Depression is a prevalent and disabling mental disorder associated with increased suicide risk and impaired quality of life. Herbal medicines such as Hypericum perforatum L. (St. John's Wort [SJW]) and Chaihu Shugan San (CSGS) have been widely used to treat depressive symptoms, yet their system-level molecular mechanisms remain incompletely understood. In this study, we applied a multi-omics strategy centered on quantitative proteomics, combined with metabolomics and microbiota profiling, to investigate the antidepressant mechanisms of CSGS and SJW in a chronic unpredictable mild stress rat model. Behavioral assessments confirmed that both treatments significantly alleviated depressive-like behaviors. Proteomic analysis identified 204 differentially expressed proteins (DEPs) in the CSGS group and 473 DEPs in the SJW group. Functional enrichment analyses suggested that CSGS was more closely associated with lipid metabolism, whereas SJW was linked to broader metabolic processes. Integrative metabolomic and microbiota analyses further supported these proteomics-driven pathway distinctions, with SJW showing stronger associations with gut microbiota alterations. CSGS and SJW alleviated depressive-like behaviors through divergent yet partially overlapping molecular mechanisms. These findings highlight the utility of multi-omics approaches for elucidating system-level mechanisms of complex herbal medicines.

Intranasal ketamine represents a rapid and minimally invasive antidepressant strategy, yet the molecular mechanisms underlying its antidepressant-like effects after intranasal administration remain incompletely understood. Male Sprague-Dawley rats were subjected to a 28-day chronic unpredictable mild stress (CUMS) paradigm and then received intranasal racemic ketamine at 8.58 mg/kg twice weekly for 14 days, with four administrations in total. Depressive-like behaviors were evaluated using the open-field, sucrose preference, and forced swimming tests. Hypothalamic histological alterations and synaptic and mitochondrial integrity were examined by Hematoxylin and eosin staining, Golgi-Cox staining, and transmission electron microscopy, and hypothalamic transcriptomics was combined with molecular validation. Intranasal ketamine improved CUMS-induced behavioral deficits, attenuated histological neuronal alterations in the hypothalamus, improved mitochondrial ultrastructure, increased synaptic density, and restored dendritic length and spine density. RNA sequencing highlighted oxidative phosphorylation-related changes and identified Ndufa10, encoding NADH:ubiquinone oxidoreductase subunit A10, as a ketamine-responsive mitochondrial complex I candidate; Real-time quantitative PCR and immunohistochemistry confirmed that, compared with the CUMS group, intranasal ketamine administration increased hypothalamic Ndufa10 mRNA and NDUFA10 protein levels. Pharmacological inhibition of mitochondrial complex I with rotenone attenuated ketamine-associated behavioral improvement and restoration of NDUFA10 expression, supporting a potential contribution of mitochondrial complex I activity. α-Synuclein (SNCA) protein abundance changed in parallel, whereas Snca mRNA levels remained unchanged, suggesting an accompanying protein-level alteration rather than a primary transcriptional response. Together, these findings suggest that hypothalamic mitochondrial complex I activity may contribute to the antidepressant-like effects of intranasal ketamine, with NDUFA10 emerging as a ketamine-responsive candidate molecule that requires further functional validation.

