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OBETICHOLIC ACID - Crossref

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Last Updated: 24 April 2022

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FXR agonist obeticholic acid reduces hepatic inflammation and fibrosis in a rat model of toxic cirrhosis

Abstract Hepatic inflammation promotes hepatic stellate cells, resulting in liver fibrosis. In healthy cirrhotic rats, we investigated the preventive and therapeutic effects of FXR agonist obeticholic acid on hepatic inflammation and fibrosis. In isolated HSC, Kupffer cells, hepatocytes, and liver sinusoidal endothelial cells, the effect of OCA was further investigated. During TAA-administration, OCA reduced hepatic inflammation and fibrogenesis, as well as reversed fibrosis in established cirrhosis. Both LSEC and Kupffer cell activation were inhibited by OCA in vitro, according to In vitro; however, HSC remained unaffected; In conclusion, OCA reduces hepatic inflammation in poor cirrhotic rats, resulting in reduced HSC activation and fibrosis.

Source link: https://doi.org/10.1038/srep33453


Obeticholic acid, a synthetic bile acid agonist of the farnesoid X receptor, attenuates experimental autoimmune encephalomyelitis

This bile acid synthesis, transport, and cholesterol metabolism is controlled by the bile acid–FXR interaction. In both animal models and human clinical trials, drugs targeting FXR activation have been shown to treat both liver and intestinal inflammatory diseases. In this research, we found that FXR knockout mice had more frequent EAE, and mice treated with a synthetic FXR agonist, obeticholic acid, reduced EAE severity.

Source link: https://doi.org/10.1073/pnas.1524890113


Formulation and Evaluation of Obeticholic Acid Solid Dispersion Tablet

The U. S. Food and Drug Administration recently approved Obeticholic acid as a farnoside X receptor agonist. Solid dispersion is one of the most efficient ways to raise Obeticholic acid's solubility. Solid dispersion can be made in a variety of ways. Fusion is one of the most cost-effective and quick methods for growing solid dispersion. Poloxamer is one of the finest polymers for solid dispersion production. Poloxamer 188 and Poloxamer 407 are both very popular. The solubility of the prepared solid dispersion has increased to 0. 347 mg/ml. In comparison to the polymer mixture, which has a 99. 63 percent drug clearance rate, the percent drug release is also higher. For the dissolution test apparatus, the Phosphate buffer 7. 4 is used. Obeticholic acid dispersion by using poloxamer gives improved solubility and increased drug dispersion, according to the All result parameter.

Source link: https://doi.org/10.9734/jpri/2021/v33i64b36003


Farnesoid X Receptor Activation by Obeticholic Acid Elevates Liver Low-Density Lipoprotein Receptor Expression by mRNA Stabilization and Reduces Plasma Low-Density Lipoprotein Cholesterol in Mice

The expression of Hu antigen R an mRNA-stabilizing factor increased during OCA treatment, but not affected expressions of mRNA degradation factors hnRNPD or ZFP36L1 in terms of mRNA degradation factors, according to a profile of known LDLR mRNA-binding proteins. Significant rises in hepatic bioluminescence signals, Luc-untranslated region chimeric mRNA levels, and endogenous LDLR protein abundance were observed in OCA-treated transgenic mice, as well as rises in hepatic HuR mRNA and protein levels. FXR activation by OCA and other agonists was demonstrated in human primary hepatiocytes and HepG2 cells, and in mouse primary hepatocytes and HepG2 cells, which caused the same inducing effect on LDLR expression as in normolipidemic mice's liver. Conclusions: Our research was the first to show that FXR activation raises LDLR expression in liver tissue by a post-transcriptional regulatory mechanism involving LDLR mRNA-stabilizing factor HuR.

Source link: https://doi.org/10.1161/atvbaha.118.311122


Detection and Evaluation of process related impurities in Obeticholic Acid Drug material using HPLC Method

Primary biliary cirrhosis and cholangitis are being treated with Obeticholic acid. An HPLC with refractive index detection for eight process related substances of OBE was designed and tested for use in quality assurance laboratories for regular analysis. At a 45:55 percent ratio, 0. 01N potassium phosphate buffer and acetonitrile were used in the mobile phase.

Source link: https://doi.org/10.52711/0974-360x.2021.00977


Obeticholic Acid Protects Against Cholestatic Liver Injury Induced by Lithocholic Acid via Inhibiting Exogenous Cell Apoptosis

Abstract Background: Lithocholic acid is one of endogenous bile acids, and it is a common measure of primary biliary cholangitis. This bile acid regulation effect of OCA was mainly due to increasing the expression of bile acid efflux transporters, bile salt export pump, multidrug resistant associated protein 2, MRP3, and multi-drug resistance 3 rather than bile acid synthesis inhibition. In addition, it was discovered that OCA reduced the activation and expression of Caspase 8/3 signaling pathway in LCA's cholestatic model without the change of p-MKL and BAX. And the inhibition of Caspase 8/3 signaling pathway was dependent on the activation of Farnesoid X receptor to impede Caspase 8 cleavage's formation of a complex complex. Conclusions: According to this research, OCA ameliorated LCA-induced cholestatic liver injury by FXR-induced exogenous cell apoptosis, which provided fresh evidence for the use of OCA to raise PBC in clinical trials.

