Isoquercitrin attenuates the progression of non-alcoholic steatohepatitis in mice by modulating galectin-3-mediated insulin resistance and lipid metabolism.

Background: Non-alcoholic steatohepatitis (NASH) is a global health problem with no effective treatment. Isoquercitrin (IQ) alters hepatic lipid metabolism and inhibits adipocyte differentiation. The underlying regulatory mechanisms of IQ in regulating insulin resistance (IR) and lipid metabolism remain unclear.

Quercetin 7-rhamnoside protects against alpha-naphthylisothiocyanate (ANIT)-induced in cholestatic hepatitis rats by improving biliary excretion and inhibiting inflammatory responses.

To explore the pharmacological effects and molecular mechanism of quercetin 7-rhamnoside (Q7R) in the treatment of cholestatic hepatitis induced by alpha-naphthylisothiocyanate (ANIT). ANIT-induced cholestatic hepatitis rat model was used to investigate the hepatoprotective effects of three different doses of Q7R (1.25 mg/kg; 2.

The combination of and herb-pair alleviated inflammation in liver fibrosis.

To explore the active components and epigenetic regulation mechanism underlying the anti-inflammatory effects of and herb-pair (LFP) in carbon tetrachloride (CCl)-induced rat liver fibrosis. The main active ingredients and disease-related gene targets of LFP were determined using TCMSP and UniProt, and liver fibrosis disease targets were screened in the GeneCards database. A network was constructed with Cytoscape 3.

Evaluation of lipid metabolism imbalance in HIV-infected patients with metabolic disorders using high-performance liquid chromatography-tandem mass spectrometry.

Human immunodeficiency virus (HIV) infection and highly active antiretroviral therapy use are associated with the disruption of lipid and glucose metabolism. Herein, a sensitive and robust high-performance liquid chromatography-tandem mass spectrometry method for the quantitation of lysophosphatidylcholines (LPCs) and acylcarnitines (ACs) in human blood serum was developed and validated to investigate them as markers of metabolic disorders in HIV-infected patients. Under optimal extraction and detection conditions, the lower limits of quantification reached 5 ng/mL (LPCs) and 0.

Delivery of Rapamycin by Liposomes Synergistically Enhances the Chemotherapy Effect of 5-Fluorouracil on Colorectal Cancer.

Background: Rapamycin is a promising agent for treating tumors, but clinical applications of rapamycin are limited due to its poor water solubility and low bioavailability. This paper constructs a liposome delivery system for rapamycin to improve the effect in treating colorectal cancer.

Methods: We prepared the rapamycin liposomes using the ethanol injection method.

T-cell death-associated gene 8 accelerates atherosclerosis by promoting vascular smooth muscle cell proliferation and migration.

Background And Aims: Atherosclerosis is a serious cardiovascular disease, featuring inflammation, abnormal proliferation and migration of vascular smooth muscle cells (VSMCs). During atherosclerosis, inflammation may cause low pH. T-cell death-associated gene 8 (Tdag8) is a proton-sensing receptor, however, the role of Tdag8 in VSMCs remains unknown.

Combinational applicaton of silybin and tangeretin attenuates the progression of non-alcoholic steatohepatitis (NASH) in mice via modulating lipid metabolism.

Silybin (SB) is widely used to treat chronic liver diseases, especially this compound is much efficient for the treatments of alcoholic and non-alcoholic steatohepatitis (NASH). However, low bioavailability seriously limits wide-application of SB in biomedical niche. Prior to this study, we found that tangeretin (TG) could remarkably increase the bioavailability of SB by the inhibition of efflux transporters, which encourges us to therapeutical discovery of SB and TG combitional use against NASH.

Identification of a new inhibitor of KRAS-PDEδ interaction targeting KRAS mutant nonsmall cell lung cancer.