AIM:This study explored the genetic interactions between Traditional Chinese Medicine (TCM) bioactive ingredients and major psychiatric disorders, namely major depressive disorder (MDD), bipolar disorder (BIP), and schizophrenia (SCZ). METHOD:Predicting TCM targets using network pharmacology. Genome-wide association study (GWAS) summary statistics were analyzed using Multi-marker Analysis of Genomic Annotation (MAGMA) for gene-set association, while local heritability mapping was performed using partitioned Heritability Estimation from Summary Statistics (ρ-HESS). Tissue and cell-type enrichment was assessed using SNP set enrichment analysis (SNPsea), and functional characterization was conducted through Gene Ontology (GO) pathway enrichment with gprofiler2. Ingredient-target interactions were validated using molecular docking and molecular dynamics (MD) simulations. RESULT:In total, 273 TCM ingredient-specific gene sets were identified to be significantly associated with BIP, MDD, or SCZ (BIP:213; MDD:29; SCZ:42, p < 0.05). 10 TCM ingredients overlapped across disorders. Across 1703 Linkage Disequilibrium (LD)-independent regions, ρ-HESS detected significant non-zero local heritability in 33 (BIP), 4 (MDD), and 435 (SCZ) regions. SNPsea identified significant enrichments for BIP (n:18) and SCZ (n:22) in central nervous system tissues and immune-related cell types. GO analysis yielded 1121 significant pathways at false discovery rate (FDR)≤ 0.05 (MDD:126; BIP:802; SCZ:192), converging on inflammation, neurotransmitter regulation, and cytokine-mediated signaling. Docking of prioritized ligand-target pairs showed favorable affinities (mean binding energy -7.36 kcal/mol) with consistent poses, and molecular dynamics simulations confirmed stable complexes with plateaued RMSD and persistent key interactions. CONCLUSION:These results demonstrate that TCM ingredients exhibit multi-target genetic associations with psychiatric disorders, mediated through brain-peripheral tissue interactions and immune-neuroinflammatory pathways. The findings provide genetic evidence supporting the potential of TCM as a polypharmacological source for novel multi-target interventions, offering insights into personalized treatment strategies for MDD, BIP, and SCZ.

Traditional Chinese medicine Chaihu Shugan San (CSGS) is a classic Chinese herb prescription for improving depression, but its specific molecular mechanism has not been fully clarified. This study integrates network pharmacology and experimental validation to investigate CSGS's antidepressant effects, focusing on its impact on GC metabolism and related pathways. In this research, the antidepressant mechanism of CSGS in relation to the depression model induced by chronic unpredictable mild stress will be discussed. High-performance liquid tandem mass spectrometry was applied for the verification of the grown metabolites' economic vitality in rat plasma and the prefrontal cortex. The revelation of behavioral test results showed that the administration of CSGS improved depression symptoms significantly at the end of the administration period, which was 8 weeks. Network pharmacology was used to assist in verifying and improving the mechanism by which the active ingredients of CSGS affect the glucocorticoid metabolic pathway to exert antidepressant effects. CSGS significantly improved glucocorticoid (GC) metabolism by reducing corticosterone (CORT) levels and increasing dehydrocorticosterone (11-DHCORT) and the 11-DHCORT/CORT ratio in plasma and PFC. It regulated GC metabolism in the liver and PFC by downregulating GC synthase (11β-HSD1) and upregulating GC metabolic enzymes (11β-HSD2). Additionally, CSGS restored GC signaling by upregulating GR and HSP-90α, downregulating FKBP51 and HSP-70, and alleviating inflammation by inhibiting NF-κB P65 and HAT expression. These effects, particularly in the liver and PFC, were stronger than those with fluoxetine. Network pharmacology revealed that CSGS targets multiple pathways including PI3K-Akt, FoxO, HIF-1, and mTOR. These results indicate that CSGS can improve the depressive state of rats by regulating glucocorticoid metabolism and other related pathways as well as downstream signaling proteins.

Arachidonic acid (AA) is an important omega-6 polyunsaturated fatty acid (PUFA) stored in esterified form within cell membrane phospholipids, and it is widely present in various cell types. The esterified AA on the inner surface of the cell membrane is primarily hydrolyzed by phospholipase A2 (PLA₂) into its free form. Subsequently, it is metabolized by cyclooxygenase (COXs), lipoxygenase (LOXs), and cytochrome P450 (CYP450) enzymes. The metabolites of AA include a range of bioactive mediators such as prostaglandins (PGs), epoxyeicosatrienoic acids (EETs), hydroxyeicosatetraenoic acids (HETEs), leukotrienes (LTs) and lipoxins (LXs). These metabolites play critical and diverse roles in cellular physiology and are implicated in the pathogenesis of major depressive disorder. This review delves into the molecular mechanisms by which arachidonic acid and its metabolites contribute to the development of major depressive disorder, providing new perspectives for the development of novel antidepressant therapies.

