Based on serum metabolomics and gut microbiota technology, this study explores the effects and mechanisms of the water extract of Ziziphi Spinosae Semen(SZRW) and the petroleum ether extract of Ziziphi Spinosae Semen(SZRO) in improving depressive-like behaviors induced by sleep deprivation. A modified multi-platform water environment method was employed to establish a rat model of sleep deprivation. Depressive-like behaviors in rats were assessed through the sucrose preference test and forced swim test. The expression of barrier proteins, such as Occludin, in the colon was determined by immunofluorescence. UPLC-Q-Orbitrap MS was utilized to analyze the serum metabolic profiles of sleep-deprived rats, screen for differential metabolites, and analyze metabolic pathways. The diversity of the gut microbiota was detected using 16S rRNA gene sequencing. Spearman correlation coefficient analysis was conducted to assess the correlation between differential metabolites and gut microbiota. The results indicated that SZRO significantly increased the sucrose preference index and decreased the immobility time in the forced swim test in rats. A total of 34 differential metabolites were identified through serum metabolomics. SZRW and SZRO shared five metabolic pathways, including phenylalanine metabolism. SZRW uniquely featured taurine and hypotaurine metabolism, while SZRO uniquely featured linoleic acid metabolism and tyrosine metabolism. Correlation analysis revealed that SZRW could upregulate the abundance of Bilophila, promoting the production of indole-3-propionic acid and subsequently upregulating the expression levels of intestinal tight junction proteins such as ZO-1, Occludin, and Claudin-1. SZRO could indirectly influence metabolic pathways such as arginine metabolism and linoleic acid metabolism by upregulating the abundance of gut microbiota such as Coprococcus and Eubacterium species. Both SZRW and SZRO can regulate endogenous metabolism, including amino acids, energy, and lipids, alter the gut microbiota microecology, and improve depressive-like behaviors. SZRO demonstrated superior effects in regulating metabolic pathways and gut microbiota structure compared to SZRW. The findings of this study provide a scientific basis for elucidating the pharmacodynamic material basis of Ziziphi Spinosae Semen.
Animals ; Rats ; Gastrointestinal Microbiome/drug effects* ; Male ; Metabolomics ; Drugs, Chinese Herbal/administration & dosage* ; Depression/blood* ; Rats, Sprague-Dawley ; Sleep Deprivation/complications* ; Ziziphus/chemistry* ; Antidepressive Agents/administration & dosage* ; Behavior, Animal/drug effects* ; Humans

This study aims to investigate the mechanism through which Xiangshao Granules treat anxiety and depression using metabolomics and gut microbiota techniques, combined with animal experiments. Sixty female ICR mice were selected for the experiment and randomly divided into six groups: a control group, a model group, a low-dose Xiangshao Granules group, a medium-dose Xiangshao Granules group, a high-dose Xiangshao Granules group, and an estradiol(positive drug) group. Except for the control group, rats in other groups were induced for anxiety and depression model by ovariectomy(OVX) combined with chronic unpredictable mild stress(CUMS). After successful modeling, the mice received oral administration of Xiangshao Granules or estradiol for three weeks. Anxiety and depression behaviors in mice were evaluated using light-dark box tests, open field tests, and elevated plus-maze tests. The levels of substances closely related to anxiety and depression, such as serotonin(5-HT) and estrogen(E_2), were quantified in plasma and hippocampal tissue using enzyme-linked immunosorbent assay(ELISA). Metabolomics and 16S rDNA amplicon sequencing techniques were employed to analyze the regulatory effects of Xiangshao Granules on plasma metabolites and metabolic pathways in anxiety and depression mice, as well as their impact on the distribution of gut microbiota. Finally, the correlation between plasma metabolites and differential gut microbiota was constructed using the Spearman correlation coefficient method. Behavioral experimental results indicated that, compared to the control group, the model group exhibited significantly decreased dwell time in the light box, reduced total distance in the open field, and diminished dwell time in the open arm. In contrast, high dose of Xiangshao Granules were found to increase the dwell time in the light box and total distance in the open field. ELISA results indicated that the levels of 5-HT, gamma-aminobutyric acid(GABA), E_2 were significantly decreased, luteinizing hormone(LH), adrenocorticotropic hormone(ACTH), and corticosterone(CORT) were significantly elevated in the anxiety and depression mice, and treatment with middle, high dose of Xiangshao Granules reversed the levels of these substances. Additionally, in the anxiety and depression mouse model, the levels of follicle-stimulating hormone(FSH) were significantly increased, whereas middle, high dose of Xiangshao Granules decreased FSH levels. Metabolomics analysis revealed that Xiangshao Granules significantly changed the metabolic profile of the anxiety and depression mice, affecting central carbon metabolism, amino acid biosynthesis, and ABC transporter pathways. The results from 16S rDNA amplicon sequencing showed that Xiangshao Granules improved the relative abundance of genera such as Bacteroidia, Bacilli, Lactobacillales, and Lactobacillus. Spearman correlation analysis indicated a close association between specific differential gut microbiota and plasma differential metabolites. This study suggests that Xiangshao Granules significantly ameliorate anxiety and depression symptoms in mice by altering the levels of substances associated with these conditions, including 5-HT, GABA, E_2, LH, and ACTH. The metabolomics and gut microbiota data suggest that the therapeutic mechanism may be closely related to the regulation of amino acid biosynthesis, central carbon metabolism, and the alteration of key microbial community compositions.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Anxiety/microbiology* ; Depression/microbiology* ; Gastrointestinal Microbiome/drug effects* ; Mice ; Female ; Mice, Inbred ICR ; Metabolomics ; Serotonin/metabolism* ; Humans ; Disease Models, Animal ; Rats ; Behavior, Animal/drug effects*

