The potential effective components from Danlou tablet attenuates acute myocardial infarction by restoring ALOX12-mediated perturbed oxylipins.

Ethnopharmacological Relevance: Danlou Tablet (DLP) was developed from the "Gualou-Xiebai-Baijiu decoction", as documented in the "Synopsis of the Golden Chamber" by Dr. Zhongjing Zhang. It is widely used for clinical treatment of different degrees of coronary heart disease (CHD).

Farnesoid X receptor regulates CYP1A1 and CYP1B1 and estradiol metabolism in mouse and human cell lines.

Human CYP1A1 and CYP1B1 are two important enzymes for the hydroxylation of estrogens. In this study, we aimed to investigate the potential role for FXR receptor in the regulation of CYP1A1 and CYP1B1 expressions and activities. First, pharmacokinetic analysis was conducted in male wild-type and Fxr mice after intraperitoneal dosing of exogenous estradiol.

Co-exposure with Copper Alters the Uptake, Accumulation, Subcellular Distribution, and Biotransformation of Organophosphate Triesters in Rice ( L.).

This study investigated the uptake pathways, acropetal translocation, subcellular distribution, and biotransformation of OPEs by rice ( L.) after Cu exposure. The symplastic pathway was noted as the major pathway for the uptake of organophosphate triesters (tri-OPEs) and diesters (di-OPEs) by rice roots.

Deciphering the benefits and intensity levels of primary metabolites from Allium macrostemon Bunge and Allium chinense G. Don.

Background: Allii Macrostemonis Bulbus is also named Xiebai in China. It is an edible vegetable, and also a famous herb for treating coronary heart disease. Allium chinense G.

Evaluation of the anti-atherosclerotic effect for Allium macrostemon Bge. Polysaccharides and structural characterization of its a newly active fructan.

Allium Macrostemon Bge. (AMB) is a well-known homology of herbal medicine and food that has been extensively used for thousands of years to alleviate cardiovascular diseases. It contains a significant amount of polysaccharides, yet limited research exists on whether these polysaccharides are responsible for its cardiovascular protective effects.

Five-layer-funnel filtering mode discovers effective components of Chinese medicine formulas: Zhishi-Xiebai-Guizhi decoction as a case study.

Background: How to screen and identify the effective components in the complex substance system is one of the core issues in achieving the modernization of traditional Chinese medicine (TCM) formulas. However, it is still challenging to systematically screen out the effective components from the hundreds or thousands of components in a TCM formula.

Purpose: An innovative five-layer-funnel filtering mode stepwise integrating chemical profile, quantitative analysis, xenobiotic profile, network pharmacology and bioactivity evaluation was successfully presented to discover the effective components and implemented on a case study of Zhishi-Xiebai-Guizhi decoction (ZXG), a well-known TCM formula for coronary heart disease (CHD).

Nasal solitary chemosensory cells govern daily rhythm in mouse model of allergic rhinitis.

Background: While the daily rhythm of allergic rhinitis (AR) has long been recognized, the molecular mechanism underlying this phenomenon remains enigmatic.

Objective: We aimed to investigate the role of circadian clock in AR development and to clarify the mechanism by which the daily rhythm of AR is generated.

Methods: AR was induced in mice with ovalbumin.

Structural and in vivo-in vitro myocardial injury protection features of two novel polysaccharides from Allium macrostemon Bunge and Allium chinense G. Don.

This study aimed to investigate the structural characteristics, in vivo antiatherosclerosis activity, and in vitro myocardial injury protection effects of polysaccharides from Allium macrostemon Bunge and Allium chinense G. Don. Thus, crude polysaccharides of Allium macrostemon Bunge and Allium chinense G.

Deciphering the diurnal rhythm regulating mechanism of flavin-containing monooxygenase 3 in mouse liver.

Circadian genes play an important role in the field of drug metabolism. Flavin-containing monooxygenase 3 is a well-known phase I enzyme which participates in metabolism of many exogenous and endogenous substances, especially production of trimethylamine N-oxide. Here, we aimed to decipher diurnal rhythms of flavin-containing monooxygenase 3 expression and activity, and explore the regulation mechanism by clock genes.

