RESUMO
Dinardokanshones C-E, three sesquiterpenoid dimers comprising an unusual nornardosinane-type sesquiterpenoid core and an aristolane-type sesquiterpenoid unit conjugated by an extra pyran or furan ring, together with monomeric sesquiterpenoids isonardoeudesmols A-D and nardoeudesmol D, were isolated from the underground parts of Nardostachys jatamansi DC. Structures of the eight compounds were elucidated by analysis of the extensive spectroscopic data, and their absolute configurations were established by analysis of NOESY and X-ray diffraction data, combined with computational electronic circular dichroism (ECD) calculations. The results of SERT activity assay revealed that isonardoeudesmol D and nardoeudesmol D significantly inhibited SERT activity, while dinardokanshones D-E and isonardoeudesmols B-C significantly enhanced SERT activity, among which dinardokanshone D exhibited the strongest effect.
Assuntos
Nardostachys/química , Sesquiterpenos/isolamento & purificação , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Raízes de Plantas/química , Sesquiterpenos/química , Sesquiterpenos/farmacologiaRESUMO
Serotonin transporter (SERT) is a classic target of drug discovery for neuropsychiatric and digestive disorders, and against those disorders, plants of Nardostachys genus have been valued for centuries in the systems of Traditional Chinese Medicine, Ayurvedic and Unani. Herein, chemical investigation on the roots and rhizomes of Nardostachys chinensis Batal. led to the isolation of forty sesquiterpenoids including six new aristolane-type sesquiterpenoids and six new nardosinane-type sesquiterprenoids. Their structures were elucidated by extensive spectroscopic methods, combined with analyses of circular dichroism and single-crystal X-ray diffraction data. To explore natural product scaffolds with SERT regulating activity, a high-content assay for measurement of SERT function in vitro was conducted to evaluate the SERT regulating properties of these isolates. In conclusion, eleven compounds could be potential natural product scaffolds for developing drug candidates targeting SERT. Among which, kanshone C of aristolane-type sesquiterpenoid inhibited SERT most strongly, while desoxo-nachinol A of nardosinane-type sesquiterpenoid instead enhanced SERT potently.
Assuntos
Nardostachys/química , Inibidores Seletivos de Recaptação de Serotonina/isolamento & purificação , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Sesquiterpenos/isolamento & purificação , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Transporte Biológico/efeitos dos fármacos , Dicroísmo Circular , Cristalografia por Raios X , Estrutura Molecular , Raízes de Plantas/química , Sesquiterpenos Policíclicos , Rizoma/química , Inibidores Seletivos de Recaptação de Serotonina/química , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Sesquiterpenos/química , Sesquiterpenos/farmacologiaRESUMO
Nardonaphthalenones A and B (1-2), one new apo-α-carotenone (3) and four new monoterpenoids (4, 8-9 and 11), along with six known compounds (5-7, 10, 12-13) were isolated from the dried roots and rhizomes of Nardostachys chinensis Batal. Their structures were elucidated by analysis of the spectroscopic data including NMR, HRESIMS and circular dichroism data. Furthermore, the serotonin transporter (SERT)-regulating activities of these isolates were evaluated, among them compound 3 showed the strongest enhancement activity while compound 12 showed a moderate inhibition activity on SERT.
Assuntos
Monoterpenos/química , Naftalenos/química , Nardostachys/química , Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Espectroscopia de Ressonância Magnética , Conformação Molecular , Monoterpenos/isolamento & purificação , Monoterpenos/farmacologia , Naftalenos/isolamento & purificação , Naftalenos/farmacologia , Nardostachys/metabolismo , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Rizoma/química , Rizoma/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/química , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismoRESUMO
A new caffeate compound, (E)-erythro-syringylglyceryl caffeate (1), was isolated from the roots and rhizomes of Nardostachys chinensis Batal., together with nine known phenolic compounds, including (+)-licarin A (2), naringenin 4', 7-dimethyl ether (3), pinoresinol-4-O-ß-D-glucoside (4), caraphenol A (5), Z-miyabenol C (6), protocatechuic acid (7), caffeic acid (8), gallic acid (9) and vanillic acid (10). Their chemical structures were elucidated on the basis of spectroscopic data and physicochemical properties. Furthermore, this is the first report of compounds 2, 5 and 6 from Nardostachys genus.
