Cinnamomum Migao oil (CMO), derived from Cinnamomum migao H.W. Li, is commonly used to alleviate stomachache in China, but its mechanism remains unclear. This research evaluated the protective influence of CMO against gastric ulcer (GU) in ethanol-treated rat models, using untargeted/targeted metabolomics combined with molecular biology experimental techniques to determine its mechanism. The data revealed that CMO significantly ameliorated gastric mucosal damage, reduced the ulcer index, decreased the contents of TNF-α, MDA, and IL-6, and elevated SOD and GSH levels in gastric tissues. Untargeted metabolomics analysis using UHPLC Q-Exactive Orbitrap HRMS revealed that CMO treatment for GU may primarily involve the regulation of purine metabolism. Further validation using UPLC-MS/MS quantitatively measured purine metabolite levels and assessed the impact on key enzymes in the purine metabolic pathway. It was found that CMO regulated the levels of uric acid, xanthine, AMP, IMP, adenosine, inosine, adenine, and hypoxanthine in the purine metabolism pathway of GU rats by modulating ADA, XOD, and PNP. Additionally, CMO altered Nrf2, Keap1, HO-1, NQO1, and NLRP3 expression. This investigation elucidated that CMO combats GUs by regulating purine metabolism and stimulating the Nrf2/HO-1/NLRP3 axis, thereby inhibiting oxidative stress and inflammation. These results furnished a theoretical foundation for future research on CMO and its application

Objective Periploca forrestii Schltr. (PF), traditionally used by the Miao ethnic group in China, has been reported to exert a therapeutic effect on rheumatoid arthritis (RA), potentially through regulating of the TNF-α signaling pathway. This study aimed to identify PF-derived TNF-α-targeting compounds and elucidate their anti-RA mechanisms. Methods TNF-α-binding constituents in PF were screened using affinity ultrafiltration plus liquid chromatography-mass spectrometry (AU-LC/MS). Initial screening for TNF-α antagonistic activity was performed in L929 cells. Binding interactions were verified by biolayer interferometry (BLI), surface plasmon resonance (SPR), cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS). LPS-induced RAW264.7 cells were used to evaluate anti-inflammatory activity, while MH7A cells were employed to assess the effects of active compounds on inflammation and TNF-α-mediated NF-κB signaling. The underlying mechanisms were further investigated using molecular docking and competitive binding assays. The anti-RA efficacy of selected compounds was evaluated in a collagen-induced arthritis (CIA) rat model. Results Nine TNF-α-binding compounds were identified, among which isochlorogenic acid B, daucosterol, and vitamin E exhibited strong TNF-α binding affinity and effectively protected L929 cells from TNF-α-induced cytotoxicity. These compounds directly interacted with TNF-α as confirmed by BLI, SPR, CETSA, and DARTS, and interfered with TNF-α/TNFR1 interaction. Consequently, they suppressed NF-κB activation, decreased phosphorylation of IκBα and p65, and reduced the levels of NO and proinflammatory cytokine (such as TNF-α, IL-6, and IL-1β). Further analyses, including molecular dynamics simulations and molecular docking, demonstrated stable binding of these compounds to TNF-α, consistent with experimental findings. In CIA rats, all three compounds markedly alleviated joint swelling, histopathological damage, and inflammatory cytokine levels. Conclusion Isochlorogenic acid B, daucosterol, and vitamin E are key TNF-α-targeting constituents of Periploca forrestii that exert anti-RA effects by blocking TNF-α/TNFR1 interaction and inhibiting NF-κB-mediated inflammatory responses. These findings suggest that PF may serve as a source of natural small-molecule TNF-α inhibitors for RA therapy.