This study aims to explore the effects and potential mechanisms of Modified Shuyu Pills in ameliorating depressive behaviors in the mouse model of vascular dementia(VaD). Seventy-two three-month-old male C57BL/6 mice were assigned into six groups: sham, model, low-, medium-, and high-dose Modified Shuyu Pills, and fluoxetine. The other five groups except the sham group underwent bilateral common carotid artery stenosis combined with chronic unpredictable stress. Depressive behaviors were assessed by the sucrose preference test and tail suspension test. Cerebral blood flow was measured by laser speckle imaging. Protein levels of low density lipoprotein receptor(LDLR), mitogen-activated protein kinase kinase(MEK), phosphorylated(p)-MEK, extracellular signal-regulated kinase(ERK), and p-ERK in the ventral tegmental area(VTA) and nucleus accumbens(NAc) were determined by Western blot. The fluorescence intensity of myelin basic protein(MBP) in the VTA and NAc were measured by immunofluorescence. Myelin sheath morphology in the VTA and NAc was observed by luxol fast blue staining, and the ultrastructure of myelin sheath in the VTA and NAc was examined by transmission electron microscopy. In the tail suspension test, the immobility time of the model group was longer than that of the sham group(P<0.01). In the sucrose preference test, the sucrose preference rate of the model group was lower than that of the sham group(P<0.01). After intervention with Modified Shuyu Pills, the immobility time in the tail suspension test was shortened(P<0.01), and the sucrose preference rate increased(P<0.01). Laser speckle imaging results showed that compared with the sham group, the model group showed reduced cerebral blood flow(P<0.01), and the reduction was reversed by medium-and high-dose Modified Shuyu Pills(P<0.01). Western blot results indicated that the relative expression levels of LDLR, p-MEK/MEK, and p-ERK/ERK in the VTA and NAc of the model group were lower than those in the sham group(P<0.01). Medium-and high-dose Modified Shuyu Pills reversed this trend(P<0.01). Immunofluorescence results showed that the fluorescence intensity of MBP in the VTA and NAc of the model group was lower than that of the sham group(P<0.01). The medium-and high-dose Modified Shuyu Pills groups showed increased fluorescence intensity of MBP in the VTA compared with the model group(P<0.01). In the NAc, the fluorescence intensity of MBP in all the groups of Modified Shuyu Pills increased to varying degrees compared with that in the model group(P<0.01). Luxol fast blue staining results showed that the model group presented lighter staining intensity and looser arrangement of myelin fibers than the sham group, indicating significant demyelination in the model group. However, after intervention with medium-and high-dose Modified Shuyu Pills, the staining intensity and myelin sheath structure in the VTA and NAc were improved. Transmission electron microscopy results revealed that the myelin sheath in the VTA and NAc of the sham group was intact and dense, while the model group exhibited extensive myelin loss, with myelin sheath degeneration and disintegration. After intervention with Modified Shuyu Pills, the myelin sheath loss in the VTA and NAc of mice was reduced, and the proportion of myelinated tissue increased. In summary, Modified Shuyu Pills may promote myelination via the VTA-NAc circuit by upregulating the LDLR/MEK/ERK signaling pathway, thereby ameliorating depressive-like behaviors in VaD mice.
Animals ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Ventral Tegmental Area/metabolism* ; Mice, Inbred C57BL ; Disease Models, Animal ; Depression/genetics* ; Receptors, LDL/genetics* ; Dementia, Vascular/psychology* ; MAP Kinase Signaling System/drug effects* ; Nucleus Accumbens/metabolism* ; Behavior, Animal/drug effects* ; Humans ; Myelin Sheath/drug effects* ; Extracellular Signal-Regulated MAP Kinases/genetics*

