Frontiers in Microbiology
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2026
·
IF 5.8
Yong Liang,Yang Zhang,Yu Shi,Qimeng Zhang,Hongxi Zhang
ObjectiveConstipation is a prevalent functional gastrointestinal disorder characterized by impaired intestinal barrier function, often driven by gut microbiota dysbiosis and metabolic disturbances. Shouhui Tongbian Capsules (SHTB), a traditional Chinese medicine formulation, has demonstrated clinical efficacy in constipation management. This study aimed to elucidate the molecular mechanisms underlying SHTB's anti-constipation effects through modulation of the gut microbiota–tryptophan metabolism–aryl hydrocarbon receptor (AhR) signaling axis.MethodsA loperamide-induced murine constipation model was established to evaluate the therapeutic efficacy of SHTB, as assessed by time to first black stool defecation, fecal pellet count, fecal water content, and small intestinal propulsion rate. Colonic histopathology was examined by hematoxylin and eosin (H&E) and Alcian blue–periodic acid–Schiff (AB-PAS) staining. 16S rRNA gene sequencing and metabolomic profiling were used to characterize gut microbiota composition and metabolite alterations in SHTB-treated constipated mice. Key findings were subsequently validated through fecal microbiota transplantation (FMT) and pharmacological AhR inhibition.ResultsSHTB significantly improved defecation parameters in constipated mice (P < 0.001). Mechanistically, SHTB may promote tryptophan metabolic flux through gut microbiota remodeling, particularly through enrichment of Bifidobacterium (P < 0.05) and Alistipes (P < 0.01), leading to activation of colonic AhR signaling (P < 0.05) and reinforced intestinal barrier integrity. FMT with SHTB-conditioned microbiota restored key bacterial populations and reactivated AhR expression (P < 0.05) in recipient mice. Critically, pharmacological blockade of AhR with CH223191 abolished all SHTB-mediated therapeutic benefits, with no significant differences observed between the CH223191 + Lop and CH223191 + Lop + SHTB groups (P > 0.05), thereby identifying AhR as an indispensable mediator of SHTB's anti-constipation mechanism.ConclusionSHTB alleviates constipation in a murine model by enhancing intestinal barrier integrity through modulation of the gut microbiota–tryptophan metabolism–AhR signaling axis, thereby providing mechanistic support for its clinical application in managing constipation.
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ADVANCED FUNCTIONAL MATERIALS
·
2026
·
IF 19.9
Tianxing Zhou,Junnian Chen,Xingya Rao,Haifeng Zhang,Huocheng Yang,Menghuan Li,Zhong Luo
Triple-negative breast cancer (TNBC) is a highly invasive malignancy that responds poorly to current standard therapies. Sonodynamic therapy (SDT) can deliver both reactive oxygen species (ROS)-dependent tumor cytotoxicity and immunostimulatory benefits that holds significant promise for TNBC treatment, but its efficacy is blunted by the elevated Indoleamine 2,3-dioxygenase 1 (IDO1)-driven tryptophan (Trp) catabolism in TNBC, which strengthens antioxidant defenses while exacerbating the immunosuppressive tumor microenvironment. Here we develop an ultrasound-activatable sonodynamic amplifier (PMFN) that reprograms TNBC-intrinsic IDO1-dependent Trp catabolism to potentiate remotely controllable sonodynamic ferroptosis-immunotherapy. We first developed Fe(III)-coordinated tetraphenylporphyrin (FeTPP) as a ferrocatalytic sonosensitizer via molecular-dynamics-assisted virtual screening, which was co-formulated with the IDO1 inhibitor Navoximod (NLG919) into cRGD-modified liposomes for TNBC-targeted delivery. Upon ultrasonication, NLG919 blocks Trp-to-kynurenine (Kyn) conversion to suppress the Nrf2-GPX4 antioxidant axis and mitigate regulatory T cells (Tregs)-associated immunosuppression, while FeTPP amplifies ROS stress through a sonodynamic reaction to drive lipid peroxidation. These effects synergistically promoted immunogenic ferroptosis of TNBC cells and relieved immune suppression, thereby enhancing ferroptosis-immunotherapeutic efficacy. In mouse models, PMFN markedly inhibited primary TNBC growth and abrogated metastasis, providing an approach for advancing TNBC treatment in the clinic.
