Identification of technological/metabolic/environmental profiles associated with cheeses accumulating the neuroactive compound tryptamine.

Tryptamine is a neuromodulator of the central nervous system. It is also a biogenic amine, formed by the microbial decarboxylation of L-tryptophan. Tryptamine accumulation in cheese has been scarcely examined. No studies are available regarding the factors that could influence its accumulation. Determining the tryptamine content and identifying the factors that influence its accumulation could help in the design of functional tryptamine-enriched cheeses without potentially toxic concentrations being reached. We report the tryptamine concentration of 300 cheese samples representing 201 varieties. 16% of the samples accumulated tryptamine, at between 3.20 mg kg-1 and 3012.14 mg kg-1 (mean of 29.21 mg kg-1). 4.7% of cheeses accumulated tryptamine at higher levels than those described as potentially toxic. Moreover, three technological/metabolic/environmental profiles associated with tryptamine-containing cheese were identified, as well as the hallmark varieties reflecting each. Such knowledge could be useful for the dairy industry to control the tryptamine content of their products.

Modulation of tryptophan metabolism via AHR-IL22 pathway mediates the alleviation of DSS-induced colitis by chitooligosaccharides with different degrees of polymerization.

Oral administration of chitooligosaccharides (COS) has been reported to alleviate colitis in mice. However, the mechanism of action of COS with specific polymerization degree on gut inflammation and metabolism remains unclear. This study aimed to investigate the effects of chitobiose (COS2), chitotetraose (COS4), and chitohexaose (COS6) on colitis, and to elucidate their underlying mechanisms. COS2, COS4, and COS6 were able to significantly alleviate colonic injury and inflammation levels. COS6 has the best anti-inflammatory effect. Furthermore, COS6 could down-regulate the level of indoleamine-2,3-dioxygenase1 (IDO1) and restore the levels of indole, indoleacetic-3-acid (IAA), and indole-3-carbaldehyde (I3A) in the cecum of chronic colitis mice (p < 0.05), thereby regulating tryptophan metabolism. In the aromatic hydrocarbon receptor-IL-22 (AHR-IL-22) pathway, although there were differences between chronic colitis and acute colitis mice, COS intervention could restore the AHR-IL-22 pathway to normal, promote the expression of MUC2, and repair the intestinal mucosal barrier. In conclusion, the results of this study suggested that COS had a good inhibitory effect on IDO1 under inflammation and the changes of AHR and IL-22 levels at different stages of disease development. This provides new insights into the potential use of COS as a functional food for improving intestinal inflammation and metabolism.

Identification of components in coriander (Coriandrum sativum L.) inhibiting degranulation of RBL-2H3 cells.

We found that a water-soluble extract of coriander (Coriandrum sativum L.) (leaves, petioles and stems) inhibits antigen-induced degranulation of RBL-2H3 cells, a rat basophil leukemia cell line. The aim of this study was to elucidate the anti-degranulation active components in the extract. The methanol-eluate fraction obtained by fractionation of the water-soluble extract using MCI gel column chromatography had strong activity, and eight components were isolated and identified. Two of them were identified as new compounds, (3S)-3-methyl-6-hydroxyisocoumarin 8-O-ß-D-glucopyranoside (compound 1) and (7S,8R)-7,8-dihydro-8-ß-D-glucopyranosyloxy-4-methoxy-7-methyl-5H-fro[2,3-g][2]benzopyran-5-one (compound 2). As a result of evaluation of anti-degranulation activity of eight components, seven of them, such as tryptophan, phenylalanine, dihydroxycoumarin glucoside, quercetin glycoside, rutin, compound 1, and compound 2, had the activity. These results indicated that the water-soluble extract of coriander contains several anti-degranulation substances.

Detection of protein oxidation products by fluorescence spectroscopy and trilinear data decomposition: Proof of concept.

Current analytical methods studying protein oxidation modifications require laborious sample preparation and chromatographic methods. Fluorescence spectroscopy is an alternative, as many protein oxidation products are fluorescent. However, the complexity of the signal causes misinterpretation and quantification errors if single emission spectra are used. Here, we analyzed the entire fluorescence excitation-emission matrix using the trilinear decomposition method parallel factor analysis (PARAFAC). Two sample sets were used: a calibration set based on known mixtures of tryptophan, tyrosine, and four oxidation products, and a second sample set of oxidized protein solutions containing UV-illuminated ß-lactoglobulin. The PARAFAC model succeeded in resolving the signals of the model systems into the pure fluorophore components and estimating their concentrations. The estimated concentrations for the illuminated ß-lactoglobulin samples were validated by liquid chromatography-mass spectrometry. Our approach is a promising tool for reliable identification and quantification of fluorescent protein oxidation products, even in a complex protein system.