In this study, serum metabolomics techniques and molecular biology methods were used to investigate the intervention effect of kaji-ichigoside F1 on chronic unpredictable mild stress(CUMS) depression mouse model and its mechanism. The CUMS depression mouse model was constructed, and the mice were divided into blank group, model group, escitalopram(ESC, 10 mg·kg~(-1)) group, and low-dose, medium-dose, and high-dose kaji-ichigoside F1 groups(1, 2, and 4 mg·kg~(-1)). CUMS modeling was performed on all mice except the blank group, and the cycle was four weeks. At the end of modelling, ESC and kaji-ichigoside F1 were administered by gavage once a day for 28 days. After the end of the administration, behavioral testing(sucrose preference test, open field test, forced swimming test, and tail suspension test) was conducted to evaluate the improvement of depression symptoms of different doses of kaji-ichigoside F1 on CUMS depression mouse model. The morphology of neurons and the number of Nissl bodies in the hippocampus were observed by Nissl staining. Metabolomics technique was used to analyze the changes in serum differential metabolites in mice. Protein expression levels of P2X7 purinergic receptor(P2X7R), adenosine A1 receptor(A1R), and adenosine receptor A2A(A2AR) in mouse hippocampus were detected by Western blot. The results showed that compared with that in the blank group, the body weight of mice in the model group was significantly decreased, and the sucrose preference rate was significantly decreased. The immobility time was significantly increased in the forced swimming and tail suspension tests, and the total moving distance was significantly decreased in the open field test. The number of Nissl bodies was significantly decreased, and the depression-like behavior and the number of Nissl bodies in the hippocampus of mice were significantly improved after administration of kaji-ichigoside F1. In the metabonomics analysis, the purine metabolism of serum after kaji-ichigoside F1 administration was involved in the metabolic passage of depression, and Western blot analysis verified the expression of P2X7R, A1R, and A2AR proteins in purine metabolic pathways. The results show that kaji-ichigoside F1 significantly decreases the expression of P2X7R and A2AR proteins in the hippocampus of CUMS model mice and increases the expression level of A1R proteins. It is suggested that kaji-ichigoside F1 may play an antidepressant role by regulating the expression of P2X7R, A1R, and A2AR proteins in the purine metabolism pathway.
Animals ; Mice ; Antidepressive Agents/administration & dosage* ; Metabolomics ; Depression/genetics* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Disease Models, Animal ; Hippocampus/metabolism* ; Behavior, Animal/drug effects* ; Humans

Androgen deprivation therapy (ADT) can negatively affect sexual function, and only a minority of patients report sexual activity. We reviewed the existing literature regarding the proportion of men who remained sexually active during and after ADT. The PubMed database was searched for studies published over the past 20 years. We selected and reviewed randomized clinical trials that provided sexual function data at baseline and during and after ADT. The primary outcome measure was the sexual function. Studies assessed sexual function using quality of life patient-reported outcome measures, which included sexual potency/activity evaluation. Information from 2947 patients was analyzed in this review. The median age of patients was 70 years. At baseline, a median of 49.9% (95% confidence interval [CI]: 49.1%-50.7%) of the patients reported being sexually active. At 6 months, 12 months, and 2 years or later of ADT treatment, a median of 10.3% (95% CI: 10.2%-10.5%), 8.9% (95% CI: 8.6%-9.2%), and 8.3% (95% CI: 8.2%-8.5%) of the patients reported being sexually active, respectively. Considering that half of the patients were sexually active at baseline, it seems probable that more than 10% of the patients who were sexually active before starting ADT remained sexually active when undergoing ADT. In conclusion, despite the common belief that ADT eliminates sexual activity, this analysis found that approximately 1 in 10 men are sexually active when on ADT, and this proportion is likely increased in men who are sexually active before starting ADT. Attention to sexual activity should not be dismissed in men on ADT.
Humans ; Male ; Prostatic Neoplasms/drug therapy* ; Androgen Antagonists/therapeutic use* ; Sexual Behavior/drug effects* ; Quality of Life ; Aged

OBJECTIVES: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis. METHODS: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats. RESULTS: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05). CONCLUSION The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.
Animals ; Hesperidin/therapeutic use* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Male ; Stress, Psychological/drug therapy* ; Brain/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Serotonin/metabolism* ; Gastrointestinal Microbiome/drug effects* ; Behavior, Animal/drug effects* ; Rats ; Brain-Gut Axis/drug effects* ; Chronic Disease ; Colon/drug effects*

