Meranzin hydrate exhibits anti-depressive and prokinetic-like effects through regulation of the shared α2-adrenoceptor in the brain-gut axis of rats in the forced swimming test.
BACKGROUND
In recent years, the brain-gut axis theory has received increasing attention in studies of depression. However, most studies separately address potential antidepressant and prokinetic treatments. Investigations of drugs that could potentially treat comorbid depression and gastrointestinal (GI) dysfunction via a common mechanism of action have not yet been performed in detail.


OBJECTIVE
To find a common mechanism of action of our patented drug, meranzin hydrate (MH), in the antidepressant and prokinetic treatment.


METHODS
The forced swimming test (FST) model of depression, plasma ghrelin measurement, and in vivo and in vitro measurements of GI motility were used.


RESULTS
1. Administration of MH (9 mg/kg) decreased the immobility time during the FST after acute treatment; this effect was inhibited by the alpha 2-adrenoceptor antagonist, yohimbine, but not by the alpha 1-adrenoceptor antagonist, prazosin. 2. After chronic treatment, the immobility time of rats during the FST was decreased significantly by MH (2.25 mg/kg). 3. MH (9 mg/kg) increased plasma ghrelin levels in rats subjected to the FST; this increase was enhanced by the ghrelin receptor agonist, GHRP-6. 4. MH (9 mg/kg) also promoted gastric emptying and intestinal transit in rats with or without FST. 5. In vitro, MH (10 μM) increased jejunal contractions in rats subjected to the FST; this effect was inhibited by yohimbine. Furthermore, the inhibitory effect of yohimbine was partly reversed by the ghrelin receptor agonist, GHRP-6.


CONCLUSIONS
Our study revealed that MH from natural resources exhibits antidepressive and prokinetic-like effects through the regulation of the common mediator, the alpha 2-adrenoceptor.
Laboratory of Ethnopharmacology, Institute of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, 87 Xiangya Road, 410008 Changsha, China.
Ying
Y
Xie
Xi
X
Huang
Sui-Yu
SY
Hu
Xin-Jian
XJ
Qiu
Ying-Jin
YJ
Zhang
Ping
P
Ren
Yang
Y
Wang
Hui
H
Ji
Chun-Hu
CH
Zhang
Wei-Bin
WB
Xie
Juan
J
He
Meng-Zhou
MZ
Xie
Hui-Yong
HY
Huang
Zhao-Qian
ZQ
Liu
Hong-Hao
HH
Zhou
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D003374:Coumarins / Q000494:pharmacology / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000502:physiology; D008297:Male; D009434:Neural Pathways / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D013550:Swimming / Q000523:psychology
D000928:Antidepressive Agents; D003374:Coumarins; D018341:Receptors, Adrenergic, alpha-2; C508408:meranzin hydrate