Oncogenic KRAS is considered a promising target for anti-cancer therapy. However, direct pharmacological strategies targeting KRAS-driven cancers remained unavailable. The prenyl-binding protein PDEδ, a transporter of KRAS, has been identified as a potential target for pharmacological inhibitor by selectively binding to its prenyl-binding pocket, impairing oncogenic KRAS signaling pathway.

Baicalein Enhances the Oral Bioavailability and Hepatoprotective Effects of Silybin Through the Inhibition of Efflux Transporters BCRP and MRP2.

Although hepatoprotective properties of silybin are well documented, the clinical therapeutic efficacy is limited by its low bioavailability due to absorption rates, extensive phase II metabolism, and biliary excretion. As our previous study indicated that metabolic enzymes may have limited effects on the pharmacokinetic (PK) behavior of silymarin, here, we intended to increase the oral bioavailability and bio-efficacy of silybin through the inhibition of active efflux. In Caco-2 and transfected MDCKII cell models, flavone baicalein significantly inhibited the efflux of silybin as a BCRP and MRP2 inhibitor.

Palmatine ameliorated murine colitis by suppressing tryptophan metabolism and regulating gut microbiota.

Inflammatory bowel disease (IBD), majorly include Crohn's disease (CD) and ulcerative colitis (UC), is chronic and relapsing inflammatory disorders of the gastrointestinal tract, which treatment options remain limited. Here we examined the therapeutic effects of an isoquinoline alkaloid, Palmatine (Pal), on mice experimental colitis induced by dextran sulfate sodium (DSS) and explored underlying mechanisms. Colitis was induced in BALB/c mice by administering 3% DSS in drinking water for 7 days.

Role of tangeretin as a potential bioavailability enhancer for silybin: Pharmacokinetic and pharmacological studies.

Biological responses of a variety of naturally occurring compounds in vivo were restrained by their poor oral bioavailability. Silybin, as one of the active ingredients of silymarin, has presented promising bioactivity for the treatment of chronic liver diseases and cancer. However, its exposure in body was limited.

Suppression of Lipogenesis via Reactive Oxygen Species-AMPK Signaling for Treating Malignant and Proliferative Diseases.

Aims: Systemic diseases often have common characteristics. The aim of this study was to investigate the feasibility of targeting common pathological metabolism to inhibit the progression of malignant and proliferative diseases.

Results: Gefitinib-resistant (G-R) nonsmall-cell lung cancer (NSCLC) and rheumatoid arthritis (RA) were studied as conditions representative of malignant and proliferative diseases, respectively.

Tangeretin, a citrus pentamethoxyflavone, antagonizes ABCB1-mediated multidrug resistance by inhibiting its transport function.

Multidrug resistance (MDR) and tumor metastasis are the main causes of chemotherapeutic treatment failure and mortality in cancer patients. In this study, at achievable nontoxic plasma concentrations, citrus flavonoid tangeretin has been shown to reverse ABCB1-mediated cancer resistance to a variety of chemotherapeutic agents effectively. Co-treatment of cells with tangeretin and paclitaxel activated apoptosis as well as arrested cell cycle at G2/M-phase.

Quantitative evaluation of berberine subcellular distribution and cellular accumulation in non-small cell lung cancer cells by UPLC-MS/MS.

Berberine, an isoquinoline alkaloid, has been demonstrated to be a safe anti-cancer agent with multiple effects on mitochondria. Intracellular concentration and distribution around the targeting sites are determinants of efficacy, but subcellular distribution of berberine has not been fully elucidated yet, which relies on the sensitive and robustness assay. In this study, a sensitive and robust UPLC-MS/MS method has been developed and validated with optimized extraction solvents and detection conditions.

[Synthesis, structure characterization and anti-tumor activity of lanthanide complex Ln[ (Phen)2 (5-Fu)3 (NO3) (NO3 )2].

Aim: To study the biochemistry of lanthanides, the cooperative action of inorganic and organic anti-tumor drugs.

Methods: A series of rare earth complexes were synthesized with Ln(NO3) 6H2O, Phen and 5-Fu. Their anti-tumor activity was measured by the improved MTT, SRB methods.