BACKGROUND:The combination of Psoraleae Fructus (PF) with Epimedii Folium (EF) can cause drug-induced liver injury (DILI), which is a common type of hepatitis. Licorice (Lic) has been reported to mitigate the effects of hepatitis. However, the extent of Lic's protective effect against PF combined with EF -induced DILI and the underlying mechanisms remain unclear. METHODS:A rat model of PF+EF-induced liver injury was established under lipopolysaccharide stimulation, and the levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β)) were determined by using a kit to evaluate the hepatoprotective effect of Lic. In addition, the potential mechanisms of Lic's hepatoprotective effects were systematically studied using a combined approach of network pharmacology and metabolomics analysis, and ERK, p-ERK, p38, and p-p38 proteins were detected by Western blotting. RESULTS:Lic treatment significantly reduced serum levels of ALT, AST, TNF-α, IL-6, and IL-1β by approximately 46%, 40%, 22%, 11%, and 27%, respectively, and improved liver histopathology. Network pharmacology analysis identified 459 common targets shared between Lic and PF+EF-induced liver injury. Metabolomics revealed 12 differential metabolites, implicating pyrimidine and purine metabolism as the primary affected pathways. An integrated analysis of these metabolites and the 459 targets highlighted the mitogen- activated protein kinase (MAPK) pathway as the potential key mechanism through which Lic alleviates PF+EF-induced liver injury. DISCUSSION:Our results indicate that Lic alleviates PF+EF-induced liver injury by suppressing inflammatory responses and correcting metabolic perturbations. The combined network pharmacology, metabolomics, and protein expression analyses consistently point to the MAPK pathway as a pivotal mechanism mediating these hepatoprotective effects. These findings provide mechanistic support for the potential use of Lic in the prevention and treatment of DILI. CONCLUSION:Lic improves tissue injury and liver inflammation induced by PF+EF via regulating the MAPK pathway. This study provides a theoretical foundation for the therapeutic use of Lic in the treatment of hepatitis.

Euphorbia helioscopia L. (Zeqi, ZQ) is a traditional Chinese herb used to treat various tumors, but its molecular mechanisms against hepatocellular carcinoma (HCC) remain unclear. This study aims to elucidate the anti-HCC mechanisms of ZQ using chemical profiling, bioinformatics, Mendelian randomization (MR), and experimental validation. A total of 104 compounds were identified from ZQ, with 18 targeting HCC-related proteins. Bioinformatics and MR analyses revealed PTK2 as a core target associated with HCC risk. ZQ significantly suppressed H22 tumor growth in male ICR mice and inhibited PTK2/PI3K/AKT phosphorylation. Molecular docking and dynamics simulations confirmed stable binding between key ZQ compounds and PTK2. These results suggest that ZQ exerts anti-HCC effects through PTK2 inhibition and modulation of the PI3K/AKT pathway, supporting its potential as a multi-targeted therapeutic for HCC.

To delineate the in vivo metabolism and excretion of Yanlishuang Oral Dripping Pills in rats,an integrated analytical strategy was implemented through chromatography-mass spectrometry technology.Biological samples(bile,feces,and urine)were collected before and after oral administration of Yanlishuang Oral Dripping Pills.Processed samples were analyzed by gas chromatography-mass spectrometry(GC-MS)and ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS).Through systematic comparison of retention time,mass-to-charge ratios,and characteristic fragment ions,a total of 4 prototype compounds and 30 metabolites were identified across biological matrices,including 18 metabolites in bile,13 in feces,and 24 in urine.Primary metabolic pathways involved hydrolysis,hydrogenation,methylation,sulfation,and glucuronidation.Quantitative analysis further determined cumulative excretion rates of prototype components(borneol,menthol,camphor,and glycyrrhizic acid)and their metabolites(borneol-2-O-glucuronide,menthol-1-O-glucuronide,glycyrrhetinic acid,and glycyrrhetinic acid-3-O-β-D-glucuronide)in bile,feces,and urine.This study systematically clarified the in vivo metabolism and excretion of Yanlishuang Oral Dripping Pills,providing critical experimental evidence for further clinical applications.