OBJECTIVE: To investigate the therapeutic effect of Xiangshao Granules (XSG) on post-stroke depression (PSD) and explore the underlying mechanisms. METHODS: Forty-three C57BL/6J mice were divided into 3 groups: sham (n=15), PSD+vehicle (n=14), and PSD+XSG (n=14) groups according to a random number table. The PSD models were constructed using chronic unpredictable mild stress (CUMS) after middle cerebral artery occlusion (MCAO). The sham group only experienced the same surgical operation, but without MACO and CUMS stimulation. The XSG group received XSG (60 mg/kg per day) by gavage for 4 weeks. The mice in the sham and vehicle groups were given the same volume of 0.9% saline at the same time. The body weight and behavior tests including open field test, sucrose preference test, tail suspension test, and elevated plus-maze test, were used to validate the PSD mouse model. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining were used to evaluate the anti-inflammatory effects of XSG. The potential molecular mechanisms were explored and verified through network pharmacology analysis, Nissl staining, Western blot, ELISA, and RT-qPCR, respectively. RESULTS: The body weight and behavior tests showed that MCAO combined with CUMS successfully established the PSD models. XSG alleviated neuronal damage, reduced the expressions of pro-apoptotic proteins Caspase-3 and B-cell lymphoma-2 (BCL-2)-associated X (BAX), and increased the expression of anti-apoptotic protein BCL-2 in PSD mice (P<0.05 or P<0.01). XSG inhibited microglial activation and the expressions of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin (IL)-1 β, and IL-6 via the toll-like receptor 4/nuclear factor kappa-B signaling pathway in PSD mice (P<0.05 or P<0.01). Furthermore, XSG decreased the expression of indoleamine 2,3-dioxygenase1 (IDO1) and increased the concentration of 5-hydroxytryptamine in PSD mice (P<0.05 or P<0.01). CONCLUSION XSG could reverse the anxiety/depressionlike behaviors and reduce the neuronal injury in the hippocampus and prefrontal cortex of PSD mice, which may be a potential therapeutic agent for PSD.
Animals ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism* ; Depression/etiology* ; Drugs, Chinese Herbal/therapeutic use* ; Hippocampus/metabolism* ; Male ; Mice, Inbred C57BL ; Prefrontal Cortex/pathology* ; Microglia/metabolism* ; Stroke/drug therapy* ; Disease Models, Animal ; Mice ; Behavior, Animal/drug effects*

OBJECTIVE: To investigate the antidepressant effects of Xiaoyao Pill (XYP) by exploring its interactions with gut microbiota and tryptophan metabolism. METHODS: Utilizing network pharmacology, the functional substance groups, key targets, and pathways of XYP in the treatment of depression were identified. The chronic unpredictable mild stress (CUMS) protocol was implemented in male Sprague-Dawley rats to establish depression model. Thirty rats were randomly divided into 3 groups according to their body weight (10 for each): control, CUMS and XYP groups (1.8 g/kg). After 28-day interventions, behavioral phenotyping including sucrose preference test (SPT) and open field test (OFT) were performed. Biochemical validation encompassed enzyme-linked immunosorbent assay for serum cortisol, hematoxylin-eosin histopathology, and immunohistochemistry. Liquid chromatography-mass spectrometry was utilized to profile serum metabolites, while fecal samples underwent metagenomic sequencing for gut microbiota characterization. RESULTS: Network pharmacology studies predicted that key components can protect the nervous system by regulating inflammatory pathways through the blood-brain barrier. SPT and OFT showed that XYP treatment significantly ameliorated depressive-like behaviors (all P<0.05). XYP treatment also restored hippocampal neuronal density, increased serum neurotransmitter levels of neurotransmitters such as 5-hydroxytryptamine and vasoactive intestinal peptide, and while suppressing inflammatory markers such as tumor necrosis factor-alpha, interleukin-1 beta (IL-1 β), and IL-6 (all P<0.05). Metagenomics revealed significant restructuring of gut microbiota, notably the regulation of Parabacteroides distasonis (P<0.05). Non-targeted metabolomics analysis showed that the level of metabolites in the tryptophan and kynurenine pathway significantly changed (variable importance in the projection >1, P<0.05), and the change of metabolic flux was significantly correlated with behavioral improvement (P<0.05). CONCLUSIONS XYP exerts antidepressant effects by increasing neurotransmitter levels, reducing inflammatory makers and modulating Parabacteroides distasonis. Through further exploration of metabolomics, we found that XYP may play a protective role in depression by regulating tryptophan metabolism.
Animals ; Tryptophan/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Gastrointestinal Microbiome/drug effects* ; Rats, Sprague-Dawley ; Depression/blood* ; Male ; Stress, Psychological/drug therapy* ; Behavior, Animal/drug effects* ; Rats ; Chronic Disease ; Hippocampus/drug effects*

