Pharmacokinetics and tissue distribution analysis of ginsenoside Rh in rats using a novel LC-MS/MS quantification strategy.

Introduction: Ginsenoside Rh3 (GRh), a rare ginsenoside, demonstrates diverse pharmacological activities ; however, the lack of pharmacokinetic and tissue distribution data has limited its translation to applications. This study aimed to develop and validate a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying GRh in rat biological matrices and to characterize its pharmacokinetic profile and tissue distribution following oral administration.

Methods: A validated LC-MS/MS method was established for the quantification of GRh in rat plasma and tissues.

Lead Optimization of Butyrolactone I as an Orally Bioavailable Antiallergic Agent Targeting FcγRIIB.

Food allergy (FA) poses a growing global food safety concern, yet no effective cure exists in clinics. Previously, we discovered a potent antifood allergy compound, butyrolactone I (BTL-I, ), from the deep sea. Unfortunately, it has a very low exposure and poor pharmacokinetic (PK) profile in rats.

Fibroblast activation protein alpha: Comprehensive detection methods for drug target and tumor marker.

Fibroblast activation protein alpha (FAP-α, EC3.4.2.

Research Progress on Dipeptidyl Peptidase Family: Structure, Function and Xenobiotic Metabolism.

Prolyl-specific peptidases or proteases, including Dipeptidyl Peptidase 2, 4, 6, 8, 9, 10, Fibroblast Activation Protein, prolyl endopeptidase, and prolyl carboxypeptidase, belong to the dipeptidyl peptidase family. In human physiology and anatomy, they have homology amino acid sequences and similarities in the structure; however, they have distinct functions and play different roles. Some of them also play important roles in the metabolism of drugs containing endogenous peptides, xenobiotics containing peptides, and exogenous peptides.

A high-throughput screening assay for dipeptidyl peptidase-IV inhibitors using human plasma.

Dipeptidyl peptidase-IV (DPP-IV) plays a critical role in glucose metabolism and has become an important target for type 2 diabetes mellitus. We previously reported a two-photon fluorescent probe glycyl-prolyl-N-butyl-4-amino-1,8-naphthalimide (GP-BAN) for DPP-IV detection with high specificity and sensitivity. In this study, a high-throughput screening (HTS) method for DPP-IV inhibitors using human plasma as the enzyme source was established and optimized.

Discovery of pyrazolones as novel carboxylesterase 2 inhibitors that potently inhibit the adipogenesis in cells.

Carboxylesterase 2 (CES2) is one of the most important Phase I drug metabolizing enzymes in the carboxylesterase family. It plays crucial roles in the bioavailability of oral ester prodrugs and the therapeutic effect of some anticancer drugs such as irinotecan (CPT11) and capecitabine. In addition to the well-known roles of CES2 in xenobiotic metabolism, the enzyme also participates in endogenous metabolism and the production of lipids.

Design, Synthesis, and Structure-Activity Relationship Study of Pyrazolones as Potent Inhibitors of Pancreatic Lipase.

Pancreatic lipase (PL), a key target for the prevention and treatment of obesity, plays crucial roles in the hydrolysis and absorption of in dietary fat. In this study, a series of pyrazolones was synthesized, and their inhibitory effects against PL were assayed by using 4-methylumbelliferyl oleate (4-MUO) as optical substrate for PL. Comprehensive structure-activity relationship analysis of these pyrazolones led us to design and synthesize a novel compound P32 (5-(naphthalen-2-yl)-2-phenyl-4-(thiophen-2-ylmethyl)-2,4-dihydro-3H-pyrazol-3-one) as a potent mixed-competitive inhibitor of PL (IC =0.

Discovery of natural alkaloids as potent and selective inhibitors against human carboxylesterase 2.

Human Carboxylesterase 2A (hCES2A), one of the most important serine hydrolases, plays crucial roles in the hydrolysis and the metabolic activation of a wide range of esters and amides. Increasing evidence has indicated that potent inhibition on intestinal hCES2A may reduce the excessive accumulation of SN-38 (the hydrolytic metabolite of irinotecan with potent cytotoxicity) in the intestinal tract and thereby alleviate the intestinal toxicity triggered by irinotecan. In this study, more than sixty natural alkaloids have been collected and their inhibitory effects against hCES2A are assayed using a fluorescence-based biochemical assay.

Pentacyclic triterpenoid acids in Styrax as potent and highly specific inhibitors against human carboxylesterase 1A.

Human carboxylesterase 1A1 (hCES1A) is a promising target for the treatment of hyperlipidemia and obesity-associated metabolic diseases. To date, the highly specific and efficacious hCES1A inhibitors are rarely reported. This study aims to find potent and highly specific hCES1A inhibitors from herbs, and to investigate their inhibitory mechanisms.

Theophylline Acetaldehyde as the Initial Product in Doxophylline Metabolism in Human Liver.

Doxophylline (DOXO) and theophylline are widely used as bronchodilators for treating asthma and chronic obstructive pulmonary disease, and DOXO has a better safety profile than theophylline. How DOXO's metabolism and disposition affect its antiasthmatic efficacy and safety remains to be explored. In this study, the metabolites of DOXO were characterized.

Catalyst-free visible-light-induced condensation to synthesize bis(indolyl)methanes and biological activity evaluation of them as potent human carboxylesterase 2 inhibitors.

A mild strategy for visible-light-induced synthesis of bis(indolyl)methanes was developed using aromatic aldehydes and indole as substrates. This reaction could be performed at room temperature under catalyst- and additive-free conditions to synthesize a series of bis(indolyl)methanes in good to excellent yields. In addition, all synthesized bis(indolyl)methanes together with β-substituted indole derivatives synthesized according to our previous work, were evaluated for their inhibitory effect against human carboxylesterase (CES1 and CES2).