Source link: https://doi.org/10.21203/rs.3.rs-1116597/v1


Obeticholic acid and INT-767 modulate collagen deposition in a NASH in vitro model

In a well-established co-culture NASH scheme, we investigated in vitro the effects of FXR agonist obeticholic acid and the dual FXR/TGR5 agonist INT-767. Human hepatoma and hepatic stellate cells were exposed to free fatty acids alone or in combination with OCA or INT-767. At 24, 96 and 144 hours, the mRNA expression of HSCs activation markers and FXR engagement was tested. Both collagen reduction agents, Tropifexor and Selonsertib were also efficient in collagen reduction, but MMP2-9 showed no change in modulation.

Source link: https://doi.org/10.1038/s41598-020-58562-x


miR-21 ablation and obeticholic acid ameliorate nonalcoholic steatohepatitis in mice

Here we demonstrate that, in a typical example of NASH-associated liver injury, microRNA-21 ablation results in a gradual decline in steatosis, inflammation, and lipoapoptosis with decreased fibrosis. MiR-21 levels in both liver and muscle increased in both liver and muscle, as well as decreasing expression of peroxisome proliferator-activated receptor, a key MiR-21 target. Mice supplemented with farnesoid X receptor antagonist obeticholic acid, inflammation, metabolic stress, and cholesterol levels were not present in mice fed the FF diet supplemented with farnesoid agonist obeticholic acid. The miR-21/PPAR axis was found amplified in liver and muscle biopsies, as well as in serum of NAFLD patients, co-establishing its involvement in the development of the metabolic syndrome. Our findings show the therapeutic value of nuclear receptor multi-targeting therapies for NAFLD by revealing that miR-21 abrogation, as well as FXR activation by OCA, has significant improvements whole body metabolic parameters in NASH.

Source link: https://doi.org/10.1038/cddis.2017.172


Obeticholic Acid Improves Aminotransferases Early during Treatment in Patients with Primary Biliary Cholangitis Not Responding to Ursodeoxycholic Acid: A Study in Clinical Practice

Obeticholic acid promotes cholestasis and is generally well tolerated in patients with primary biliary cholangitis that is not responding or intolerant to ursodeoxycholic acid. This review reviewed the effectiveness of OCA therapy on both alkaline phosphatase and alanine aminotransferase in clinical practice, finding new healthy ranges for aminotransferases in this review. Fifteen PBC patients, non-responders to UDCA, were tested at baseline and after OCA therapy for serial measurement of cholestasis indexes and ALT, which were then analyzed using updated normal ranges. ALT levels were normal in 6. 7% of patients at baseline and in 33. 3% of patients after 18 months of therapy using new normal ranges. With a decrease in necro-inflammatory activity even before the rise in cholestasis, OCA therapy improves cholestesis and, also, indicators of hepatocyte necrosis, as well as indices of hepatocyte necrosis, as well as indices of hepatocyte necrosis. A useful way to determine hepatic histological condition and its response with OCA therapy can be a recalibrated healthy range for aminotransferases.

Source link: https://doi.org/10.3390/immuno1040033


Obeticholic acid ameliorates hepatorenal syndrome in ascitic cirrhotic rats by down-regulating the renal 8-iso-PGF2α-activated COX-TXA2 pathway

In ascitic cirrhotic rats with hepatorenal syndrome, the present study examines the possibility of chronic therapy with the Foresaid X receptor agonist obeticholic acid, which delays oxidative stress-related pathogenesis, and was published 6 weeks after bile duct ligation. Methods: In ascitic BDL and sham rats receiving 2-weeks of either vehicle or OCA treatments, NRK-52E cells, rat kidney tubular epithelial cells, were measured. BDL-OCA rats' chronic OCA therapy improved portal hypertension, glomerular filtration rate, urine production, and renal blood flow; reduced ascites, renal vascular resistance, serum creatinine, and the releasing of renal tubular damage markers such as urinary neutrophil gelocalin and kidney injury moleculae-1. Conclusions: Our research shows that chronic OCA therapy can reduce the HRS in ascitic cirrhotic rats by the inhibition of renal 8-iso-PGF2 production and down-regulation of the COX-TXA2 pathway.

Source link: https://doi.org/10.1042/cs20200452

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions