The target-based drug discovery (TBDD) alongside the resurgence of phenotypic drug discovery (PDD) constitute the dual-track paradigm for modern drug discovery. These two approaches are interactively applied and validated, accelerating the R&D of novel therapeutics. The microscopic structure of drugs (molecular structure and formulation properties) forms the basis for their macroscopic representations (pharmacological efficacy, physicochemical properties, adverse reactions, etc.), while these macroscopic properties represent the emergent characteristics arising from the interactions of microstructures. The applications of principles and techniques from molecular biology, biophysics, biochemistry, and analytical chemistry reveal the material essence and mechanisms of action at the micro-level, simultaneously mapping them onto various macro-level manifestations. Over three decades ago, the Chinese traditional medicines Danggui Lu Hui Wan (Angelica sinensis and Aloe Pill), investigated through phenotypic research, led to the development of meisoindigo for the treatment of chronic myeloid leukemia. Although its molecular target and mechanism of action were poorly understood at the time, it remains in clinical use today. Advances in science and technology have now enabled rigorous experimental design and execution, revealing meisoindigo's function as a molecular glue. It binds the target protein PKMYT1 while recruiting the E3 ligase TRIM25, forming a ternary complex that catalyzes the target protein's entry into the ubiquitin-proteasome system for degradation and functional loss. This micro-level elucidation explains its macro-level therapeutic efficacy. This article attempts to provide a concise commentary on this over-30-year R&D chain: "Danggui Lu Hui Wan → Indigo Naturalis → Indirubin → Meisoindigo → Molecular Glue, " aiming to bridge the gap between PDD and TBDD.

Cytochrome P450 (CYP450) is the body's most important family of metabolic enzymes and plays an important role in eicosanoid metabolism. High-altitude hypoxia affects the expression and activity of CYP450, which further leads to changes in eicosanoid metabolism. The alteration of eicosanoid metabolites under hypoxia may be an important mechanism for the development of high-altitude diseases and the body's adaptation to hypoxia; however, the specific roles of CYP450 and eicosanoids in the pathophysiological processes of high-altitude diseases, as well as the molecular mechanisms by which hypoxia regulates CYP450, are still unclear. In this paper, we reviewed the changes of CYP450 and eicosanoid metabolites and the mechanisms of CYP450 regulation by cytokines, nuclear receptors, and epigenetic modifications under hypoxic environment and explored the possible mechanisms by which CYP450 and eicosanoid metabolites are involved in the development of high-altitude diseases through the pathways of vasoregulation, inflammation, and oxidative stress. This article aims to provide a new theoretical basis and potential targets for the prevention and treatment of high-altitude diseases.

Macrophages, as the main effector cells of innate immune response, exist in all tissues in the body, has become a new target of immunotherapy because of their high plasticity. Lipid droplets are storage organelles related to fat metabolism and energy homeostasis, but they are not simple lipid reservoirs, but multi-functional organelles with active metabolism. Recent studies have found that lipid droplets, as a hub integrating metabolism and inflammation, play a central role in the regulation of macrophage inflammatory phenotype. This article reviews the relationship and regulation mechanism between macrophage inflammatory phenotype and lipid droplet loading. Based on the regulation and main mechanism analysis of lipid droplet loading on macrophage inflammatory phenotype in atherosclerosis, tumor, tuberculosis and other inflammatory diseases, it discusses the therapeutic potential of regulating targeted lipid droplet loaded macrophages in the treatment of inflammatory diseases.

Inflammatory bowel disease (IBD), which mainly includes Crohn's disease and ulcerative colitis, is a chronic intestinal inflammatory disease whose etiology is not fully understood. As its global incidence increased, the clinical management of IBD still face multiple challenges, such as side effects, drug resistance, and high healthcare costs, prompting the medical community to actively search for safer and more effective alternative/complementary treatments. In this context, traditional Chinese medicine (TCM), with its holistic view and the theory of syndrome differentiation-based treatment, demonstrates significant potential in regulating immune responses, exerting anti-inflammatory effects, and repairing the damaged intestinal barrier through its multi-component and multi-target characteristics. Here we reviewed the recent progresses in the application of TCM formulae (e.g., Wumei pills, Lizhong decoction, Sishen pills, etc.) and active monomers (e.g., magnolol, ferulic acid, chlorogenic acid, etc.) in the treatment of IBD, as well as their possible mechanisms of action, in order to provide new therapeutic strategies for the clinical management of IBD and promote the integration between TCM and modern science.