OBJECTIVE: To elucidate the modulation mechanism of Suanzaoren Decoction (SZRD) on basolateral amygdala (BLA) neuronal activity to alleviate chronic restraint stress (CRS)-related behavioral deficits. METHODS: The male C57BL/6J mice were assigned to 4 groups using the complete randomization method, including control (CON, n=19), CRS (n=19), SZRD (n=21), and fluoxetine (Flu, n=22) groups. Mice were restrained for 6 h per day, over a 21-d period to establish CRS models. The CON group remained in their cages without food or water during the 6-h matching period. SZRD and Flu groups received intragastric administration of SZRD (4.68 g/kg) and Flu (20 mg/kg) daily, respectively, 30 min before restraint for 21 consecutive days. The therapeutic effects of SZRD were evaluated using behavioral tests including the tail suspension test, elevated plus maze test, and forced swimming test. The cellular Fletcher B. Judson murine osteosarcoma proto-oncogene (c-Fos) expression in the BLA was measured using immunofluorescence, while action potential (AP) firing and synaptic transmission in BLA pyramidal neurons were evaluated using whole-cell patch-clamp recordings. RESULTS: SZRD administration significantly increased time spent in the open arms and open-arm entries while reducing immobility time (P<0.05 or P<0.01). It downregulated CRS-induced c-Fos expression and AP firing of pyramidal neurons in the BLA (P<0.01). Additionally, SZRD selectively attenuated excitatory (P<0.01), but not inhibitory, synaptic transmission onto BLA pyramidal neurons. CONCLUSION SZRD alleviated CRS-induced anxiety- and depression-like behaviors in mice by modulating the excitability and synaptic transmission of BLA pyramidal neurons.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Depression/complications* ; Pyramidal Cells/pathology* ; Male ; Mice, Inbred C57BL ; Basolateral Nuclear Complex/pathology* ; Restraint, Physical ; Anxiety/complications* ; Behavior, Animal/drug effects* ; Stress, Psychological/physiopathology* ; Mice ; Proto-Oncogene Proteins c-fos/metabolism* ; Action Potentials/drug effects* ; Synaptic Transmission/drug effects*

OBJECTIVES: To explore the bioactive components in Jiawei Xiaoyao Pills (JWXYP) and their mechanisms for alleviating depression-like behaviors. METHODS: The active compounds, key targets, and pathways of JWXYP were identified using TCMSP and TCMIP databases. Thirty-six SD rats were randomized equally into 6 groups including a control group and 5 chronic unpredictable mild stress (CUMS)-induced depression groups. After modeling, the 5 model groups were treated with daily gavage of normal saline, 1.8 mg/kg fluoxetine hydrochloride (positive control drug), or JWXYP at 1.44, 2.88, and 4.32 g/kg. The depression-like behaviors of the rats were evaluated using behavioral tests, and pathological changes in the liver and hippocampus were examined with HE staining. The biochemical indicators in the serum and brain tissues were detected using ELISA. Serum metabolomics analysis was performed to identify the differential metabolites using OPLS-DA, and gut microbiota changes were analyzed using 16S rDNA sequencing. RESULTS: Network pharmacology revealed that menthone and paeonol in JWXYP were capable of penetrating the blood-brain barrier to regulate inflammatory pathways and protect the nervous system. In the rat models subjected to CUMS, treatment with JWXYP significantly improved body weight loss, sucrose preference and open field activities, reduced liver inflammation, alleviated structural changes in the hippocampal neurons, decreased serum levels of TNF‑α, IL-1β, IL-6 and LBP, and increased 5-HT and VIP concentrations in the serum and brain tissue, and these effects were the most pronounced in the high-dose group. Metabolomics analysis showed changes in such metabolites as indole-3-acetamide and acetyl-L-carnitine in JWXYP-treated rats, involving the pathways for bile acid biosynthesis and amino acid metabolism. 16S rDNA analysis demonstrated increased gut microbiota diversity and increased abundance of Lactobacillus species in JWXYP-treated rats. CONCLUSIONS JWXYP alleviates depression-like symptoms in rats by regulating the neurotransmitters, inhibiting inflammation and oxidation, and modulating gut microbiota.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Gastrointestinal Microbiome/drug effects* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Neurotransmitter Agents/metabolism* ; Rats ; Inflammation ; Male ; Hippocampus ; Behavior, Animal/drug effects*