This study aimed to investigate the protective effect and potential mechanism of total flavonoids of Dracocephalum moldavica L. (TFDM) against doxorubicin (DOX)-induced cardiotoxicity (DIC) via the STING/NLRP3 signaling pathway. The protocol was approved by the Animal Ethics Committee of Xinjiang Institute of Materia Medica (approval No.: XJIMM-20250201). The DIC model was established by a single intraperitoneal injection of DOX (20 mg·kg^-1). Body weight, heart weight, heart index, and cardiac function (evaluated by echocardiography) were measured in each group. HE staining and Masson staining were used to observe myocardial tissue damage. Myocardial enzyme activities in serum, as well as oxidative stress indicators and inflammatory factor levels in myocardial tissue, were detected by corresponding kits. Western blot was performed to assess the expression of STING/NLRP3 pathway-related and pyroptosis key proteins in myocardial tissue. Additionally, the effects of TFDM (100 µg·mL^-1) on inflammatory factors and the STING/NLRP3 pathway in rat H9c2 cardiomyocytes stimulated by DOX or the STING agonist vadimezan (DMXAA) were further evaluated in vitro. In vivo experiments showed that TFDM effectively increased body weight, heart weight ratio, left ventricular ejection fraction (LVEF), and left ventricular fractional shortening (LVFS), while decreasing left ventricular internal diameter at end-diastole (LVIDd) and left ventricular internal diameter at end-systole (LVIDs) in DIC mice. TFDM inhibited the abnormal elevation of myocardial enzymes, oxidative stress indicators and inflammatory factors, and ameliorated myocardial inflammatory infiltration and fibrosis. Furthermore, TFDM suppressed the activation of the STING/NLRP3 pathway and the expression of pyroptosis-related proteins in DIC mice. In vitro results demonstrated that TFDM intervention reduced the release of inflammatory factors; Western blot confirmed that both DOX and DMXAA significantly upregulated the expression of STING pathway and pyroptosis-related proteins, which were markedly downregulated after TFDM treatment. In conclusion, TFDM pretreatment exerts a protective effect against DIC by alleviating myocardial injury and improving cardiac function, and its mechanism may be associated with the inhibition of the STING/NLRP3 pathway to suppress cell pyroptosis and inflammatory cascade reaction.

Mycobacterial polyketide synthase 13 (Pks13) is responsible for catalyzing the synthesis of the precursor of mycolic acids and represents a promising target for the development of novel antituberculosis drugs. Based on the hit compound 6 previously identified through virtual screening, a series of benzofuran-3(2H)-one derivatives were designed and synthesized using a structure-based drug design strategy. Among them, compounds 7k and 7o exhibited potent inhibitory activities against Pks13, with IC₅₀ values of 1.01 and 0.64 μmol·L^-1, respectively. This study lays a foundation for the investigation of novel Pks13 inhibitors.

Secreted aspartic protease 2 (SAP2) stands as one of the most pivotal virulence factors in Candida albicans (C. albicans). Consequently, the development of potent small-molecule inhibitors targeting SAP2 represents a critical stride toward the treatment of invasive candidiasis. In our previous studies, the lead compound SAP2-IN-1 was successfully identified and synthesized via integrated strategies of virtual screening and scaffold hopping. Preliminary structure-activity relationship (SAR) investigation was performed through rational design, synthesis, and biological evaluation of 10 novel indolin-2-one derivatives derived from the SAP2-IN-1 scaffold. Enzymatic inhibition and cell-based assays confirmed that compound A1 possesses favorable SAP2 inhibitory activity, with an IC₅₀ of 0.87 μmol·L^-1. Notably, when combined with fluconazole (FLC), compound A1 effectively suppressed the growth of fluconazole-resistant C. albicans 0304103, yielding fractional inhibitory concentration index (FICI) of 0.047. Furthermore, preliminary mechanistic studies revealed that A1 significantly impeded biofilm formation and hyphal transition in drug-resistant C. albicans. It possesses great potential as a novel antifungal lead compound and provides a new theoretical basis and research strategy for the development of virulence factor-targeted inhibitors to overcome the drug resistance of C. albicans.

