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Carbonic anhydrase inhibitors. Preparation of potent sulfonamides inhibitors incorporating bile acid tails.

Reaction of TBDMS-protected bile acids (cholic, chenodeoxycholic, deoxycholic, lithocholic, ursodeoxycholic acids) or dehydrocholic acid with aromatic/heterocyclic sulfonamides possessing free amino/hydroxy moieties, in the presence of carbodiimides, afforded after deprotection of the OTBDMS ethers, a series of sulfonamides incorporating bile acid moieties in their molecules. Many such derivatives showed strong inhibitory properties against three isozymes of carbonic anhydrase (CA, EC 4.2.1.1), that is CA I, II and IV, zinc enzymes playing critical roles in many pathologies, and which represen

[Effects of urso-deoxycholic acid (UDCA) on alpha-naphthyl-isothiocyanate (ANIT) induced intrahepatic cholestasis in rats].

Using the ANIT induced model of cholestasis in rats, the therapeutic effects of UDCA to the intrahepatic cholestasis were evaluated by chang … ologically. Moreover, the elevation of serum levels of chenodeoxy-cholic acid, deoxycholic acid and lithocholic acid was accompanied. On the other hand, in the recovery stage of the bile duct epithelium, serum bilirubin was decreased significantly in the UDCA group which seemed to be related with the potent choleretic effect of UDCA. These results may indicate tha …

Sex differences in gallstone formation in mice on a lithogenic diet are driven by gut microbiota-mediated bile acid metabolism.

Sex differences in gallstone formation involve the gut microbiota, but the specific mediating mechanisms remain unclear. This study established gallstone and pseudo-germ-free mouse models and found that male mice maintained higher gut microbiota diversity, whereas females showed an increased Firmicutes/Bacteroidota ratio, with enrichment of Clostridium_sensu_stricto_13 and Lactobacillus. This shift led to increased production of toxic secondary bile acids-deoxycholic acid and lithocholic acid-resulting in elevated bile hydrophobicity and higher cholesterol saturation, which significantly incre…

[Analysis of the serum bile acid profile to facilitate diagnosis and differential diagnosis of NA(+)-taurocholate cotransporting polypeptide deficiency].

Objective: This study focuses on Na(+)-taurocholate cotransporting polypeptide (NTCP) deficiency to analyze and investigate the value of the … ith NTCP deficiency, but the bile acid levels such as glycodeoxycholic acid, glycolithocholate, and lithocholic acid were decreased (P < 0.05). The serum levels of secondary bile acids such as lithocholic acid, deoxycholic acid, and hyodeoxycholic acid were significantly higher in children with NTCP deficiency than those in other CLD groups such as NICCD, Alagille …

The biocompatibility and the metabolic impact of thermoresponsive, bile acid-based nanogels on auditory and macrophage cell lines.

Deoxycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) are bile acids that may serve as permeation enhancers when incorporated within the nanogel matrix for drug delivery in the inner ear. In this study, thermoresponsive nanogels were formulated with DCA, LCA and UDCA and their rheological properties and biocompatibility were assessed. The impact of nanogel on cellular viability was evaluated via cell viability assay, the impact of nanogels on cellular bioenergetic parameters was estimated by Seahorse mito-stress test and glycolysis-stress test, while the presence of i…

Производимые микробиотой иммунные регуляционные метаболиты желчных кислот контролируют автонепроницаемость центральной нервной системы.

Микробиота комменсового кишечника играет определенную роль в патогенезе внекишечных аутоиммунных заболеваний, таких как множественный склероз (MS) с неизвестными механизмами. Деоксихоловая кислота (DCA) и литохолическая кислота (LCA) представляют собой вторичные метаболиты желчных кислот (BAM), получаемые из первичных желчных кислот кишечными микробиотами, которые играют ключевые функции по регулированию иммунной системы путем поощрения дифференциации клеток FOXP3+, регулируемой Т (Treg), за счет клеток TH17. Здесь мы показываем, что бактерии, выделяющие ферменты, ответственные за вторичное пр

Совпадение в аннотации оригинала
The commensal gut microbiota has a role in the pathogenesis of extra-intestinal autoimmune diseases such as multiple sclerosis (MS) with unknown mechanisms. Deoxycholic acid (DCA) and lithocholic acid (LCA) are secondary bile acid metabolites (BAMs) produced from primary bile acids by gut microbiota that play key immune regulatory functions by promoting FOXP…

A microbial metabolite remodels the gut-liver axis following bariatric surgery.

