Antidepressant-like effects and cognitive enhancement of the total phenols extract of Hemerocallis citrina Baroni in chronic unpredictable mild stress rats and its related mechanism.
BACKGROUND
Depression induce distressed emotional state and cognitive deficits simultaneously, which both should be improved in the treatment. Hemerocallis citrina Baroni (HC) is a traditional herbal medicine in Eastern-Asia areas and the total phenols extract of HC (HCPE) contains the main active ingredients. It has been reported that HC has the emotional improvement effect. But the cognitive effect of HC was seldom researched.


OBJECTIVE
We designed to evaluate the antidepressant and cognitive improvement effect of HCPE using a chronic unpredictable mild stress (CUMS) model, and the potential mechanisms were explored by investigating the corticosterone (CORT), monoamine neurotansmitters, brain-derived neurotropic factor (BDNF) and oxidative stress.


METHODS
The depression rats were induced by CUMS procedures and treated with HCPE (10, 20, 40mg/kg/day, by gastric gavage). The antidepressant effect was evaluated by sucrose preference test, open field test and body weight, while the cognitive improvement was investigated using morris water maze test. Besides, the levels of monoamine neurotransmitters in the hippocampus and frontal cortex were measured by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The serum CORT and BDNF in hippocampus were test using enzyme-linked immunosorbent assay (ELISA) kits. The oxidative stress indicators in frontal cortex were also analyzed.


RESULTS
HCPE (40mg/kg) improved the emotion and cognition related behaviors in depression effectively. Moreover, HCPE increased the neurotransmitters concentration (5-HT, DA and NE) in the hippocampus and frontal cortex compared with CUMS rats. Meanwhile, the CUMS induced changes of serum corticosterone level and the hippocampus BDNF level were reversed. Besides, HCPE reduced malondialdehyde (MDA) in the frontal cortex of model rats.


CONCLUSIONS
It suggested that HCPE could improve the depression-like emotional status and associated cognitive deficits in CUMS rats, which might be mediated by regulation of neurotransmitters and BDNF levels in brain, alleviation of corticosterone level as well as the alleviation of oxidative stress.
Research Center of Pharmacology and Toxicology, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
Pan
P
Xu
Research Center of Pharmacology and Toxicology, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
Ke Zhu
KZ
Wang
Research Center of Pharmacology and Toxicology, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
Cong
C
Lu
Research Center of Pharmacology and Toxicology, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
Li Ming
LM
Dong
Research Center of Pharmacology and Toxicology, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
Jun
J
Le Zhai
Research Center of Pharmacology and Toxicology, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
Yong Hong
YH
Liao
Department of Pharmacology and Toxicology Laboratory, Xinjiang Institute of Traditional Uighur Medicine, Urumqi, Xinjiang 830049, China.
Silafu
S
Aibai
China Astronauts Research and Training Center, Beijing 100094, China.
Yanyan
Y
Yang
Research Center of Pharmacology and Toxicology, Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China. Electronic address: liuxinmin@hotmail.com.
Xin Min
XM
Liu
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D015306:Biogenic Monoamines / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D003345:Corticosterone / Q000378:metabolism; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D031421:Hemerocallis / Q000737:chemistry*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism; D018697:Nootropic Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000188:drug therapy* / Q000378:metabolism
D000928:Antidepressive Agents; D015306:Biogenic Monoamines; D019208:Brain-Derived Neurotrophic Factor; D018377:Neurotransmitter Agents; D018697:Nootropic Agents; D010636:Phenols; D010936:Plant Extracts; D003345:Corticosterone
Antidepressant; BDNF; Cognition; Hemerocallis citrina; Neurotransmitters