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BRITISH JOURNAL OF PHARMACOLOGY
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2024
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IF 6.8
Qian-Wen Zhang,Meng-Jiao Yang,Chun-Yu Liao,Reham Taha,Qing-Yu Li,Mohammed Ismail Abdelmotalab,Si-Yu Zhao,Yan Xu,Zhen-Zhou Jiang,Cheng-Han Chu,Xin Huang,Chun-Hua Jiao,Li-Xin Sun
Background and Purpose Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease, and the range of current clinical treatments is not ideal. We previously found that polysaccharide of Atractylodes macrocephala Koidz (PAMK) is beneficial in DSS-induced colitis, and we aimed to investigate the underlying mechanisms in this study. Experimental Approach PAMK was used to treat DSS-induced colitis in mice, 16S rRNA sequencing analysis was used to detect changes in the intestinal microbiota, targeted metabolomics analysis was used to determine the content of tryptophan-metabolizing bacteria, and western blotting was used to determine aryl hydrocarbon receptor (AhR) and pregnane X receptor (PXR) levels. Furthermore, antibiotic-mediated depletion of gut microbiota and faecal microbiota transplantation were performed to assess the role of the gut microbiota in PAMK alleviation of colitis. Key Results PAMK treatment relieved intestinal microbiota dysbiosis in mice with colitis, contributed to the proliferation of tryptophan-metabolizing bacteria, and increased the levels of tryptophan metabolites, resulting in a significant increase in the nuclear translocation of PXR and expression of PXR and its target genes, but not AhR. The gut microbiota is important in PAMK treatment of colitis, including in the alleviation of symptoms, inhibition of inflammation, maintenance of the integrity of the intestinal barrier, and the regulation of the Th17/Treg cell balance. Conclusion and Implications Based on our findings, we elucidate a novel mechanism by which PAMK alleviates DSS-induced colitis and thus provides evidence to support the potential development of PAMK as a new clinical drug against UC.
研究领域:
免疫学
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微生物学
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药理学
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胃肠病学
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ACS Nano
·
2024
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IF 15.8
Wen Li,Yichen Liu,Xiaoming Zheng,Jing Han,Anchen Shi,Chi Chun Wong,Ruochen Wang,Xunan Jing,Yan Li,Shu Fan,Cuiyu Zhang,Yinnan Chen,Gang Guo,Jun Yu,Junjun She
Intestinal dysbiosis and the associated l-tryptophan metabolic disorder are pivotal in inflammatory bowel disease progression, leading to a compromised intestinal barrier integrity. Remedying the dysfunction in tryptophan metabolism has emerged as a promising therapeutic strategy. Herein, we reprogram the tryptophan metabolism in situ by EcN-TRP@A/G, encapsulating the engineered probiotic, EcN-TRP, with enhanced tryptophan synthesis capacity, for sustained modulation, thereby restoring intestinal barrier function and microbial homeostasis. The pH-responsive dual-layered EcN-TRP@A/G microcapsule developed via high-voltage electrospraying and liquid interface self-assembly, preserved probiotic viability in the harsh gastrointestinal milieu, and facilitated targeted colon release. Bioluminescent tracking in mice reveals a 22.84-fold increase in EcN-TRP@A/G viability and distribution compared to naked EcN-TRP. Targeted metabolomics highlights EcN-TRP@A/G’s modulation of the tryptophan–indole pathway. Oral administration of EcN-TRP@A/G sustained elevates indole metabolites, particularly indole-3-acetic acid and indole-3-propionic acid, in colon tissue for up to 7 days. In IBD mice, EcN-TRP@A/G improves intestinal permeability, reduces inflammation, and recovers the gut microbiome by enhancing beneficial bacteria abundance like Prevotellaceae_UCG-001 and Anaerostipes while suppressing pathogenic strains like Escherichia–Shigella. Our findings offer a cost-effective approach, harnessing the probiotic metabolic potential in situ through engineered modifications for effective IBD treatment.