The optimization of drug molecular structure is a crucial step in enhancing the efficacy and safety of drugs. Its primary objective is to rationally adjust the molecular structure to meet the strict requirements for the comprehensive performance of drugs during the research and development process. However, the vast chemical space of drugs and the complex multi-objective optimization tasks pose significant challenges to this process. In recent years, machine learning techniques, represented by deep learning and reinforcement learning, have been widely applied in the optimization of drug molecular structures due to their powerful capabilities in information mining, feature extraction, and nonlinear fitting, providing new ideas and methods for drug design. This paper systematically reviews the latest research progress of machine learning in the optimization of drug molecular structures, deeply analyzes and compares their application advantages and characteristics in different structural optimization scenarios, summarizes the main challenges currently faced in the optimization of drug molecular structures, and provides a technical perspective on the possible research directions for future structural optimization.

Biologics have experienced rapid development on a global scale in recent years. Their analytical techniques, encompassing molecular structural characterization, purity and impurities analyses, function and stability assessment, play a crucial role in ensuring biologics' quality. Quality by design (QbD), as a systematic approach, has been widely adopted in the pharmaceutical industry to optimize manufacturing processes and ensure the reliability of final product quality. Derived from QbD, analytical quality by design (AQbD) ensures the quality of analytical methods by providing confidence and assurance in their development. AQbD begins with defining the analytical target profile (ATP) and employs risk assessment to identify and analyze critical method attributes (CMAs) and critical method parameters (CMPs). By design of experiments (DoE), mathematical models are constructed to explore the relationships between CMPs and CMAs, ultimately establishing the method operable design region (MODR) and an analytical control strategy. Compared to traditional analytical method development, AQbD-based methods offer greater robustness within the MODR, reducing the occurrence of out-of-trend (OOT) or out-of-specification (OOS) results due to method-related factors. This, in turn, enhances regulatory flexibility and reduces analytical costs. This review outlines the AQbD workflow, discusses its current applications in biologics analytical method development, and explores the opportunities and challenges associated with its implementation in this field.

Diabetes is a chronic disease caused by metabolic disorders due to abnormal blood glucose levels, and insulin is a commonly used drug in the treatment of diabetes. Different types of insulin exhibit different clinical efficacy due to their mechanisms and duration of action in the body, the basal long-acting release and postprandial controlled release of insulin have always been hot topics among clinical researchers. With the development of nanotechnology, the research and development of new nano-drug carriers with excellent drug release properties have become an important opportunity to solve clinical targeted medication, especially the loading of insulin by metal-based nanocarriers is expected to be an effective path to enhance the therapeutic efficacy in clinical diabetic patients. Herein, around the controllable release of insulin, the basic categories and characteristics of clinical insulin are briefly introduced, and the synthesis of metal-based nanocarriers and their drug release performance for insulin are emphasized. The performance of gold-based, iron-based, copper-based, and zinc-based metal-based nanocarriers in insulin loading are analyzed, the characteristics of different metal-based nanocarriers in insulin loading are introduced through specific comparative parameter, the mechanism and typical features of insulin loading elaborated by metal-based nanocarriers, and the influencing factors of carrier size, carrier morphology, and surface functionalization on the insulin release from carriers are also discussed. Finally, reflects on existing issues and provides insights into future directions, aiming to offer technical references and new ideas for the treatment of clinical diabetes.

With the rapid development of contemporary medical technology, long-acting in situ forming preparations have emerged as a pivotal area of investigation in the field of drug delivery. Owing to its unique drug release characteristics, sustained therapeutic effect, enhanced dosing precision and other notable benefits, it represents a transformative approach for clinical treatment. In this study, an in-depth analysis of the characteristics of different technology platforms, the critical technical challenges in the process of industrialization and the emerging trends was conducted through a comprehensive review of products approved by FDA, EMA and other regulatory authorities and the research pipelines global and domestic. The findings aim to provide a strategic framework to support the industrialization of long-acting preparations in China.