Bariatric surgery is the most effective treatment for type 2 diabetes and is associated with changes in gut metabolites. Previous work uncovered a gut-restricted TGR5 agonist with anti-diabetic properties-cholic acid-7-sulfate (CA7S)-that is elevated following sleeve gastrectomy (SG). Here, we elucidate a microbiome-dependent pathway by which SG increases CA7S production. We show that a microbial metabolite, lithocholic acid (LCA), is increased in murine portal veins post-SG and by activating the vitamin D receptor, induces hepatic mSult2A1/hSULT2A expression to drive CA7S production. An SG-in…

Effects of bile acids on development of pepsinogen-altered pyloric glands in rats.

The effects of dietary bile acids on the development of pepsinogenaltered pyloric glands (PAPG) were examined. Male WKY/NCrj rats were given a single dose of 160 mg/kg body wt. of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) by gastric intubation and fed basal diet containing 0.3% sodium taurocholate (Na-TC), 0.3% sodium cholate (Na-C), 0.3% sodium glycocholate (Na-GC), 0.3% sodium tauroglycocholate, 0.3% sodium deoxycholate, 0.1% chenodeoxycholic acid or 0.5% lithocholic acid for 14 weeks. All rats also received 1 ml of saturated NaCl solution 4 times by i.g. intubation. At the end of week 16,…

Bile Acid Metabolism Affects Muscle Regeneration in Aging Skeletal Muscle in a Manner Associated with Regulation of ABCB1 Expression.

The role of bile acid metabolism within the skeletal muscle microenvironment in sarcopenia remains unclear. This study investigated bile acid alterations and the function of the ATP Binding Cassette Subfamily B Member 1 (ABCB1) transporter in muscle microvascular endothelial cells (MMECs) during aging. Using a sarcopenic mouse model stratified by muscle density, we found elevated deoxycholic acid (DCA) and lithocholic acid (LCA) levels but reduced tauroursodeoxycholic acid (TUDCA) levels in muscle, correlating with downregulated ABCB1/P-glycoprotein expression. In vitro, inhibition of ABCB1 in…

Bile acids and biliary carcinoma in pancreaticobiliary maljunction.

Pancreaticobiliary maljunction is frequently associated with biliary carcinoma, whether or not there is choledochal dilatation. In this anom … ochal dilatation with pancreaticobiliary maljunction, the concentrations of deoxycholic acid (DCA), lithocholic acid (LCA) and unconjugated bile acid fractions were increased regardless of the presence of cancer. Increases of these bile acid fractions, which are known to have a cancer-promoting effect, were also seen in gallbladder bile from the cancer patients wi …

Serum bile acid profile in thyroid dysfunction and effect of medical treatment.

1. Serum non-esterified bile acid profile was examined in patients with thyroid dysfunction. Sixteen hyperthyroid patients, six hypothyroid patients, nine patients taking thyroid or antithyroid drugs and 26 healthy controls were studied. The medicated patients were euthyroid when serum samples were collected. Bile acid concentration was determined by the simplified microassay method involving mass fragmentation spectrometry. 2. The sum of the concentrations of the individual bile acids was not significantly different among the four groups. However, the composition of bile acid reflected the th

GPR39-mediated molecular signaling by bile acids.

Bile acids (BAs), long known for roles in food emulsion, also function as biological signals. By measuring intracellular calcium, we have recently discovered that GPR39, a G protein-coupled receptor, is a receptor for 3-O-sulfated BAs including lithocholic acid 3-sulfate (LCAS), taurolithocholic acid 3-sulfate (TLCAS) and glycolithocholic acid 3-sulfate (GLCAS) in cultured cells and in pancreatic acinar cells. We have now used multiple assays from electrophysiologic recording in Xenopus oocytes, Ca2+ imaging, NanoBiT, ONE-GO, and TANGO to validate GPR39 activation by BAs. Among 30 BAs, only su…

Bile acids LCA and CDCA inhibited porcine deltacoronavirus replication in vitro.

Porcine deltacoronavirus (PDCoV) is an emerging enteric coronavirus that causes gastroenteritis in pigs and no vaccines or antiviral drugs are available. Bile acids are active factors in intestines and influence the replication of enteric viruses. Currently, the role of bile acids on PDCoV replication is unknown. In this study, we tested the effects of different types of bile acids on the replication of PDCoV in cell culture. We found that physiological concentrations of bile acids chenodeoxycholic acid (CDCA) and lithocholic acid (LCA) had antiviral activity against PDCoV in porcine kidney ce…

Suppression of Hepatic PPARα in Primary Biliary Cholangitis Is Modulated by miR-155.

