• Anxiety
• Brain
• Depression
• Soyo-san
• Traditional herbal medicine
• Xiaoyao-san

• Animals
• Antidepressive Agents/pharmacology
• Anti-Anxiety Agents/pharmacology
• Disease Models, Animal
• Anxiety/drug therapy
• Depression/drug therapy
• Drugs, Chinese Herbal/pharmacology
• Behavior, Animal/drug effects

• Chinese medicine
• Xiaoyaosan
• depression
• hippocampal neuroplasticity

• Hippocampus/drug effects
• Hippocampus/physiology
• Drugs, Chinese Herbal/pharmacology
• Drugs, Chinese Herbal/therapeutic use
• Humans
• Neuronal Plasticity/drug effects
• Antidepressive Agents/pharmacology
• Antidepressive Agents/therapeutic use
• Animals
• Depression/drug therapy
• Depression/physiopathology
• Medicine, Chinese Traditional

• adjunctive therapy
• antidepressants
• herbal medicine
• network meta analysis
• post-stroke depression

• Antidepressant
• Depression
• Systematic review
• Traditional Chinese medicine
• Xiao-Yao-San

• Animals
• Antidepressive Agents/pharmacology
• Antidepressive Agents/therapeutic use
• Depression/drug therapy
• Depression/psychology
• Drugs, Chinese Herbal/pharmacology
• Drugs, Chinese Herbal/therapeutic use
• Hypothalamo-Hypophyseal System
• Pituitary-Adrenal System
• Humans

Depression is an emotional disorder that is problematic in psychiatry owing to its unclear etiology and unknown pathogenesis. Traditional Chinese medicine formulations such as Xiaoyaosan have been widely used throughout history to treat depression. In this review, we have focused on recent evidences elucidating the links between Xiaoyaosan and the treatment of depression. Data from animal and clinical studies, focusing on the pharmacological mechanisms, clinical applications, and effective materials that form the basis for the treatment of depression are presented and discussed. We found that the antidepressant effects of Xiaoyaosan are related to the effects of monoamine neurotransmitters, regulation of the hypothalamic-pituitary-adrenal axis, neuroplasticity, synaptic plasticity, inflammatory response, neuroprotection, brain-gut axis, regulation of intestinal microbiota, oxidative stress, and autophagy for reducing neuronal apoptosis. This review highlights the current evidence supporting the use of Xiaoyaosan as an antidepressant and provides an overview of the potential mechanisms involved.

• National Natural Science Foundation of China

• Cognitive impairment
• HMGB1
• Microglia
• Neural plasticity
• Neuro-inflammation
• Neuropathic pain
• Novel object recognition

• Xiaoyaosan
• chronic immobilization stress
• gene expression profile
• network regulating gene transcription
• signal pathways
• the hippocampus

• Depression
• HPLC-MS/MS
• Kynurenine metabolism pathway
• Xiaoyao san

• Animals
• Antidepressive Agents/pharmacology
• Behavior, Animal/drug effects
• Brain-Derived Neurotrophic Factor/genetics
• Brain-Derived Neurotrophic Factor/metabolism
• Cyclic AMP Response Element-Binding Protein/genetics
• Cyclic AMP Response Element-Binding Protein/metabolism
• Depression/drug therapy
• Depression/metabolism
• Depression/physiopathology
• Depression/psychology
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drugs, Chinese Herbal/pharmacology
• Hippocampus/drug effects
• Hippocampus/metabolism
• Hippocampus/physiopathology
• Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics
• Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism
• Kynurenine/blood
• Kynurenine/metabolism
• Kynurenine 3-Monooxygenase/genetics
• Kynurenine 3-Monooxygenase/metabolism
• Locomotion/drug effects
• Male
• Neural Cell Adhesion Molecules/genetics
• Neural Cell Adhesion Molecules/metabolism
• Quinolinic Acid/metabolism
• Rats, Sprague-Dawley
• Signal Transduction/drug effects
• Tryptophan/metabolism

Chronic stress induces endocrine disturbance, which contributes to the development of polycystic ovary syndrome (PCOS), a condition that remains a challenge for clinicians to cope with. The present study investigated the effect of Xiao-Yao-San (XYS), a traditional Chinese medicine formula used for treatment of gynecological disease, on the chronic stress-induced polycystic ovary and its underlying mechanism. Female Sprague-Dwaley rats underwent a 3 weeks chronic unpredictable mild stress (CUMS) procedure to establish the PCOS model, followed by 4 weeks treatment with XYS (0.505 g/kg or 1.01 g/kg) by gavage. Granulosa cells were exposed to noradrenaline (1 mM) in vitro for 24 h, followed by incubation with or without XYS-treated rat serum for 24 h. Post-treatment with XYS ameliorated CUMS-induced irregular estrous cycles and follicles development abnormalities, decrease of estradiol and progesterone level as well as increase of luteinizing hormone in serum, reduced cystic follicles formation and the apoptosis and autophagy of granulosa cells, attenuated the increase in dopamine beta hydroxylase and c-fos level in locus coeruleus, the noradrenaline level in serum and ovarian tissue, and the expression of beta 2 adrenergic receptor in ovarian tissue. Besides, XYS alleviated the reduction of phosphorylation of ribosomal protein S6 kinase polypeptide I and protein kinase B, as well as the increase of microtubule-associated protein light chain 3-I to microtubule-associated protein light chain 3-II conversion both in vivo and in vitro. This study demonstrated XYS as a potential strategy for CUMS induced polycystic ovary, and suggested that the beneficial role of XYS was correlated with the regulation of the sympathetic nerve activity.

