The abnormal activation of NOD-like receptor protein 3 (NLRP3) inflammasome is related to the development of a variety of inflammatory and autoimmune diseases. In this study, the indole compound A-3 was found to inhibit the activation of the NLRP3 inflammasome pathway. A total of 19 derivatives Ⅰ-1-Ⅰ-4, Ⅱ-1-Ⅱ-6, Ⅲ-1-Ⅲ-3, Ⅳ-1-Ⅳ-6 were synthesized by structural modification of A-3, and 4 compounds Ⅲ-3, Ⅳ-1, Ⅳ-5, Ⅳ-6 could inhibit inflammasome activation at the cellular level. Preliminary mechanistic studies have shown that the compound Ⅳ-5 can inhibit pyroptosis in J774A.1 cell. In addition, we analyzed the structure-activity relationship of the series of compounds based on 3D pharmacophore model. This study provides lead compounds for the development of novel NLRP3 inflammasome pathway inhibitors.

Metastatic castration-resistant prostate cancer (mCRPC) is an advanced stage of prostate cancer. It is resistant to first-line prostate cancer treatments and poses a significant threat to men's health. The prostate-specific membrane antigen (PSMA)-targeting radiopharmaceutical [¹⁷⁷Lu]Lu-PSMA-617 has been approved by the FDA in 2022 to treat PSMA-positive patients with mCRPC, demonstrating significant clinical benefits on patients. In this work, we introduced a chelator, p-SCN-Bn-DOTA, instead of DOTA for radiolabeling and constructed the radioligand, PSMA-SCN, and systematically evaluated its diagnostic and therapeutic performance in prostate cancer. Both molecular docking and cellular competitive inhibition assays indicated that the introduction of p-SCN-Bn-DOTA enhanced the binding affinity of PSMA-SCN for the target protein PSMA compared to PSMA-617. For diagnosis, [⁶⁸Ga]Ga-PSMA-SCN was used to evaluate the tumor imaging capability and in vivo metabolic profiling by microPET/CT. Quantitative analysis of microPET images shows higher tumor uptake of [⁶⁸Ga]Ga-PSMA-SCN [(46.27 ± 0.45) and (31.15 ± 0.21)%ID·g^-1] than that of [⁶⁸Ga]Ga-PSMA-617 [(16.8 ± 0.98) and (13.38 ± 1.44)%ID·g^-1] in LNCaP and RM-1 (PSMA⁺) tumor-bearing mouse models, respectively. [⁶⁸Ga]Ga-PSMA-SCN also has faster clearance rates in non-targeted organs. The possible reason is that the introduction of p-SCN-Bn-DOTA improves the affinity of PSMA-SCN to the targeting protein and has no significant effect on pharmacokinetic metabolism. For therapeutics, [¹⁷⁷Lu]Lu-PSMA-SCN was used in the treatment of tumor-bearing mice to assess its inhibitory effect on tumor growth, and the results demonstrated a favorable safety profile. These results confirm that PSMA-SCN has significant advantages in the theranostics of prostate cancer in comparison with PSMA-617. In conclusion, both theoretical analysis and biological evaluation of the PSMA-targeting molecule PSMA-SCN confirm its potential value for the diagnosis and treatment of prostate cancer. All experimental procedures involving animals were conducted in strict accordance with the ethical guidelines of the Institute of Materia Medica, Chinese Academy of Medical Sciences (ethics approval No. 00002217).

Fifteen compounds were successfully isolated from the total alkaloid content of Corydalis delicatula D. G. Long using a variety of chromatographic techniques, including silica gel, basic alumina, MCI, Sephadex LH-20 column chromatography, and HPLC. The structures of the isolated compounds were identified as (-)-tetrahydrocorysamine (1), corysamine (2), berberrubine (3), (-)-scoulerine (4), bicuculline (5), (-)-corlumine (6), scoulerine-β-N-oxide (7), salutaridine N-oxide (8), allocryptopine (9), protopine (10), coryximine (11), cryptopine (12), cis-N-methylstylopine (13), hunnemannine (14), and corlicatine A (15) through spectroscopic methods such as MS, NMR, and UV. These compounds were isolated for the first time from C. delicatula, and corlicatine A (15) is a new compound. Pharmacological testing revealed that compound 1 demonstrated excellent inhibition against Jack bean urease (JBU), with an IC₅₀ value of 1.28 µmol‧L^-1, surpassing the effectiveness of the positive control AHA. The synergistic inhibitory influence on JBU activity by compounds 1, 6, 11, 12 and inorganic reagents NaF and BA were proved by addition of competitive inhibitors NaF or BA. The molecular docking experiment between the most active alkaloid (-)-tetrahydrocorysamine (1) and the urease protein of the JBU was not found to interact with Ni²⁺, which is recognized as the active site of urease. Consequently, considering the impact of inorganic reagents on the inhibitory properties of alkaloids against JBU, it is hypothesized that the inhibitory effect of isoquinoline alkaloids on urease may involve targets or mechanisms other than Ni²⁺.

