Excessive exercise makes the body consume more oxygen and produce excessive free radicals. The increased free radicals lead to oxidative stress injury and dysfunctions in liver tissue. Our previous study showed that Anwulignan, an active monomer in Schisandra sphenanthera Rehd. et Wils. (Schisandra), had anti-fatigue effects in mice. However, whether Anwulignan has a protective effect on liver damage in exhausted mice and the mechanism underlying remain elusive. An exhaustive swimming mice model was used to study the protective effects of Anwulignan on liver damage. The involvement of the nuclear factor (erythroid-derived 2)-like 2 (NRF2)/antioxidant responsive element (ARE) antioxidative pathway in Anwulignan-mediated anti-fatigue was analyzed using NRF2 inhibitor ML385 in HepG2 cells treated with H₂O₂. Animal welfare and experimental process follow the regulations of the Animal Ethics Committee of Beihua University. Anwulignan significantly lowered serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, reduced liver tissue damages, increased superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT), and decreased malondialdehyde (MDA) and 8-hydroxy-2 deoxyguanosine (8-OHdG) contents in the livers of exhausted mice, demonstrating a strong antioxidant effect. Furthermore, Anwulignan up-regulated the NRF2/ARE antioxidant pathway in liver tissue, increased B-cell lymphoma 2 (Bcl-2) expression, and decreased Bcl-2-like protein 4 (Bax) and caspase3 expression. In HepG2 cells, Anwulignan improved the cell viability and SOD activity, reduced reactive oxygen species (ROS) and MDA contents, up-regulated the expression of the NRF2/ARE signaling pathway and Bcl-2, and decreased Bax and caspase3 expression in the cells. Furthermore, pretreated ML385 partly abolished all these effects of Anwulignan. Anwulignan protects the liver from damage in the exhausted mice by its antioxidant effects and related to its activation of the NRF2 pathway.

This study investigates the protective role of IMM-H004, a novel coumarin derivative, on hepatic ischemia-reperfusion injury (HIRI) in mice. All animal experiments in this paper have been approved by the Ethics Committee of Institute of Materia Medica, Chinese Academy of Medical Sciences. The experimental animals were divided into three groups, including sham group, model group, and IMM-H004 treatment group. Serum biochemical indicators were detected and H&E staining was used to assess liver damage. Real-time quantitative PCR (qPCR) was performed to analysis the mRNA content of inflammatory factors. Immunohistochemistry and immunofluorescence were used to observe neutrophil infiltration. Western blot was used to examine the protein levels of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), cysteinyl aspartate specific proteinase-1 (caspase-1), and interleukin-1β (IL-1β). The results showed that IMM-H004 could significantly reduce the serum levels of alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH). H&E results showed IMM-H004 could alleviate liver damage caused by HIRI. The mRNA expression of tumor necrosis factor-α (TNF-α), IL-1β, and interleukin-6 (IL-6) were decreased by IMM-H004 administration. Meanwhile, IMM-H004 could markedly inhibit neutrophil infiltration. Furthermore, IMM-H004 could significantly down-regulate the protein expression of NLRP3, ASC, caspase-1, and IL-1β, inhibiting the activation of NLRP3 inflammasome pathway. Our results confirmed that IMM-H004 could protect mice from HIRI and provide a theoretical foundation for IMM-H004 application for treating HIRI.

Hepatocellular carcinoma (HCC) is a serious threat for human health, the incidence of HCC in China accounts for more than 50% worldwide. There is an urgent need to develop novel anticancer agents for the treatment of HCC patients. Here we characterized the inhibitory effect and the molecular mechanism of protopine on HCC cancer cells. The results of a CCK-8 assay indicated that protopine displays anticancer activities on HCC cells. Flow cytometry and JC-1 staining confirmed that treatment with protopine decreased the mitochondrial membrane potential and induced apoptosis in HCC cells. Western blot analysis showed that protopine was able to increase protein expression in the mitochondrial apoptotic pathway; the level of cytochrome C, apoptotic protease activating factor-1 (Apaf-1), Bax, cleaved-poly ADP-ribose polymerase (cleaved-PARP), cleaved-caspase-3, and cleaved-caspase-9 were increased while the expression of Bcl-2 was suppressed significantly. An in vivo study revealed that protopine significantly suppressed the growth of tumors in nude mice bearing HepG2 cells. Administration of protopine intraperitoneally at a concentration of 50 mg·kg^-1 inhibited tumor growth by 72.46%. Animal experiments were carried out according to the Regulation of the Animal Ethics Committee of Southwest Medical University. This study provides preliminary evidence that there is potential to develop protopine as a lead compound for the treatment of HCC.

