Mechanism of tryptanthrin in treatment of ulcerative colitis in mice based on serum metabolomics / 中国中药杂志

This study aims to explore the effect of tryptanthrin on potential metabolic biomarkers in the serum of mice with ulcerative colitis(UC) induced by dextran sulfate sodium(DSS) based on liquid chromatography-mass spectrometry(LC-MS) and predict the related metabolic pathways. C57BL/6 mice were randomly assigned into a tryptanthrin group, a sulfasalazine group, a control group, and a model group. The mouse model of UC was established by free drinking of 3% DSS solution for 11 days, and corresponding drugs were adminsitrated at the same time. The signs of mice were observed and the disease activity index(DAI) score was recorded from the first day. Colon tissue samples were collected after the experiment and observed by hematoxylin-eosin(HE) staining. The levels of interleukin-4(IL-4), interleukin-10(IL-10), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-8(IL-8) in the serum were measured by enzyme linked immunosorbent assay(ELISA). The serum samples were collected from 6 mice in each group for widely targeted metabolomics. The metabolic pathways were enriched by MetaboAnalyst 5.0. The results showed that compared with the model group, tryptanthrin treatment decreased the DAI score(P<0.05), alleviated the injury of the colon tissue and the infiltration of inflammatory cells, lowered the levels of proinflammatory cytokines, and elevated the levels of anti-inflammatory cytokines in the serum. The metabolomic analysis revealed 28 differential metabolites which were involved in 3 metabolic pathways including purine metabolism, arachidonic acid metabolism, and tryptophan metabolism. Tryptanthrin may restore the metabolism of the mice with UC induced by DSS to the normal level by regulating the purine metabolism, arachidonic acid metabolism, and tryptophan metabolism. This study employed metabolomics to analyze the mechanism of tryptanthrin in the treatment of UC, providing an experimental basis for the utilization and development of tryptanthrin.

Effects of moxibustion on behaviors and tryptophan metabolism-related products in mice with irritable bowel syndrome / 针灸推拿医学（英文版）

Objective: To observe the effect of moxibustion on behaviors and related products of tryptophan (Trp) metabolism in the colon of mice with irritable bowel syndrome (IBS), and to explore the mechanism of moxibustion in the IBS treatment.Methods: Twenty-four mice were randomly divided into a normal group, a model group, a moxibustion group, and a probiotic group, with 6 mice in each group. The visceral pain model of IBS was established by enema with 2,4,6-trinitrobenzene sulfonic acid (TNBS) solution. Mice in the moxibustion group were treated with mild moxibustion at bilateral Zusanli (ST36), and those in the probiotic group were treated with probiotics such as Bifidobacterium by gavage. Abdominal withdrawal reflex (AWR) test, elevated plus-maze (EPM) test, and forced swimming test (FST) were performed after treatment. The expression levels of 5-hydroxytryptamine (5-HT) and tryptophan hydroxylase 1 (TPH1) in the colon were detected by immunofluorescence, and the expression levels of Trp, kynurenine (Kyn), and indole-2,3-oxygenase (IDO) in the colon were detected by enzyme-linked immunosorbent assay. Results: Compared with the normal group, the AWR scores were increased significantly in the model group under different pressure values (P<0.01), the open-arm staying time and open-arm entries in the EPM test were decreased significantly (P<0.01, P<0.05), the motionless time in the FST was increased significantly (P<0.01), and the expression levels of colonic Trp, TPH1, IDO, 5-HT, and Kyn were increased significantly (P<0.01) in the models. Compared with the model group, the AWR scores were differently decreased (P<0.05 or P<0.01), the open-arm entries in the EPM test were increased (P<0.05), the motionless times in the FST were decreased (P<0.05), and the colonic expression levels of Trp, TPH1, IDO, and 5-HT were decreased (P<0.01 or P<0.05) in the moxibustion and probiotic groups; the open-arm staying time was significantly increased in the moxibustion group (P<0.01), and the colonic expression level of Kyn was significantly decreased in the probiotic group (P<0.01). Conclusion: Moxibustion at Zusanli (ST36) improves visceral pain and pain mood and down-regulates the expression levels of colonic TPH1, IDO, Trp, 5-HT, and Kyn in IBS mice.