DL-3-n-butylphthalide (NBP) is isolated from the seeds of Apium graveolens L., and has been recently used as a neuroprotective agent for acute ischemic stroke. The present study aimed to determine the efficacy and safety of the combined use of dual antiplatelet therapy (DAPT) and NBP for treating of acute ischemic stroke in rats and to explore the synergistic mechanism of this treatment strategy in rat middle cerebral artery occlusion models. The efficacy of DAPT combined with NBP was evaluated by determining neurological deficits, infarction status, and histological changes. Changes in body weight, blood glucose level, blood count, and serum biochemical parameters were detected to evaluate the safety. To explore the synergistic pharmacological mechanism, the mRNA expression and protein levels of key proteins in the pyroptosis-inflammatory pathway, and the pyroptosis ratio of microglias were examined. Compared with the administration of NBP or DAPT alone, combination of them significantly improved neurological deficits, reduced infarct area, and repaired tissue injury and inflammation after cerebral ischemia. No hepatorenal toxicity was observed. The mRNA expression and protein levels of key proteins in the pyroptosis-inflammation pathway, and the pyroptosis ratio of microglias were significantly downregulated in the combined administration group than in the monotherapy group. We demonstrated that the combined use of NBP and DAPT exhibits better efficacy and high safety and plays a synergistic role by inhibiting the pyroptosis-inflammation pathway in the brain tissues, particularly in microglial cells.

Yinzhihuang (YZH), a traditional Chinese medicine prescription, was widely used to treat cholestasis. Cholestatic liver injury limited the use of the immunosuppressive drug cyclosporine A (CsA) in preventing organ rejection after solid organ transplantation. Clinical evidences suggested that YZH could enhance bile acids and bilirubin clearance, providing a potential therapeutic strategy against CsA-induced cholestasis. Nevertheless, it remains unclear whether YZH can effectively alleviate CsA-induced cholestatic liver injury, as well as the molecular mechanisms responsible for its hepatoprotective effects. The purpose of the present study was to investigate the hepatoprotective effects of YZH on CsA-induced cholestatic liver injury and explore its molecular mechanisms in vivo and vitro. The results demonstrated that YZH significantly improved the CsA-induced cholestatic liver injury and reduced the level of liver function markers in serum of Sprague-Dawley (SD) rats. Targeted protein and gene analysis indicated that YZH increased bile acids and bilirubin efflux into bile through the regulation of multidrug resistance-associated protein 2 (Mrp2), bile salt export pump (Bsep), sodium taurocholate cotransporting polypeptide (Ntcp) and organic anion transporting polypeptide 2 (Oatp2) transport systems, as well as upstream nuclear receptors farnesoid X receptor (Fxr). Moreover, YZH modulated enzymes involved in bile acids synthesis and bilirubin metabolism including Cyp family 7 subfamily A member 1 (Cyp7a1) and uridine 5'-diphosphate (UDP) glucuronosyltransferase family 1 member A1 (Ugt1a1). Furthermore, the active components geniposidic acid, baicalin and chlorogenic acid exerted regulated metabolic enzymes and transporters in LO2 cells. In conclusion, YZH may prevent CsA-induced cholestasis by regulating the transport systems, metabolic enzymes, and upstream nuclear receptors Fxr to restore bile acid and bilirubin homeostasis. These findings highlight the potential of YZH as a therapeutic intervention for CsA-induced cholestasis and open avenues for further research into its clinical applications.