Acne vulgaris is a chronic inflammatory skin disease, mainly caused by clogged and inflamed hair follicles, and is the eighth most common disease worldwide, severely affecting people's quality of life. Although several treatment options are available, such as pharmacotherapy and physiotherapy, most medications suffer from significant side effects, poor chemical stability, and low targeting efficacy. Drug delivery systems (DDS) have potential applications in acne treatment, particularly in enhancing drug efficacy and minimizing side effects. Therefore, the development of novel DDS has become the focus of current research. This review firstly analyzes the pathological mechanisms of acne vulgaris and its therapeutic targets, secondly systematically outlines the existing therapeutic approaches, and finally focuses on the potential applications of DDS in acne treatment, aiming to provide new perspectives and options for future acne treatment.

As one of the classic Chinese herbs, spore powder has a long history of medicinal value, not only in terms of therapeutic efficacy, but also through the defatting and removal of the contents can be constructed sporopollenin (SP) cavity structure, which can be used as a highly efficient drug carrier. Compared with synthetic carriers, sporopollenin, as a natural biomaterial, has demonstrated multiple applications in biomedical fields by virtue of its excellent biocompatibility, physicochemical stability, and dimensional homogeneity, and has successfully achieved efficient loading of anti-tumour drugs, proteins, and other active ingredients, and can be further developed into a smart drug delivery system by surface modification technology. In this paper, we summarise the preparation process, loading mechanism, drug delivery system design principle of sporopollenin from traditional Chinese medicine, and its research progress on intelligent drug delivery system, such as targeted delivery and responsive release, and discuss its development prospect, with a view to providing theoretical references and technological support for the promotion of the wide application of traditional Chinese medicine-derived sporopollenin microcapsules in the field of biomedicine.

Artificial intelligence (AI) has progressively integrated into various fields and plays a significant role. With the advent of China's aging population era and the growing public demand for healthcare, the application of AI in the field of clinical pharmacy has garnered considerable attention. Clinical pharmacy is crucial for ensuring the safety and effectiveness of clinical medication use by optimizing drug therapy and preventing medication errors. Due to its advantages, such as powerful data processing and analysis capabilities, and robust model-based predictive abilities, AI holds broad application prospects in the field of clinical pharmacy. This article introduces the current progress in AI applications within clinical pharmacy, focusing on its use in enhancing drug efficacy and safety. These applications include: assisting drug selection, optimizing dosage and administration timing, providing intelligent pharmaceutical services, predicting drug-drug interactions, pharmacovigilance, and preventing medication errors. Building on a review of current advancements, the article also discusses the challenges faced in implementing these AI applications. It proposes potential solutions, aiming to provide a reference for subsequent research and relevant practitioners.

This study aimed to investigate the inhibitory effects of Hua Chan Su (HCS) on non-small cell lung cancer (NSCLC) both in vitro and in vivo, and to elucidate the molecular mechanism by which it induces endoplasmic reticulum (ER) stress. Firstly, using the CCK-8 assay to assess the proliferation of human lung adenocarcinoma A549 cells, it was found that HCS significantly inhibited cell proliferation and reduced migratory capacity. Transcriptome sequencing revealed that HCS down-regulated anti-apoptotic genes such as B-cell lymphoma-2 (Bcl2) and was enriched in signaling pathways related to the cell cycle, apoptosis, and ER stress. Further studies demonstrated that HCS enhanced mitochondrial oxidative stress, increased the expression of Bcl2 associated X, decreased the expression of Bcl2, and induced apoptosis. Western blot analysis showed that HCS significantly activated the protein kinase RNA-like endoplasmic reticulum kinase (PERK)-eukaryotic initiation factor 2α (eIF2α)- activating transcription factor 4 (ATF4) signaling pathway in vitro. Combined with a PERK inhibitor, it was confirmed that HCS could trigger apoptosis through the ER stress pathway. In animal experiments, oral administration of HCS (2 and 4 g·kg^-1) for 14 consecutive days significantly inhibited the growth of NSCLC xenografts, with no observed toxicity in major organs. TUNEL staining and Western blot analysis further confirmed that HCS induced tumor cell apoptosis in vivo (all animal experiments were approved by the Institutional Animal Ethics Committee of Nanjing University of Chinese Medicine, approval number: ACU240307). Serum biochemical results suggested that HCS improved liver function and oxidative stress status. In addition, immunohistochemical analysis showed that HCS down-regulated mesenchymal markers such as vimentin, α-smooth muscle actin (α-SMA), and fibroblast activation protein 1 (FAP1), while up-regulating E-cadherin levels, significantly inhibiting the epithelial mesenchymal transition (EMT) process in NSCLC cells. In conclusion, HCS can activate the PERK-eIF2α-ATF4 signaling pathway to induce tumor cell apoptosis and inhibit EMT, indicating its potential application value in the treatment of non-small cell lung cancer.

