Bile acid derivative

After receiving a typical diet for a week, Sprague-Dawley rats were split into two groups at random. The NAFLD group was given a high-fat diet (60 kcal%; 18 weeks), while the control group was fed a typical diet (10 kcal%) [1]. Ten BAs, including four taurine-conjugated BAs (taurolithocholic acid (TLCA), taurodeoxycholic acid (TDCA), and tauromega-murinecholic acid), were considerably reduced in the liver of the NAFLD group. (TMC). Furthermore, the NAFLD group had reduced levels of βDCA, HDCA, 6-ketoLCA, 23-nordeoxycholic acid (NorDCA), LCA, and 3β-chenodeoxycholic acid (βCDCA) [2].

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Prematurity significantly influenced ‘rare’ BA levels [1]
The influence of prematurity on ‘rare’ BA metabolism was investigated in a group of 22 non-septic PT neonates. In summary, C-6-hydroxylated BA levels in PT neonates were below the detection limit except for TAMCA, whose median concentration was 0.1 µmol/L (IQR: 0–0.2). In total, C-6-hydroxylated BA levels were significantly higher in non-septic FT neonates than in non-septic PT neonates (Fig. 2; p < 0.01). Interestingly, TAMCA was the only ‘rare’ BA found in healthy PT neonates (Fig. 3b). Unlike in non-septic FT neonates, GMCA, TGMCA, TωMCA/TOMCA, GGMCA, and BMCA were absent in non-septic PT neonates.

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EOS FT neonates show alterations in ‘rare’ BA’ composition but not in levelss [1]
C-6-hydroxylated BA levels were determined in 20 FT neonates with diagnosed EOS. Interestingly, levels were comparable in FT neonates with EOS and in FT controls with 0.5 µmol/L (IQR: 0.3–1.3) and 0.6 µmol/L (IQR: 0.1–1.6), respectively. However, the ‘rare’ BA profile in EOS term neonates differed from that in healthy FT neonates: TωMCA/TOMCA was significantly higher in EOS (p < 0.01) and accounted for 95% of all C-6-hydroxylated BA (Fig. 3c). TAMCA was significantly lower in EOS (p < 0.01). TGMCA, GMCA, BMCA, and GGMCA, which were—in addition to TAMCA—the most abundant ‘rare’ BA in FT controls, were below the detection limit in EOS.

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EOS in PT infants was marked by significantly increased ‘rare’ BA levels caused by a rise of TωMCA/TOMCAs [1]
The influence of EOS was investigated since ‘classical’ human BA levels were found to be significantly decreased in EOS.1 C-6-hydroxylated BA levels were determined significantly higher in 13 EOS PT neonates compared to PT controls (0.6 µmol/L [IQR: 0.2–1.5] vs. 0 µmol/L [IQR: 0.0–0.2]; p < 0.01). As in EOS FT neonates, the BA profile in EOS PT neonates included a significantly higher amount of TωMCA/TOMCA (p < 0.01) than did that of PT controls. Overall, TOMCA accounted for 72% of all ‘rare’ BA, followed by GBMCA (17%), TAMCA (8%), and BMCA (3%; Fig. 3d). TAMCA values—the only C-6-hydroxylated BA in PT controls—were significantly lower in EOS (p < 0.01).

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TOMCA/TωMCA levels are independently associated with EOSs [1]
Last, we evaluated the autonomous potential of TOMCA/TωMCA as a biomarker in EOS. EOS biomarker are listed in Table 3. Multivariate regression analysis revealed that TOMCA levels were independent of EOS biomarkers CRP, PCT, IL-6, and bilirubin (r = 0.75, p = 0.85).

Study design and patient characteristics [1]
Prematurity was diagnosed when neonates were born at <37 weeks’ gestation. EOS was confirmed by complete white blood cell count with a positive blood culture and CRP concentrations above 5 mg/L. All neonates with primary liver or biliary-tract disorders or asphyxia were excluded and EOS was excluded in controls. Fasting blood sampling in non-septic and EOS neonates was performed during routine screening for phenylketonuria or routine measurements, respectively. Blood sampling was within 48 h after starting antibiotics. Neonates not fed within 2 h were considered ‘fasted’. Overnight fasting blood sample collection was not possible since newborn infants are fed at least every 4 h. Finally, serum samples were stored at −80°C until assays. Analyses including concentrations of CRP, IL-6, PCT, and bilirubin were measured by standard laboratory methods. In addition, C-6 hydroxylated BA levels were measured by HPLC-HRMS, including unconjugated and taurine (T)- and glycine (G)-conjugated species (Table 1). Individual BA were separated by HPLC using a reversed-phase C18 column and a kinetex pentafluorophenyl column. Quantification and characterization was achieved using a mass spectrometer Q Exactive™ MS/MS and a high-performance quadrupole precursor selection with high-resolution and accurate-mass (HR/AM) Orbitrap™ detection according to the method published by Amplatz 2017.14

[1]. Neonatal sepsis leads to early rise of rare serum bile acid tauro-omega-muricholic acid (TOMCA).Pediatr Res. 2018 Jul;84(1):66-70.
[2]. Turnover of bile acids in liver, serum and caecal content by high-fat diet feeding affects hepatic steatosis in rats. Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Oct;1864(10):1293-1304

