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1.
Eur J Med Chem ; 210: 112960, 2021 Jan 15.
Article in English | MEDLINE | ID: mdl-33148492

ABSTRACT

Medicinal plants are well-known in affording clinically useful agents, with rich medicinal values by combining with disease targets through various mechanisms. Plant secondary metabolites as lead compounds lay the foundation for the discovery and development of new drugs in disease treatment. Genus Uncaria from Rubiaceae family is a significant plant source of active alkaloids, with anti-hypertensive, sedative, anti-Alzheimer's disease, anti-drug addiction and anti-inflammatory effects. This review summarizes and discuss the research progress of Uncaria based on alkaloids in the past 15 years, mainly in the past 5 years, including biosynthesis, phytochemistry, pharmacology and structural chemistry. Among, focusing on representative compounds rhynchophylline and isorhynchophylline, the pharmacological activities surrounding the central nervous system and cardiovascular system are described in detail. On the basis of case studies, this article provides a brief overview of the synthesis and analogues of representative compounds types. In summary, this review provides an early basis for further searching for new targets and activities, discussing the mechanisms of pharmacological activity and studying the structure-activity relationships of active molecules.


Subject(s)
Alkaloids/chemistry , Alkaloids/pharmacology , Uncaria/chemistry , Alkaloids/metabolism , Animals , Biosynthetic Pathways , Drug Discovery , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/metabolism , Drugs, Chinese Herbal/pharmacology , Humans , Oxindoles/chemistry , Oxindoles/metabolism , Oxindoles/pharmacology , Uncaria/metabolism
2.
Behav Brain Res ; 266: 153-60, 2014 Jun 01.
Article in English | MEDLINE | ID: mdl-24613238

ABSTRACT

Gastrodin (GAS), an active constituent of the Chinese herbal medicine tianma, has antidepressant-like activity in animals but no specific molecular mechanisms have been identified. In the present study, chronic unpredictable stress (CUS) was used to establish a rat depression model; The sucrose preference test, forced swim test and Morris water maze test were used to assess depression-like behaviors (anhedonia, behavioral despair, motor retardation, and poor spatial memory), and the proliferation of hippocampal stem cells was tested by BrdU immunohistochemistry. The stress and inflammatory responses were assayed by measuring IL-RA, NF-κB, and p-iκB expression by Western blot and IL-1ß production by ELISA. Direct and indirect effects of GAS on NSC viable cell number were examined in vitro by WST-1 and BrdU assays. It was found that GAS (200 mg/kg daily) reversed all tested depression-like behaviors in CUS model rats and up-regulated NSCs proliferation in the hippocampus. Enhanced expression of p-iκB, NF-κB, and IL-1ß by CUS was also reversed by GAS. Moreover, in vitro experiments revealed that GAS alone did not increase the viability of NSCs but protected them from IL-1ß-induced damage. These results support the antidepressant and neuroprotective effects of GAS, and GAS may reduce depression-like behaviors by protecting hippocampal NSCs against the proinflammatory cytokine IL-1ß.


Subject(s)
Antidepressive Agents/therapeutic use , Benzyl Alcohols/therapeutic use , Depression/drug therapy , Glucosides/therapeutic use , Hippocampus/cytology , Neural Stem Cells/drug effects , Up-Regulation/drug effects , Animals , Antidepressive Agents/pharmacology , Benzyl Alcohols/pharmacology , Cell Survival/drug effects , Cells, Cultured , Depression/etiology , Disease Models, Animal , Dose-Response Relationship, Drug , Embryo, Mammalian , Food Preferences/drug effects , Glucosides/pharmacology , Male , Maze Learning/drug effects , Rats , Stress, Psychological/complications , Sucrose/administration & dosage , Swimming/psychology
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