Colla corii asini (CCA), also called Ejiao, is a protein-rich, healthy food prepared from the dried or fresh skins of donkeys with high nutritional and medicinal value. Therefore, identifying CCA and its non-donkey adulterating ingredients is of great significance. In this study, liquid chromatography-tandem mass spectrometry proteomics technology combined with bioinformatics was used to discover the specific peptide biomarkers in CCA and its non-donkey adulterating ingredients (sheep, horse, pig, camel, and cattle). A total of nine specific peptide biomarkers (one from CCA; one each from horse and pig skin gelatin; and two each from sheep, camel, and cow skin gelatin) with good signal responses were screened. After synthesizing these nine specific peptide biomarkers, an ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) multireaction monitoring (MRM) analysis method was established and the limits of specific peptide biomarkers of non-donkey adulterating ingredients content in CCA were proposed. This study established a rapid, simple, highly sensitive, and specific method for the authenticity certification and quality assessment of CCA, ensuring product quality and safety. The method enables identification of specific peptide biomarkers in ass hide glue while simultaneously detecting five adulterated ingredients: sheep, horse, pig, camel, and cattle skins.

This study investigated the effects of Shuganning Injection(SGN) on the enzymatic activities of cytochrome P450(CYP450) and its interaction with bicyclol(BIC). In vitro assessments were performed utilizing the Cocktail probe drug method in combination with a human liver microsome incubation system. UPLC-MS/MS analysis revealed that SGN inhibited the enzymatic activities of CYP1A2, CYP2D6, CYP2C9, CYP2C19, CYP3A4, and CYP2E1 in a concentration-dependent manner. In vivo experiments demonstrated that SGN significantly altered the pharmacokinetic parameters of caffeine, dextromethorphan, midazolam, and omeprazole in rats, primarily characterized by a marked increase in the area under the curve(AUC)(P<0.05) and a significant decrease in clearance(CL)(P<0.05). These findings suggest that SGN may inhibit the activities of CYP1A2, CYP2C19, CYP2D4, and CYP3A2. After co-administration with BIC, the exposure level(AUC_(0-t)) of BIC was significantly increased, while its CL significantly decreased. Further analysis using real-time quantitative PCR and Western blot confirmed that SGN significantly downregulated the mRNA and protein expression of CYP2C19 and CYP3A2 in rat liver. The results indicate that SGN can inhibit the activities of CYP1A2, CYP2C19, CYP2D4, and CYP3A2 in rats. By inhibiting CYP2C19 and CYP3A2, SGN slowed down the metabolic clearance of BIC, leading to elevated plasma drug concentrations. These findings suggest a potential risk of increased drug exposure when SGN is used in combination with BIC in clinical practice.