Tryptophan and tumor immunity / 药学学报

As an essential amino acid, tryptophan (Trp) has various physiological functions and is of great significance in the metabolic process of tumors. In the human body, tryptophan is mainly transformed through kynurenine metabolic pathway, which not only promotes the inherent malignant properties of tumor cells, but also leads to immune-suppressive tumor microenvironment. Changes in tryptophan metabolism often occur in tumors, accompanied by abnormal gene expression of tryptophan-related enzymes, among which indoleamine 2,3-bioxygenase (IDO)-related gene expression and tryptophan 2,3-dioxygenase (TDO)-related gene changes are the most significant. A large number of clinical trials on IDO inhibitors, TDO inhibitors and combination therapy have been carried out. This paper reviewed the tryptophan metabolic pathway, regulation of IDO (TDO), kynurenine (KYN) and other related genes in tumor cells, and outlined the development of therapeutic schedule targeting tryptophan-related genes. The new progress provides new ideas for the further exploration of tumor treatment options.

Investigation of Neuroprotective Effect of Geniposide on Chronic Alcoholism Rats Based on Metabonomics / 中国实验方剂学杂志

ObjectiveMetabolomics was used to identify biomarkers of chronic alcoholism， and to evaluate the neuroprotective effect of geniposide， providing reference for the diagnosis and treatment of chronic alcoholism. MethodThe rat model of chronic alcoholism was established by intragastric administration of 50% ethanol with 8 mL·kg-1 for 14 days， and then increased to 12 mL·kg-1 for 21 days. Meanwhile， the intervention was performed by continuous gavage of geniposide （15 mg·kg-1） for 35 days. At the end of the experiment， the biochemical indexes and histopathological morphology of liver and brain tissues of rats were detected. Ultra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry （UPLC-Q-TOF-MS） was used for urine metabonomics. The chromatographic conditions was as follows：ACQUITY UPLC™ HSS T3 column （2.1 mm×100 mm， 1.8 μm）， mobile phase of 0.1% formic acid acetonitrile solution （A）-0.1% formic acid aqueous solution （B） for gradient elution （0-2.5 min， 1%-11%A； 2.5-4.5 min， 11%-21%A； 4.5-7.0 min， 21%-40%A； 7.0-8.5 min， 40%-99%A； 8.5-10.5 min， 99%A； 10.5-10.6 min， 99%-1%A； 10.6-13.0 min， 1%A）， the flow rate of 0.4 mL·min-1. The conditions of mass spectrometry were electrospray ionization （ESI）， positive and negative ion modes， scanning range of m/z 50-1 200. Progenesis QI 2.0 and MassLynx 4.1 were used for data analysis， and biomarkers were identified by matching element composition and secondary fragments with Human Metabolome Database （HMDB）. ResultThe pathological results showed that on the 35th day of model replication， compared with the model group， the cortical neurons in the geniposide group showed a significantly improved state of disorder， nuclear pyknosis， hyperchromatism and cell membrane boundary blurred necrosis. The biochemical results showed that geniposide could significantly increase the activities of glutathione peroxidase （GSH-Px） and superoxide dismutase （SOD）， decrease the activity of acetylcholinesterase （AChE）， decrease the levels of β-endorphin （β-EP） and malondialdehyde （MDA）. A total of 48 biomarkers of chronic alcoholism were identified by metabonomics， involving seven metabolic pathways of tryptophan metabolism， phenylalanine metabolism， pentose and glucuronate interconversions， pyrimidine metabolism， ascorbate and aldarate metabolism， steroid hormone biosynthesis and purine metabolism. The main pathway is 5-hydroxytryptamine pathway of tryptophan metabolism. ConclusionBiomarkers related to nerve injury in chronic alcoholism are mainly derived from the 5-hydroxytryptamine metabolic pathway. Geniposide can regulate this pathway so as to improve oxidative stress in the brain and play a neuroprotective role.

Significance and Prospect of Tryptophan Metabolism in Treatment of Tumor Immune Checkpoint Inhibitors / 肿瘤防治研究

Although immune checkpoint inhibitors (ICIs) have great breakthrough in cancer treatment in recent years, most patients have not benefited from it on account of immune microenvironment. Studies have shown that tryptophan metabolism is not only involved in the formation of tumor immunosuppressive microenvironment but also plays an important role in the therapeutic application of ICIs. At present, inhibiting the kynurenine pathway of tryptophan metabolism is now in various stages of clinical trials, while the other two metabolic pathways, 5-HT and the indole pathway, also have aroused wide concern. This article reviews the latest developments in this field.