目的:探索替加环素对患者纤维蛋白原的影响，并分析其临床特点，为临床合理应用提供一定的参考。方法:通过检索PubMed、中国知网、维普数据库，收集整理关于替加环素致低纤维蛋白原血症的个案报道，统计分析患者基本信息、基础疾病、替加环素使用时间、低维蛋白原血症发生时间及转归等信息，并利用Naranjo’s评估表判断其不良反应的关联性。结果:共检索15例个案报道，Naranjo’s评分多为“很可能”,男性患者10例，7例采用常规推荐给药方案，6例采用较高剂量治疗。所有患者中共有11例使用替加环素后纤维蛋白原低于1 g·L -1 ,4例介于1～2 g·L -1 。发生低纤维蛋白原血症的时间多为使用替加环素后3～10 d,多数患者在停药、对症治疗3～7 d后指标基本恢复正常。结论:替加环素可致患者出现危及生命的低纤维蛋白原血症，使用期间应密切检测凝血功能。

Breast cancer resistance protein (BCRP/Abcg2 in human, Bcrp/Abcg2 in rat), a member of the ATP-binding cassette (ABC) transporter family, acts as an efflux pump for xenobiotics, with ability to transport various drugs out of cells. Capsaicin may have the potential to modulate the function of Bcrp transport. This study was to evaluate the effects of capsaicin on the pharmacokinetics of sulfasalazine, a Bcrp substrate, in rats and investigate the mechanism of this food-drug interaction. The rats were pre-treated with 5% carboxymethylcellulose sodium (vehicle), capsaicin (3, 8, 25 mg/kg) and cyclosporine A (10 mg/kg) by gastric gavage for 7 days. On day 7, blood, liver and intestine samples were collected after sulfasalazine administered. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to study the effects of capsaicin on the pharmacokinetics of sulfasalazine in rats. RT-PCR and western blotting were used to study the mechanism in biomolecules in rats, respectively. Compared with vehicle group, AUC(0-infinity) of sulfasalazine in rats were increased by 1.5-folds, 1.6-folds and 1.7-folds in 3, 8 and 25 mg/kg/d capsaicin pre-treated groups. At the same time, the CL/F in rats were decreased by 33%, 38% and 42% in the three groups. In addition, we found Bcrp mRNA levels and protein expressions in rat livers and intestines were decreased in 3, 8 and 25 mg/kg/d capsaicin-treated groups. Our study demonstrated that long-term ingestion of capsaicin significantly enhanced the AUC of sulfasalazine involved down-regulate Bcrp gene and protein expression in rat liver and intestine.

目的:建立高效液相色谱-串联质谱测定柴胡疏肝散水提物冻干粉中柴胡皂苷(A、B1、C、D)、橙皮苷、柚皮苷、甘草苷、芍药苷、没食子酸、阿魏酸、槲皮素和异甘草素含量的方法.方法:采用Welch Ultimate XB-C18色谱柱(2.1mm×100mm,5μm);流动相组成为A相:乙腈,B相:0.1％甲酸-水;以0.3mL·min-1的流速进行梯度洗脱,进样量为10 μL;采用电喷雾离子源(ESI),负离子模式,以多反应监测方式(MRM)进行定量分析.结果:柴胡疏肝散水提物中的12种成分在检测范围内与峰面积之间的线性关系良好.测定结果表明,每克柴胡疏肝散水提物冻干粉中含:柴胡皂苷A6.712mg,柴胡皂苷B15.810 mg,柴胡皂苷C 16.700mg,柴胡皂苷D 0.034mg,橙皮苷101.600mg,柚皮苷172.000mg,甘草苷3.300mg,芍药苷50.483 mg,没食子酸1.870 mg,阿魏酸4.945 mg,异甘草素0.032mg,槲皮素0.051mg.结论:本方法灵敏度高,简便可靠,可用于柴胡疏肝散水提物冻干粉中12种主要成分的定量分析,并为建立柴胡疏肝散的质量标准提供方法学基础.