研究领域:
胃肠病学
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微生物学
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药学
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生物技术
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Foods
·
2026
·Vol. 15
·期 6
·
IF 6
Guyue Zhou,Ning Jiang,Jixian Liu,Xiangjunlin Zhang,Yanfei Xu,Xinmin Liu,Mengzhou Xie
Depression-related mood disturbances are increasingly recognized as nutrition-sensitive conditions associated with chronic stress-induced neuroinflammation and metabolic imbalance.Polygonatum sibiricum,Poria cocos,Lilium brownii, andRadix Glycyrrhizae Preparataare edible medicinal plants commonly used in functional foods. In this study, we evaluated the antidepressant effects of aPolygonatum sibiricum-based functional formula (PSF) in a chronic restraint stress (CRS) mouse model. CRS induced prominent anhedonia and behavioral despair, accompanied by microglial overactivation, activation of the NLRP3 inflammasome, and dysregulated tryptophan metabolism. PSF supplementation significantly alleviated depressive-like behaviors and inhibited NLRP3–caspase-1–GSDMD-mediated pyroptosis, leading to reduced hippocampal IL-1β and IL-18 levels. Importantly, PSF restored tryptophan metabolism toward serotonin production, stabilized monoaminergic and glutamate/GABA neurotransmission, and protected hippocampal neurons. Moreover, PSF partially reversed stress-induced gut microbiota dysbiosis. Collectively, these results demonstrate that PSF acts as a neuroimmune–metabolic modulator that improves mood-related behaviors by regulating inflammatory signaling, tryptophan metabolism, and neurotransmitter homeostasis, supporting its potential development as a functional food intervention for stress-induced depression.
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2016
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IF 2.653
Man Qiao,Junze Jiang,Jidong Yang,Shaopu Liu,Zhongfang Liu,Xiaoli Hu
Based on l -tryptophan-Pd(II) system, a sensitive and selective fluorimetric assay for the quantification of ceftriaxone (CTRX) had been developed. The experimental results showed that in pH 4.0 Britton–Robinson (BR) buffer medium, the fluorescence of l -tryptophan ( l -Trp) ( λ ex / λ em = 276 nm/352 nm) could be efficiently quenched by Pd(II). When CTRX was added to the mixed solution of the l -tryptophan and Pd(II), the fluorescence of l -Trp recovered. The reaction mechanism and the reasons for the fluorescence recovery were also discussed. Pd(II) reacted with l -Trp to form a 1:1 chelate complex, and then, after CTRX was added in l -Try-Pd(II) system, the ligand exchange reaction occurred between l -Trp and CTRX, which resulted in the fluorescence recovery. Under the optimized experimental conditions, the recovered fluorescence intensities at 352 nm showed excellent linear relationship with the concentration of CTRX over the range of 6.0 × 10 − 8 –2.4 × 10 − 6 mol L − 1 (0.040–1.59 μg mL − 1 ). The correlation coefficient (R) was 0.9997 and the detection limit was 1.8 × 10 − 8 mol L − 1 (11.9 ng mL − 1 ). Furthermore, the assay had been applied to determine trace amount of CTRX human urine samples with satisfactory results.
研究领域:
分析化学
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环境与生物医学分析
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荧光传感器
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SEPARATION AND PURIFICATION TECHNOLOGY
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2022
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IF 9.136
Xiaoping Bai,Jian Ke,Xin Qiu,Huixian Liu,Yibing Ji,Jianqiu Chen
The separation of racemic drugs remains significance and challenge for pharmaceutical production. Recently, chiral drugs permeation separation based on membrane is a promising technology with advantages of energy efficient, continuous operation and cost-effectiveness. Herein, ethylenediamine-β-cyclodextrin (EDA-β-CD) mixed matrix membranes (EDA-β-CD MMMs) and EDA-β-CD modified graphene oxide thin-film nanocomposite membranes (GO/EDA-β-CD TFNMs) were fabricated via precipitation phase inversion and interfacial polymerization process, respectively. The corresponding membrane structure and GO nanosheets were characterized by SEM, TEM, ATR FT-IR, EA. Subsequently, the water flux, BSA rejection and stability of the membranes were studied. Moreover, enantioseparation performances of GO/EDA-β-CD TFNMs and EDA-β-CD MMMs toward (DL)-tryptophan (Trp) and (RS)-propranolol (Prop) were examined. Results showed that the GO/EDA-β-CD TFNMs exhibited extraordinary enantioselectivity, which remained high percent enantiomeric excess (ee.%) of Trp (100.00%) and Prop (75.34%). GO nanosheets with a multilayer structure and an interlayer spacing not only provided bonding site of EDA-β-CD but also improved permeation flux of the membrane. Finally, molecular docking technology was used to study the separation mechanism of the membranes. These findings demonstrate that GO/EDA-β-CD TFNMs might possess possibilities of high permeability and high enantioselectivity for chiral drugs separation.
