tph1 inhibitor telotristat ethyl lx1606 125 mg kg  (MedChemExpress)

Journal: Translational Pediatrics

Article Title: Chenodeoxycholic acid activates the TGR5/TRPA1-5-HT pathway to regulate intestinal motility in breastfed infants and mouse models

doi: 10.21037/tp-2025-100

Figure Lengend Snippet: Impact of increasing concentrations of CDCA enemas on intestinal motility, fecal characteristics, colonic histology, and expression of serotonin pathway components. Mice received CDCA at different concentrations (Control, 5, 10, 20, and 40 mg/kg) via enema for 7 consecutive days and were then analyzed. (A) Representative images of GI transit distance after gavage of carmine red solution for 30 minutes, showing dose-dependent increases in transit. The red arrow points to the area reached by carmine red. (B) Representative images of fecal appearance, demonstrating increased water content with higher CDCA doses. (C) Quantitative measurements of fecal water content, GI transit time, and colonic transit distance after gavage of carmine red solution for 60 minutes. (D) Representative images of HE-stained ileum tissue sections showing no significant tissue damage across treatment groups. (E) Western blot analysis of key serotonin pathway proteins in colon tissue: Tph1, 5-HT3R, 5-HT4R, SERT, TGR5, and TRPA1. (F) ELISA measurements of 5-HT and cAMP levels, and qPCR analysis of mRNA expression for Tph1, 5-HT3R, 5-HT4R, SERT, TGR5, and TRPA1 in colon tissue. Data were presented as mean ± SD or median (IQR). *, P<0.05; **, P<0.01; ***, P<0.001; ****, P<0.0001. n=5/group. 5-HT, 5-hydroxytryptamine (serotonin); 5-HT3R, 5-HT receptor 3; 5-HT4R, 5-HT receptor 4; cAMP, cyclic adenosine monophosphate; CDCA, chenodeoxycholic acid; ELISA, enzyme-linked immunosorbent assay; GI, gastrointestinal; HE, hematoxylin and eosin; IQR, interquartile range; qPCR, quantitative polymerase chain reaction; SD, standard deviation; SERT, serotonin transporter; TGR5, Takeda G protein-coupled receptor 5; Tph1, tryptophan hydroxylase 1; TRPA1, transient receptor potential A1.

Article Snippet: LX1606 (T171759, Aladdin; listed in ) was used as a Tph1 inhibitor , while alosetron (A125218, Aladdin; listed in ) and GR113808 (HY-103152, Mce; listed in ) served as 5-HT3R and 5-HT4R antagonists, respectively ( , ).

Techniques: Expressing, Control, Staining, Western Blot, Enzyme-linked Immunosorbent Assay, Real-time Polymerase Chain Reaction, Standard Deviation

Journal: Translational Pediatrics

Article Title: Chenodeoxycholic acid activates the TGR5/TRPA1-5-HT pathway to regulate intestinal motility in breastfed infants and mouse models

doi: 10.21037/tp-2025-100

Figure Lengend Snippet: Impact of serotonin pathway inhibition on CDCA-induced changes in intestinal motility as described in . After CDCA treatment (20 mg/kg via enema for 7 days), mice received inhibitors targeting different components of the serotonin signaling pathway. (A) Representative images of GI transit distance after carmine red gavage (30 min) in mice treated with: Control (PBS), CDCA only, Alosetron (5-HT3R antagonist, 1 mg/kg, blocking serotonin receptor signaling), GR113808 (5-HT4R antagonist, 1 mg/kg, blocking a different serotonin receptor subtype), or LX1606 (Tph1 inhibitor, 200 mg/kg, blocking serotonin synthesis). The red arrow as in . (D) Similar transit images for mice treated with Control, CDCA only, SBI-115 (TGR5 antagonist, 15 mg/kg, blocking the bile acid receptor upstream of serotonin signaling), or HC-030031 (TRPA1 inhibitor, 150 mg/kg, blocking another upstream component in the signaling pathway). The red arrow as in . (B,E) Representative images of fecal appearance from corresponding treatment groups. (C,F) Quantitative measurements of fecal water content, GI transit time, colonic transit distance (60 min post-carmine), and ELISA results for 5-HT and cAMP levels in colon tissue for all treatment groups. The experimental design systematically targets different points in the TGR5/TRPA1-5-HT signaling axis as detailed in the Methods section (2.8 and 2.9). Data were presented as mean ± SD. *, P<0.05; **, P<0.01; ***, P<0.001; ****, P<0.0001. n=5/group. 5-HT, 5-hydroxytryptamine (serotonin); 5-HT3R, 5-HT receptor 3; 5-HT4R, 5-HT receptor 4; cAMP, cyclic adenosine monophosphate; CDCA, chenodeoxycholic acid; ELISA, enzyme-linked immunosorbent assay; GI, gastrointestinal; PBS, phosphate-buffered saline; SD, standard deviation; Tph1, tryptophan hydroxylase 1; TRPA1, transient receptor potential A1.