Objective to study the efficacy and mechanism of Renzhu Jianwei Granules in treating chronic atrophic gastritis (CAG) with the precancerous lesions of gastric cancer, CAG rat models were induced using N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) comprehensive factor modeling method. After successful modeling, Renzhu Jianwei Granules were administered by gavage. Evaluating the efficacy of Renzhu Jianwei Granules by observing their effects on gastric acid pH, food intake, body weight, serum levels of pepsinogen (PG), gastrin (GAS), motilin (MTL), and inflammatory factors TNF-α, IL-1α, and IL-6 in CAG rats; Hematoxylin-Eosin (H&E) staining and Alcian blue-periodic acid Schiff (AB-PAS) staining were used to observe pathological changes in the gastric antral tissue; TUNEL fluorescence staining was used to observe apoptosis of gastric mucosal epithelial cells; immunofluorescence staining was used to detect the expression of PCNA and p53 proteins in the gastric mucosa; qRT-PCR was used to detect the mRNA expression of p53, Mdm2, Bcl-2, Bax, and Tnf-α, Il-1α, Il-6 in gastric tissue; Western blot was used to detect the protein expression of PTEN, Akt, NF-κB, p53, MDM2, Bcl-2, Bax in gastric tissue, and immunofluorescence staining technology was used to detect the protein expression of Bcl-2/Bax in gastric tissue. Animal experiments approved by the Ethics Committee of China Pharmaceutical University (approval No. 2022-09-029). The results show Renzhu Jianwei Granules significantly reduced the gastric acid pH in rats, increased food intake and body weight, and decreased the serum levels of PGI/PGⅡ, GAS, MTL, TNF-α, IL-1α, IL-6 (P < 0.01); increased the mRNA expression levels of p53, Bax in the gastric antral tissue (P < 0.05, P < 0.01), and decreased the mRNA expression levels of Mdm2, Bcl-2, Tnf-α, Il-1α, Il-6 in the gastric tissue (P < 0.01); significantly increased the protein expression levels of PTEN, p53, Bax in the gastric tissue (P < 0.05, P < 0.01), and downregulated the expression of p-NF-κB, p-Akt, MDM2, Bcl-2 proteins (P < 0.05, P < 0.01). To sum up, Renzhu Jianwei Granules treat CAG by intervening in the PTEN/Akt/p53 pathway, inducing cell apoptosis, and preventing precancerous lesions.