目的:评价聚乙二醇脂质体阿霉素+贝伐珠单抗+卡铂(CD-BEV)化疗方案与吉西他滨+贝伐珠单抗+卡铂(CG-BEV)化疗方案治疗复发性卵巢癌的经济性.方法:基于已发表的一项Ⅲ期临床随机对照试验,根据疾病发展过程建立Mark-ov模型,将患者的疾病发展过程分为无进展状态、进展状态和死亡状态,对CD-BEV方案与CG-BEV方案进行成本-效果分析,并对模型结果的稳定性进行单因素敏感性分析和概率敏感性分析.结果:根据Markov模型分析结果,CD-BEV方案对比CG-BEV方案的增量成本-效果比(ICER)值为565409.69元/QALY,高于中国居民意愿支付阈值(217341.00元/QALY).单因素敏感性分析结果显示:聚乙醇脂质体阿霉素成本、无进展状态效用值、进展状态效用值对成本-效果分析结果的影响最大;概率敏感性分析结果显示:ICER值大于WTP(3倍GDP)的概率为100％.结论:与CG-BEV方案相比,CD-BEV方案治疗复发性卵巢癌不具有成本-效果优势.

Steroid hormones such as glucocorticoids and their metabolites are closely related to mental diseases and neuroendocrine diseases. Quantitative analysis of these substances will help in understanding their roles in related research fields. In this study, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed to detect the concentration of corticosterone (CORT) and its metabolites, progesterone (PROG) and testosterone in rat plasma and prefrontal cortex (PFC), and was applied to investigate the changes in hormones in rats with depression induced by chronic unpredictable mild stress (CUMS). The method was shown to be linear in the quantitation range for all analytes. Intra- and inter-day accuracy and precision were between 80% and 120%. Furthermore, we found that the level of CORT in plasma and PFC increased, whereas that of 11-dehydrocorticosterone (11-DHCORT) as well as the ratio of 11-DHCORT and CORT declined in rats with CUMS-induced depression. The trends of these changes in central PFC and peripheral plasma were consistent. In conclusion, this study successfully established an UPLC-MS/MS method for simultaneous measurement of CORT and its metabolites, PROG and testosterone in rat plasma and PFC, and applied it to rats with depression. The method could be further applied to the research of depression and diseases related to these steroid hormones.

Steroid hormones such as glucocorticoids and its metabolites are closely related to mental diseases and neuroendocrine diseases. Quantitative analysis of these substances will help understanding their roles in related research fields. In this study, an UPLC-MS/MS method was developed to detect the concentration of corticosterone (CORT) and its metabolites, progesterone, and testosterone in rat plasma and prefrontal cortex (PFC), and was applied to investigate the changes in hormones in depression rats induced by chronic unpredictable mild stress (CUMS). The method was shown to be linear in the quantitation range for all analytes. Intra- and inter-day accuracy and precision were between 80% and 120%. Furthermore, we found the level of CORT in plasma and PFC increased, while the level of 11-dehydrocorticosterone (11-DHCORT), as well as the ratio of 11-DHCORT and CORT declined in CUMS induced depression rats. The trends of these changes in central PFC and peripheral plasma were consistent. In conclusion, this study successfully established an UPLC-MS/MS method for simultaneous measurement of CORT and its metabolites, progesterone, and testosterone in rat plasma and PFC, and applied it to depression rats. The method could be further applied to the research of depression and diseases related to these steroid hormones.