Background: We investigated the potential of “rare” bile acids (BAs) as a marker for neonatal sepsis. Methods: High-performance liquid chromatography-high-resolution mass spectrometry (HPLC-HRMS) was used to determine the levels of “rare” (C-6-hydroxylated bile acids) and “classical” bile acids in 102 newborns. Subjects were divided into four groups based on gestational age (full-term infants, FT vs. preterm infants, PT) and sepsis status (early-onset neonatal sepsis, EOS vs. CTR; non-sepsis control group): FT-CTR group (n = 47), PT-CTR group (n = 22), FT-EOS group (n = 20), and PT-EOS group (n = 13). Results: First, the levels of “rare” bile acids were significantly higher in the FT-CTR group than in the PT group (FT-CTR: 0.5 µmol/L, IQR: 0.3–1.3 vs. PT-CTR: 0.01 µmol/L, IQR: 0.01–0.2; p < 0.01). The most common “rare” bile acids in the FT-CTR group were taurine-γ-(TGMCA) and taurine-α-mouse bile acid (TAMCA). Second, in early pregnancy (EOS), the absolute levels of “rare” bile acids were comparable between the two gestational weeks (FT-EOS: 0.6 µmol/L, IQR: 0.1–1.6; PT-EOS: 0.6 µmol/L, IQR: 0.2–1.5). Therefore, the median “rare” bile acid (BA) level in EOS was significantly higher than in non-infectious PT newborns (p < 0.01). In preterm and full-term newborns, the relative content of taurine-ω-mouse bile acid (TOMCA) in the “rare” bile acid pool was significantly higher in the preterm group (FT-CTR) than in the control group (FT-EOS and PT-CTR vs. PT-EOS; p < 0.01). Therefore, TOMCA is the major “rare” bile acid in the preterm group. Conclusion: TOMCA is an independent factor associated with the preterm group and has diagnostic potential. [1]

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Background: Bile acids (BA) are involved in lipid absorption and play a metabolic regulatory role in gut-liver communication. To date, no studies have explored the systemic distribution patterns of bile acids in serum, liver, and intestine in the same non-alcoholic fatty liver disease (NAFLD) model. Methods: Bile acid profiles and their association with gut microbiota were identified using targeted metabolomics and 16S rRNA sequencing. The effects of bile acid alterations on liver function and their mechanisms were investigated. This study explored steatosis. The results showed that in the liver, taurocholic acid (TCA) levels increased, while taurodeoxycholic acid (THDCA) and ursodeoxycholic acid (UDCA) levels decreased. In the intestine, the levels of unconjugated forms of TCA (cholic acid (CA)) increased, while the levels of unconjugated forms of THDCA (α-deoxycholic acid (HDCA)) and ω-mouse cholic acid (ωMCA) decreased. In serum, TCA levels increased, while HDCA and THDCA levels decreased. RNA sequencing analysis indicated that THDCA induced the expression of apolipoproteins, bile secretion-related proteins, and cytochrome P450 family genes in steatotic hepatocytes, but inhibited the expression of inflammatory response genes. THDCA improved the accumulation of neutral lipids and increased insulin sensitivity in primary rat hepatocytes. Decreased HDCA levels were correlated with Bacteroidetes levels, while CA levels were correlated with Bacteroidetes levels. HDCA levels were positively correlated with Firmicutes and Verrucous microbes, but negatively correlated with Bacteroidetes levels. Conclusion: In a rat model of non-alcoholic fatty liver disease, the bile acid profile in serum, liver and cecal contents was altered, which may affect hepatic lipid accumulation and be associated with gut microbiota dysbiosis. [2]

C26H44NNAO7S

537.684838294983

537.273

2456348-84-6

146047145

White to off-white solid powder

4

7

7

36

897

11

C[C@H](CCC(=O)NCCS(=O)(=O)[O-])[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2[C@H]([C@@H]([C@H]4[C@@]3(CC[C@H](C4)O)C)O)O)C.[Na+]

NYXROOLWUZIWRB-JTNLMKNRSA-M

InChI=1S/C26H45NO7S.Na/c1-15(4-7-21(29)27-12-13-35(32,33)34)17-5-6-18-22-19(9-11-25(17,18)2)26(3)10-8-16(28)14-20(26)23(30)24(22)31;/h15-20,22-24,28,30-31H,4-14H2,1-3H3,(H,27,29)(H,32,33,34);/q;+1/p-1/t15-,16-,17-,18+,19+,20+,22+,23-,24-,25-,26-;/m1./s1

sodium;2-[[(4R)-4-[(3R,5R,6R,7R,8S,9S,10R,13R,14S,17R)-3,6,7-trihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]ethanesulfonate

Tauro-ω muricholic acid sodium; T-ω-MCA; TOMCA; 2456348-84-6; Tauro-omega-muricholic acid sodium; Tauro-; O-muricholic acid (sodium); Tauro-?-muricholic Acid Sodium Salt; Sodium 2-((R)-4-((3R,5R,6R,7R,8S,9S,10R,13R,14S,17R)-3,6,7-trihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanamido)ethanesulfonate; Tauro-?-muricholic Acid (sodium salt); Tauro-; Tauro ω muricholic acid sodium

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)