Cell-penetrating peptides (CPPs), such as TAT and L17E, have demonstrated significant potential in drug delivery, particularly in protein delivery. Previous studies have shown that TAT fusion proteins exhibit superior delivery efficiency compared to non-fusion counterparts and under non-covalent conjugation conditions, L17E demonstrates superior delivery efficiency compared to TAT in transporting EGFP into cells. Therefore, this study investigates the ability of TAT and L17E to deliver target proteins via covalent fusion strategies, along with their molecular-level mechanisms of action. The fusion proteins TAT-EGFP and L17E-EGFP were expressed and purified. They were evaluated for their abilities to penetrate B16-F10 cells using flow cytometry and fluorescence microscopy. The results revealed that TAT-EGFP exhibited stronger membrane-penetrating ability, with delivery efficiency positively correlated with fusion protein concentration. Structural simulations using AlphaFold3 indicated that TAT-EGFP possesses two outward-extending hydrophobic side chains, a structural feature likely enhancing its interaction with the cell membrane and thereby improving penetration efficiency. In contrast, L17E-EGFP displayed inward-retracted side chains and intramolecular electrostatic interactions, which may reduce binding sites and contact area with the cell membrane, impairing penetration efficacy. This study demonstrates that the structural characteristics of cationic cell-penetrating peptides, such as TAT and L17E (including side chain conformation, hydrophobicity, and charge distribution) are critical determinants of their delivery efficiency, providing a pivotal foundation for optimizing CPP design and advancing CPP-mediated protein drug development.

This study is based on the "indirect regulation" strategy to explore the effects of astragaloside Ⅳ (AG) and its analogs cycloastragenol (CAG) and astragenol (HG) in regulating the gut microbiota to improve Parkinson's disease (PD). Through the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mouse model, combined with behavioral experiments, immunofluorescence staining, Western blot, and 16S rRNA sequencing, the therapeutic effects and potential mechanisms of the three compounds were systematically evaluated (the animal experiment was approved by the Animal Medical Ethics Committee of Shanxi University of Chinese Medicine, the approval number is AWE202307367). The results showed that AG, CAG, and HG (30 mg·kg^-1) could significantly improve the behavioral phenotypes such as gait abnormalities and bradykinesia in PD mice, and restore the number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra region, and inhibit the expression of ionized calcium binding adapter molecule 1 (Iba-1), a marker of microglial cell activation. Among them, CAG had the best effect among the three, which was comparable to that of the positive drug levodopa (70 mg·kg^-1). The analysis of the gut microbiota indicated that all three compounds could reverse the decrease in microbiota diversity induced by MPTP and adjust the abundances of PD disease-related genera Akkermansia, Lactobacillus, and Ruminococcus. AG specifically promoted the enrichment of the genus Allobaculum, while CAG and HG significantly increased the abundance of the genus Blautia, suggesting that they inhibited neuroinflammation by regulating microbiota metabolites (such as short-chain fatty acids). The study demonstrates that AG, CAG, and HG can indirectly regulate the structure of the gut microbiota through the "gut-brain axis" and inhibit central neuroinflammation, thus improving the pathological process of PD. This provides a multi-target intervention strategy based on natural products for the treatment of PD.

Previous investigations have established that ferulic acid demonstrates anti-fibrosis effects and could inhibit the activation of hepatic stellate cell. Injury, proliferation and capillarization of hepatic sinusoidal endothelial cell are important forms of angiogenesis during liver fibrosis, and is important for liver fibrosis regression. This study investigates the effects of ferulic acid on sinusoidal capillarization and explores its anti-fibrotic mechanism. In vitro, SK-HEP-1 cells were injured by cobalt chloride, while human hepatic sinusoidal endothelial cells (HHSECs) were induced by endothelial cell growth supplement (ECGs). Cell viability was detected using thiazolyl blue tetrazolium bromide (MTT); nitric oxide (NO) and nitric oxide synthase (NOS) were visualized through the fluorescence probe method; antiangiogenesis effects were assessed using the tube formation assay and transgenic zebrafish (VEGFR: GFP). Animal experiments complied with the regulations of the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (approval No. PZSHUTCM2503280008). Mice were received intraperitoneal injection of carbon tetrachloride (CCl₄) for 6 weeks to induce hepatic fibrosis and then treated with 10 mg·kg^-1 of sorafenib, 50 and 100 mg·kg^-1 of ferulic acid for 3 weeks from the fourth week. Liver inflammation and fibrosis were assessed through serum liver function [alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB)] tests, H & E and Sirius red staining, hydroxyproline (HYP) quantification, and the immumohistochemical staining of α-smooth muscle actin (α-SMA). Sinusoidal fenestrations were observed via scanning electron microscopy (SEM), and the phenotype of liver sinusoidal endothelial cells were labeled by platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1). Results showed that ferulic acid protected SK-HEP-1 cells from CoCl₂-induced hypoxic injury, significantly increased NO and NOS levels. It suppressed the proliferation and tube formation of HHSEC, and inhibited angiogenesis of VEGFR: GFP zebrafish model. In vivo experiments, ferulic acid reduced serum AST/ALT and HYP levels and increased ALB. Histopathological analyses confirmed that it reduced inflammation and fibrosis, downregulated α-SMA expression, ameliorated sinusoid capillarization and downregulated the expression of CD31 and LYVE1. These findings indicate that ferulic acid can inhibit liver fibrosis through alleviating sinusoidal capillarization.

