TY - JOUR

T1 - Seahorse treatment improves depression-like behavior in mice exposed to CUMS through reducing inflammation/oxidants and restoring neurotransmitter and neurotrophin function

AU - Li, Kangwei

AU - Yan, Ling

AU - Zhang, Yongping

AU - Yang, Zhiyou

AU - Zhang, Cai

AU - Li, Yajuan

AU - Kalueff, Allan V.

AU - Li, Wenbao

AU - Song, Cai

PY - 2020/3/25

Y1 - 2020/3/25

N2 - Ethnopharmacological relevance: Seahorses (Hippocampus erectus), belonging to syngnathidae of syngnathiformes, are a traditional Chinese medicine for increasing and balancing vital energy within the body and brain, as well as calming mood and improving sleep. Aim of the study: Based on the hypothesis of monoamine neurotransmitter deficiency, current antidepressant treatments, with many side effects, are ineffective. Thus, novel hypotheses, inflammation, oxidative stress and neurotrophin dysfunction were proposed. Since seahorses can modulate immune function, reduce oxidants and nourish brain function, it may effectively treat depression. Therefore, this study aimed to detect the predominant chemical characterization of seahorses and investigate the mechanism by which seahorses exert antidepressant effects by using a chronic unpredictable mild stress (CUMS)-induced model of depression. Methods: Control and CUMS-exposed mice were fed normal or seahorse diet (0.018 g seahorses power) for 8-weeks. After behavioral tests, serum corticosterone, hippocampal expression of CD11b, glial fibrillary acidic protein (GFAP), and brain derived neurotrophic factor (BDNF), and the concentration of interleukin (IL)-1β and monoamine neurotransmitters were measured, while amygdala IL-1β and IL-10, anti-oxidative and oxidative enzyme were also studied. Then main phytoconstituents of seahorses was analyzed using liquid chromatography–mass spectrometry (LC-MS) methods. Results: Compared to controls, sucrose preference, exploration in open field, social interaction, entry numbers into and times spent on the open arms of elevated plus maze were significantly decreased, while immobility times in forced-swimming was increased in CUMS mice. These changes were associated with significantly reduced levels of serotonin, noradrenaline and dopamine, also expressions of GFAP and BDNF. Moreover, CUMS elevated IL-1β concentrations and reactive oxygen species (ROS), while decreased IL-10 concentration and anti-oxidative super oxide dismutase and glutathione peroxidase. Seahorse diet significantly reversed anxiety- and depression-like behaviors, which were correlated with reducing IL-1β and ROS, but increasing neurotransmitter concentrations and BDNF expression. Several compounds were found in seahorses, including docosahexaenoic acid, eicosapentaenoic acid, bis(2-ethylheptyl) phthalate, chrysophanol, and hypoxanthine. Conclusion: Seahorses could attenuate the CUMS-induced anxiety- and depression-like behaviors by reducing oxidative stress and inflammation, and normalizing neurotransmitter and neurotrophin function, which are possibly due to the activities of one or more or mixture of these identified compounds.

AB - Ethnopharmacological relevance: Seahorses (Hippocampus erectus), belonging to syngnathidae of syngnathiformes, are a traditional Chinese medicine for increasing and balancing vital energy within the body and brain, as well as calming mood and improving sleep. Aim of the study: Based on the hypothesis of monoamine neurotransmitter deficiency, current antidepressant treatments, with many side effects, are ineffective. Thus, novel hypotheses, inflammation, oxidative stress and neurotrophin dysfunction were proposed. Since seahorses can modulate immune function, reduce oxidants and nourish brain function, it may effectively treat depression. Therefore, this study aimed to detect the predominant chemical characterization of seahorses and investigate the mechanism by which seahorses exert antidepressant effects by using a chronic unpredictable mild stress (CUMS)-induced model of depression. Methods: Control and CUMS-exposed mice were fed normal or seahorse diet (0.018 g seahorses power) for 8-weeks. After behavioral tests, serum corticosterone, hippocampal expression of CD11b, glial fibrillary acidic protein (GFAP), and brain derived neurotrophic factor (BDNF), and the concentration of interleukin (IL)-1β and monoamine neurotransmitters were measured, while amygdala IL-1β and IL-10, anti-oxidative and oxidative enzyme were also studied. Then main phytoconstituents of seahorses was analyzed using liquid chromatography–mass spectrometry (LC-MS) methods. Results: Compared to controls, sucrose preference, exploration in open field, social interaction, entry numbers into and times spent on the open arms of elevated plus maze were significantly decreased, while immobility times in forced-swimming was increased in CUMS mice. These changes were associated with significantly reduced levels of serotonin, noradrenaline and dopamine, also expressions of GFAP and BDNF. Moreover, CUMS elevated IL-1β concentrations and reactive oxygen species (ROS), while decreased IL-10 concentration and anti-oxidative super oxide dismutase and glutathione peroxidase. Seahorse diet significantly reversed anxiety- and depression-like behaviors, which were correlated with reducing IL-1β and ROS, but increasing neurotransmitter concentrations and BDNF expression. Several compounds were found in seahorses, including docosahexaenoic acid, eicosapentaenoic acid, bis(2-ethylheptyl) phthalate, chrysophanol, and hypoxanthine. Conclusion: Seahorses could attenuate the CUMS-induced anxiety- and depression-like behaviors by reducing oxidative stress and inflammation, and normalizing neurotransmitter and neurotrophin function, which are possibly due to the activities of one or more or mixture of these identified compounds.

KW - BDNF

KW - Depression

KW - Inflammation

KW - Neurotransmitters

KW - Oxidative stress

KW - Seahorse

KW - Reactive Oxygen Species/metabolism

KW - Smegmamorpha

KW - Medicine, Chinese Traditional/methods

KW - Oxidants/metabolism

KW - Nerve Growth Factors/metabolism

KW - Mice, Inbred C57BL

KW - Stress, Psychological/drug therapy

KW - Depression/drug therapy

KW - Anxiety/drug therapy

KW - Brain-Derived Neurotrophic Factor/metabolism

KW - Oxidative Stress/drug effects

KW - Animals

KW - Behavior, Animal/drug effects

KW - Female

KW - Inflammation/drug therapy

KW - Mice

KW - Disease Models, Animal

KW - ANTIOXIDANT ACTIVITY

KW - CHRYSOPHANOL

KW - CYTOKINES

KW - ETHYL-EICOSAPENTAENOATE

KW - IN-VITRO

KW - DOPAMINE

KW - NF-KAPPA-B

KW - INFLAMMATORY RESPONSES

KW - INTERLEUKIN-1-BETA

KW - EXPRESSION

UR - http://www.scopus.com/inward/record.url?scp=85076533473&partnerID=8YFLogxK

U2 - 10.1016/j.jep.2019.112487

DO - 10.1016/j.jep.2019.112487

M3 - Article

C2 - 31857128

AN - SCOPUS:85076533473

VL - 250

JO - Journal of Ethnopharmacology

JF - Journal of Ethnopharmacology

SN - 0378-8741

M1 - 112487

ER -