Exploring the risk "time interval window" of sequential medication of Reduning injection (RDN) and penicillin G injection (PG) by detecting the correlation between serum biochemical indexes and plasma metabonomic characteristics, in order to reduce the risk of adverse reactions caused by the combination of RDN and PG. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). The changes of biochemical indexes in serum of rats were detected by enzyme-linked immunosorbent assay. It was determined that RDN combined with PG could cause pseudo-allergic reactions (PARs) activated by complement pathway. Further investigation was carried out at different time intervals (1.5, 2, 3.5, 4, 6, and 8 h PG+RDN). It was found that sequential administration within 3.5 h could cause significant PARs. However, PARs were significantly reduced after administration interval of more than 4 h. LC-MS was used for plasma metabolomics analysis, and the levels of serum biochemical indicators and plasma metabolic profile characteristics were compared in parallel. 22 differential metabolites showed similar or opposite trends to biochemical indicators before and after 3.5 h. And enriched to 10 PARs-related pathways such as arachidonic acid metabolism, steroid hormone biosynthesis, linoleic acid metabolism, glycerophospholipid metabolism, and tryptophan metabolism. In conclusion, there is a risk "time interval window" phenomenon in the adverse drug reactions caused by the sequential use of RDN and PG, and the interval medication after the "time interval window" can significantly reduce the risk of adverse reactions.

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

Aim To explore the mechanism and mate-rial basis of Shenkang injection(SKI)in the treatment of renal fibrosis(RF)by bioinformatics and in vitro experiments.Methods The differentially expressed genes of RF were screened by GEO database.With the help of CMAP database,based on the similarity princi-ple of gene expression profile,the drugs that regulated RF were repositioned,and then the components of SKI potential treatment RF were screened by molecular fin-gerprint similarity analysis.At the same time,the core targets and pathways of SKI regulating RF were predic-ted based on network pharmacology.Finally,it was verified by molecular docking and cell experiments.Results Based on the GEO database,two RF-related data sets were screened,and CMAP was relocated to three common RF therapeutic drugs(saracatinib,da-satinib,pp-2).Molecular fingerprint similarity analysis showed that RF therapeutic drugs had high structural similarity with five SKI components such as salvianolic acid B and hydroxysafflor yellow A.Molecular docking results showed that salvianolic acid B,hydroxysafflor yellow A and other components had good binding abili-ty with MMP1 and MMP13,which were the core targets of SKI-regulated potential treatment of RF.Network pharmacology analysis suggested that the core targets of SKI were mainly enriched in signaling pathways such as Relaxin and AGE-RAGE.Cell experiments showed that SKI could significantly reduce the mRNA expres-sion levels of AGER,NFKB1,COL1A1,SERPINE1,VEGFC in AGE-RAGE signaling pathway and MMP1 and MMP13 in Relaxin signaling pathway in RF model cells,and significantly increase the mRNA expression level of RXFP1.Conclusions SKI can play a role in the treatment of RF by regulating Relaxin and AGE-RAGE signaling pathways,and its material basis may be salvianolic acid B,hydroxysafflor yellow A and other components.