Single injection by LC-ESI-MS/MS for simultaneous determination of organophosphate tri- and di-esters in plant tissue based on ultrasonic-assisted sequential extraction and single-step purification.

A novel methodology based on ultrasonic-assisted sequential extraction, dispersive-SPE purification, and single-injection on liquid chromatography-tandem mass spectrometry (LC-MS/MS) is proposed, for the first time, to simultaneously measure 14 tri-OPEs and 9 di-OPEs in plant tissues. The samples were successively ultrasonicated with a mixture of hexane:dichloromethane (1:1, v/v) and 8% acetic acid in acetonitrile for extracting tri- and di-OPEs purified with graphitized carbon black and quantitated on LC-MS/MS at the same time. The recoveries of targeted tri- and di-OPEs in the matrix spike ranged from 66% to 120% and 71% to 110% respectively.

A compounds annotation strategy using targeted molecular networking for offline two-dimensional liquid chromatography-mass spectrometry analysis: Yupingfeng as a case study.

Component overlapping and long-time consumption hinder the data processing of offline two-dimensional liquid chromatography mass spectrometry (offline 2D-LC MS) system. Although molecular networking has been commonly employed in data processing of liquid chromatography mass spectrometry (LC-MS), its application in offline 2D-LC MS is challenged by voluminous and redundant data. In light of this, for the first time, a data deduplication and visualization strategy combining hand-in-hand alignment with targeted molecular networking (TMN) for compounds annotation of offline 2D-LC MS data was developed and applied to the chemical profile of Yupingfeng (YPF), a classical traditional Chinese medicine (TCM) prescription, as a case study.

Reprogramming of rhythmic liver metabolism by intestinal clock.

Background & Aims: Temporal oscillations in intestinal nutrient processing and absorption are coordinated by the local clock, which leads to the hypothesis that the intestinal clock has major impacts on shaping peripheral rhythms via diurnal nutritional signals. Here, we investigate the role of the intestinal clock in controlling liver rhythmicity and metabolism.

Methods: Transcriptomic analysis, metabolomics, metabolic assays, histology, quantitative (q)PCR, and immunoblotting were performed with Bmal1-intestine-specific knockout (iKO), Rev-erba-iKO, and control mice.

Pharmacokinetics integrated with network pharmacology to clarify effective components and mechanism of Wendan decoction for the intervention of coronary heart disease.

Ethnopharmacological Relevance: Coronary heart disease (CHD), one of the leading causes of mortality in the world among chronic non-infectious diseases, is closely associated with atherosclerosis, which ultimately leads to myocardial injury. Wendan decoction (WDD), a classical famous formula, exerted an intervention effect on CHD according to numerous reports. However, the effective components and underlying mechanisms for the treatment of CHD have not been fully elucidated.

PER2 integrates circadian disruption and pituitary tumorigenesis.

The role of circadian clock in pituitary tumorigenesis remains elusive. Here we investigate whether and how circadian clock modulates the development of pituitary adenomas. We found altered expression of pituitary clock genes in patients with pituitary adenomas.

Analysis and subcellular distribution of organophosphate esters (OPEs) in rice tissues.

Recent studies have identified the ability of plants to uptake and translocate organophosphate esters (OPEs) within cells. In response to the increasing interest in OPEs and their occurrence in paddy fields and rice, the current study aimed to present an effective and sensitive GC-MS based methodology for quantitative determination of 11 OPEs with octanol-water coefficients ranging from 1.6 to 10.

Determination of polyoxymethylene-water partition coefficients for diverse organophosphate esters (OPEs) and prediction of the free-dissolved OPEs in OPE-contaminated soil.

Increasing attention on the estimation of bioavailability of organophosphate esters (OPEs) in soil or sediment has urged the development of techniques to measure soil-/sediment-associated porewater concentrations of OPEs. In this study, we investigated the sorption dynamics of 8 OPEs to polyoxymethylene (POM) spanning one order of magnitude of aqueous OPE concentrations and proposed POM-water partitioning coefficients (K) for OPEs. The results showed that the K values were mainly affected by the hydrophobicity of OPEs.