Antidepressant mechanism of Shugan Lipi recipe in regulating tryptophan metabolism and its common pharmacodynamic substances / 中国中药杂志

This article is to explore the antidepressant mechanism of Shugan Lipi recipe in regulating tryptophan metabolism,and to find out their common pharmacodynamic substances. UPLC-Q-TOF-MS technology was used to establish fingerprints of Shugan Lipi recipe,and 124 components were identified. The depressed mouse model was replicated by triple-one multiple stress method. Chaihu Shugan Powder,Sini Powder and Xiaoyao Powder were administered in groups to observe the changes in body weight and behavior of the mice. The results showed that compared with the model group,the body weight,sucrose preference percentage and autonomous activity behavior of each administration group were improved. Among them,the effect of Chaihu Shugan Powder was better than that of Sini Powder and Xiaoyao Powder. LC-MS/MS method was used to determine the contents of 5-hydroxytryptamine( 5-HT),kynurenine( KYN) and tryptophan( TPP) in blood,liver,brain,colon and other tissues,as well as TDO enzyme activity in liver. Western blot and RT-PCR were used to detect the protein and gene expression of TDO enzyme,respectively. It was found that the three prescriptions increased the ratio of 5-HT/KYN in different degrees,decreased the ratio of KYN/TRP in liver,colon and brain,and decreased the expression level and activity of TDO enzyme in liver. The order of their ability to regulate tryptophan metabolism was Chaihu Shugan Powder>Sini Powder>Xiaoyao Powder. In addition,the correlation between the chromatographic peaks in the fingerprints of Shugan Lipi recipes and the pharmacodynamic indexes of tryptophan metabolism was analyzed by the grey relation analysis. The grey relation analysis found that the chemical components with the highest correlation with tryptophan metabolism were mainly from Paeoniae Radix Alba,Citri Reticulatae Pericarpium,Aurantii Fructus Immaturus and Aurantii Fructus. UPLC-Q-TOF-MS was used to analyze the migration components in the plasma of mice after administration of Shugan Lipi recipe,and to verify the common pharmacodynamic substances of Shugan Lipi recipe. The migration of these detected components in plasma was studied,and a total of 18 prototype components and 36 metabolites were identified. Therefore,it was believed that Chaihu Shugan Powder,Sini Powder and Xiaoyao Powder could play an antidepressant role by reducing the expression of TDO enzyme in the liver and regulating the metabolism of tryptophan.The components contained in Paeoniae Radix Alba,Citri Reticulatae Pericarpium,Aurantii Fructus Immaturus and Aurantii Fructus were the common pharmacodynamic substances of Shugan Lipi recipe,which played an important role in regulating tryptophan metabolism.

Purple urine bag syndrome: an unusual clinical presentation

Purple Urine Bag Syndrome (PUBS) is a rare presentation of urinary tract infection caused by certain bacteria that produce sulphatases and phosphatases that bring about metabolism of tryptophan, leading to production of pigments indigo and indirubin that together impart purple colour of urine. It is a benign condition, most often associated with long term urinary catheterization, renal diseases, chronic constipation and female gender. Commonly implicated organisms include Proteus mirabilis, Klebsiella pneumoniae, Providencia stuartii. Diagnosis is made on urinary culture. Treatment includes reassurance and antibiotics for UTI. We present a case of purple urinary bag syndrome in a female patient of carcinoma stomach presenting with gastric outlet obstruction.

Analysis on Urine Metabolomics of Dioscoreae Nipponicae Rhizoma Extract Against Acute Gouty Arthritis / 中国实验方剂学杂志