Accurate assessment of the risks associated with traditional Chinese medicine(TCM), such as the potential to induce serious cardiovascular adverse reactions including cardiac arrhythmias, is crucial. This article introduced the pharmacological evaluation strategies for cardiac safety and the progress in cardiac organ research, with a focus on discussing the application prospects of human induced pluripotent stem cells(hiPSCs) and organoids in assessing the risks of TCM-induced cardiac arrhythmias. Compared with traditional animal models, hiPSCs and organoid models provide better reference and predictive capabilities, allowing for more accurate simulation of human cardiac responses. Researchers have successfully generated various cardiac tissue models that mimic the structure and function of the heart to evaluate the effects of TCM on the heart. The hiPSCs model, by reprogramming adult cells into pluripotent stem cells and differentiating them into cardiac cells, enables the generation of personalized cardiac tissue, which better reflects individual differences and drug responses. This provides guidance for the assessment of TCM cardiac toxicity risks. By combining organoid model with cardiac safety pharmacology strategies such as electrocardiogram monitoring and ion channel function assessment, the impact of TCM on the heart can be comprehensively evaluated. In addition, the application of the Comprehensive in Vitro Proarrhythmia Assay(CiPA) approach improves the accuracy of evaluation. Applying the CiPA approach to TCM research reveals potential risks and provides a scientific basis for the clinical application and industrial development of TCM. In conclusion, organoid model and cardiac safety pharmacology evaluation strategies provide important tools for assessing the cardiac toxicity risks of TCM. The combination of hiPSCs model, comprehensive assessment methods, and the CiPA strategy enables an accurate assessment of the risks of TCM-induced cardiac arrhythmias, thus providing a scientific basis for the safe use and international recognition of TCM in clinical practice. This contributes to ensuring the safety and efficacy of TCM and promoting its clinical application and global acceptance.
Animals ; Humans ; Medicine, Chinese Traditional/adverse effects* ; Cardiotoxicity ; Induced Pluripotent Stem Cells ; Arrhythmias, Cardiac/chemically induced* ; Myocytes, Cardiac ; Organoids ; Drugs, Chinese Herbal/adverse effects*

This study used UPLC-TQ-MS technology to replicate a Henoch-Schonlein purpura(HSP) model in rats by administering warm drugs by gavage and injecting ovalbumin with Freund's complete adjuvant emulsion. The distribution differences and characteristics of eight major components(ferulic acid, caffeic acid, neochlorogenic acid, cryptochlorogenic acid, benzoyl oxypaeoniflorin, tracheloside, loganin, and paeoniflorin) in rat liver, lung, heart, spleen, and kidney tissues were determined after oral administration of the Liangxue Tuizi Mixture at a dose of 42 g·kg~(-1) in both normal physiological and HSP states at 0.5, 1, 2, 6, and 12 hours. The results showed that the distribution patterns of the eight components of Liangxue Tuizi Mixture in the tissues of normal and HSP model rats were different. The main component, paeoniflorin, in Moutan Cortex and Paeoniae Radix Alba had higher content in all tissues. The eight components were predominantly distributed in the liver, lung, and kidney tissues, followed by spleen and heart tissues.
Rats ; Animals ; IgA Vasculitis/drug therapy* ; Monoterpenes ; Administration, Oral ; Liquid Chromatography-Mass Spectrometry

This study was designed to explore the alleviating effect and mechanism of Glycyrrhizae Radix et Rhizoma against Psora-leae Fructus-induced liver injury based on network pharmacology and cell experiments. The active components of Glycyrrhizae Radix et Rhizoma and Psoraleae Fructus were first retrieved from the Encyclopedia of Traditional Chinese Medicine(ETCM), Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Comparative Toxicogenomics Database(CTD), and literature and further screened by SwissADME. The obtained 25 potential toxic components of Psoraleae Fructus and 29 flavonoids in Glycyrrhizae Radix et Rhizoma were input into the SwissTargetPrediction for target predication. A total of 818 targets related to liver injury were screened out based on GeneCards and MalaCards, and 91 common targets of Psoraleae Fructus, Glycyrrhizae Radix et Rhizoma, and liver injury were obtained from Venny. STRING was applied for constructing the PPI network, and Metascape for analyzing the biological processes and signaling pathways that common targets participated in. Cytoscape was used to construct the component-target-disease network and component-target-pathway network for Glycyrrhizae Radix et Rhizoma against Psoraleae Fructus-induced liver injury. The predicted core targets were proto-oncogene tyrosine-protein kinase(SRC), phosphatidylinositol 4,5-bisphosphate 3-kinase subunit alpha(PIK3 CA), RAC-alpha serine/threonine-protein kinase(AKT1), etc, with PI3 K-AKT signaling pathway, MAPK signaling pathway, apoptosis, Toll-like receptor signaling pathway, and NF-κB signaling pathway mainly involved. Following the scree-ning of the main toxic and pharmacodynamic components, the pharmacodynamic effects were investigated by cell experiments. The results showed that licochalcone A was mainly responsible for alleviating coryfolin-induced liver injury, licochalcone B for coryfolin-and psoralidin-induced liver injury, and echinatin for corylifolinin-and bakuchiol-induced liver injury. The preliminary revealing of the alleviating effect of Glycyrrhizae Radix et Rhizoma on Psoraleae Fructus-induced liver injury and the prediction of related mechanisms will provide reference for further mechanism research and reasonable clinical compatibility.
Chemical and Drug Induced Liver Injury, Chronic ; Drugs, Chinese Herbal/pharmacology* ; Glycyrrhiza ; Humans ; Medicine, Chinese Traditional ; Network Pharmacology