This study developed a local pharmacokinetic-pharmacodynamic (PK-PD) model for Laportea bulbifera extract (LBE) in the joint cavity of adjuvant-induced arthritis (AA) rats using microdialysis technology. A stable intra-articular microdialysis sampling system was established, and the PK behavior of LBE in the joint cavities of normal and AA rats was compared using ultra performance liquid chromatography-tandem mass spectrometry analysis. The results demonstrated that the time to peak concentration and absorption half-life of the components were shortened in AA rats, whereas the area under the concentration-time curve increased. An increase in the apparent volume of distribution and a decrease in clearance were also observed, indicating accelerated absorption, increased exposure, and prolonged retention. An integrated PK-PD model was constructed by combining these data with pharmacodynamic data for tumor necrosis factor-alpha, interleukin-6, interleukin-1β, and rheumatoid factor (RF) obtained by enzyme-linked immunosorbent assay. Based on half maximal inhibitory concentration, the inhibitory potency of the five components against the four biomarkers was ranked as follows: kaempferol-3-O-rutinoside > neochlorogenic acid > rutin > chlorogenic acid > cryptochlorogenic acid. The effect compartment model revealed a linear relationship between RF and multiple components, underscoring RF's potential role as a key therapeutic target in the joint cavity. This study represents the first systematic elucidation of the local PK-PD characteristics of LBE, providing a scientific basis for developing this Miao medicinal herb and its clinical application in rheumatoid arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE:Shuganning injection (SGN), a traditional Chinese medicine formula, derived from the traditional Yinchenhao decoction, is commonly used in the clinical management of acute liver injury (ALI). Nonetheless, the specific active ingredients together with mechanisms of action are still uncertain. AIM OF THE STUDY:To investigate SGN's mechanisms of action and active components against acetaminophen (APAP)-induced ALI. METHODS:The chemical constituents of SGN were analyzed and identified. The protective properties of SGN were evaluated in HepG2 cells and a rat APAP-induced ALI model. Integrated network pharmacology and metabolomics were employed to investigate the potential active components of SGN and their key biological pathways in alleviating ALI. All active components were screened using pharmacokinetic-pharmacodynamic (PK-PD) modeling, cellular thermal shift assay, biolayer interferometry, and molecular docking. The effects of active components on the alleviation of ALI were verified by molecular biology experiments. RESULTS:Chemical analysis revealed 21 constituents in SGN. In both a rat model and HepG2 cells, SGN demonstrated protective effects against APAP-induced ALI. SGN could regulate phenylalanine metabolism, arachidonic acid metabolism, biosynthesis of phenylalanine and others, and the tricarboxylic acid cycle in ALI rats. Integrated analysis of metabolomics and network pharmacology data suggested that SGN might alleviate ALI by regulating MAPK signaling pathways, of which ERK and p38 signaling pathways were identified as those most affected by SGN. The active compounds included baicalein, oroxylin A, scutellarin, baicalin, and oroxylin A-7-O-glucuronide. The five active components were found to bind to ERK and p38. The therapeutic effects of active components on ALI were consistent with those of SGN, and their regulation of ERK and p38 signaling in the treatment of ALI was validated experimentally. CONCLUSION:SGN alleviated ALI by inhibiting ERK and p38 signaling, regulating arachidonic acid and phenylalanine metabolism, among other metabolism, and reducing inflammatory mediator production. The active components were baicalein, oroxylin A, scutellarin, oroxylin A-7-O-glucuronide, and baicalin.

This study aims to screen quality markers(Q-markers) of Pleione yunnanensis for the treatment of liver inflammation and Alzheimer's disease(AD) based on the concept of "same treatment for different diseases" using ultra-high-performance liquid chromatography(UHPLC) fingerprinting combined with network pharmacology and molecular docking, and to perform quantitative analysis of the identified Q-markers. The UHPLC fingerprints of 15 batches of P. yunnanensis were established and subjected to similarity evaluation, cluster analysis(CA), principal component analysis(PCA), and orthogonal partial least squares discriminant analysis(OPLS-DA) to identify characteristic components responsible for quality variations. Network pharmacology and molecular docking were employed to explore the potential active components, related targets, and signaling pathways underlying the "same treatment for different diseases" mechanism for liver inflammation and AD. Based on the criteria of effectiveness, specificity, and measurability, Q-markers of P. yunnanensis were identified and quantified. Ten common peaks were identified in the UHPLC fingerprints of 15 batches, with eight components identified. Similarity scores ranged from 0.774 to 0.987. Chemical pattern recognition analysis identified that shancigusin H, militarine, and gymnoside Ⅴ were the major characteristic components contributing to quality differences among batches. RESULTS:: of network pharmacology and molecular docking revealed that dactylorhin A and militarine were the key active components exerting anti-inflammatory and neuroprotective effects. These components acted on 13 core targets, including SRC, CASP3, and CTNNB1, and regulated signaling pathways such as the PI3K-Akt signaling pathway and arachidonic acid metabolism. Based on the effectiveness, specificity, and measurability of Q-marker, dactylorhin A and militarine were selected as the Q-markers of P. yunnanensis. Quantitative analysis demonstrated that the content of dactylorhin A ranged from 0.527% to 2.21%, and militarine ranged from 0.731% to 2.58% across the 15 batches. The UHPLC fingerprint method and Q-marker-based quantification approach are robust and reliable, providing experimental evidence for quality control and standardization of P. yunnanensis.