• beta 2 adrenergic receptor
• chronic unpredictable stress
• granulosa cells autophagy
• noradrenaline
• polycystic ovary

Although the anxiolytic-like effects of Xiaoyaosan, a Chinese herbal formula, have been described in many previous studies, its underlying mechanism remains undefined. The cytokine tumour necrosis factor-α (TNF-α) and its closely associated janus kinase 2 (JAK2)-signal transducer and activator of transcription (STAT3) signalling pathway regulate the neuro-inflammatory response in the brain, thus participating in the development of anxiety. Our purpose was to investigate whether the anxiolytic-like effects of Xiaoyaosan are related to the TNF-α/JAK2-STAT3 pathway in the hippocampus. We examined the effects of Xiaoyaosan on behaviours exhibited in the elevated plus maze test, open field test and novelty-suppressed feeding test as well as hippocampal neuron damage and changes in the TNF-α/JAK2-STAT3 pathway in a rat model of chronic immobilization stress (CIS)-induced anxiety. Xiaoyaosan exerts anxiolytic-like effects on CIS-induced anxiety, with a significant alleviation of anxiety-like behaviours, an attenuation of hippocampal neuron damage, and a reversal of the activation of the TNF-α/JAK2-STAT3 pathway in the hippocampus that are similar to the effects of the JAK2 antagonist AG490. However, Xiaoyaosan and AG490 failed to effectively regulate apoptosis-related factors, including Bax and Caspase-3. These results suggest that Xiaoyaosan attenuates stress-induced anxiety behaviours by down-regulating the TNF-α/JAK2-STAT3 pathway in the rat hippocampus.

Jieyuanshen decoction (JYAS-D) - a traditional Chinese medicine was invented by Professor Nie based on classic formulas, chaihu jia longgu muli decoction has been proved as having favorable curative effects on depression in clinical practices. The aim of this study was to investigate the antidepressant effects and its molecular mechanism of JYAS-D.

The model of depression was established by Chronic Unpredictable Stress. Different doses (8.2 g/kg, 16.3 g/kg, 32.7 g/kg) of JYAS-D was orally administered; Fluoxetine was orally administered with 10mg/kg. All treatments lasted for 28 days. Sucrose preference and open-field tests were adopted to observe the behavior of rats. OPA (ortho-phthalaldehyde) derivatization method was used to detect the contents of amino acid neurotransmitter. RIA (Radiation immunity analysis) method was used to measure the serum concentrations of CORT (Corticosterone), ACTH (Adrenocorticotropic hormone) and CRH (Corticotropin-releasing hormone). ELISA (Enzyme linked immunosorbent assay) method was adopted to examine the contents of Glucocorticoid receptor (GR) and Mineralocorticoid receptor (MR) in hippocampus.

Compared with the model group, sucrose preference was increased in all treatment groups. The concentration of serum CORT was reduced in the middle dose of JYAS-D and control groups; the concentration of serum ACTH was reduced in the low and high-dose of JYAS-D; the concentration of serum CRH was reduced in the middle and high-dose of JYAS-D. The content of hippocampus GR was increased in the middle and high-dose of JYAS-D; the content of hippocampus Glu (Glutamic acid) was reduced among the low, middle and high-dose of JYAS-D and fluoxetine group, the ratio of Glu/γ-GABA (y-aminobutyric acid was reduced in the low and high-dose of JYAS-D.

JYAS-D had a significant antidepressant-like effect on rat model through regulating serum concentration of CORT, ACTH and CRH, increasing the content of hippocampus GR and regulating the equilibrium of amino acids neurotransmitter.