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BIOORGANIC CHEMISTRY
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2022
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IF 5.307
Tingting Ma,Huanli Cheng,Tongxi Li,Yifan Chen,Tianying Cai,Junjie Bai,Ziming Wu,Xianming Xia,Tiancheng Liang,Yichao Du,Wenguang Fu
Background Although liver fibrosis is a key pathologic process in many liver diseases, therapeutic approaches for inhibiting liver fibrosis are still very limited. N-Acetyl- l -tryptophan ( l -NAT) has a hepatoprotective effect via inhibiting the destruction of liver cells, enhancing cell viability and reducing the inflammation. However, the effect of l -NAT on liver fibrosis is not determined. Purpose The present study investigated the effect of l -NAT on liver fibrosis and explored it potential molecular mechanism. Methods To address this concern, this study was carried out via fibrotic mice model induced by CCl 4 and many approaches such as various histological staining methods, western blot assay, etc. Result l -NAT decreased the levels of alanine aminotransferase (ALT) and aspartate transaminase (AST) in fibrotic mice model induced by carbon tetrachloride (CCl 4 ). Histological staining showed that l -NAT ameliorated liver injury and fibrosis, and reduced the expression of α-smooth muscle actin (α-SMA) and Collagen I protein. l -NAT also attenuated apoptosis by down-regulating the level of pro-apoptotic protein Bax and up-regulating that of anti-apoptotic protein Bcl-2. Moreover, l -NAT inhibited the expressions of TGF-β1/SMAD and matrix metalloproteinase 9 (MMP9) proteins, and reversed the expression of YAP1 protein in CCl 4 -induced liver fibrosis. Conclusion These results clearly demonstrated that l -NAT attenuated CCl 4 -induced liver fibrosis in mice, and this protective mechanism might relate to TGF-β1/SMAD and Hippo/YAP1 signaling pathway. Thus, this study provided data basis for the prevention and treatment of liver fibrosis.
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Food & Function
·
2022
·Vol. 13
·期 18
·9513-9522
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IF 6.317
Cong Lu,Zhen Wei,Yongquan Wang,Shuying Li,Litao Tong,Xinmin Liu,Bei Fan,Fengzhong Wang
Depression is highly prevalent in patients suffering from chronic inflammatory diseases. Dysregulated neuroinflammation and concomitant-activated microglia play a pivotal role in the pathogenesis of depression. As one of the biologically functional phytochemicals in soybeans, soy isoflavones (SI) have been reported to exhibit anti-inflammatory, antioxidant, estrogen-like and neuroprotective activities. However, there is no research on how SI administration affects the depressive-like behavior induced by neuroinflammation. Therefore, this study was conducted to evaluate the antidepressant-like action of SI in acute lipopolysaccharide (LPS)-treated mice and to explore its underlying mechanisms. An open field test, a sucrose preference experiment, a tail suspension test and a forced swimming task were conducted to assess the influence of SI on the depressive-like behavior induced by LPS injection. Then, the levels of the pro-inflammation cytokines, tryptophan (Trp) metabolism in the cortex and hippocampus, and the synaptic plasticity-related signal pathway in the hippocampus, which are involved in the pathophysiology of depression, were examined. The results showed that SI administration remarkably alleviated LPS-induced depressive-like behavior as indicated by the increased sucrose preference index and the decreased immobility time both in the tail suspension test and the forced swimming task. SI significantly suppressed neuroinflammation in the hippocampus of LPS mice, as indicated by a decrease in the levels of interleukin (IL)-1β, IL-10, tumor necrosis factor (TNF-α) and suppression of the signal pathway of TLR4/NF-κB. Additionally, SI administration regulated tryptophan (Trp) metabolism by increasing 5-hydroxytryptamine (5-HT) levels, inhibiting the release of kynurenine (KYN) in the cortex and hippocampus, and elevating the expressions of synaptic plasticity-related protein markers such as postsynaptic density-95 (PSD-95) and synaptophysin (SYN). The current study demonstrated that soy isoflavones could reverse LPS-induced depressive-like behavior by suppressing neuroinflammation, normalizing the Trp metabolism, up-regulating the expressions of synaptic plasticity-related proteins, and inhibiting the TLR4/NF-κB pathway activation in the hippocampus of mice, exerting their antidepressant-like action.