This study systematically analyzed commercially available traditional Chinese medicines for As, Hg, Pb, Cd, and Cu, classifying them into roots and rhizomes (underground parts), stems and leaves, whole herbs, flowers, fruits and seeds (aboveground parts), and animal-derived decoction pieces. The concentration ranges of five elements in underground parts were 0~7.09, 0~0.29, 0~4.1, 0~1.1 and 0~49.2 mg/kg, with exceedance rates of 0–2.3%. Aboveground parts showed ranges of 0~1.54, 0~1.02, 0~13, 0~0.96 and 0~43.4 mg/kg, with exceedance rates of 0–8.8%. Animal-derived decoction pieces showed ranges of 0.07~27.18, 0~1, 0~55, 0~4.11 and 0.23~43.9 mg/kg, with exceedance rates of 6.7–41.3%. Principal component and cluster analyses indicated distinct contamination sources between animal-derived and plant-derived materials. The pollution index showed that animal-derived materials required special attention. Among plant-derived materials, Notoginseng Radix et Rhizoma, and Artemisiae Argyi Folium were also of concern. Health risk assessment indicated low non-carcinogenic risks across all categories (HI < 1), and uncertainty analysis showed a 0% probability of HI > 1. The 95th percentile carcinogenic risk for all categories was <1 × 10−4. Sensitivity analysis identified metal concentrations and daily intake as key uncertainty contributors. The findings underscore distinct contamination patterns between material types, highlighting the need for targeted control strategies, including strengthened source management and standardized dosing.

BackgroundTumor microenvironment (TME) represents the key factor inducing leukemia development. As stromal cells within the leukemia microenvironment, Bone Marrow Mesenchymal Stem Cells (BM-MSCs) can trigger leukemia progression under certain conditions. As a critical transcription factor, nuclear factor erythroid related factor 2 (Nrf2) can modulate antioxidant response and antioxidant enzyme gene expression, and prevent various oxidative changes. We previously identified a novel mechanism by which Nrf2 promotes leukemia resistance, providing a potential therapeutic target for the treatment of drug-resistant/refractory leukemias. However, the role of Nrf2 in BM-MSCs from B-cell acute lymphoblastic leukemia (B-ALL) patients has not been clearly reported. The present work focused on investigating the effect of Nrf2 overexpression within MSCs on leukemia cell invasion, extramedullary infiltration and proliferation as well as its downstream pathway.MethodsThrough clinical sample detection, in vitro cell experiments and in vivo animal experiments, the role of Nrf2 within MSCs within adult B-ALL cell migration and invasion and its potential molecular mechanism was explored through transcriptome sequencing analysis, RT-PCR, Western blot, cell migration, cell invasion, lentivirus transfection and other experiments.ResultsNrf2 was highly expressed in BM-MSCs from patients with B-ALL as well as in BM-MSCs co-cultured with leukemia cells. Overexpression of Nrf2 within MSCs significantly promoted leukemia cell migration, invasion and proliferation. The extramedullary organ infiltration rate in B-ALL model mice receiving the combined infusion of both cell types dramatically increased relative to that of leukemia cells alone, accompanied by the significantly shortened survival time. Mechanism study found that Nrf2 overexpression within MSCs promoted PI3K-AKT/ERK1/2 phosphorylation in the downstream pathway by activating SDF-1/CXCR4 axis, ultimately leading to extramedullary infiltration of leukemia cells.ConclusionHigh Nrf2 expression with in MSCs enhances leukemia cell invasion and migration, which then accelerates infiltration in leukemic extramedullary organs. Targeting Nrf2 or inhibiting its downstream signal molecules may be the effective interventions for B-ALL patients treatment.