• Amino acid neurotransmitter
• Chronic Unpredictable Stress (CUS)
• Glucocorticoid/Mineralocorticoid receptor (G/MR)
• Hypothalamic-pituitary-adrenal (HPA) axis
• Jieyuanshen decoction(JYAS-D)

• Angelica sinensis
• Butylphthalide (PubChem CID: 61361)
• Chemical analysis
• Ethnopharmacology
• Ferulic acid (PubChem CID: 445858)
• Phytochemistry
• Senkyunolide A (PubChem CID: 3085257)
• Vanillic acid (PubChem CID: 8468)
• Z- ligustilide (PubChem CID: 529865)
• n-Butylidenephthalide/Z-Butylidenephthalide (PubChem CID: 5352899)

• Angelica sinensis/chemistry
• Angelica sinensis/classification
• Chemical Fractionation/methods
• China
• Drugs, Chinese Herbal/chemistry
• Drugs, Chinese Herbal/isolation & purification
• Drugs, Chinese Herbal/pharmacology
• Drugs, Chinese Herbal/toxicity
• Ethnobotany
• Ethnopharmacology
• Humans
• Medicine, Chinese Traditional
• Phytochemicals/chemistry
• Phytochemicals/isolation & purification
• Phytochemicals/pharmacology
• Phytochemicals/toxicity
• Phytotherapy
• Plant Extracts/chemistry
• Plant Extracts/isolation & purification
• Plant Extracts/pharmacology
• Plant Extracts/toxicity
• Plants, Medicinal

• Chinese herbal formula
• antidepressant
• pharmacological bioactivity
• phytochemistry
• traditional Chinese medicine

AIM: To investigate the distribution and expression of C-type natriuretic peptide (CNP)/natriuretic peptide receptor B (NPR-B) in the rectum of a rodent depression model and the interventional effect of Xiaoyaosan (XYS).

METHODS: Male rats (n = 45) of clean grade (200 ± 20 g) were divided into five groups after one week of adaptive feeding: primary control, depression model, low dose XYS, middle dose XYS, and high dose XYS. The animal experiment continued for 3 wk. Primary controls were fed normally ad libitum. The rats of all other groups were raised in solitary and exposed to classic chronic mild unpredictable stimulation each day. XYS groups were perfused intragastrically with low dose, middle dose, and high dose XYS one hour before stimulation. Primary control and depression model groups were perfused intragastrically with normal saline under similar conditions as the XYS groups. Three weeks later, all rats were sacrificed, and the expression levels of CNP and NPR-B in rectum tissues were analyzed by immunohistochemistry, real-time polymerase chain reaction, and Western blotting.

RESULTS: CNP and NPR-B were both expressed in the rectum tissues of all rats. However, the expression levels of CNP and NPR-B at both gene and protein levels in the depression model group were significantly higher when compared to the primary control group (n = 9; P < 0.01). XYS intervention markedly inhibited the expression levels of CNP and NPR-B in depressed rats. The expression levels of CNP and NPR-B in the high dose XYS group did not significantly differ from the expression levels in the primary control group. Additionally, the high and middle dose XYS groups (but not the low dose group) significantly exhibited lower CNP and NPR-B expression levels in the rectum tissues of the respectively treated rats compared to the untreated depression model cohort (n = 9; P < 0.01).

CONCLUSION: The CNP/NPR-B pathway is upregulated in the rectum of depressed rats and may be one mechanism for depression-associated digestive disorders. XYS antagonizes this pathway at least partially.

• C-Type natriuretic peptide
• Natriuretic peptide receptor type B
• Rectum
• Depression
• Gastrointestinal motility

• Animals
• Antidepressive Agents/pharmacology
• Behavior, Animal/drug effects
• Depression/drug therapy
• Depression/genetics
• Depression/metabolism
• Depression/psychology
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drugs, Chinese Herbal/pharmacology
• Male
• Natriuretic Peptide, C-Type/genetics
• Natriuretic Peptide, C-Type/metabolism
• RNA, Messenger/metabolism
• Rats, Sprague-Dawley
• Receptors, Atrial Natriuretic Factor/drug effects
• Receptors, Atrial Natriuretic Factor/genetics
• Receptors, Atrial Natriuretic Factor/metabolism
• Rectum/drug effects
• Rectum/metabolism
• Signal Transduction/drug effects
• Time Factors
• Up-Regulation

Most research focuses on the hypothalamic-pituitary-adrenal (HPA) axis, hypothalamus-pituitary-thyroid (HPT) axis, and hypothalamus-pituitary-gonadal (HPGA) axis systems of abnormalities of emotions and behaviors induced by stress, while no studies of Chinese herbal medicine such as Xiao Yao San (XYS) on the mechanisms of locus coeruleus-norepinephrine (LC-NE) system have been reported. Therefore, experiments were carried out to observe mechanism of LC-NE system in response to chronic immobilization stress (CIS) and explore the antidepressant effect of XYS. Rat model was established by CIS. LC morphology in rat was conducted. The serum norepinephrine (NE) concentrations and NE biosynthesis such as tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH), and corticotrophin-releasing-factor (CRF) in LC were determined. Results showed that there were no discernible alterations in LC in rats. The serum NE concentrations, positive neurons, mean optical density (MOD), and protein levels of TH, DBH, and CRF in model group were significantly increased compared to the control group. But XYS-treated group displayed a significantly decreased in NE levels and expressions of TH, DBH, and CRF compared to the model group. In conclusion, CIS can activate LC-NE system to release NE and then result in a significant decrease in rats. XYS treatment can effectively improve depressive-like behaviors in rats through inhibition of LC-NE neurons activity.