This study investigated the intervention effect and possible mechanism of ophiopogonin D (OPD) in protecting cardiomyocytes against ophiopogonin D' (OPD')-induced injury, and provided relevant experimental data for the clinical use of Ophiopogon japonicas. Cell counting kit-8 (CCK-8) assay was used to evaluate the effect of OPD and OPD' on H9c2 cell viability. The content of reaction oxygen species (ROS) in cells were detected by flow cytometry. The contents of Fe²⁺ in cells were detected by FerroOrange's fluorescence imaging. The content of glutathione (GSH) and glutathione peroxidase (GSH-Px) were detected by kits. The expression of transferrin receptor 1 (TFR1), cyclooxygenase 2 (COX2), NADPH oxidase 1 (NOX1), long-chain acyl-CoA synthetase 4 (ACSL4), cationic amino acid transporter 11 (SLC7A11), glutathione peroxidase 4 (GPX4), and ferritin heavy chain 1 (FTH1) was detected by Western blot. Results showed that OPD' (1 μmol·L^-1) significantly induced the expression of ferroptosis-related proteins, the contents of Fe²⁺, ROS, and GSH-Px were increased, and the content of GSH were decreased. In addition, different concentrations of OPD (0.5, 1, and 2 μmol·L^-1) could partially reverse the myocardial cell injury caused by OPD', and the best effect was obtained when the dose range was 1-2 μmol·L^-1. The experimental results show that OPD can interfere with the ferroptosis caused by OPD', and then have a protective effect on H9c2 cells.

Plant-derived extracellular vesicles (EVs) are membranous vesicles secreted by plants, which include lipid bilayer as the basic framework and encapsulate various proteins, nucleic acid and other active substances. They play an important role in plant growth and development, tissue repair and self-defense. In recent years, extracellular vesicle-like nanoparticles (EVNs) are prepared from plant samples referring to the separation method of EVs and show unique functions. In this review, the above structures are collectively called plant-derived vesicles (PDVs). The biogenesis, separation and characterization methods, in vivo and in vitro properties of PDVs have been reviewed. The biomedical applications of PDVs as natural therapeutic agents and functional drug carriers are described, and finally some opinions on the existing problems and future prospect in this field are put forward.

Gastric pH is an important factor that affects drug absorption, as gastric pH may lead to lower bioavailability, especially for weak-base drugs. Acid-reducing agents (ARAs) such as antacids, histamine-2 receptor antagonists, and proton pump inhibitors, are susceptible to drug-drug interactions (DDIs), potentially resulting in the loss of efficacy. Physiologically based pharmacokinetic (PBPK) modeling is an important tool for the evaluation of oral drug-drug interactions and the most commonly used models include the advanced comparative absorption and transport (ACAT) model and the advanced dissolution, absorption and metabolism (ADAM) model. These models can be used for adjustment of the dosage regimen and the screening of candidate drugs in drug development by simulating the change of gastric pH to predict the change in drug absorption. This review summarizes the theoretical basis, the most common PBPK models used to predict drug absorption, and the effects of different kinds of ARAs drugs on gastric pH. Some successful applications of PBPK modeling in predicting the effects of gastric pH on drug absorption are also presented.

Desorption electrospray ionization mass spectrometry (DESI-MS) is a newly emerging in-situ ionization mass spectrometry analysis technology. The ionization process occurs in an open ambient environment at atmospheric pressure, and has the characteristics of simple sample pretreatment, quick and sensitive analysis, and is widely used in biomedicine, pharmaceutical analysis, food safety, environmental monitoring, and material characterization. Natural medicines, such as Chinese herbal medicines, contain a variety of chemical components. Extraction, separation, identification, and in vitro and in vivo efficacy evaluation of natural medicines, especially research on active ingredients with significant efficacy, have received long-term attention. The development of DESI-MS technology provides many new opportunities for direct and rapid analysis of active ingredients in natural medicines. This article briefly introduces the principles, characteristics, influencing factors, and technical progress of DESI-MS technology, and systematically summarizes progress in the research and application of this technology to natural medicines such as Chinese herbal medicines and other plant samples with pharmacological activity. The future application prospects in this field are further presented.

The active ingredients in traditional Chinese medicine have been reported to possess significant pharmacological activity and played an important role in clinical treatments. However, lots of the active ingredients in traditional Chinese medicine suffer from disadvantages such as low solubility, high melting point and low stability that results in low bioavailability and limit its clinical application. Crystal structure plays an important role in improving physicochemical properties and efficacy of the active ingredients in traditional Chinese medicine. This review concludes the research advances of several crystal forms used in the active ingredients in traditional Chinese medicine in terms of polymorph, cocrystal, amorphous/coamorphous and nanocrystal. And the effects of crystal forms on the physicochemical properties and efficacy of the active ingredients in traditional Chinese medicine were reviewed. This research may be useful for the formulation preparation and development of the active ingredients in traditional Chinese medicine.

Artificial intelligence technology is being widely applied in drug screening. This paper introduces the characteristics of artificial intelligence, and summarizes the application and progress of artificial intelligence technology especially deep learning in drug screening, from ligand-based and receptor structure-based aspects. This paper also introduces how to apply artificial intelligence to drug design from these two aspects. Finally, we discuss the main limitations, challenges, and prospects of artificial intelligence technology in the field of drug screening.

Ginsenoside Rg1 is one of the most important active components of the "king of herbs" Panax ginseng, which is an important angiogenic protective agent. The research results have shown that Rg1 has a wide range of cardiovascular pharmacological effects in vivo and in vitro, mainly through promoting the proliferation of smooth muscle cells, inhibiting endothelial cell aging, antioxidant stress, inhibiting inflammatory response, activating key factors of angiogenesis, improving vasodilation and other ways. Many miRNAs participate in the process of Rg1 promoting angiogenesis, mediate the regulation of the specific expression of downstream related targets to promote angiogenesis and vascular remodeling, and have the potential to become new clinical biomarkers and therapeutic targets. New preparation technologies and materials are used to make up for the weakness of Rg1's blood-brain barrier permeability, and further promote and enrich the clinical application of Rg1.