This study predicts the quality markers(Q-markers)for the cough-relieving and phlegm-expelling effects of Kening Gran-ules based on pharmacodynamics,plasma drug chemistry,network pharmacology,and pharmacokinetics.Strong ammonia solution spray and phenol red secretion assays were employed to evaluate the cough-relieving and phlegm-expelling effects of Kening Granules.Twenty-six absorbed prototype components of Kening Granules were identified by ultra high performance liquid chromatography coupled with Q-Exactive Plus quadrupole/Orbitrap high resolution mass spectrometry(UHPLC-Q-Exactive Plus Orbitrap HRMS).Through network phar-macology,11 potential active components were screened out for the cough-relieving and phlegm-expelling effects of Kening Granules.The 11 components acted on 40 common targets such as IL6,TLR4,and STAT3,which mainly participated in PI3K/Akt,HIF-1,and EGFR signaling pathways.Pharmacokinetic quantitative analysis was performed for 7 prototype components.Three compounds including azelaic acid,caffeic acid,and vanillin were identified as Q-markers for the cough-relieving and phlegm-expelling effects of Kening Granules based on their effectiveness,transmissibility,and measurability.The results of this study are of great significance for clarifying the phar-macological substance basis,optimizing the quality standards,and promoting the clinical application of Kening Granules.

Biancaea decapetala (Roth) O. Deg. (Fabaceae), traditionally used by the Hmong people to treat rheumatoid arthritis (RA), has not been extensively studied for the correlation between its anti-inflammatory activity and its active components. Protosappanoside D (PTD), a new component, has been isolated for the first time from the extract of Biancaea decapetala. This study focused on the anti-arthritic and anti-inflammatory effects of Biancaea decapetala extracts (BDE) and PTD, along with their pharmacokinetic–pharmacodynamic (PK-PD) analysis. In the adjuvant-induced arthritis (AA) rat model, HE staining and cytokine assays showed that BDE alleviated joint damage and reduced inflammatory cytokines, similar to the positive control. In the LPS-induced inflammatory cell model, both BDE and PTD demonstrated anti-inflammatory effects by inhibiting the secretion of inflammatory factors. A PK-PD analysis of BDE in AA rats and inflammatory cells, as well as an analysis of PTD as a monomer, was conducted. The results indicated that PTD had different regulatory effects on cytokines like TNF-α, with a certain lag and sustained effects. These findings suggest the potential of BDE and PTD as treatments for rheumatoid arthritis, though further in vivo studies and clinical trials are needed.

Risedronate sodium (RIS) is a primary treatment for postmenopausal osteoporosis, but oral administration requires patients to remain upright to prevent side effects like esophagitis, gastritis, and ulcers, which can be difficult for those with fatigue or bone pain. This study developed RIS-loaded Bletilla striata polysaccharide microneedles (RIS-BMNs) with sufficient mechanical strength for effective skin penetration and drug delivery. Franz diffusion cell experiments showed that RIS-BMNs achieved 3 times higher in vitro transdermal absorption than the RIS solution and 2.6 times more than RIS patches. The stimulation test found that RIS-BMNs caused minimal skin irritation, which resolved within 12 h. RIS-BMNs also promoted cell proliferation and wound healing, as shown by in vitro cell viability and migration tests, and improved bone trabeculae and density in osteoporotic rats, according to micro-CT imaging and H&E staining. Biochemical markers (BGP, IL-6, CTX-I, TRAP, OPG, and PINP) indicated that RIS-BMNs had anti-osteoporotic effects comparable to oral RIS but without gastrointestinal side effects, as confirmed by H&E staining. Our new transdermal method for RIS could improve adherence in treating postmenopausal osteoporosis.

The content levels of borneol,borneol-2-O-glucuronide(B2G),menthol,menthol-1-O-glucuronide(M1G),camphor,and glycyrrhizic acid in various rat tissue were determined after administration of Yanlishuang Oral Dripping Pills,and their distribution characteristics in different tissue were investigated.Normal SD rats were given Yanlishuang Oral Dripping Pills by gavage.Plasma and nine types of tissue(heart,liver,spleen,lung,kidney,intestine,brain,stomach,and pharynx)were collected at different time points after administration.Quantitative analysis methods using gas chromatography-mass spectrometry(GC-MS)and ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)were established to determine the content of the six components in plasma and tissue samples,and to compare the distribution differences among tissue.The results showed that all six prototype components and metabolites were absorbed into the blood and widely distributed in the body,reaching peak levels in plasma and tissue within 30 min and being gradually eliminated at 90 min.The prototype components borneol,menthol,and camphor were mainly distributed in the stomach and intestine;glycyrrhizic acid was mainly distributed in the stomach,intestine,and pharynx,with only small amounts in other tissue.The metabolites B2G and M1G were mainly distributed in the intestine,liver,and kidney.Among them,B2G and glycyrrhizic acid were more abundant in the pharynx.This study revealed the differences in tissue distribution of the prototype components and metabolites of Yanlishuang Oral Dripping Pills in vivo,providing theoretical reference for the study of its pharmacological effects and clinical application.