BACKGROUND: PPARα is a ligand-activated transcription factor that shows protective effects against metabolic disorders, inflammation and apo … holangiocytes (NHCs) following exposure to lipopolysaccharide (LPS), glycodeoxycholic acid (GCDCA), lithocholic acid (LCA) and/or ursodeoxycholic acid (UDCA). RESULTS: A reduction of PPARα in primary biliary cholangitis (PBC) livers was associated with miR-21 and miR-155 upregulation. Experimental overexpression of either miR-155 or miR-21 inhibited PPARα in hepa …

Modulatory Nano/Micro Effects of Diabetes Development on Pharmacology of Primary and Secondary Bile Acids Concentrations.

BACKGROUND: Recent studies have suggested that hyperglycaemia influences the bile acid profile and concentrations of secondary bile acids in … eoxycholic acid, in the plasma, intestine, and brain, and higher levels of the secondary bile acid, lithocholic acid, in the plasma and pancreas. Levels of the bile acid ursodeoxycholic acid were undetected in healthy mice but were found to be elevated in T1D and T2D mice. CONCLUSION: Bile acid profiles in other organs were variably influenced by T1D and T2D deve …

Maternal glucose homeostasis is impaired in mouse models of gestational cholestasis.

Women with intrahepatic cholestasis of pregnancy (ICP), a disorder characterised by raised serum bile acids, are at increased risk of develo … mice are also insulin resistant. Furthermore, fecal bile acids are reduced in pregnant Fxr-/- mice. Lithocholic acid and deoxycholic acid, the principal ligands for TGR5, are decreased in particular. Therefore, we propose that raised serum bile acids and reduced FXR and TGR5 activity contribute to the altered glucose metabolism observed in ICP.

Identification of 1,3,4-Thiadiazolyl-Containing Thiazolidine-2,4-dione Derivatives as Novel PTP1B Inhibitors with Antidiabetic Activity.

Forty-one 1,3,4-thiadiazolyl-containing thiazolidine-2,4-dione derivatives (MY1-41) were designed and synthesized as protein tyrosine phosphatase 1B (PTP1B) inhibitors with activity against diabetes mellitus (DM). All synthesized compounds (MY1-41) presented potential PTP1B inhibitory activities, with half-maximal inhibitory concentration (IC50) values ranging from 0.41 ± 0.05 to 4.68 ± 0.61 μM, compared with that of the positive control lithocholic acid (IC50 = 9.62 ± 0.14 μM). The most potent compound, MY17 (IC50 = 0.41 ± 0.05 μM), was a reversible, noncompetitive inhibitor of PTP1B. Circula…

Multi-Omics Analysis of Gut Microbiota and Sperm Quality in Tibetan Breeding Boars.

BACKGROUND/OBJECTIVES: Reproductive efficiency in breeding boars critically impacts swine industry productivity, with sperm quality being mu … key metabolites positively correlated with sperm quality (e.g., butyrate, phenyllactic acid), while lithocholic acid showed negative associations. KEGG analysis revealed predominant involvement in butanoate metabolism and bile acid biosynthesis. Core microbiota (e.g., Ruminococcus) modulated sperm quality through short-chain fatty acid networks and bile acid homeo …

Ultrastructural changes in rat colorectal epithelium and tumors after treatment with N-methyl-N'-nitro-N-nitrosoguanidine and secondary bile acids.

Transmission electron microscopy (TEM) was used to study ultrastructural changes that accompanied the tumorous transformation of the descending rat colon epithelial cells, following short treatment with a direct carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), with subsequent prolonged treatment with secondary bile acids, lithocholic (LCA) and deoxycholic (DCA), which enhanced tumor formation. Colon epithelial cells after long treatment with bile acids alone were characterized by the presence of an irregular nuclear membrane, ring-shaped rough endoplasmic reticulum (RER), collagen-like

Serum bile acid profiling reflects enterohepatic detoxification state and intestinal barrier function in inflammatory bowel disease.

AIM: To determine free and conjugated serum bile acid (BA) levels in inflammatory bowel disease (IBD) subgroups with defined clinical manifestations. METHODS: Comprehensive serum BA profiling was performed in 358 IBD patients and 310 healthy controls by liquid chromatography coupled to electrospray ionization tandem mass spectrometry. RESULTS: Serum levels of hyodeoxycholic acid, the CYP3A4-mediated detoxification product of the secondary BA lithocholic acid (LCA), was increased significantly in Crohn's disease (CD) and ulcerative colitis (UC), while most other serum BA species were decrease…