目的 建立HPLC-MS/MS测定刺五加提取物、贯叶连翘提取物主要活性成分在大鼠血浆中药物浓度的方法,应用于刺五加提取物、贯叶连翘提取物及其联用时主要活性成分在大鼠体内的药动学研究,并使用DAS3.2.8软件对主要活性成分的药动学参数进行非房室模型拟合.方法 以Welch Ultimate XB-C18(2.1 mm×100 mm,4.6 μm)为色谱柱,乙腈(含0.1％甲酸)-0.1％甲酸水溶液(含5 mumol·L-1乙酸铵)为流动相,以300 μL·min-1的流速进行梯度洗脱,采用电喷雾离子源进行正负离子同时扫描,多反应监测模式进行监测.结果 所建立的方法精密度、准确度良好,提取回收率基本符合生物样品分析方法要求.结论 药动学结果表明,相比于单独给药,联合用药后刺五加苷Etmax缩短,金丝桃素ρmax升高、t1/2延长.该药动学结果表明,刺五加提取物、贯叶连翘提取物联用时,很可能通过增加金丝桃素血药浓度、缩短刺五加苷E 的达峰时间,从而在体内产生协同抗抑郁作用.

Steroid hormones such as glucocorticoids and their metabolites are closely related to mental diseases and neuroendocrine diseases. Quantitative analysis of these substances will help in understanding their roles in related research fields. In this study, an ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed to detect the concentration of corticosterone (CORT) and its metabolites, progesterone (PROG) and testosterone in rat plasma and prefrontal cortex (PFC), and was applied to investigate the changes in hormones in rats with depression induced by chronic unpredictable mild stress (CUMS). The method was shown to be linear in the quantitation range for all analytes. Intra- and inter-day accuracy and precision were between 80% and 120%. Furthermore, we found that the level of CORT in plasma and PFC increased, whereas that of 11-dehydrocorticosterone (11-DHCORT) as well as the ratio of 11-DHCORT and CORT declined in rats with CUMS-induced depression. The trends of these changes in central PFC and peripheral plasma were consistent. In conclusion, this study successfully established an UPLC–MS/MS method for simultaneous measurement of CORT and its metabolites, PROG and testosterone in rat plasma and PFC, and applied it to rats with depression. The method could be further applied to the research of depression and diseases related to these steroid hormones.

Irinotecan (CPT-11) is a broad spectrum agent for the treatment of solid tumor malignancies, despite severe diarrhea is limiting its widespread usage. The local effects of SN-38 in the small intestine were considered to be responsible for the irinotecan-induced delayed diarrhea. It was proposed that cyclosporin A (CsA) inhibiting biliary excretion could attenuate this side effect, but in fact, it could not improve the therapeutic index of irinotecan. At present, most studies focused on the inhibition of bile excretion by cyclosporin A through the transporters MRP2 and MDR1 and its effect the irinotecan treatment in vivo. However, UDP glucuronyltransferase-1 polypeptide A1 (UGT1A1) was related to a significantly altered disposition of irinotecan and its metabolites, and was therefore associated with irinotecan-induced toxicity. This study focused on UGT1A1-mediated conversion of SN-38 to SN-38G, and systematically investigated the CsA-irinotecan interactions in vitro and in vivo. After treatment with 10 mg·kg-1 CsA for 7 days, the bile excretion of irinotecan and its metabolites decreased and AUC0-∞ increased significantly. The AUC0-∞ (SN-38G)/AUC0-∞ (SN-38) was significantly reduced when compared with that in vehicle-treated rats. In the liver microsome incubation system, the IC50 of CsA for UGT1A1 enzyme was 9.4 μM. Furthermore, the UGT1A1 mRNA and protein expression levels were significantly reduced. The present study indicated that CsA treatment could enhance the systemic exposure and toxicity of SN-38 by inhibiting the UGT1A1 enzyme. The inhibition of UGT1A1 enzyme might be a critical factor in the failure of CsA improving irinotecan's treatment index.

细胞色素P450酶在生物体内参与多种化合物的生物转化.除肝脏外,细胞色素P450酶也在脑内分布,参与脑内多种内源性物质的合成及代谢,对维持神经系统内环境的稳态具有重要的作用.此外,脑内细胞色素P450酶广泛参与曲马多等中枢药物的脑内代谢,其活性或表达的变化可能会影响药物在脑内的药效和不良反应.鉴于细胞色素P450酶在脑内内源和外源性物质生物转化中的重要作用,其活性及表达的变化在神经精神疾病中的重要性也逐渐被发现.因此,笔者查阅了近年来关于脑内细胞色素P450酶的功能及其在神经精神疾病中的研究进展,以期为深入探索脑内细胞色素P450酶是否可能作为中枢疾病的治疗靶点,及开发相关的靶向治疗药物提供理论基础.