This study explored the rationality of incorporating ammonium glycyrrhizinate in Yanlishuang Oral Dripping Pills from the perspectives of pharmacodynamics and pharmacokinetics. An acute pharyngitis rat model was established using 10% ammonia solution. From the pharmacodynamic perspective, the rationality of ammonium glycyrrhizinate in the formulation was evaluated by detecting routine blood indices, serum levels of inflammatory factors tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6), and pathological changes of pharyngeal tissue. A two-preparation, two-period, self-crossover design was adopted to conduct a bioequivalence study between Yanlishuang Oral Dripping Pills(R) and a preparation without ammonium glycyrrhizinate(T). Rabbits were divided into two groups, namely the T/R group and the R/T group. Gas chromatography-tandem mass spectrometry(GC-MS/MS) was used to investigate the pharmacokinetic characteristics of menthol, borneol, and camphor, thereby exploring the rationality of ammonium glycyrrhizinate in the formulation from the pharmacokinetic perspective. Pharmacodynamic results showed that both Yanlishuang Oral Dripping Pills and ammonium glycyrrhizinate alone reduced serum IL-6 and TNF-α levels, decreased white blood cell counts in rats with pharyngitis, and improved pathological injury of pharyngeal tissue. However, when ammonium glycyrrhizinate was absent, the therapeutic effect of Yanlishuang Oral Dripping Pills on acute pharyngitis was weakened, indicating that ammonium glycyrrhizinate enhances the anti-inflammatory effect and plays a synergistic role in the formulation. Pharmacokinetic results showed that, compared with the ammonium glycyrrhizinate-deficient preparation, Yanlishuang Oral Dripping Pills accelerated the absorption of menthol, borneol, and camphor and increased their systemic exposure, suggesting that ammonium glycyrrhizinate promotes the absorption of other components and increases their exposure in vivo. This reveals, from the pharmacokinetic perspective, the reason why ammonium glycyrrhizinate enhances the efficacy of Yanlishuang Oral Dripping Pills and further supports the rationality of its formulation. In conclusion, ammonium glycyrrhizinate significantly enhances the anti-inflammatory effect of Yanlishuang Oral Dripping Pills, promotes the absorption of active components, and increases bioavailability. The rationality of its formulation was explored through pharmacodynamic and pharmacokinetic experiments, providing a theoretical basis for the further development and clinical application of Yanlishuang Oral Dripping Pills.

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a critical target for herbicides. Excessive herbicide use causes environmental and health issues. Currently, limited information is available on the fate of the new HPPD inhibitor quinotrione in vegetables. This study employs dual-position and high-radioactivity 14C labeling combined with high-resolution mass spectrometry (DP-HA-14C-HRMS) to investigate the uptake and metabolism of quinotrione ([quinazoline-2-14C]- and [cyclohexene-4-14C]-quinotrione) in Chinese flower cabbage. Results showed that 24.7-27.4 % of 14C-quinotrione was accumulated in cabbage after 20 days. 14C-quinotrione was primarily concentrated in roots (132.4-138.3 mg kg-1) and does not easily transport to edible parts (9.6-11.3 mg kg-1). In cabbage, 80 % of quinotrione was degraded into eight metabolites, and the identification process of two metabolites depended on the labeling location. The metabolic profile involved hydroxylation, dehydrogenation, denitrification, nitration, glycosylation, dexylene, and demethylation. The findings significantly advance our understanding of quinotrione's behavior in vegetables, with important implications for environmental and food safety risk assessments.