Ginkgolides,the unique terpenoids in Ginkgo biloba,have a significant effect on the prevention and treatment of cardiovascular and cerebrovascular diseases. Metabolic regulation and synthetic biology strategies are efficient methods to obtain high-quality ginkgolides. The present study reviewed the cloning and functions of genes related to the biosynthetic pathway of ginkgolides,as well as relevant studies of omics,genetic transformation,and metabolic regulation in recent years,and predicted the research trends and prospects,aiming to provide a reference for discovering the key genes related to the biosynthetic pathway and the biosynthesis of ginkgolides.
Ginkgo biloba/genetics* ; Ginkgolides ; Humans ; Lactones ; Plant Extracts ; Terpenes

PURPOSE: To evaluate the impact of five different tooth preparation designs on the marginal and internal fit discrepancies of cobalt-chromium (CoCr) crowns produced by computer-aided designing (CAD) and selective laser melting (SLM) processes. MATERIALS AND METHODS: Five preparation data were constructed, after which design crowns were obtained. Actual crowns were fabricated using an SLM process. After the data of actual crowns were obtained with structural light scanning, intaglio surfaces of the design crown and actual crown were virtually superimposed on the preparation. The fit-discrepancies were displayed with colors, while the root means square was calculated and analyzed with one-way analysis of variance (ANOVA), Tukey’s test or Kruskal-Wallis test (α =.05). RESULTS: The marginal or internal color-coded images in the five design groups were not identical. The shoulder-lip and sharp line angle groups in the CAD or SLM process had larger marginal or internal fit discrepancies compared to other groups (P < .05). In the CAD process, the mean marginal and internal fit discrepancies were 10.0 to 24.2 µm and 29.6 to 31.4 µm, respectively. After the CAD and SLM processes, the mean marginal and internal fit discrepancies were 18.4 to 40.9 µm and 39.1 to 47.1 µm, respectively. The SLM process itself resulted in a positive increase of the marginal (6.0 – 16.7 µm) and internal (9.0 – 15.7 µm) fit discrepancies. CONCLUSION The CAD and SLM processes affected the fit of CoCr crowns and varied based on the preparation designs. Typically, the shoulder-lip and sharp line angle designs had a more significant effect on crown fit. However, the differences between the design groups were relatively small, especially when compared to fit discrepancies observed clinically.