Objective::To explore the effect of Dioscoreae Nipponicae Rhizoma extract (DNRe) on rats with acute gouty arthritis (AGA) based on urine metabolomics and to search for the related potential biomarkers and metabolic pathways. Method::Rat model of AGA induced by monosodium urate (MSU) was selected, 40 rats were randomly divided into the blank group (k), the DNRe group (g), the model group (m), and the DNRe treatment group (gm), with 10 rats in each group. The drug-administered group was administered with DNRe at a dose of 0.48 g·kg-1 once a day for 5 days. The urine was gathered after the last administration, and analyzed with UPLC-Q-TOF/MS coupled with pattern recognition techniques, electrospray ionization (ESI) under positive and negative ion scanning mode was adopted, data collection range was m/z 100-1 500 with full scanning mode. Result::A total of 12 common potential biomarkers were identified as sarcosine, dimethylglycine, deoxycytidine, uric acid, 5-hydroxytryptamine (5-HT), L-cystathionine, 4-pyridoxic acid, deoxyuridine, melatonin, 5-methoxytryptamine, fumaric acid and cytidine. Compared with the blank group, the 12 potential biomarkers in the DNRe group were significantly down-regulated. Compare with the model group, 10 metabolites were up-regulated and 2 metabolites were down-regulated in the 12 potential biomarkers of the DNRe treatment group, the abnormal expression of 10 markers including sarcosine, uric acid, L-cystathionine, 4-pyridoxic acid, deoxyuridine, 5-methoxytryptamine, cytidine, dimethylglycine, melatonin, fumaric acid could be modulated by DNRe. The strongest metabolic pathways associated with AGA were cysteine and methionine metabolism, and tryptophan metabolism. Conclusion::The effect of DNRe on AGA may be related to the promotion of conversion level from cystathionine to cysteine in the cysteine and methionine metabolism, and the up-regulating melatonin level in tryptophan metabolism.

Effect of Compatibility of Alcohol Extract of Magnoliae Officinalis Cortex and Alcohol Extract of Polygalae Radix on Fecal Metabolites of Rats / 中国实验方剂学杂志

Objective:To investigate the effect of alcohol extract of Magnoliae Officinalis Cortex,alcohol extract of Polygalae Radix and their compatibility on fecal metabolites of rats,analyze its potential metabolic pathways,and provide experimental basis for exploring the possible mechanism of Magnoliae Officinalis Cortex relieving gastrointestinal motility disorders induced by Polygalae Radix. Method:Forty male SD rats were randomly divided into the normal group,alcohol extract of Magnoliae Officinalis Cortex group(3.50 g·kg-1),alcohol extract of Polygalae Radix group(1.75 g·kg-1) and compatibility group (3.5 g·kg-1 of alcohol extract of Magnoliae Officinalis Cortex+1.75 g·kg-1 of alcohol extract of Polygalae Radix).Fecal samples were collected within 24 h after continuous gavage for 3 days.The fecal metabolites in each group was detected by ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometry(UPLC-Q-TOF-MS),mobile phase was acetonitrile-0.1%formic acid solution for gradient elution,data collection range was m/z 50-1 200 under positive and negative ion mode of electrospray ionization.The characteristic biomarkers and corresponding metabolic pathways were analyzed or screened by Progenesis QI v2.0,SIMCA-P 14.0,SPSS 20.0,MetaboAnalyst 4.0 and other softwares. Result:A total of 17 characteristic metabolic markers were screened out,including 5-formiminotetrahydrofolic acid,L-3-hydroxykynurenine,7,8-dihydropteroic acid,etc.The main related pathways included biosynthesis of unsaturated fatty acids,linoleic acid metabolism,vitamin B6 metabolism,etc. Conclusion:The mechanism of Magnoliae Officinalis Cortex relieving gastrointestinal motility disorders induced by Polygalae Radix may be related to purine metabolism,folate biosynthesis,tryptophan metabolism and primary bile acid biosynthesis.

Intervention Effect of Dachuanxiong Fang Multi-component Preparation on Acute Migraine Rat Model by Urine Metabolomics / 中国实验方剂学杂志