Leukemia stem cells (LSCs) exhibit unique characteristics distinct from those of leukemia cells and are insensitive to conventional chemotherapeutics; thus, these cells ultimately contribute to treatment failure and relapse in acute myeloid leukemia (AML) patients. A critical challenge remains as strategies are needed to precisely target the diverse molecular drivers of leukemia stem cells (LSCs), particularly in the context of their protective microenvironment, to achieve optimal therapeutic outcomes. In this study, we investigated the role of aldehyde dehydrogenase 2 (ALDH2) in chemotherapy resistance in patients with relapsed/refractory AML and demonstrated that elevated ALDH2 expression in LSCs is closely associated with AML relapse and treatment resistance. Mechanistically, ALDH2 sustains mitochondrial homeostasis in LSCs by increasing the expression of protein kinase C delta (PKC delta) and serine hydroxymethyltransferase 2 (SHMT2), revealing a previously unidentified mechanism of metabolic reprogramming that facilitates LSC adaptation to chemotherapy-induced stress. The ALDH2‒PKC delta-SHMT2 axis plays a pivotal role in conferring resistance to chemotherapy in LSCs. Notably, rhoifolin, a compound designed to inhibit the specific binding site of ALDH2-PKC delta, significantly increased chemosensitivity. It could target LSCs within the bone marrow microenvironment, work synergistically with conventional chemotherapy drugs, and exhibit no toxicity toward normal cells. These findings underscore the therapeutic potential of targeting the ALDH2‒PKC delta axis as a novel and effective strategy for the treatment of AML and the eradication of minimal residual disease.

The combination of Aidi Injection(ADI) and doxorubicin(DOX) is a common strategy in the treatment of cancer, which can achieve synergistic anti-tumor effects while attenuating the cardiotoxicity caused by DOX. This study aims to investigate the mechanism of ADI in attenuating DOX-induced cardiotoxicity by multi-omics. DOX was used to induce cardiotoxicity in mice, and the cardioprotective effects of ADI were evaluated based on biochemical indicators and pathological changes. Based on the results, transcriptomics, proteomics, and metabolomics were employed to analyze the changes of endogenous substances in different physiological states. Furthermore, data from multiple omics were integrated to screen key regulatory pathways by which ADI attenuated DOX-induced cardiotoxicity, and important target proteins were selected for measurement by ELISA kits and immunohistochemical analysis. The results showed that ADI significantly reduced the levels of cardiac troponin T(cTnT) and N-terminal pro-B-type natriuretic peptide(NT-proBNP) and effectively ameliorated myocardial fibrosis and intracellular vacuolization, indicating that ADI showed therapeutic effect on DOX-induced cardiotoxicity. The transcriptomics analysis screened out a total of 400 differentially expressed genes(DEGs), which were mainly enriched in inflammatory response, oxidative stress, and myocardial fibrosis. After proteomics analysis, 70 differentially expressed proteins were selected, which were mainly enriched in the inflammatory response, cardiac function, and energy metabolism. A total of 51 differentially expressed metabolites were screened by the metabolomics analysis, and they were mainly enriched in multiple signaling pathways, including the inflammatory response, lipid metabolism, and energy metabolism. The integrated data of multiple omics showed that linoleic acid metabolism, arachidonic acid metabolism, and glycerophosphate metabolism pathways played an important role in DOX-induced cardiotoxicity, and ADI may exert therapeutic effects by modulating these pathways. Target validation experiments suggested that ADI significantly regulated abnormal protein levels of cyclooxygenase-1(COX-1), cyclooxygenase-2(COX-2), prostaglandin H2(PGH2), and prostaglandin D2(PGD2) in the model group. In conclusion, ADI may attenuate DOX-induced cardiotoxicity by regulating linoleic acid metabolism, arachidonic acid metabolism, and glycerophosphate metabolism, thus alleviating inflammation of the body.