Article Snippet: LX1606 (T171759, Aladdin; listed in ) was used as a Tph1 inhibitor , while alosetron (A125218, Aladdin; listed in ) and GR113808 (HY-103152, Mce; listed in ) served as 5-HT3R and 5-HT4R antagonists, respectively ( , ).

Techniques: Inhibition, Control, Blocking Assay, Enzyme-linked Immunosorbent Assay, Saline, Standard Deviation

Journal: Translational Pediatrics

Article Title: Chenodeoxycholic acid activates the TGR5/TRPA1-5-HT pathway to regulate intestinal motility in breastfed infants and mouse models

doi: 10.21037/tp-2025-100

Figure Lengend Snippet: Induction of serotonin pathway components in rat insulinoma-derived RIN-14B cells. These cells were used as an in vitro model of enterochromaffin cells to examine direct effects of CDCA treatment. (A) ELISA measurements of 5-HT secretion in response to 15 μM CDCA treatment, alongside cell proliferation assays showing no toxicity of CDCA at concentrations of 5–25 μM over 24–72 hours. (B) qPCR analysis of mRNA expression for Tph1, SERT, TGR5, and TRPA1 in RIN-14B cells following 15 μM CDCA treatment, demonstrating significant upregulation of these serotonin pathway components. Data were presented as mean ± SD. *, P<0.05; **, P<0.01; ***, P<0.001; ****, P<0.0001. CDCA, chenodeoxycholic acid; ELISA, enzyme-linked immunosorbent assay; qPCR, quantitative polymerase chain reaction; SD, standard deviation; SERT, serotonin transporter; TGR5, Takeda G protein-coupled receptor 5; Tph1, tryptophan hydroxylase 1; TRPA1, transient receptor potential A1.

Article Snippet: LX1606 (T171759, Aladdin; listed in ) was used as a Tph1 inhibitor , while alosetron (A125218, Aladdin; listed in ) and GR113808 (HY-103152, Mce; listed in ) served as 5-HT3R and 5-HT4R antagonists, respectively ( , ).

Techniques: Derivative Assay, In Vitro, Enzyme-linked Immunosorbent Assay, Expressing, Real-time Polymerase Chain Reaction, Standard Deviation

Journal: Nature Communications

Article Title: Harnessing intestinal tryptophan catabolism to relieve atherosclerosis in mice

