Ursolic Acid, a Novel Liver X Receptor α (LXRα) Antagonist Inhibiting Ligand-Induced Nonalcoholic Fatty Liver and Drug-Induced Lipogenesis.

Nonalcoholic fatty liver disease (NAFLD) is a very common liver disease, and its incidence has significantly increased worldwide. The liver X receptor α (LXRα) is a multifunctional nuclear receptor that controls lipid homeostasis. Inhibition of LXRα transactivation may be beneficial for NAFLD and hyperlipidemia treatment.

Modulation of pregnane X receptor (PXR) and constitutive androstane receptor (CAR) activation by ursolic acid (UA) attenuates rifampin-isoniazid cytotoxicity.

Background: Interactions between transcriptional inducers of cytochrome P450 (CYP450) enzymes and therapeutic drugs may be prevented by antagonizing the activation of a nuclear receptor (NR), pregnane X receptor (PXR, NR1I2), thus improving therapeutic efficacy.

Purpose: In the present study, we aim to identify that ursolic acid (UA), a widely distributed pentacyclic triterpene, may act as an effective antagonist of PXR and its sister NR receptor, constitutive androstane receptor (CAR, NR1I3).

Methods: The hepatocellular carcinoma cell line, HepG2, was used to evaluate the promoter activity of PXR and CAR target genes, CYP3A4 and CYP2B6, respectively.

Tamoxifen Treatment and the Reduced Risk of Hyperlipidemia in Asian Patients With Breast Cancer: A Population-Based Cohort Study.

Purpose: The association between tamoxifen (TMX) treatment and the risk of developing hyperlipidemia remains unclear.

Methods: The records of 41,726 patients with breast cancer (28,266 received TMX and 13,460 did not) were obtained from the Taiwan National Health Insurance Research Database for the period from January 2000 to December 2008. Three-fold women without breast cancer were the control group (N = 125, 178).

Antiarrhythmic agents and the risk of malignant neoplasm of liver and intrahepatic bile ducts.

Background: The objective of this study was to determine the association between the use of antiarrhythmic agents and the risk of malignant neoplasm of liver and intrahepatic bile ducts (MNLIHD).

Methods: We used the research database of the Taiwan National Health Insurance Program to conduct a population-based, case-control study. We identified 9944 patients with antiarrhythmic history who were first diagnosed as having MNLIHD between 2005 and 2010.

Increased risk of deep vein thrombosis and pulmonary thromboembolism in patients with organophosphate intoxication: a nationwide prospective cohort study.

Organophosphate (OP) poisoning is a critical cause of morbidity and mortality worldwide. We conducted a nationwide longitudinal cohort study to investigate the development of deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE) among patients admitted with OP intoxication.We identified patients with OP intoxication by using the Taiwan National Health Insurance Research Database and enrolled 9223 patients who were hospitalized for OP intoxication between 2000 and 2011.

Inhibition of cytochrome P450 2C9 expression and activity in vitro by allyl isothiocyanate.

The growing interest in the use of natural herbal products and dietary supplements to treat and prevent diseases raises the question of medicinal drug safety. Allyl isothiocyanate, a hydrolysis product of a glucosinolate, sinigrin, has multiple beneficial properties, and based on this fact, allyl isothiocyanate-containing dietary supplements have been developed. To date, no studies of the effects of this compound on the cytochrome P450 2C9 have been reported.

Allyl isothiocyanate (AITC) inhibits pregnane X receptor (PXR) and constitutive androstane receptor (CAR) activation and protects against acetaminophen- and amiodarone-induced cytotoxicity.

Antagonizing the action of the pregnane X receptor (PXR) may have important clinical implications for preventing inducer-drug interactions and improving therapeutic efficacy. We identified a widely distributed isothiocyanate, allyl isothiocyanate (AITC), which acts as an effective antagonist of the nuclear receptor pregnane X receptor (PXR, NR1I2) and constitutive androstane receptor (CAR, NR1I3). HepG2 cells were used to assay reporter function, mRNA levels, and protein expression.