Development, validation, and uncertainty measurement of HPLC-DAD method for determination of some free amino acids in infant formula and medical food products for inborn errors of metabolism.

This research aims at determining some free amino acids in amino acid-based infant formulas and amino acid-modified medical foods for inborn errors of metabolism to prove their quality. A method based on high-performance liquid chromatography and diode array detection was developed and validated. Then, overall uncertainty was estimated by the bottom-up approach. Applying the weighted least squares regression method suggested good linearity with coefficient of determinations ≥ 0.9960. The limits of detection were calculated between 0.01 and 0.28 µg/mL. The most repetitive recovery values were obtained in the range of 91-108%, with RSDs ≤ 15%. The expanded uncertainties were below 20% for most amino acids. The contributions of linear regression and repeatability are two main factors in estimating overall uncertainty. The results offer this method as a simple and easy procedure for analyzing free amino acids in seven powdered medical foods designed for phenylketonuria, maple syrup urine disease, methylmalonic, and propionic acidemia.

Photostability of l-tryptophan in aqueous solution: Effect of atmosphere and antioxidants addition.

l-Tryptophan (l-Trp) is an amino acid important in nutrition, and mainly provided by food supplements. However, it is known to be unstable under light irradiation, which is an issue for the nutrition and feed industry. In the present study, the photostability of l-Trp was studied in acidic aqueous solutions under air and under an inert atmosphere, N2. The photodegradation was followed using UV-visible and fluorescence spectroscopy after photolysis. Moreover, molecular orbitals and bond dissociation energies calculations, and electron spin resonance spectroscopy were performed. From all these results, a photodegradation occurring through a free radical pathway was suggested. Interestingly, several antioxidants were tested to improve the photostability of l-Trp, especially during irradiation under air, since the l-Trp was evidenced to be much less stable under air than under N2. The results showed that sodium benzoate or EDTA were not efficient, but antioxidants such as chlorogenic acid, ascorbic acid or potassium sorbate improved significantly the photostability of l-Trp in acidic solutions.

AHR canonical pathway: in vivo findings to support novel antihypertensive strategies.

Essential hypertension (HTN) is a disease where genetic and environmental factors interact to produce a high prevalent set of almost indistinguishable phenotypes. The weak definition of what is under the umbrella of HTN is a consequence of the lack of knowledge on the players involved in environment-gene interaction and their impact on blood pressure (BP) and mechanisms. The disclosure of these mechanisms that sense and (mal)adapt to toxic-environmental stimuli might at least determine some phenotypes of essential HTN and will have important therapeutic implications. In the present manuscript, we looked closer to the environmental sensor aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor involved in cardiovascular physiology, but better known by its involvement in biotransformation of xenobiotics through its canonical pathway. This review aims to disclose the contribution of the AHR-canonical pathway to HTN. For better mirror the complexity of the mechanisms involved in BP regulation, we privileged evidence from in vivo studies. Here we ascertained the level of available evidence and a comprehensive characterization of the AHR-related phenotype of HTN. We reviewed clinical and rodent studies on AHR-HTN genetic association and on AHR ligands and their impact on BP. We concluded that AHR is a druggable mechanistic linker of environmental exposure to HTN. We conclude that is worth to investigate the canonical pathway of AHR and the expression/polymorphisms of its related genes and/or other biomarkers (e.g. tryptophan-related ligands), in order to identify patients that may benefit from an AHR-centered antihypertensive treatment.

Evaluation of polyphenol bioaccessibility and kinetic of starch digestion of spaghetti with persimmon (Dyospyros kaki) flours coproducts during in vitro gastrointestinal digestion.

The aim was to study the in vitro starch digestibility, the free and bound polyphenol profile and their bioaccessibility and antioxidant activity during in vitro gastrointestinal digestion of durum wheat semolina spaghetti added with two types of persimmon flour concentrates ("Rojo Brillante" flour and "Triumph" flour) at two concentrations (3 and 6%). Results obtained showed that persimmon flour improves the polyphenol profile of spaghetti by addition gallic acid and coumaric acid-o-hexoside, and increasing 2-fold and around 3-fold its content in spaghetti with 3% and 6% persimmon flours, respectively. Cooked process and digestion affected more to free polyphenol content than bound. Furthermore, 3% persimmon flour enriched spaghetti reduce kinetic of starch digestion, while 6% enriched spaghetti increased it. In conclusion, persimmon flours (Rojo Brillante and Triumph) at low concentrations could be used to develop spaghetti with more polyphenol content and less starch digestibility than traditional spaghetti.

Cluster bagging promotes melatonin biosynthesis in the berry skins of Vitis vinifera cv. Cabernet Sauvignon and Carignan during development and ripening.

Melatonin, a tryptophan derivative, is an important functional component in grape berries. We investigated the effect of cluster bagging on melatonin biosynthesis in the berries of two wine grape cultivars, Cabernet Sauvignon and Carignan, during fruit development and ripening. Cluster bagging delayed fruit coloring and ripening, and bag-treated berries of both grape cultivars synthesized more melatonin and most of the precursor compounds including L-tryptophan, N-acetylserotonin, tryptamine, and serotonin compared to those exposed to light (control) conditions. Interestingly, 5-methoxytryptamine was only detected in the berries of Carignan and not of Cabernet Sauvignon, both in the cluster bagging and control groups. In addition, melatonin and most of its precursors, decreased after veraison. VvSNAT1 and VvT5H expression levels were positively correlated with melatonin content. Our findings suggested that melatonin synthesis pathways differ among grape cultivars, and that VvSNAT1 and VvT5H may show key regulatory roles in the melatonin synthesis of grape berries.

Serotonin, hematopoiesis and stem cells.

A large number of studies have focused on the role of serotonin as a neurotransmitter in the central nervous system, although only a small percentage of the body's serotonin (∼5%) can be found in the mature brain of mammals. In the gut, the enterochromaffin cells are scattered in the enteric epithelium from the stomach through the colon and produce over 95% of the body's serotonin. Since the generation of tryptophan hydroxylase (Tph1 and Tph2) knockout mice, unsuspected roles have been identified for serotonin synthesized outside the brain. Moreover, the murine model deficient in peripheral serotonin (Tph1-/-) is a unique experimental tool for exploring the molecular and cellular mechanisms involving serotonin's local effects through microserotonergic systems. In this review, we focus on peripheral serotonin and its role on progenitor or stem cells as well as on hematopoietic progenitors. We discuss the possible role of serotonin in hematopoietic diseases, and whether targeting the serotonergic system could be of therapeutic value for the regulation of normal and pathological hematopoiesis.

Effect of low-frequency magnetic field on the gel properties of pork myofibrillar proteins.

This study aimed to investigate the effect of a low-frequency magnetic field (LF-MF; 0, 0.25, 0.5, and 1.4 mT) on the gel properties of pork myofibrillar protein (MP) and to explore potential mechanisms. The water-holding capacity (WHC) and rheological properties of MP gels treated at 0.5 mT were better than those from other treatments. The water mobility did not change significantly as intensity increased, while the ratios of immobilized water (PT21) and free water (PT22) significantly decreased and increased, respectively. This suggested that the effect of LF-MF on MP hydration might be related to the formation of water clusters. Raman spectra suggested that α-helices unfolded and ß-sheets, ß-turns, and random coils were formed in MP gels (from 0.25 to 1.4 mT). Furthermore, the intensities of characteristic peaks in the tryptophan and aliphatic residues band were highest at 0.5 mT, indicating that 0.5 mT was the optimum intensity for hydrophobic interactions.

UPLC-Orbitrap-MS/MS combined with chemometrics establishes variations in chemical components in green tea from Yunnan and Hunan origins.

Multi-components of green tea from different origins were identified by UPLC-Orbitrap-MS/MS, including alkaloids, amino acids, catechins, flavones, flavone glycosides, phenolic acids and theaflavins. Quantitative chemical profiles of 72 samples of Yunnan green tea (YGT) and Hunan green tea (HGT) established the influence of origin on green tea. In addition, three variable selection methods, based on partial least squares-discriminant analysis (PLS-DA), were employed to screen characteristic components of YGT and HGT. The results of variable importance on projection (VIP) method showed better performance than coefficients ß and the least absolute shrinkage and selection operator (LASSO) for this dataset. Three characteristic components, named, gallocatechin gallate (GCG), epicatechin-(4ß → 8)-epigallocatechin-3-O-gallate, and vitexin were selected by VIP, with a correct rate of 98.61% and an AUC value of 0.9706. The results indicated that the combination of UPLC-Orbitrap-MS/MS and chemometrics could serve as a valid strategy to analyze complex analytical objects, such as green tea.

Colorimetric aptasensors for determination of tobramycin in milk and chicken eggs based on DNA and gold nanoparticles.

Colorimetric aptasensors were designed for detection of tobramycin (TOB) based on unmodified gold nanoparticles (AuNPs) and single-strand DNA (ssDNA). In the absence of TOB, the DNA aptamer was coated on the surface of AuNPs to keep it against salt-induced aggregation. In the presence of TOB, aptamer will bind with TOB and detach from the surface of AuNPs because of higher affinities between aptamer and TOB. Then less protection of DNA may result in the aggregation of AuNPs by salt and an apparent color change from red to purple-blue. The developed aptasensors showed a high selectivity and sensitivity for TOB detection. The linearity range and the detection limit were 40-200 nM and 23.3 nM respectively. The validity of the procedure and applicability of aptasensors were successfully used to detect TOB in milk and chicken eggs, and the results were excellent in accord with the values obtained by spectrofluorimetric detection.

Patchouli alcohol ameliorates dextran sodium sulfate-induced experimental colitis and suppresses tryptophan catabolism.

Despite the increased morbidity of ulcerative colitis (UC) in recent years, available treatments remain unsatisfactory. Pogostemon cablin has been widely applied to treat a variety of gastrointestinal disorders in clinic for centuries, in which patchouli alcohol (PA, C15H26O) has been identified as the major active component. This study attempted to determine the bioactivity of PA on dextran sulfate sodium (DSS)-induced mice colitis and clarify the mechanism of action. Acute colitis was induced in mice by 3% DSS for 7 days. The mice were then given PA (10, 20 and 40mg/kg) or sulfasalazine (SASP, 200mg/kg) as positive control via oral administration for 7 days. At the end of study, animals were sacrificed and samples were collected for pathological and other analysis. In addition, a metabolite profiling and a targeted metabolite analysis, based on the Ultra-Performance Liquid Chromatography coupled with mass spectrometry (UPLC-MS) approach, were performed to characterize the metabolic changes in plasma. The results revealed that PA significantly reduced the disease activity index (DAI) and ameliorated the colonic injury of DSS mice. The levels of colonic MPO and cytokines involving TNF-α, IFN-γ, IL-1ß, IL-6, IL-4 and IL-10 also declined. Furthermore, PA improved the intestinal epithelial barrier by enhancing the level of colonic expression of the tight junction (TJ) proteins, for instance ZO-1, ZO-2, claudin-1 and occludin, and by elevating the levels of mucin-1 and mucin-2 mRNA. The study also demonstrated that PA inhibited the DSS-induced cell death signaling by modulating the apoptosis related Bax and Bcl-2 proteins and down-regulating the necroptosis related RIP3 and MLKL proteins. By comparison, up-regulation of IDO-1 and TPH-1 protein expression in DSS group was suppressed by PA, which was in line with the declined levels of kynurenine (Kyn) and 5-hydroxytryptophan (5-HTP) in plasma. The therapeutic effect of PA was evidently reduced when Kyn was given to mice. In summary, the study successfully demonstrated that PA ameliorated DSS-induced mice acute colitis by suppressing inflammation, maintaining the integrity of intestinal epithelial barrier, inhibiting cell death signaling, and suppressing tryptophan catabolism. The results provided valuable information and guidance for using PA in treatment of UC.

Regulation of the nitric oxide oxidase activity of myeloperoxidase by pharmacological agents.

The leukocyte-derived heme enzyme myeloperoxidase (MPO) is released extracellularly during inflammation and impairs nitric oxide (NO) bioavailability by directly oxidizing NO or producing NO-consuming substrate radicals. Here, structurally diverse pharmacological agents with activities as MPO substrates/inhibitors or antioxidants were screened for their effects on MPO NO oxidase activity in human plasma and physiological model systems containing endogenous MPO substrates/antioxidants (tyrosine, urate, ascorbate). Hydrazide-based irreversible/reversible MPO inhibitors (4-ABAH, isoniazid) or the sickle cell anaemia drug, hydroxyurea, all promoted MPO NO oxidase activity. This involved the capacity of NO to antagonize MPO inhibition by hydrazide-derived radicals and/or the ability of drug-derived radicals to stimulate MPO turnover thereby increasing NO consumption by MPO redox intermediates or NO-consuming radicals. In contrast, the mechanism-based irreversible MPO inhibitor 2-thioxanthine, potently inhibited MPO turnover and NO consumption. Although the phenolics acetaminophen and resveratrol initially increased MPO turnover and NO consumption, they limited the overall extent of NO loss by rapidly depleting H2O2 and promoting the formation of ascorbyl radicals, which inefficiently consume NO. The vitamin E analogue trolox inhibited MPO NO oxidase activity in ascorbate-depleted fluids by scavenging NO-consuming tyrosyl and urate radicals. Tempol and related nitroxides decreased NO consumption in ascorbate-replete fluids by scavenging MPO-derived ascorbyl radicals. Indoles or apocynin yielded marginal effects. Kinetic analyses rationalized differences in drug activities and identified criteria for the improved inhibition of MPO NO oxidase activity. This study reveals that widely used agents have important implications for MPO NO oxidase activity under physiological conditions, highlighting new pharmacological strategies for preserving NO bioavailability during inflammation.