This study aims to investigate the chemical constituents of the soft coral Sinularia sp. collected from Ximao Island in the South China Sea, and to evaluate the peroxisome proliferator-activated receptor (PPARs) agonistic and anti-inflammatory activities of the isolated compounds. The chemical constituents were isolated using silica gel column chromatography, Sephadex LH-20 gel column chromatography, and high-performance liquid chromatography (HPLC). The structures of the compounds were elucidated by comprehensive analysis of NMR, MS, and IR data and comparing them with those reported in the literature. Eleven compounds were isolated from the soft coral Sinularia sp., including two norsesquiterpenes, two furanosesquiterpenes, and seven steroids. Their structures were elucidated by spectroscopic data analysis as (2E,6E)-3,7-dimethyl-nona-2,6,8-trienoic acid (1), (3S,6E)-3,7-dimethyl-nona-6,8-dienoic acid (2), (1′E,5′E)-5-(2′,6′-dimethylocta-1′,5′,7′-trienyl)-furan-3-carboxylic acid (3), (5′E)-5-(2′,6′-dimethylocta-5′,7′-dienyl)-furan-3-carboxylic acid (4), (24S)-24-methylcholesterol (5), 24R-7α- hydroxyergosta-5-en-3β-ol (6), brassicasterol (7), pregn-5,20-dien-3β-ol (8), gorgosterol (9), β-sitosterol (10), 24-methylenecholesterol (11). Compound 1 was identified as a new compound. Compounds 6 and 10 were obtained from Sinularia sp. for the first time. Luciferase reporter gene assay revealed that compounds 8 and 9 selectively activated the PPAR-α transcription factor at a concentration of 5 μmol·L^-1, while compound 5 acted as a dual agonist of PPAR-α and PPAR-β isomers. In addition, compounds 5, 7, and 8 exhibited in vitro anti-inflammatory activities. Compound 5 significantly inhibited the production of the inflammatory mediators inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS) stimulated mouse macrophages RAW264.7.

Thirteen oligosaccharides were isolated from the water-eluted fraction of Scutellaria baicalensis Georgi extract on macroporous adsorption resin, using techniques such as medium-pressure liquid chromatography, semi-preparative high performance liquid chromatography (HPLC), and a HPLC system equipped with a charged aerosol detector (CAD) as a trigger for fraction collector automatically. The structures of these compounds were identified by mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (NMR) as α-D-galactopyranosyl-(1→6)-α-D-glucopyranosyl-(1→2)-β-D-fructofuranosyl-(6→1)-α-D-galactopyranosyl-(6→1)-α-D-galactopyranoside (1), α-D-galactopyranosyl-(1→6)-α-D-galactopyranosyl-(1→6)-α-D-glucopyranosyl-(1→2)-β-D-fructofuranosyl-(4→1)-α-D-galactopyranoside (2), and α-D-galactopyranosyl-(1→2)-α-D-galactopyranosyl-(1→6)-α-D-galactopyranosyl-(1→6)-α-D-glucopyranosyl-(1→2)-β-D-fructofuranoside (3), raffinose (4), stachyose (5), verbascose (6), ajugose (7), umbelliferose (8), erlose (9), loliose (10), α-D-galactopyranosyl-(1→6)-α-D-galactopyranosyl-(1→6)-α-D-glucopyranosyl-(1→2)-β-D-fructofuranosyl-(1→1)-α-D-galactopyranoside (11), rehmaglupentasaccharide E (12), and rehmaglupentasaccharide F (13). All oligosaccharides with degrees of polymerization ranging from 3 to 6 were isolated from Scutellaria baicalensis Georgi for the first time. Compounds 1-3 are new compounds belonging to the non-classical raffinose-family oligosaccharides. Furthermore, compounds 11-13 are non-classical raffinose-family oligosaccharides and compounds 4-7 are raffinose-family oligosaccharides.

Using various separation and purification techniques including silica gel and recrystallization, two new cyclic dipeptides involving non-proteinogenic amino acids were first isolated and purified from the ethyl acetate fraction of the ethanol (95%) extract of Angelica dahurica. Through the modern spectroscopic methods such as NMR, HR-ESI-MS, IR, OR, UV, and CD, their structures were identified as angelidaphine A (1) and angelidaphine B (2).

A total of four alkaloid compounds, serratinine A (1), fawcettimine (2), 7-hydroxylycopodine (3), and huperzine I (4) were isolated from Huperzia serrata by AB-8 macroporous adsorption resin, Octadecylsilyl, Sephadex LH-20 and silica gel column chromatography combined with the semi-pre HPLC. The isolated compounds were structurally characterized by mass spectrometry (MS), nuclear magnetic resonance spectroscopy (NMR), X-ray single crystal diffraction and circular dichroism (CD). Among them, compound 1 was a square crystalline form with the stereo configuration of (4R, 7S, 8S, 12S, 13S, 15S)-serratinine, named serratinine A. Compound 1 is a new serratinine alkaloid, the first crystal culture and stereo configuration of compound 1 were confirmed in this study.

Hepatic injury caused by pyrrolizidine alkaloids (PAs) has attracted widespread global attention. Establishing a rapid evaluation model for PA toxicity is of great significance for risk assessment of PA exposure. Therefore, this study used senecionine as a representative component to investigate its metabolic characteristics in adult zebrafish, providing core metabolic support for the use of the zebrafish model in rapid screening and evaluation of PA toxicity. Adult zebrafish were orally gavaged with senecionine (0.6 mmol·kg^-1). Liver tissues were collected at 0.25, 0.5, 1, 2, 6, 12 and 24 hours post-administration. Metabolites were identified using ultra-performance liquid chromatography coupled with tandem mass spectrometry (LC-MSⁿ). Concentration-time profiles of major metabolites were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and pharmacokinetic parameters were fitted. Five metabolites of senecionine were identified in the zebrafish liver, including N-oxide, hydroxylation products, N-glucuronide conjugate of senecionine, and glucuronide conjugate of senecionine hydroxylation product. The parent compound and phase Ⅰ metabolites reached their peaks and were cleared rapidly. Among the phase Ⅱ metabolites, the glucuronide conjugate of the hydroxylation product showed the latest peak and became the predominant form in the zebrafish liver at later time points. This study for the first time systematically elucidated the metabolic profile and kinetic patterns of senecionine in adult zebrafish, confirming that zebrafish possess glucuronidation detoxification capabilities similar to humans. These findings provide a crucial experimental basis for using zebrafish as a model for PA metabolism and toxicity studies, and also offer scientific data for the risk assessment of traditional Chinese medicine preparations containing PAs. This experiment was approved by the Laboratory Animal Ethics Committee of Zhejiang University (Grant No: ZJU20250602).