The n-butanol fraction of Curcuma phaeocaulis was separated and purified using a combination of chromatographic techniques, including reversed-phase medium-pressure liquid chromatography, gel column chromatography, silica gel column chromatography, preparative thin-layer chromatography and reversed-phase semi-preparative high-performance liquid chromatography. The structures of the isolated compounds were elucidated through comprehensive spectroscopic analyses, including high-resolution mass spectrometry, infrared spectroscopy, and nuclear magnetic resonance spectroscopy. Finally, three ionone glycosides were isolated from C. phaeocaulis and identified as (6Z, 9S)-4, 6-megastigmadien-3-one-9-O-β-D-glucopyranoside (1), (3R, 9S)-megastigman-5-en-3, 9-diol 3-O-β-D-glucopyranoside (2), and blumenol C glucoside (3). Notably, compound 1 was a new ionone, while compounds 2 and 3 were isolated from C. phaeocaulis for the first time. Subsequent evaluation of cytotoxic and anti-inflammatory activities revealed that all three compounds exhibited cytotoxic and anti-inflammatory effects.

Nine compounds were isolated and identified as (±)-diosniponol G (1), neo-olivil (2), isolariciresinol (3), bombasin (4), isoschaftoside (5), saponarin (6), apigenin 6-C-α-L-arabinopyranosyl-7-O-β-D-glucopyranoside (7), 2-hydroxy-3, 5, 7-trimethoxy-9, 10-dihydrophenanthrene (8), and albibrissinoside B (9) from bulbils of Dioscorea opposite Thunb. by multiple column chromatographic methods including Diaion HP-20, MCI gel CHP-20, and Sephadex LH-20. Compound 1 was a new pair of diarylheptanoid enantiomers, and the other compounds were isolated from D. opposite for the first time. The α-glucosidase inhibitory activities of the isolates were screened, and no compound exhibited significantly inhibitory activity against α-glucosidase at the concentration of 100 μmol·L^-1.

Seventeen phenolic compounds were isolated from the aqueous extract of the stems of Ephedra sinica using various column chromatographic techniques, including silica gel and Sephadex LH-20, combined with semi-preparative HPLC. Their structures were elucidated by modern spectroscopic methods such as NMR, UV, IR, and MS. Compounds 1 and 2 were identified as new phenols, and compounds 3-17 were isolated from this plant for the first time. The proliferation inhibitory activities of all the compounds on human non-small cell lung cancer cells (A549) was screened. The results showed that compounds 1-17 exhibited no proliferation inhibitory activity on A549 cells at a concentration of 10 μmol·L^-1.

In order to investigate the potential active components and mechanism of action of Xintongshu Spray (XTS) in the treatment of acute myocardial infarction (AMI), ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry (UPLC-Orbitrap-HRMS) was used to analyze and identify the blood-entry prototype components and metabolites of XTS in both positive and negative ion modes. A total of 41 blood-entry prototype components and metabolites were identified, including 16 phthalides, 15 organic phenolic acids, 4 monoterpenes, 3 acetophenones, 2 coumarins, and 1 sugar; 46 metabolites were identified, including 22 phthalide-related metabolites, 16 organic phenolic acids, 7 acetophenone-related metabolites, and 1 monoterpene-related metabolite. Combined with network pharmacological analysis, the target of action and signaling pathway of XTS into blood components for the treatment of AMI were predicted. The results showed that organic phenolic acids, phthalides, monoterpenes are the main active components of XTS for AMI, through the regulation of PI3K/Akt pathway, AGE-RAGE pathway, MAPK pathway to treat AMI. The results of molecular dynamics simulation showed that that the target proteins have good binding ability with the active ingredients. The use of all experimental animals has been approved by the Ethics Committee of Laboratory Animal of Anhui University of Traditional Chinese Medicine (AHUCM-rats-2021105).