Multiresponse optimization of a UPLC method for the simultaneous determination of tryptophan and 15 tryptophan-derived compounds using a Box-Behnken design with a desirability function.

A Box-Behnken design was used in conjunction with multiresponse optimization based on the desirability function to carry out the simultaneous separation of tryptophan and 15 derivatives by Ultra Performance Liquid Chromatography. The gradient composition of the mobile phase and the flow rate were optimized with respect to the resolution of severely overlapping chromatographic peaks and the total run time. Two different stationary phases were evaluated (hybrid silica and a solid-core-based C18 column). The methods were validated and a suitable sensitivity was found for all compounds in the concentration range 1-100µgL-1 (R2>0.999). High levels of repeatability and intermediate precision (CV less than 0.25% and 1.7% on average for the retention time and the signal area, respectively) were obtained. The new method was applied to the determination tryptophan and its derivatives in black pigmented glutinous and non-glutinous rice grain samples.

Ginkgo biloba exocarp extracts induces apoptosis in Lewis lung cancer cells involving MAPK signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: A fruit of Ginkgo biloba L. is known as Ginkgo nuts. It is an edible traditional Chinese medicine, and could be used for the treatment of cancer thousands of years ago in China. The extracts prepared from the exocarp of Ginkgo biloba (Ginkgo biloba exocarp extracts, GBEE) has the effects of anti-cancer, immune promotion, anti-aging and etc. AIM OF STUDY: To study the effects of GBEE inducing apoptosis in Lewis lung cancer (LLC) cells and the role of Mitogen-activated protein kinase(MAPK) signaling pathways in it. MATERIALS AND METHODS: The LLC solid tumor model was established in C57BL/6J mice. The tumor-bearing mice were randomly divided into 5 groups. A normal control group without tumor cells was established additionally. There were 10 mice in each group, and they were dosed 24h after inoculation. The GBEE (50, 100, 200mg/kg b.w.) groups were dosed by intragastric gavage (i.g.). The mice in positive control group were intraperitoneal (i.p.) injected with cyclophosphamide (CPA) at a dose of 20mg/kg (b.w.). The model control group and the normal control group were both given normal saline (NS) by i.g.. All the groups were dosed at a volume of 0.1mL/10g (b.w.), once a day for 18d. The day after the last administration, the transplanted tumors was stripped and weighed, and the inhibition rate was calculated. In vitro experiments, MTT method was applied to detect the effects of GBEE on LLC cells and primary cultured mouse lung cells. Annexin V-FITC/PI method was used to detect the apoptosis rate of LLC cells. Rhodamine 123 method was used to detect the Mitochondrial transmembrane potential (MTP). Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the levels of Fas mRNA. Western Blot was used to detect the expression of Bax, Bcl-2, Cyt C, cleaved Caspase-3 and MAPK proteins in the corresponding parts of LLC cells. RESULTS: GBEE (50-200mg/kg) inhibited the growth of LLC transplanted tumors with a dose-effect relationship. GBEE (5-160µg/mL) inhibited the proliferation of LLC cells in vitro with the half maximal inhibitory concentration (IC50) value of 162.43µg/mL, while it had no significant inhibitory effects on the primary cultured mouse lung cells. After GBEE (10, 20 and 40µg/mL) acted on the LLC cells, the apoptosis rate was increased and the MTP was decreased. The ratio of Bax/Bcl-2 was increased in the cells. Meanwhile, it also promoted the translocation of Bax/Bcl-2 in mitochondrial membrane and the release of Cyt C from mitochondria to cytosol. In addition, it up-regulated the cleaved-Caspase-3 protein expression. The mRNA levels of Fas and the protein levels of Fas, FasL and p-p38 in the cells were both increased. The levels of p-ERK1/2 and p-JNK1/2 protein were down-regulated but the p38, ERK1/2 and JNK1/2 were not significantly changed. CONCLUSIONS: GBEE induces apoptosis in LLC cells via mitochondrial-mediated intrinsic pathway and death receptor-mediated extrinsic pathway, which may be closely relevant to the regulation of MAPK signaling pathways.

