A novel strategy for identifying hepatotoxic constituents in traditional Chinese medicine using dose-normalized intracellular accumulation as a cytotoxicity indicator: a case study of Jinlingzi San.

Introduction: Herb-induced liver injury associated with traditional Chinese medicine (TCM) has increasingly attracted scientific attention. However, the rapid and effective methods for elucidating the material basis of hepatotoxicity in TCM are still lacking. This study developed a strategy based on the use of dose-normalized intracellular accumulation as a cytotoxicity indicator to identify key hepatotoxic components in TCM.

Transplacental transfer of metformin and interaction of metformin with the uptake transporters of placental trophoblast cells.

Metformin is among the most widely prescribed antidiabetic agents, with increasingly accepted by women with gestational diabetes mellitus due to its more convenient administration. Knowledge of the interaction of metformin with the uptake transporters of placental trophoblast cells is important for robust evaluation of the safety usage in pregnancy. Herein, the pregnancy pharmacokinetic study and distribution in placenta and fetus study were employed and showed that metformin could distribute quickly into the placenta and fetus, and the content of MET in the placenta was obvious higher than that in fetus.

Deglycosylated azithromycin alleviates cisplatin-evoked constipation in mice by altering host metabolome and gut microbiota composition.

Introduction: Chemotherapy induced constipation (CIC) is a gastrointestinal side effect that occurs in patients receiving chemotherapy, which can further deteriorate the living quality of cancer patients. Deglycosylated azithromycin (Deg-AZM), a newly developed Class I drug with good therapeutic effects on chronic constipation, has been approved for clinical trials in 2024. However, it is unclear whether Deg-AZM has any impact on gut microbiota of CIC mice.

Bergenin and vitexin delivery platform using mouse lung fibroblasts-derived exosomes for bleomycin-induced pulmonary fibrosis therapy.

Idiopathic pulmonary fibrosis (IPF) is characterized by symptoms such as shortness of breath, persistent dry cough, and hypoxemia. The disease can progress rapidly, often leading to respiratory failure. Given its complex and multifactorial nature, pulmonary fibrosis involves multiple pathological progress, such as inflammation, oxidative stress, and fibroblast activation.

Lenalidomide attenuates cardiac fibrosis and inflammation induced by β-adrenergic receptor activation.

β-Adrenergic receptor (β-AR) excessive activation assumes a vital role in various cardiovascular diseases and mediates cardiac fibrosis and cardiac inflammation. Lenalidomide (Len) has shown anti-fibrosis effects in diverse fibrotic diseases. However, it is unclear whether and how Len suppresses cardiac fibrosis and cardiac inflammation triggered by β-AR overactivation.

PAR1 inhibition sensitizes HPV-negative HNSCC cells to ferroptosis through inhibition of the STAT3-mediated regulation of iron and lipid metabolic pathways.

Ferroptosis, a cell death mechanism characterized by the accumulation of lipid peroxides and subsequent membrane disruption, is emerging as a promising strategy for cancer treatment. However, many tumors, including head and neck squamous cell carcinoma (HNSCC), show resistance to ferroptosis, which reduces its therapeutic effect. Protease-activated receptors (PARs) are highly expressed in many tumors and are closely associated with tumor progression.

Formononetin-Loaded PLGA Large Porous Microparticles via Intratracheal Instillation for Bleomycin-Induced Pulmonary Fibrosis Treatment.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease of unknown cause, with few effective therapies available and high mortality rates. Our preceding research indicated that formononetin (FMN) could improve the symptoms of the bleomycin-induced pulmonary fibrosis and be a promising drug against IPF. In this study, an inhalable formononetin-loaded poly(lactic-co-glycolic) acid (PLGA) large porous microspheres (FMN-PLGA-MSs) was prepared by the method of emulsion solvent evaporation.

Treatment of Bleomycin-induced Pulmonary Fibrosis by Intratracheal Instillation Administration of Ellagic Acid-Loaded Chitosan Nanoparticles.

Idiopathic Pulmonary Fibrosis (IPF) is a rare and serious chronic interstitial lung disease that may endanger the lives of patients. The median survival time of patients with idiopathic pulmonary fibrosis is short, and the mortality rate is higher than that of many types of cancer. At present, pirfenidone (PFD) and nintedanib (NDNB) have been approved by FDA for IPF, but they can only delay the process of pulmonary fibrosis and cannot cure the disease.

Daidzein alleviates skin fibrosis by suppressing TGF-β1 signaling pathway via targeting PKM2.

Skin fibrosis including keloids, which are characterized including excessive deposition, abnormal proliferation, aggressiveness, and migration of the extracellular matrix of dermal fibroblasts. TGF-β signaling is a classical pro-fibrotic pathway, and it plays a crucial part in the occurrence and progression of skin fibrosis. Daidzein (Dai), an isoflavone compound, has been proved to possess anti-fibrosis effect by TGF-β signaling in various inflammatory and fibrotic diseases.

Macrophage membrane entrapped rapamycin-loaded TPGS/F127 micelles through intratracheal instillation for enhanced drug delivery and therapy to lung cancer with pulmonary fibrosis.

Purpose: Patients with pulmonary fibrosis are prone to developing lung cancer. Pulmonary fibrosis and lung cancer have many common pathogenic factors and similar pathological features. For patients with IPF combined with lung cancer, there is currently no better treatment method available now.

Miglustat ameliorates isoproterenol-induced cardiac fibrosis via targeting UGCG.

