with metabolites of the glucose metabolism, arachidonic acid metabolism, tyrosine metabolism and phospholipid metabolism pathways in serum. Next, in vivo and in vitro pharmacological investigations revealed that PCA regulated Aß25-35-induced disruption of glucose metabolism through activation of PI3K/AKT/Glut1 signaling. Additionally, PCA ameliorated Aß25-35-induced neuroinflammation by inhibiting nuclear translocation of NF-κB and by modulating upstream MAPK signaling. In conclusion, PCA ameliorated cognitive deficits in Aß25-35-induced AD mice by regulating glucose metabolism and neuroinflammation, and the mechanism is related not only to restoring homeostasis of gut microbiota and serum metabolites, but also to PI3K/AKT/Glut1 and MAPK/NF-κB signaling.
Assuntos
Doença de Alzheimer , Microbioma Gastrointestinal , Doenças Neurodegenerativas , Camundongos , Animais , Peptídeos beta-Amiloides/metabolismo , Transportador de Glucose Tipo 1/metabolismo , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Doenças Neuroinflamatórias , Doenças Neurodegenerativas/patologia , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Glucose/metabolismo , EncéfaloRESUMO
Eight new sesquiterpenes (1-8) and one new norsesquiterpene (9) named calamusins A-I were isolated from the ethanol extract of Acorus calamus rhizomes. The absolute configuration of compound 8 was determined by comparing its experimental and calculated ECD spectra. The absolute configurations of the other compounds were determined from their CD spectra. Furthermore, in in vitro assays, compounds 3, 4, 7, and 9 (10 µM) exhibited weak hepatoprotective activities against APAP-induced HepG2 cell damage.
Assuntos
Acorus/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Sesquiterpenos/isolamento & purificação , Acetaminofen/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Células Hep G2 , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Rizoma/química , Sesquiterpenos/química , Sesquiterpenos/farmacologiaRESUMO
Eleven new iridoid glycosides, rehmaglutosides A-K (1-11), together with 20 known analogues were isolated from the air-dried roots of Rehmannia glutinosa. The structures of these compounds were elucidated on the basis of spectroscopic data analysis and chemical evidence. Furthermore, in in vitro assays, compounds 3, 7, and 9-11 (10 µM) exhibited moderate hepatoprotective activities against D-galactosamine-induced HL-7702 cell damage.
Assuntos
Glicosídeos/isolamento & purificação , Hepatócitos/efeitos dos fármacos , Glicosídeos Iridoides/isolamento & purificação , Glicosídeos Iridoides/farmacologia , Rehmannia/química , Galactosamina/química , Galactosamina/farmacologia , Glicosídeos/química , Glicosídeos/farmacologia , Humanos , Glicosídeos Iridoides/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Raízes de Plantas/químicaRESUMO
A pair of new guaiane-type sesquiterpene tautomers (1) was isolated from rhizomes of Acorus calamus. Meanwhile, three pairs of known compounds, including a pair of dihydroflavone glycoside tautomers (2), a pair of 4-hydroxybenzoic acid ester glycoside tautomers (3), as well as a pair of secoiridoid glycoside tautomers (4) were isolated from fruits of Cornus officinalis. Their structures were elucidated by extensive spectroscopic and computational methods. Furthermore, the tautomeric mechanisms were discussed.
RESUMO
Seven undescribed lignans, equiselignan A-F, and six undescribed terpenoids, equiseterpenoid A-E (including two pairs of enantiomers, (+/-)-equiselignan A and (+/-)-equiseterpenoid E), were isolated from the stems of Ephedra equisetina Bunge. Their structures were elucidated by spectroscopic methods, and the absolute configurations of the undescribed compounds were determined by interpretation of their electronic circular dichroic (ECD) and optical rotation data. In ß-hexosaminidase (ß-Hex) release assay, anti-asthmatic activities of all of the compounds were evaluated by releasing ß-Hex in C48/80-induced RBL-2H3 cells. The ß-Hex release rates of equiselignan B and equiseterpenoid B were 0.86 ± 0.094 and 0.86 ± 0.012 by comparing with model group, whereupon equiselignan B and equiseterpenoid B exhibited significant anti-asthmatic activities.
Assuntos
Antiasmáticos , Ephedra , Lignanas , Ephedra/química , Lignanas/química , Lignanas/farmacologia , Estrutura Molecular , Estereoisomerismo , Terpenos/farmacologiaRESUMO
Three novel sesquinlignans, tatanans A (1), B (2), and C (3), have been isolated from the rhizomes of Acorus tatarinowii Schott. Their structures were established by spectroscopic techniques and single-crystal X-ray analysis. Tatanans A-C potently increase GK enzymatic activity with EC(1.5) values in the range of 0.16-1.85 µM. The potent GK activity and unique structural features of tatanans make them promising leads for therapeutic development of antihyperglycemic drugs.
Assuntos
Acorus/química , Glucoquinase/química , Glucoquinase/farmacologia , Lignanas/química , Lignanas/farmacologia , Rizoma/química , Cristalografia por Raios X , Lignanas/isolamento & purificação , Estrutura Molecular , EstereoisomerismoRESUMO
Seven oleanane-type triterpenoid saponins, named clethroidosides A-G (1-7), an ursane-type triterpenoid saponin, clethroidoside H (8), and six known saponins were isolated from the aerial parts of Lysimachia clethroides. The structures of the saponins were elucidated on the basis of physical data analysis (1D and 2D NMR, HR-ESIMS) and chemical evidence. The cytotoxic activities of compounds 1-14 were evaluated against five human tumor cell lines (HT-29, HePG2, BGC-823, A549, and A375). Compounds 3, 4, 6, and 11-13 exhibited moderate cytotoxic activity, with IC50 values of 0.75-2.62 µM, while compound 5 showed selective cytotoxic activity.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Primulaceae/química , Saponinas/isolamento & purificação , Saponinas/farmacologia , Triterpenos/isolamento & purificação , Antineoplásicos Fitogênicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Células HT29 , Células Hep G2 , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Saponinas/química , Triterpenos/química , Triterpenos/farmacologiaRESUMO
Pyridine-based ring systems are one of the most extensively used heterocycles in the field of drug design, primarily due to their profound effect on pharmacological activity, which has led to the discovery of numerous broad-spectrum therapeutic agents. In the US FDA database, there are 95 approved pharmaceuticals that stem from pyridine or dihydropyridine, including isoniazid and ethionamide (tuberculosis), delavirdine (HIV/AIDS), abiraterone acetate (prostate cancer), tacrine (Alzheimer's), ciclopirox (ringworm and athlete's foot), crizotinib (cancer), nifedipine (Raynaud's syndrome and premature birth), piroxicam (NSAID for arthritis), nilvadipine (hypertension), roflumilast (COPD), pyridostigmine (myasthenia gravis), and many more. Their remarkable therapeutic applications have encouraged researchers to prepare a larger number of biologically active compounds decorated with pyridine or dihydropyridine, expandeing the scope of finding a cure for other ailments. It is thus anticipated that myriad new pharmaceuticals containing the two heterocycles will be available in the forthcoming decade. This review examines the prospects of highly potent bioactive molecules to emphasize the advantages of using pyridine and dihydropyridine in drug design. We cover the most recent developments from 2010 to date, highlighting the ever-expanding role of both scaffolds in the field of medicinal chemistry and drug development.