doi: 10.1038/s41467-024-50807-x

Figure Lengend Snippet: A 5-HT levels in small intestine extracts ( n = 5 mice/group), B plaque quantification in the aortic sinus and representative images of male Ldlr −/− treated with Tryptophan Hydroxylase 1 (TPH1) inhibitor (LP533401, n = 6 mice) or vehicle ( n = 8 mice) and fed HFD + HCD for 8 weeks; scale bar 200 µm. C , D representative images and quantifications of macrophages (MOMA-2+ in red) and lymphocytes (CD3+ in red) accumulation in the aortic sinus ( Ldlr −/− Vehicle n = 8, Ldlr −/− LP533401 n = 6); scale bar 100 µm. E representative pictures and quantifications of plaque size in the aortic sinus male Ldlr −/− IEC IDO KO and littermate control Ldlr −/− IEC IDO mice treated with either LP533401 or vehicle and fed HFD + HCD for 8 weeks (IEC IDO Vehicle n = 11 mice, IEC IDO KO Vehicle n = 7 mice, IEC IDO LP533401 n = 11 mice, IEC IDO KO LP533401 n = 9 mice); scale bar 200 µm. F Colon pathohistological scoring (IEC IDO Vehicle n = 5 mice, IEC IDO KO Vehicle n = 10 mice, IEC IDO LP533401 n = 5 mice, IEC IDO KO LP533401 n = 10 mice). G lipocalin-2 (Lcn2) levels in feces (IEC IDO Vehicle n = 5 mice, IEC IDO KO Vehicle n = 7 mice, IEC IDO LP533401 n = 5 mice, IEC IDO KO LP533401 n = 10 mice). Individual data are presented as scattered dot plots, with the mean and s.e.m. The p values were determined using the two-tailed Mann-Whitney test for A – D , Kruskal-Wallis, followed by post-Hoc Dunn’s test for F , and one-way ANOVA test followed by Tukey’s multiple comparison test for E and G . Source data are provided as a Source Data file.

Article Snippet: Other groups of mice were daily injected with TPH1 inhibitor LP533401 (25 mg/kg, Dalton Pharma Services, Canada) or an equal volume of vehicle along the 8 weeks of HFD + HCD feeding period.

Techniques: Control, Two Tailed Test, MANN-WHITNEY, Comparison

Journal: Frontiers in Oncology

Article Title: A positive feedback loop between tryptophan hydroxylase 1 and β-Catenin/ZBP-89 signaling promotes prostate cancer progression

doi: 10.3389/fonc.2022.923307

Figure Lengend Snippet: Tryptophan hydroxylase 1 (TPH1) drives prostate cancer cell proliferation and migration. (A) Immunofluorescence staining of TPH1 in tumor tissues from patients with metastatic (M) and nonmetastatic (NM) prostate cancer (n = 10 per group). The scale bar is 60 μm. (B) Western blotting of TPH1 in DU145/PC-3 and TPH1-overexpressing DU145/PC-3 cells. (C) Relative proliferation of DU145/PC-3 and TPH1-overexpressing DU145/PC-3 cells using the CCK-8 assay. (D) Relative number of migrating DU145/PC-3 and TPH1-overexpressing DU145/PC-3 cells determined using the transwell assay. (E) Overall survival of patients with prostate cancer divided into the high TPH1 (n = 96) and low TPH1 expression (n=150) groups. ** p < 0.01.

Article Snippet: Chemotherapeutic paclitaxel (PTX), TPH1 inhibitor 4-chloro- dl -phenylalanine (PCPA), and 5-HT were purchased from Sigma (USA). β-Catenin inhibitor LF3 was purchased from MedChemExpress (USA).

Techniques: Migration, Immunofluorescence, Staining, Western Blot, CCK-8 Assay, Transwell Assay, Expressing

Journal: Frontiers in Oncology

Article Title: A positive feedback loop between tryptophan hydroxylase 1 and β-Catenin/ZBP-89 signaling promotes prostate cancer progression

doi: 10.3389/fonc.2022.923307

Figure Lengend Snippet: TPH1 promotes tryptophan (Trp) hydroxylation and 5-hydroxytryptamine (5-HT) production. (A) Culture of 10 5 DU145/PC-3 and TPH1-overexpressing DU145/PC-3 cells in 2 ml of culture medium for 48 h. Trp consumption was examined using a human Trp enzyme-linked immunosorbent assay (ELISA) kit. (B) 5-HT production in (A) was examined using a human 5-HT ELISA kit. (C) Relative proliferation of DU145/PC-3 cells treated with phosphate-buffered saline (PBS) or 5-HT (5 μM). (D) Relative number of migrating DU145/PC-3 cells treated with PBS or 5-HT (5 μM). (E) Quantification of 5-HT in tumor tissues from patients with M and NM prostate cancer (n = 10 per group) using ELISA. ** p < 0.01.

Article Snippet: Chemotherapeutic paclitaxel (PTX), TPH1 inhibitor 4-chloro- dl -phenylalanine (PCPA), and 5-HT were purchased from Sigma (USA). β-Catenin inhibitor LF3 was purchased from MedChemExpress (USA).

