Isorhynchophylline Exerts Antidepressant-like Effects in Mice Involvement of PI3K/Akt/GSK-3β Signaling Pathway
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AbstractIsorhynchophylline (IRN), an oxindole alkaloid isolated from Uncaria rhynchophylla, elicited distinct anti-depressant-like activity in mice. The present study aimed to investigate the antidepressant-like effects of IRN in chronic unpredictable mild stress (CUMS) induced depressive-like behavior in mice, and to illustrate its possible mechanism(s) of action. The mice were subjected to CUMS for 6 weeks and administered with IRN (20 or 40 mg/kg) daily by oral gavage for 3 weeks. PI3K/Akt inhibitor and GSK-3β inhibitors were used to determine the involvement of PI3K/Akt/GSK-3β pathway in the antidepressant-like effects of IRN in mice. The results showed that CUMS caused depression-like behavior in mice, such as behavioral despair by forced swim test and anhedonia by sucrose preference test. In addition, CUMS could significantly reduce the levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), but markedly increase the release of tumor necrosis factor-α (TNF- α) and interleukin 6 (IL-6) in the hippocampus and cerebral cortex of the mice. Western blotting analysis showed that CUMS could markedly suppress the levels of p-GSK-3β (Ser9) and p-Akt (Ser473), but significantly enhance the expressions of p-p65 in nucleus of the hippocampus and cerebral cortex of the mice. CUMS could also significantly increase the NF-κB binding activity in the hippocampus and cerebral cortex of the mice. IRN treatment could significantly reverse the behavioral and biochemical changes induced by CUMS in mice. Moreover, the anti-depressant-like effect of IRN could be completely abolished by PI3K/Akt inhibitor. Combination treatment with IRN and GSK-3β inhibitors in mice exerted a synergistic anti-immobility action in forced swim test. These results suggest that the antidepressant-like action of IRN, some of its possible mechanisms of action, may be mediated at least in part by enhancing neurotrophins and attenuating neuro-inflammation via modulating the PI3K/Akt/GSK-3β and NF-κB signaling pathway.
All Author(s) ListYan-Fang Xian, Zhi-Xiu Lin, Chang Qu, Siu-Po Ip
Name of ConferenceInternational Symposium on Good Pharmacology Practice for Chinese Medicines and the 2nd International Symposium on Wudang Local Chinese Medicines 中藥藥理学规范研究国际论坛暨第二届武当中药国际论坛
Start Date of Conference17/05/2019
End Date of Conference20/05/2019
Place of ConferenceShiyan
Country/Region of ConferenceChina
Proceedings TitleInternational Symposium on Good Pharmacology Practice for Chinese Medicines and the 2nd International Symposium on Wudang Local Chinese Medicines
Year2019
Month5
LanguagesEnglish-United Kingdom

Last updated on 2019-05-12 at 09:16