Background: Cardiac fibrosis is significant global health problem, which is associated with numerous cardiovascular diseases, and ultimately leads to the progression to heart failure. β-adrenergic receptor (β-AR) overactivation play a role in the development of cardiac fibrosis. Miglustat (Mig) has shown anti-fibrosis effects in multiple fibrotic diseases.

The metabolic pathway of Deg-AZM and investigations into the contribution of drug metabolizing enzymes and drug transporters in the drug interactions of Deg-AZM, a clinical-stage new transgelin agonist.

Introduction: Deglycosylated azithromycin (Deg-AZM), a new transgelin agonist with positive therapeutic effects on slow transit constipation, has been approved for clinical trials in 2024. This work investigated the drug metabolism and transport of Deg-AZM to provide research data for further development of Deg-AZM.

Methods: A combination of UPLC-QTOF-MS was used to obtain metabolite spectra of Deg-AZM in plasma, urine, feces and bile.

PK-PD relationship of poorly absorbable active ingredients from traditional Chinese medicines explaining by metabolic enzyme of gut microbiota: A case study of Dehydrocorydaline.

Many active ingredients in traditional Chinese medicines generally have the characteristic of poor oral absorption but definite efficacy. It is necessary to establish a comprehensive technical system to explain the "PK-PD relationship" of them. Dehydrocorydaline (DHC), the quality control component in the Chinese patent drug "Kedaling Tablets", has poor oral absorption but clear efficacy for coronary heart disease.

Preclinical pharmacokinetic studies and prediction of human PK profiles for Deg-AZM, a clinical-stage new transgelin agonist.

Introduction: Deglycosylated azithromycin (Deg-AZM), a newly developed Class I drug with good therapeutic effects on slow transit constipation, is a small-molecule transgelin agonist that has been approved for clinical trials in 2024. The preclinical pharmacokinetic profile of Deg-AZM was investigated to support further development.

Methods: A LC-MS/MS method was established and validated to detected the concentration of Deg-AZM in various biological samples.

Iron-Catalyzed C-H Arylphosphorylation of Quinoxalines.

A one-pot strategy for iron-catalyzed C2,3-H arylphosphorylation of electron-deficient quinoxalines with phosphines and aryl compounds is reported. The proposed method features the use of non-noble metal catalysts, the capacity of utilizing multiple aryl compounds as substrates, the simultaneous formation of C-P and C-C bonds in one pot, the simplicity of its operation, the mildness of the reaction conditions, and its compatibility with a wide range of substrates. Moreover, it offers a practical route for direct access to 2-aryl-3-phosphino -heteroarenes, a class of potential cyclometalated C^N and N^P bidentate ligands that are difficult to prepare with existing C(sp)-H functionalization methods.

Baricitinib alleviates cardiac fibrosis and inflammation induced by chronic sympathetic activation.

Cardiac fibrosis is characterized by the over-proliferation, over-transdifferentiation and over-deposition of extracellular matrix (ECM) of cardiac fibroblasts (CFs). Cardiac sympathetic activation is one of the leading causes of myocardial fibrosis. Meanwhile, cardiac fibrosis is often together with cardiac inflammation, which accelerates fibrosis by mediating inflammatory cytokines secretion.

Iron-Catalyzed Friedel-Crafts-type 3,5-Diacylation of Indoles.

The exploration of remote functionalization of indoles is impeded by the inherently dominant reactivity intrinsic to the pyrrole moiety. Herein, we delineate a novel strategy facilitated by Lewis acid mediation, enabling the remote C-H functionalization, which culminates in the synthesis of an array of selectively functionalized indole derivatives, encompassing 3-trifluoroacetyl and 5-benzoyl motifs, utilizing trifluoroacetic anhydride and various acyl chlorides. Notably, the protocol exhibits versatility, as epitomized by the extension of C5-acylation to alkylation and sulfonation reactions.

Iodine-mediated oxidative triple functionalization of indolines with azoles and diazonium salts.

We report an innovative synthetic strategy for the generation of polysubstituted indoles from indolines, aryldiazonium salts, and azoles. The methodology encompasses an electrophilic substitution reaction affording C5-indoline intermediates which undergo an iodine-mediated oxidative transformation coupled with C-H functionalization to yield the indole derivatives.

Favipiravir ameliorates bleomycin-induced pulmonary fibrosis by reprogramming M1/M2 macrophage polarization.

Corona Virus Disease 2019 (COVID-19) is an infectious disease that seriously endangers human life and health. The pathological anatomy results of patients who died of the COVID-19 showed that there was an excessive inflammatory response in the lungs. It is also known that most of the COVID-19 infected patients will cause different degrees of lung damage after infection, and may have pulmonary fibrosis remaining after cure.

Systematic screening of hepatoprotective components from traditional Chinese medicine: Zuojin Pill as an example.

Ethnopharmacological Relevance: Zuojin Pill (ZJP), composed of Coptis chinensis Franch. and Euodia ruticarpa (A. Juss.

Imrecoxib attenuates bleomycin-induced pulmonary fibrosis in mice.

Idiopathic pulmonary fibrosis (IPF) is an incurable chronic progressive disease with a low survival rate and ineffective therapeutic options. We examined the effects of imrecoxib, a nonsteroidal anti-inflammatory drug, on experimental pulmonary fibrosis. The mouse IPF model was established by intratracheal instillation of bleomycin.