Ulcerative colitis (UC) is a chronic relapsing inflammatory disease primarily affecting the colonic and rectal mucosa. Its complex pathogenesis, involving immune dysregulation, intestinal barrier dysfunction, gut microbiota dysbiosis, and other pathological factors, has led to the current lack of effective therapeutic agents in clinical practice. This study focused on extracting and characterizing polysaccharide components from the Rhubarb-Astragalus herb pair (GJ-2 and GJ-3) and evaluating their therapeutic effects on dextran sulfate sodium (DSS)-induced UC in mice. Crude polysaccharides were extracted from Rheum palmatum and Astragalus membranaceus via aqueous extraction-alcohol precipitation. Two polysaccharide fractions (GJ-2 and GJ-3) were isolated and purified using anion-exchange cellulose column. Structural characteristics, including total polysaccharide content (phenol-sulfuric acid method), uronic acid quantification (m-hydroxydiphenyl assay), infrared spectral features (FT-IR), and monosaccharide composition analysis 1-phenyl-3-methyl-5-pyrazolone (PMP) derivatization coupled with HPLC were systematically characterized. In vivo, a DSS-induced UC model was established using 2.5% dextran sulfate sodium (DSS). After intragastric administration of different doses of polysaccharide fractions, pathological changes of the colon tissue were observed by hematoxylin-eosin (HE) staining, while the levels of inflammatory factors in mouse serum and myeloperoxidase (MPO) activity in colon tissue were quantified by enzyme-linked immunosorbent assay (ELISA). Tight junction proteins (ZO-1, claudin-1) were analyzed via immunofluorescence, and tumor necrosis factor α (TNF-α)/interleukin 6 (IL-6) mRNA expression was quantified by qRT-PCR. Gut microbiota composition was evaluated through 16S rDNA sequencing of cecal contents. Consequently, two weakly acidic polysaccharide fractions, GJ-2 and GJ-3, were isolated from the Rheum palmatum-Astragalus membranaceus herb pair. Monosaccharide analysis revealed GJ-2 was composed of glucose (Glc), galactose (Gal), and arabinose (Ara), whereas GJ-3 predominantly contained Gal and Ara, both exhibiting carboxyl groups and pyranose configurations (FT-IR). In DSS-treated mice, GJ-2 and GJ-3 significantly ameliorated colon shortening, body weight loss, and elevated DAI scores. Histopathology demonstrated reduced mucosal damage, while ELISA and qRT-PCR showed decreased TNF-α and IL-6 levels in serum and colon tissues. Moreover, the polysaccharide fractions significantly upregulated the expression levels of ZO-1 and claudin-1 and restored gut microbiota diversity in DSS-induced mice, and enriched beneficial taxa, including f.__Clostridiales and g.__Vagococcus. In conclusion polysaccharide fractions from the Rheum palmatum-Astragalus membranaceus herb pair exhibit therapeutic potential against UC, likely serving as a key material basis for the efficacy of this herb pair. The animal operation was approved by the Zhejiang Center of Labortory Animals (No: ZJCLA-IACUC-20011023). All experiments were conducted in accordance with relevant guidelines and regulations.

Through network pharmacology and molecular docking technology, combined with in vivo experiment verification through aged db/db mice, we explored the anti-neuroinflammation mechanism of Dracocephalum rupestre Hance in aging type 2 diabetes. Neuroinflammatory targets were collected through Gene Cards, and nerve related differential genes (DEGs) in elderly patients with diabetes were screened by GEO NCBI database; 56 component targets and 31 component targets were obtained by Venny 2.1.0 software from core component targets of Dracocephalum rupestre Hance between neuroinflammatory targets and DEGs; protein-protein interaction (PPI) networks were constructed using STRING database, visualize PPI and medicine-composition-target network through Cytoscape software, and the Top 10 core targets were elected using Maximum Clique Centrality (MCC); GO (gene ontology) functional enrichment and KEGG (kyoto encyclopedia of genes and genes) pathway analysis were conducted by DAVID database. It was found that the neuroprotection effect of Dracocephalum rupestre Hance mainly include alleviated aging diabetes neuroinflammation through regulated MAPK, NF-κB and other pathway proteins. Molecular docking results showed that the core active ingredients of Dracocephalum rupestre Hance, chlorogenic acid, diosmetin, and kaempferol, have good binding activity with targets AKT1, IL-1β, BCL2, and HMOX1. In vivo experiments showed that Dracocephalum rupestre Hance can reduce blood glucose and lipid levels in aging db/db mice, ameliorate the disorder of liver tissue cell arrangement and lipid vacuoles, and reduce the level of serum pro-inflammatory cytokines; down-regulate the expression of brain TNF-α, IL-1β, TLR4, and nuclear NF-κB; inhibit the overactivation of Iba-1 in mouse brain. What's more, Dracocephalum rupestre Hance could decreased the activation of NLRP3 inflammasome. This study preliminarily revealed that the therapeutic effect of Dracocephalum rupestre Hance on aging diabetes encephalopathy may be related to improve the neuroinflammatory signal pathway, such as the regulation of TLR4/NF-κB, inhibition of NLRP3 inflammasome, etc. This experiment was approved by the Medical Ethics Committee of Shenyang Pharmaceutical University (No. SYPU-IACOC-2024-1016-103).

To explore the reasons for the uneven quality of commercial Eucommia ulmoides leaves, an HPLC method based on deep eutectic solvent (DES) and microwave-assisted extraction (MAE) was developed to determine the contents of eucommiol, aucubin, geniposidic acid, chlorogenic acid and asperuloside. A DES composed of choline chloride and urea (molar ratio 1∶2) with water content of 40% exhibited the highest efficacy. MAE was selected and the optimized conditions were microwave power of 70 W and extraction time of 15 s. The contents of five compounds in green leaves were significantly higher than those in yellow-brown leaves. Part of yellow-brown leaves even lacked aucubin, geniposidic acid and asperuloside. The contents of five compounds were the highest in the leaves treated with sun-drying and low-temperature drying, followed by the deactivated enzymes leaves and shade-drying leaves. The content of each chemical component, especially iridoids, decreased significantly in room temperature. However, the contents of the compounds decreased slowly in low temperature. There was a significant difference in the quality of commercially available green and yellow-brown Eucommia ulmoides leaves, which may be related to the drying and storage methods.