Aim To investigate the influence of Schisandrae Fructus ( Wuweizi in Chinese) and com¬patible with Glycyrrhiza ( Gancao in Chinese ) on the levels of serum lipids and their influence on liver syn¬thesis pathway of triglyceride ( TG ). Methods ICR mice were divided, according to weight randomized block method, into four groups; normal control group ( Control, C ), Schisandrae Fructus ethanolic extract group (SF) , Schisandrae Fructus compatible with Gly¬cyrrhiza ethanolic extract (SG) 1 : 1 and 1 : 1.5. The control group was intragastrically given normal saline (10 mL • kg-1), SF group, SG 1 : 1 and 1 : 1. 5 group were given the extract 3. 9 g • kg"1 in crude of Schisandrae Fructus for 10 days. The levels of TG, to¬tal cholesterol (TC) , low-density lipoprotein-cholester¬ol ( LDL-C ) and high-density lipoprotein-cholesterol ( HDL-C ) were detected by biochemical method, as well as alanine aminotransferase (ALT) activity. The activities of liver fatty acid synthase (FAS) and acctyl-COA carboxylase ( ACC ), and levels of GPAT, acy- CoA oxidase ( ACO ) were detected by enzyme immu¬noassay ( ELISA ). The protein expressions of sterol regulatory element-binding protein-lc (SREBP-lc) and peroxisome proliferator-activiated receptor-a ( PPARa ) were detected by immunohistochemistry technique. Results Compared with C group, the lev¬els of TG and TC increased significantly, the level of serum LDL-C decreased significantly, the activities of liver ACC and GPAT level increased markedly, the protein expression of SREBP-1 c was markedly up-regu¬lated, and the protein expression of PPARa was evi¬dently down-regulated in SF group. When compared with SF group, the levels of serum TG and ACO, the activities of serum ALT and GPAT apparently de¬creased in SG 1 : 1 group. The protein expression of SREBP-1 c in SG 1 : 1 and 1 : 1.5 group was signifi¬cantly down-regulated, and the protein expression of PPARa was markedly up-regulated. Conclusions High dose of SF can increase the serum TG and TC levels , and the mechanisms may be related to that SF can promote the expression of liver SREBP-lc, in¬crease the activities and levels of FAS, ACC and GPAT in TG synthesis pathway, and down-regulate protein expression of PPARct and ACO for promoting liver TG synthesis. Compatible with Glycyrrhiza can significantly improve the elevated blood lipids and the proteins in the TG synthesis pathway.

Aim To study the effect of drug-containing serum of Schisandra Chinensis Fructus and compatible with Glycyrrhizae Radix Et Rhizoma -on lipid accumulation in hepatocytes and explore the related mechanism. Methods SD rats were given Schisandra Chinensis Fructus (SF, 3.9 g • kg"1), Schisandrae Chinensis Fructus-Glycyrrhizae Radix Et Rhizoma (SG, 1 : 1, 1 '• 1. 5, the extract 3. 9 g • kg"1 in crud of Schisandrae Chinensis Fructus), once per day, the drug-containing serum was prepared after seven days of continuous administration. Conventional cultivation of human normal hepatocytes (L02 cells) in vitro, cells were divided into blank control group, SF group, and SG(1 : 1 and 1 : 1.5) group. After 48 hours' treatment , lactate dehydrogenase ( LDH) release was detected by the kit, the levels of intracellular triglyceride (TG) and total cholesterol (TC) were detected by biochemical method. The mRNA expression levels of PPAR-a, PPAR-7, Fabpl/2, SREBPlc, ACCa and FAS were detected by the real-time reverse tran scrip- tion polymerase chain reaction ( RT-PCR ). Results The biochemical results showed that compared with the blank group, the content of TG and TC in SF group increased significantly (P < 0. 05 ) , the mRNA expres sion of PPAR-a and PPAR-7 in SF group was significantly reduced, and the mRNA expression of SREBPlc and ACCa markedly increased ( P < 0.05, P < 0.01). When compared with SF group, the levels of TG and TC in SG (1 : 1) group were significantly reduced (P <0. 05) , the mRNA expressions of Fabpl/2 and FAS in SG (1 : 1) group were significantly reduced, while the mRNA expression of SREBPlc significantly increased ( P < 0. 05, P < 0. 01 ). TC content in SG (1 : 1.5) group significantly decreased (P < 0.05 ) and the mRNA expression of PPAR-7, SREBP1 c in SG (1 : 1.5) significantly increased, but the Fabpl/2 and FAS markedly decreased (P <0. 05, P < 0. 01). Conclusions SF containing serum can significantly increase the content of TG and TC in hepatocytes , and the SG containing serum can significantly improve the elevated TG and TC contents and reduce lipid accumulation. The mechanism may be related to the regulation of mRNA expression of PPAR-a, PPAR- 7, Fabpl/2, SREBPlc, ACCa and FAS.