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.

Effect of heating rate on the dehydration process of borax was studied by using thermogravimetric analysis, and the optimal heating rate was determined. The calcined temperature, calcined time, and sample laying thickness were selected as influencing factors, with the dehydration rate, content of sodium tetraborate, fluffiness, and minimal inhibitory concentration as evaluation indices, the calcination process of borax was optimized by the method of analytic hierarchy process (AHP)-criteria importance through intercriteria correlation (CRITIC) combined with response surface test. The changes in microscopic morphology and compositional structure of borax before and after calcination were analyzed by scanning electron microscopy, infrared spectroscopy, and Raman spectroscopy. The anti-inflammatory activity of calcined borax was investigated by lipopolysaccharide (LPS)-induced RAW264.7 cell model. The antioxidant capacity of calcined borax was assessed by the scavenging rate of 2, 2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) radical for furtherly evaluating the quality of calcined borax. The results showed that the optimal heating rate for the calcination of borax was 10 ℃·min^-1, and the optimized technical conditions were as follows: the calcined temperature was 293.31 ℃, calcined time was 47.44 min, and sample laying thickness was 0.54 cm. After calcination, the microscopic morphology and compositional structure of borax were all changed, and the in vitro anti-inflammatory and anti-oxidation capacities of calcined borax were enhanced compared to those of crude one. The established calcination technique of borax is stable and feasible, which can provide guidance for the industrial production of calcined borax.

This study aimed to optimize the extraction process of Polygonatum kingianum polysaccharide (PKP), purify it to obtain the component PKP-1, analyze its chemical composition, and evaluate its anti-aging activity based on the Caenorhabditis elegans (C. elegans) model. Single-factor and orthogonal tests determined the optimal extraction conditions as follows: extraction time 2 h, liquid-to-material ratio 10∶1 mL·g^-1, and 3 extraction cycles. Subsequently, PKP was purified through ethanol precipitation, decolorization, deproteinization, dialysis, and DEAE-52 cellulose column chromatography, yielding the major fraction PKP-1. Analysis using the phenol-sulfuric acid method, BCA assay, sulfuric acid-carbazole method, Fourier transform infrared spectroscopy (FT-IR), and gas chromatography-mass spectrometry (GC-MS) revealed that PKP-1 had a total sugar content of 86.36% ± 3.16%, contained no detectable protein or uronic acid, and its monosaccharides were primarily composed of fructose, glucose, and arabinose. Anti-aging activity assays in the C. elegans model demonstrated that PKP-1 significantly enhanced the worms' stress resistance, reduced the accumulation of reactive oxygen species (ROS) and lipofuscin, and effectively prolonged their lifespan. The results demonstrate that the optimized extraction process is efficient and feasible, and the purified PKP-1 exhibits high purity, is primarily composed of fructose, glucose, and arabinose, and possesses significant anti-aging bioactivity.