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JOURNAL OF CHROMATOGRAPHY A
·
2021
·
IF 4.759
Shaoping Ma,Fenfang Li,Zhijian Tan
The hydrophobic organic solvents/water biphasic system had been always used in the traditional enantioselective liquid-liquid extraction (ELLE). In recent years, aqueous biphasic systems (ABSs) are considered as a promising method used in the ELLE. In the present work, a recyclable ABS composed of a temperature-responsive polymer poly(MAH- β -CD- co -NIPAAm) (P N-CD ) and a pH-responsive polymer poly(AA-DMAEMA-BMA) (P ADB ) was employed in the enantioseparation of tryptophan enantiomers . The polymer P N-CD acted as not only the phase-forming component but also the chiral selector, which can be recycled by changing the temperature. The polymer P ADB can be used as the phase-forming component, which can also be recycled by adjusting the pH. The phase behaviors of this P N-CD /P ADB ABS had been studied. The influencing parameters were studied for this chiral separation process, including the polymer concentration, initial tryptophan concentration, extraction temperature, and system pH. The maximum separation factor ( α ) of 1.42 was obtained by one-step extraction under the optimal conditions. Meanwhile, the distribution coefficients of L -tryptophan ( L -Trp) and D -tryptophan ( D -Trp) were 2.79 and 1.96, respectively. This study develops a green and sustainable strategy for enantioseparation by using the ELLE.
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CHIRALITY
·
2021
·Vol. 33
·期 5
·248-260
·
IF 2.437
Xiaohui Niu,Xing Yang,Hongxia Li,Qiuyun Shi,Kunjie Wang
Due to the crucial role of amino acids in life sciences and pharmaceutics, identification of optical amino acid molecules is of great significance. In this study, the two materials (CNT and PANI) were combined together to obtain the magnification of electrochemical signal by substrate material (CNT/PANI). Then a self-assembled multiwalled carbon nanotubes/polyaniline/sodium alginate (CNT/PANI/SA) nanocomposite with chiral sites and conductive material was synthesized as the electrochemical sensing interface. Next, a novel electrochemical sensing interface was fabricated via modifying the as-prepared chiral material on a polished glassy carbon electrode (CNT/PANI/SA/GCE) for precisely, efficiently, and rapidly differentiation of tryptophan (Trp) enantiomers. It was observed that CNT/PANI/SA/GCE showed desirable stereoselective recognition effect in the variety of signal strength to peak current (Ip) to the different optical activity of Trp enantiomers. In the case of optimal conditions, the peak current ratio in the solution of l -Trp and d -Trp ( I D / I L ) was observed to be 2.1 at CNT/PANI/SA/GCE by differential pulse voltammogram (DPV). UV–visible spectroscopy further showed that CNT/PANI/SA had a greater binding energy to l -Trp. Also different factors affecting the enantioselectivity of CNT/PANI/SA/GCE, such as the incubation time, pH, and dropcoating volume of CNT/PANI/SA were optimized. Moreover, the proposed CNT/PANI/SA/GCE showed excellent specific stereoselectivity and anti-interference ability. Besides, the proposed chiral sensing platform can be effectively applied in real samples to detect Trp enantiomers sensitively. This work inspires us a new path for the preparation of substrate material with excellent electrical conductivity, as well as extend its application potential in chiral recognition.
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Microorganisms
·
2021
·Vol. 9
·期 7
·1511
·
IF 4.128
Jia Yin,Yujie Song,Yaozhong Hu,Yuanyifei Wang,Bowei Zhang,Jin Wang,Xuemeng Ji,Shuo Wang
Akkermansia muciniphila, a potential probiotic, has been proven to lessen the effects of several diseases. As established, the relative abundance ofAkkermansiais positively correlated with tryptophan metabolism. However, the reciprocal interaction between tryptophan andAkkemansiais still unclear. Herein, for the first time, the possible effects of tryptophan and its derived metabolites onA. muciniphilawere preliminarily investigated, including growth, physiological function, and metabolism. Obtained results suggested that 0.4 g/L of tryptophan treatment could significantly promote the growth ofA. muciniphila. Notably, when grown in BHI with 0.8 g/L of tryptophan, the hydrophobicity and adhesion ofA. muciniphilawere significantly improved, potentially due to the increase in the rate of cell division. Furthermore,A. muciniphilametabolized tryptophan to indole, indole-3-acetic acid, indole-3-carboxaldehyde, and indole-3-lactic acid. Indoles produced by gut microbiota could significantly promote the growth ofA. muciniphila. These results could provide a valuable reference for future research on the relationship between tryptophan metabolism andA. muciniphila.Keywords:Akkermansia;tryptophan metabolites;indole;indole derivates
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