Objective: To investigate the intervention effect of Dachuanxiong Fang multi-component preparation on acute migraine rats, in order to explore the possible mechanism by using urine metabolomics technology. Method: The forty SD rats were randomly divided into 5 groups (n=8), control group, model group, low-dose Dachuanxiong Fang multi-component preparation (DCXF) group (0.19 g·kg-1), medium-dose DCXF group (0.37 g·kg-1), and high-dose DCXF group (0.74 g·kg-1). Rats were subcutaneously injected with 10 mg·kg-1 nitroglycerin for modeling, and Dachuanxiong Fang multi-component preparation was administered through intragastric administration. After half an hour of administration, blood was collected from the abdominal aorta, and the content of 5-hydroxytryptamine (5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA), nitric oxide (NO), nitric oxide synthase (NOS), calcitonlin gene related peplide (CGRP), dopamine(DA) in plasma were determined by enzyme-linked immuno sorbent assay (ELISA) kits. The contents of 5-HT and NOS in the hypothalamus and brainstem of the control group and the model group were analyzed, and the average optical density value was used for statistical analysis. UPLC-TOF/MS combined with principal component analysis (PCA) analysis was used to analyze different groups of rats and discover differential metabolites. Differential metabolites were analyzed by MetaboAnalyst 3.0 software for possible metabolic pathways. Result: After modeling, compared with the control group, the content of neurotransmitters in the model group was significantly increased (PPPβ-hydroxybutyrate showed an upward trend. According to the metabolic pathway prediction study, metabolic pathways with a higher correlation were found to be alanine, aspartic acid and glutamate metabolism, propionic acid metabolism, nitrogen metabolism and tryptophan metabolism. Conclusion: The possible metabolism pathway of Dachuanxiong Fang multi-component preparation is mainly amino acid metabolism in urine, and kynurenine is also the product of tryptophan metabolism pathway. The kynurenine metabolic pathway is also one of the main pathways of tryptophan metabolism.

Sinalização e metabolismo celulares durante a diferenciação de linfócitos B humanos em secretores de anticorpos na presença do vírus da Dengue in vitro e em pacientes com Dengue / B cell signaling and metabolism during antibody-secreting cell differentiation in the presence of Dengue virus in vitro and in Dengue patients

A Dengue é uma doença viral sistêmica, transmitida por mosquitos, que afeta anualmente cerca de 100 milhões de pessoas em todo o mundo. Causada por quatro sorotipos do vírus da Dengue (DENV), suas manifestações clínicas podem variar de assintomáticas à formas que podem levar a óbito. Curiosamente, os pacientes com Dengue apresentam uma resposta exacerbada das células secretoras de anticorpos (ASCs) no sangue cerca de sete dias após o início dos sintomas. A frequência dessas ASCs induzidas pelo DENV representa mais de 50% de todas as células B circulantes no sangue. Essa quantificação é maior que aquelas encontradas em outras infecções virais, contextos de imunização e até mesmo em pacientes com neoplasias de ASCs. Além disso, a magnitude dessa resposta transitória se correlaciona com a gravidade da doença. Então, como a infecção pelo DENV induz essa resposta enorme? Para responder à essa pergunta, combinamos abordagens in vitro e in silico. Células mononucleares do sangue periférico (PBMCs) obtidas de indivíduos saudáveis foram cultivadas in vitro durante sete dias na presença do DENV ou mitógenos. Após a estimulação pelo DENV, as células B presentes nas PBMCs foram capazes de se diferenciarem em ASCs, tanto fenotipicamente quanto funcionalmente, em magnitude similar àquelas estimuladas com mitógenos. Essa diferenciação demonstrou ser dependente da presença de outras células contidas nas PBMCs, assim como do contato célula-célula. Embora ambos os estímulos tenham sido capazes de induzir a diferenciação de ASCs, eles diferiram metabolicamente e transcricionalmente. PBMCs estimuladas pelo DENV apresentaram um maior consumo de triptofano, associado à maior expressão de IDO1 e IDO2 e maior síntese de quinurenina, bem como maiores expressões de IL-10, BAFF e SYK. Ainda, as concentrações de quinurenina foram positivamente correlacionadas com a enumeração de ASCs nessas culturas. Dados de transcriptoma públicos de pacientes com Dengue também suportam esses achados. Outros flavivírus, como o vírus Zika e a cepa vacinal da Febre Amarela não foram capazes de induzir a mesma magnitude de diferenciação das células B em ASCs in vitro. Tão pouco apresentaram correlação entre a enumeração de ASCs e a síntese de quinurenina. Por fim, através da construção de uma hipotética via de diferenciação de células B em ASCs durante infecção pelo DENV, através da combinação de dados da literatura e transcriptomas públicos, demonstramos que moléculas relacionadas à via do STAT3 (IL-10, IL-6, IRF4 e BLIMP1) estão mais expressas nos pacientes infectados e moléculas que respondem aos sinais de cálcio (Calcineurina, NFATC1, DOK3 e GRB2) estão menos expressas nos pacientes infectados. Esses dados proporcionam um melhor entendimento da resposta de células B durante a infeção pelo DENV, particularmente sobre como o metabolismo e a sinalização das células B estão conectados nesse processo