The study aims to investigate the pharmacokinetics (PK) and preliminary safety of desaminotyrosine (DAT) in Sprague-Dawley (SD) rats and establish an ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for determining DAT content in blood and tissues, obtaining pharmacokinetic parameters and tissue distribution characteristics of DAT in rats after intragastric administration of three single doses and multiple doses. Evaluate the safety after 7 days of administration, including general condition, toxic reactions and mortality, organ-to-body weight ratios, hematological parameters, blood biochemistry and electrolyte levels, as well as observe pathological changes in organs. The results indicated that the detection methods conformed to the requirements for biological sample analysis. The absorption and elimination of DAT in rats occurred rapidly, with PK parameters such as C_max and AUC_0-t values increasing in accordance with the dose ratio. No significant differences were observed between single and multiple administrations. DAT was primarily distributed in the kidneys > liver > testes > lungs > heart > spleen, with minimal penetration through the blood-brain barrier. Administration for 7 days at doses ≥100 mg·kg^-1·d^-1 induced gastrointestinal irritation, body weight loss, and liver/kidney injury. The UPLC-MS/MS analysis in the study was sensitive, accurate, and rapid. The PK parameters aligned with a linear PK profile at single doses ranging from 25 to 125 mg·kg^-1, with no accumulation observed after multiple doses. DAT demonstrated good safety at the dose of 50 mg·kg^-1·d^-1, which will provide a basis for further development of its pharmaceutical value. This experiment was approved by the Laboratory Animal Ethics Committee of Guangdong Provincial Hospital of Traditional Chinese Medicine (Grant No: 2021042).

Triple-negative breast cancer (TNBC) is characterized by high invasiveness, a high risk of recurrence and metastasis, and poor prognosis. The accumulation of lactate in the tumor microenvironment produced by tumor cell glycolysis is a key factor driving the malignant progression of TNBC. In this study, we developed a lactate metabolism-regulating self-assembled galloflavin-Fe lipid peroxidation accelerator (SGF) to inhibit the growth of TNBC. The system was constructed by coordinating iron ions with the hydroxyl groups of galloflavin to form a metal-polyphenol network, which encapsulates the drug sorafenib. By adjusting the drug loading ratio of sorafenib to galloflavin at 1:1, SGF nanoparticles with a size of 136.20 ± 0.83 nm and a polydispersity index of 0.103 ± 0.012 were prepared, achieving efficient co-loading of both drugs. The metal-polyphenol network of SGF exhibits photothermal conversion properties, generating localized heat under 808 nm laser irradiation, effectively killing tumor cells. Under the low pH conditions of the tumor microenvironment and lysosomes, iron ions and galloflavin dissociate to release sorafenib, accelerating the Fenton reaction through iron ion supplementation and glutathione downregulation, which cooperatively promotes lipid peroxidation in tumor cells. Furthermore, galloflavin inhibits lactate dehydrogenase A, downregulating the conversion of pyruvate to lactate and reducing lactate production, thereby improving the acidic tumor microenvironment and efficiently suppressing the progression of TNBC. The SGF nanosystem designed and constructed in this study integrates three synergistic mechanisms-photothermal effect, lipid peroxidation induction, and lactate metabolism regulation to provide a synergistic and precise strike against TNBC and its high-lactate microenvironment, offering a new therapeutic strategy to improve the clinical prognosis of this highly invasive cancer.

The genus Fusarium is a prevalent contaminant in medicinal herbs, posing a dual threat to both the effective components and safety of traditional Chinese medicine (TCM), as well as a common pathogen in agriculture and clinical settings. Accurate identification of closely related species within this genus has always been a key challenge. In this study, we employed analysis of whole-GEnome (AGE) to conduct bioinformatics analysis on 304 genomes from 173 species of Fusarium, successfully constructing a species-specific target sequence library. The number of specific target sequences predominantly ranges from 10 001 to 50 000. To validate the reliability of the species-specific target sequences, we selected seven representative species of high concern in contaminated medicinal herbs and agricultural pathogens: Fusarium oxysporum, F. solani, F. fujikuroi, F. sambucinum, F. culmorum, F. incarnatum, and F. equiseti. Species-specific target sequence was selected from each species and subjected to detection using Sanger sequencing and CRISPR-Cas12a technology. The results showed that the species-specific target sequences exhibited high specificity, solving the identification challenge of closely related species F. incarnatum and F. equiseti. Furthermore, AGE enabled the visualization of identification results, offering an advantage for field detection. This study demonstrates that AGE can accurately identify closely related species of the genus Fusarium, providing technical support for the safety monitoring and quality assurance of medicinal herbs.