Cytochrome P450 metabolism studies of [6]-gingerol, [8]-gingerol, and [10]-gingerol by liver microsomes of humans and different species combined with expressed CYP enzymes.

Gingerols, mainly [6]-gingerol (6G), [8]-gingerol (8G), and [10]-gingerol (10G), are the functional and specific pungent phytochemicals in ginger. However, poor oral bioavailability limits their applications owing to extensive metabolism. The present study aims to characterize the cytochrome P450 (CYP) metabolic characteristics of 6G, 8G, and 10G by using pooled human liver microsomes (HLM), different animal liver microsomes, and the expressed CYP enzymes.

Development of a three-step-based novel strategy integrating DMPK with network pharmacology and bioactivity evaluation for the discovery of Q-markers of traditional Chinese medicine prescriptions: Danlou tablet as an example.

Background: Quality marker (Q-marker) serves an important role in promoting the standardization of the quality of traditional Chinese medicine (TCM) prescriptions. However, discovering comprehensive and representative Q-markers from TCM prescriptions composed of multiple components remains difficult.

Purpose: A three-step-based novel strategy integrating drug metabolism and pharmacokinetics (DMPK) with network pharmacology and bioactivity evaluation was proposed to discover the Q-markers and applied to a research example of Danlou tablet (DLT), a famous TCM prescription with remarkable and reliable clinical effects for coronary heart disease (CHD).

Metabolic profile and potential mechanisms of Wendan decoction on coronary heart disease by ultra-high-performance quadrupole time of flight-mass spectrometry combined with network pharmacology analysis.

Wendan decoction, a well-known classical traditional Chinese medicine prescription, has been widely used in the clinical application of coronary heart disease for thousands of years. However, due to a lack of research on the overall metabolism of Wendan decoction, the bioavailable components responsible for the therapeutic effects remain unclear, hindering the revelation of its mechanisms against coronary heart disease. Consequently, an efficient joint research pattern combined with characterization of the metabolic profile and network pharmacology analysis was proposed.

Inhibition of estrogen sulfation by Xian-Ling-Gu-Bao capsule.

Xian-Ling-Gu-Bao capsule (XLGB) is a widely prescribed traditional Chinese medicine used for the treatment of osteoporosis. However, it significantly elevates levels of serum estrogens. Here we aimed to assess the dominant contributors of sulfotransferase (SULT) enzymes to the sulfation of estrogens and identify the effective inhibitors of this pathway in XLGB.

Identification of naturally occurring inhibitors in Xian-Ling-Gu-Bao capsule against the glucuronidation of estrogens.

Xian-Ling-Gu-Bao (XLGB) capsule, a well-known traditional Chinese medicine prescription, is widely used for the treatment of osteoporosis. It could significantly increase the levels of estrogen in ovariectomized rats and mice. However, this working mechanism has not been well elucidated.

Population Pharmacokinetics of Mycophenolic Acid in Renal Transplant Patients: A Comparison of the Early and Stable Posttransplant Stages.

Mycophenolic acid (MPA) is an antimetabolic immunosuppressive drug widely used in solid organ transplantation and autoimmune diseases. Pharmacokinetics (PK) of MPA demonstrates high inter- and intra-variability. The aim of this study was to compare the population PK properties of MPA in adult renal transplant patients in the early and stable post-transplant stages and to simulate an optimal dosing regimen for patients at different stages.

Dose Optimisation of Posaconazole and Therapeutic Drug Monitoring in Pediatric Patients.

Experience in the clinical use of posaconazole (PCZ) in pediatric patients is limited, and no specific dose recommendations exist. This study aimed to investigate an appropriate dosing regimen, and assess the exposure-response relationships of PCZ in children. We reviewed the medical records of inpatients aged <18 years who subjected to PCZ concentrations monitoring.