Dengue is a mosquito-borne viral disease that affects annually about 100 million people worldwide. Caused by four Dengue virus (DENV) serotypes, it ranges from asymptomatic to life threatening forms. Curiously, Dengue patients present an exacerbated blood antibody-secreting cell (ASCs) response around seven days after the symptoms onset. The frequency of those DENV-induced ASCs represents more than 50% of all circulating blood B cells. This is greater than found in others viral infections, immunization contexts and even in ASCs related-leukemia patients. Moreover, the magnitude of that transitory response correlates with the disease severity. So, how does the DENV infection induce this enormous response? In order to answer this question we have combined in vitro and in silico approaches. Peripheral blood mononuclear cells (PBMC) obtained from healthy individuals were cultured in vitro during seven days in the presence of DENV or mitogens. Upon the DENV stimulation, PBMC-contained B cells were able to differentiate phenotypically and functionally into ASCs, both phenotypically and functionally, in a similar magnitude than mitogen-stimulated cells. This differentiation was demonstrated to be dependent of the presence of the remaining PBMCs, as well as of the cell-cell contact. Although both stimuli were able to induce the ASCs differentiation, they differed metabolically and transcriptionally. DENV-stimulated PBMCs showed higher tryptophan consumption, associated with higher IDO1 and IDO2 expression and higher kynurenine synthesis, as well as higher IL-10, BAFF and SYK expressions compared to mitogen-exposed counterparts. Additionally, the kynurenine concentrations were positively correlated with the ASCs-enumeration in those cultures. Public transcriptome data supports these findings as well. Other flaviviruses, such as Zika virus and the attenuated vaccine Yellow Fever were not able to induce the same magnitude of ASCs differentiation in vitro. Hence, they did not present a correlation between the number of generated ASCs and the supernatant kynurenine levels. Based on the combination of the literature and public transcriptome data, we have constructed a hypothetical B cell differentiation pathway that might be occurring during DENV infection. It displays that STAT3 pathway-related molecules (IL-10, IL-6, IRF4 and BLIMP1) are more expressed in Dengue patients and molecules that respond to calcium signals (Calcineurin, NFATC1, DOK3 and GRB2) are less expressed in Dengue patients than in control. These data provide a better understanding of the B cell response elicited by DENV infection, particularly about how the B cell metabolism and signaling can be connected into this process

Role of tryptophan catabolism in pediatric allergic diseases / 国际儿科学杂志

With the change of environment and life-style,the incidence of allergic diseases in children is increasing,but its pathogenesis is not entirely elucidated.It is shown that tryptophan catabolism mediated by indoleamine 2,3-dioxygenase plays a significant role in the pathophysiology of allergic diseases of children such as asthma and allergic rhinitis.These roles include inducing Treg cell,inhibiting Th2 cell response,mediating immune tolerance and so forth.Therefore,it is a new target for the prevention and treatment of allergic diseases by stimulating the immune cells and changing the diet structure to regulate tryptophan catabolism.This article reviews the role of tryptophan decomposition in children allergic diseases.

Quercetin inhibits proliferation of human cervical carcinoma HeLa cells through affecting tryptophan metabolism / 中国药理学通报

Aim To investigate the mechanism of inhibition on the proliferation of human cervical carcinoma HeLa cells by quercetin.Methods Cell proliferation was detected by CCK-8 method.Flow cytometry was used to detect the cell cycle changes.OD480 values which reflected the metabolism of tryptophan and the production of kynurenine were measured by UV-Vis spectrophotometer.The mRNA levels of IDO1 were detected by qPCR.The expression and purification of IDO1 protein were detected by Western blot.Enzyme activity reaction was performed in vitro,and the content changes of tryptophan and kynurenine were detected by HPLC.Results Quercetin inhibited the proliferation of HeLa cells and led to cell cycle arrest.Quercetin inhibited the metabolism of tryptophan.Quercetin significantly inhibited the enzymatic activity of IDO1 in vitro,but did not affect the expression of IDO1.The addition of kynurenine could reverse the inhibition of cell proliferation induced by quercetin.Conclusion Quercetin affects tryptophan metabolism through inhibiting the enzymatic activity of IDO1.This may be one of the mechanisms by which quercetin exerts its effect on the proliferation of HeLa cells.