To identify a new treatment strategy for acute severe pneumonia and solve the bioavailability of apigenin in formulation, the research utilized dipalmitoylphosphatidylcholine (DPPC), as well as 2-hydroxypropyl-β-cyclodextrin as respiratory carriers, to develop the apigenin β-cyclodextrin inclusion complexe DPPC liposomal dry powder inhalers (ACDLDPIs). The ACDLDPIs were prepared by grinding, film-dispersion and freeze drying. The formulation was optimized by orthogonal design, and its particle size, entrapment efficiency, electric potential, in vitro release and lung deposition were studied. Lipopolysaccharide (LPS)-induced rat acute lung injury model was used to evaluate acute severe pneumonia in vivo. The optimal formulation for apigenin cyclodextrin inclusion was obtained with the mole ratio of apigenin/cyclodextrin as (2∶1), concentration of cyclodextrin as 20% and grinding time as 90 min. The optimized prescription of the ACDLDPIs was apigenin inclusion complex/DPPC (1∶2), 15 min hydration time and the mass ratio of mannitol/DPPC (1∶1). Its encapsulation efficiency was (71.46 ± 3.18)%, and the drug loading was (8.36 ± 0.42)%. The particle size was 198.6 ± 4.4 nm (before rehydration) and 221.6 ± 5.5 nm (after rehydration). The zeta potential was 15.3 ± 2.1 mV. The aerodynamic particle size was 4.28 ± 0.77 μm. The pulmonary deposition rate (FPF) was 43.02%. The experiment was approved by the Experimental Animal Ethics Committee of Tongji University Affiliated Yangpu Hospital (No: LL-2023-ZRKX-002). The pharmacodynamic evaluation of acute severe pneumonia was evaluated in vivo. ACDLDPIs group had better therapeutic effect than apigenin group. The ACDLDPIs had suitable particle size, uniform distribution, good stability, high lung deposition rate and good therapeutic effect on acute severe pneumonia in vivo. The ACDLDPIs are promising medicines for the treatment of acute severe pneumonia.

This study utilized monomethoxyl poly (ethylene glycol) 2000-poly (ε-caprolactone) 2000 (mPEG_2K-PCL_2K) and a self-synthesized functional carrier material, fructose-polyethylene glycol 2000-deoxycholic acid (Fru-PEG_2K-DC), which targets the apical sodium-dependent bile acid transporter (ASBT) and glucose transporter 5 (GLUT5) on intestinal epithelial cells, to construct fructose-polyethylene glycol 2000-deoxycholic acid-polymeric micelles/curcumin (FD-PMs/Cur) with the aim of improving drug transintestinal transport efficiency. First, Fru-PEG_2K-DC was synthesized via an azide-alkyne click chemical reaction, and the structure of the synthesized product was confirmed by nuclear magnetic resonance (NMR) and infrared spectroscopy (IR). Subsequently, the film dispersion method was employed to prepare curcumin-loaded targeted micelles. The preparation process and formulation of the drug-loaded nanomicelles were optimized and screened based on evaluation indicators such as particle size, polymer dispersity index (PDI), encapsulation efficiency, and drug loading capacity. Finally, in vitro cell experiments were conducted to evaluate the cellular uptake of the constructed targeted formulation and lysosomal escape function. The prepared FD-PMs/Cur exhibited a near-spherical shape, uniform size, and good dispersibility, with an average particle size of 25.86 ± 0.160 4 nm, PDI of 0.169 ± 0.015, and surface charge of -5.74 ± 0.707 mV. The encapsulation efficiency and drug loading capacity were (92.31 ± 0.40)% and (7.69 ± 0.04)%, respectively. The micelles demonstrated slow release and high stability in gastrointestinal fluids. In vitro cell experiments revealed that the targeted micelles significantly enhanced cellular uptake compared to free drugs and non-targeted micelles, indicating excellent intestinal targeting ability and lysosomal escape function. The constructed FD-PMs/Cur exhibited good gastrointestinal stability, intestinal epithelial cell-targeting capability and lysosomal escape function, effectively enhancing transintestinal transport efficiency. This study provides a novel strategy for improving the oral bioavailability of lipophilic drugs.