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• W2904283498 abstract "Traditional Chinese medicines (TCMs) are fascinating sources for natural drug candidates. Uncaria rhynchophylla (Gouteng) is a famous TCM used for alleviating central nervous system (CNS) disorders, while its antidepressant constituents are still disputed. The present study was designed to assess the antidepressant property of U. rhynchophylla and characterize the active constituents targeting melatonin receptors which are closely related to CNS diseases. The total extract and each fraction of U. rhynchophylla were extensively assessed for their agonistic activity on melatonin receptors in vitro. The following bioassay-guided fractionation yielded the active constituents, whose activity was confirmed by dose-dependent bioassay and antagonistic experiment on HEK293 cells. Their antidepressant effects were evaluated on forced swimming test (FST), tail suspension test (TST) and open-field test (OFT) mice models in vivo. Their metabolic profiles in mice plasma were analyzed by LCMS-IT-TOF. The stems and hooks of U. rhynchophylla were revealed with agonistic activity on melatonin receptors (MT1 and MT2). Under the guidance of bioassay, two flavanols, catechin and epicatechin were obtained and showed obviously activity agitating MT1 (EC50 = 25.8 and 156.1 μM) and MT2 (EC50 = 47.3 and 208.8 μM) receptors. The agonistic activity of catechin on melatonin receptors can be antagonized by luzindole at the concentrations of 1.57–100 μM. Catechin could significantly reduce the immobility time in both FST and TST mice models at doses of 80 and 40 mg/kg, without obvious effect on locomotor activity in OFT mice model. Five phase II (M1-M5) and one phase I (M6) metabolites of catechin were detected in mice plasma after intragastric (i.g.) administration. Catechin is a potent antidepressant candidate from U. rhynchophylla by targeting melatonin receptors. The main metabolic pathways of catechin in mice plasma are glucuronidation (M3) and methylated glucuronidation (M4 and M5). This study provides valuable information for understanding the antidepressant potency of Gouteng and its active constituents." @default.
• W2904283498 created "2018-12-22" @default.
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• W2904283498 date "2019-03-01" @default.
• W2904283498 modified "2023-10-04" @default.
• W2904283498 title "Antidepressant potential of Uncaria rhynchophylla and its active flavanol, catechin, targeting melatonin receptors" @default.
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• W2904283498 doi "https://doi.org/10.1016/j.jep.2018.12.013" @default.
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• W2904283498 hasPublicationYear "2019" @default.
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