Melatonin and derived l-tryptophan metabolites produced during alcoholic fermentation by different wine yeast strains.

Melatonin is a neurohormone involved in the regulation of circadian rhythms in humans. Evidence has recently been found of its occurrence in wines and its role in the winemaking process. The yeast Saccharomyces cerevisiae is consequently thought to be important in Melatonin synthesis, but limited data and reference texts are available on this synthetic pathway. This paper aims to elucidate whether the synthetic pathway of Melatonin in Saccharomyces and non-Saccharomyces strains involves these intermediates. To this end, seven commercial strains comprising Saccharomyces cerevisiae (Red Fruit, ES488, Lalvin QA23, Uvaferm BC, and Lalvin ICV GRE) and non-Saccharomyces (Torulaspora delbrueckii and Metschnikowia pulcherrima) were monitored, under controlled fermentation conditions, in synthetic must, for seven days. Samples were analysed using a UHPLC-HRMS system (Qexactive). Five out of the seven strains formed Melatonin during the fermentation process: three S. cerevisiae strains and the two non-Saccharomyces. Additionally, other compounds derived from l-tryptophan occurred during fermentation.

Antioxidant peptides from corn gluten meal: Orthogonal design evaluation.

Protamex catalyzed corn gluten meal (CGM) hydrolysis peptides (CHP) were prepared. Orthogonal design L16 (4(5)) was used to optimize processing variables of CGM concentration, CGM heat pretreatment (121 °C) time, and enzymolysis pH, temperature, and time. Degree of hydrolysis (DH), undigested residue ratio, molecular weight (MW) distribution and DPPH radical inhibition were selected as analysis indicators. Optimum variables were CGM concentration of 18%, heat pretreatment time of 40 min, and enzymolysis pH, temperature and time of 7.5, 55 °C and 24h, respectively. Verification test showed that CHP IC50 for scavenging hydroxyl radical was the best and then followed by reducing power. Oligopeptides improved after hydrolysis at the expense of di- and tripeptides, suggesting formation of soluble aggregates from low MW peptides. The increase in the DH, oligopeptides, Alanyl-Tyrosine, and antioxidant free amino acids coincided with the improvement in the antioxidant activity of CHP.

Danzhi Xiaoyao San ameliorates depressive-like behavior by shifting toward serotonin via the downregulation of hippocampal indoleamine 2,3-dioxygenase.

ETHNOPHARMACOLOGICAL RELEVANCE: Danzhi Xiaoyao San (DXS) is a canonical Chinese medicine formula from Principles of Internal Medicine, which was written during the Ming dynasty. This formula is approved and commercialized for use in the prevention and treatment of affective disorders. This study is aimed to investigate the hypothesis that DXS treats depressive-like behavior by shifting the balance of the kynurenine (Kyn)/serotonin (5-HT) pathway toward the 5-HT pathway through the downregulation of hippocampal indoleamine 2,3-dioxygenase (IDO). MATERIALS AND METHODS: Chemical fingerprints of gardenoside, paeoniflorin, ferulic acid, paeonol, and ligustilide in standard extraction were used as the material bases of DXS. Rats with depressive-like behavior induced by chronic unpredictable mild stress (CUMS) were randomly divided into four groups, namely the control, model, DXS, and fluoxetine groups. Cytokines, IDO, and tryptophan (Trp) catabolites were analyzed by enzyme-linked immunosorbent assay, western blot, and liquid chromatography-electrospray ionization tandem mass spectrometry, respectively. RESULTS: DXS significantly increased crossing grid numbers, sucrose consumption, and body weight. This treatment significantly decreased the serum levels of tumor necrosis factor-α and interleukin 6 (IL-6). However, DXS elicited no significant effects on IL-1ß, IL-2, and interferon γ. DXS downregulated the activity of IDO and subsequent production of Kyn in the hippocampus. This treatment upregulated the hippocampal contents of Trp and 5-HT but did not influence 5-HT turnover. CONCLUSIONS: DXS exhibited antidepressant-like effects on rats exposed to CUMS. DXS reduced IDO activity to shift the balance of the Kyn/5-HT pathway toward the 5-HT pathway.