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Loganin ameliorates depression-like behaviors of mice via modulation of serotoninergic system

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Abstract

Rationale

Depression is a serious neuropsychiatric disorder, which is characterized by sustaining mood disorders. Loganin, a major iridoid glycoside from Corni fructus, has a variety of pharmacological activities, including neuroprotective effect and hypnotic effect. However, little is known about the effects of loganin on stress-induced depression.

Objective

To investigate the effects of loganin on behavioral despair of mice, and whether serotonin (5-HT) and/or noradrenaline (NE) are involved in this process.

Methods

We tested the effectiveness of loganin using tail suspension test (TST). The possible mechanism was explored using reserpine-induced ptosis and hypothermia, and 5-HTP-induced head-twitch response in mice. The changes of 5-HT and NE in the prefrontal cortex, hippocampus, and striatum were measured through high-performance liquid chromatography (HPLC) analysis. Then, we identified the effects of depleting 5-HT and NE by PCPA (p-chlorophenylalanine) and DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride) pretreatment, respectively.

Results

Loganin (12.5/50 mg/kg) induced antidepressant-like effects in mice submitted to TST. Loganin (12.5/50 mg/kg) ameliorated the reserpine-induced hypothermia and ptosis, as well as increased 5-HTP-induced head-twitch responses in mice. Loganin (50 mg/kg) significantly increased the levels of 5-HT in the prefrontal cortex, hippocampus, and striatum. Furthermore, only PCPA treatment could eliminate loganin-induced antidepressant-like effects in TST.

Conclusion

Loganin exerts antidepressant-like effect in the TST depending on 5-HT levels in the central nervous system, which provide a potential agent for depression therapy.

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Acknowledgements

This work was supported by Beijing Municipal Natural Science Foundation (No.7204302, 7204303), G20 Engineering Innovation Research Project of Beijing Municipal Science & Technology Commission (No. Z171100001717009), National Natural Science Foundation of China (No. 82073731, 81903827), Chinese Academy of Medical Sciences Basic Research Business Fund Youth Medical Talent Award Project (No. 2018RC350019), and Distinguished Young Talents Project of Beijing University of Chinese Medicine (No. 2018-JYB-XJQ007).

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  1. Chen-Hao Pan and Cong-Yuan Xia these authors have contributed equally to this work

Authors and Affiliations

  1. School of Life Sciences & School of Chinese Medicine Sciences, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China

    Chen-Hao Pan, Yan Han, Rui Shi, Ze-Xing Wang, Yu-Ming Wang & Jie-Kun Xu

  2. Institute of Clinical Medical Sciences & Department of Pharmacy, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China

    Chen-Hao Pan, Cong-Yuan Xia, Yu Yan, Yan Han, Rui Shi, Jun He, Ze-Xing Wang, Yu-Ming Wang & Wei-Ku Zhang

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  1. Chen-Hao Pan
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Pan, CH., Xia, CY., Yan, Y. et al. Loganin ameliorates depression-like behaviors of mice via modulation of serotoninergic system. Psychopharmacology 238, 3063–3070 (2021). https://doi.org/10.1007/s00213-021-05922-8

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