Sensitive and comprehensive measurement of systemic metabolites of tryptophan, phenylalanine and glutamate metabolism in biological samples is effective for understanding the pathogenesis of depression and other neurological diseases. Therefore, this study developed an underivatized liquid chromatography tandem mass spectrometry (LC-MS/MS) method for simultaneous monitoring the 3 components of glutamate metabolism in rat hippocampus and 11 components of tryptophan and phenylalanine metabolism in rat hippocampus, plasma and urine, and applied it to investigate their changes in rats induced by chronic unpredictable mild stress (CUMS). The investigated analytes are as follows: tryptophan, serotonin, 5-hydroxyindoleacetic acid, kynurenine, kynurenic acid, xanthurenic acid, 3-hydroxyanthranilic acid, quinolinic acid, phenylalanine, tyrosine, tyramine, glutamate, glutamine and gamma-aminobutyric acid. The method was verified to be sensitive and effective with satisfactory linearity, accuracies in the range of 78.2%-120.4%, and precisions less than 17.8% for all identified analytes. A series of significant changes in CUMS-induced rats can be detected: tryptophan, serotonin and tyrosine levels decreased and quinolinic acid increased in both hippocampus and plasma. In addition, the kynurenine/tryptophan ratios increased in hippocampus and plasma, the kynurenic acid/quinolinic acid ratios of plasma and urine were significantly reduced. These findings demonstrated that the CUMS procedure could lead to the central and peripheral imbalances of tryptophan and phenylalanine metabolism. In conclusion, a LC-MS/MS method for simultaneous measurement of several neurotransmitters in rat hippocampus, plasma and urine was developed and successfully applied to investigation of the central and peripheral changes in CUMS-induced rats. The method would be expected to provide applicability to the study of the mechanisms of depression and other related diseases associated with these neurotransmitters. (C) 2019 Elsevier B.V. All rights reserved.

Depression is highly prevalent worldwide and a leading cause of disabilty. However, the medications currently available to treat depression fail to adequately relieve depressive symptoms for a large number of patients. Research into the aberrant overactivation of the kynurenine pathway and the production of various active metabolites has brought new insight into the progression of depression. IDO and TDO are the first and rate-limiting enzymes in the kynurenine pathway and regulate the production of active metabolites. There is substantial evidence that TDO and IDO enzyme are activated during depression, and therefore, IDO and TDO inhibitors have been identified as ideal therapeutic targets for depressive disorder. Hence, this review will focus on the kynurenine branch of tryptophan metabolism and describe the role of IDO and TDO in the pathology of depression. In addition, this review will compare the relative imbalance between KYNA and neurotoxic kynurenine metabolites in different psychiatric disorders. Finally, this review is also directed toward assessing whether IDO and TDO are potential therapeutic target in depression associated with other diseases such as diabetes and/or cancer, as well as the development of potent IDO and TDO inhibitors.

With the continuously clinical study of capsaicin,capsaicin-drug interaction has become increasingly prominent.In recent years,the studies indicate that capsaicin shows a significant inducing or inhibitory effect on a variety of drug metabolism enzymes and transporters,thereby leading to the occurrence of complex drug interactions and affecting the other drugs in vivo process.In this paper,the modulation effect of capsaicin on drug metabolizing enzymes and transporters by reviewing the relevant research at home and abroad in recent years were summarized,and the drug-drug interactions associated with capsaicin in order to provide theoretical guidance for clinical rational drug use were explored.Furthermore,complex drug-drug interaction studies can be provided with prior examples.