Techniques: Enzyme-linked Immunosorbent Assay, Saline

Journal: Frontiers in Oncology

Article Title: A positive feedback loop between tryptophan hydroxylase 1 and β-Catenin/ZBP-89 signaling promotes prostate cancer progression

doi: 10.3389/fonc.2022.923307

Figure Lengend Snippet: 5-HT mediates Axin/β-catenin activation in prostate cancer. (A) Western blotting of Axin 1 in DU145/PC-3 cells (treated with PBS or 5 μM 5-HT) and TPH1-overexpressing DU145/PC-3 cells. (B) Western blotting of β-catenin in DU145/PC-3 cells (treated with PBS or 5 μM 5-HT) and TPH1-overexpressing DU145/PC-3 cells. (C) Proliferation of DU145/PC-3 cells treated with 5-HT (5 μM) combined with LF3 (2 μM) or not. (D) Proliferation of TPH1-overexpressing DU145/PC-3 cells treated with PBS or LF3 (2 μM). (E) Relative number of migrating DU145/PC-3 cells treated with 5-HT (5 μM) combined with LF3 (2 μM) or not. (F) Relative number of migrating TPH1-overexpressing DU145/PC-3 cells treated with PBS or LF3 (2 μM). (G) Immunofluorescence staining of β-catenin in tumor tissues from patients with M and NM prostate cancer (n = 10 per group). The scale bar is 60 μm. ** p < 0.01.

Article Snippet: Chemotherapeutic paclitaxel (PTX), TPH1 inhibitor 4-chloro- dl -phenylalanine (PCPA), and 5-HT were purchased from Sigma (USA). β-Catenin inhibitor LF3 was purchased from MedChemExpress (USA).

Techniques: Activation Assay, Western Blot, Immunofluorescence, Staining

Journal: Frontiers in Oncology

Article Title: A positive feedback loop between tryptophan hydroxylase 1 and β-Catenin/ZBP-89 signaling promotes prostate cancer progression

doi: 10.3389/fonc.2022.923307

Figure Lengend Snippet: β-Catenin cooperates with zinc finger binding protein (ZBP)-89 to promote TPH1 and forms a signaling feedback loop. (A) Western blotting of TPH1 in DU145/PC-3 cells treated with PBS, 5-HT (5 μM), and 5-HT (5 μM) combined with LF3 (2 μM). (B) Relative expression of ZBP-89 in DU145/PC-3 cells treated with Scr and ZBP-89 siRNA, as determined by quantitative polymerase chain reaction (qPCR). (C) Western blotting of TPH1 in DU145/PC-3 cells treated with 5-HT (5 μM) and 5-HT (5 μM) combined with ZBP-89 siRNA. (D) Proliferation of TPH1-overexpressing DU145/PC-3 cells treated with PBS, paclitaxel (PTX) (0.5 μg/ml), 4-chloro- dl -phenylalanine (PCPA) (2 μM), and a combination of the same. (E) Relative number of migrating TPH1-overexpressing DU145/PC-3 cells treated with PBS, PTX (0.5 μg/ml), PCPA (2 μM), and a combination of the same. (F) Tumor volume of TPH1-overexpressing PC-3–bearing mice treated with PBS, PTX, PCPA, and a combination of the same. (G) Overall survival of TPH1-overexpressing PC-3–bearing mice treated with PBS, PTX, PCPA, and a combination of the same. (H) M nodule numbers and hematoxylin and eosin (H&E) staining of lung tissues from TPH1-overexpressing PC-3–bearing mice treated with PBS, PTX, PCPA, and a combination of the same. The scale bar is 100 μm. (I) Schematic diagram of the 5-HT/β-catenin/ZBP-89/TPH1 signaling loop in prostate cancer. *p < 0.05; **p < 0.01.

Article Snippet: Chemotherapeutic paclitaxel (PTX), TPH1 inhibitor 4-chloro- dl -phenylalanine (PCPA), and 5-HT were purchased from Sigma (USA). β-Catenin inhibitor LF3 was purchased from MedChemExpress (USA).

Techniques: Binding Assay, Western Blot, Expressing, Real-time Polymerase Chain Reaction, Staining