Latest ArticlesA HPLC-QAMS method was established for the simultaneous determination of 15 components in Xiao'er Kechuanling oral liquid, providing a method for its quality control. The analysis was performed on a 30 ℃ Kromasil C18 column (250 mm × 4.6 mm, 5 μm), with the mobile phase comprising of acetonitrile-0.1% formic acid flowing at 1.0 mL·min-1 in a gradient elution manner. The injection volume was 5 μL and the detection wavelength was set at 254 nm. Chlorogenic acid was used as an internal standard to calculate the relative correction factors of the other fourteen components, after which the content determination was made. Cluster analysis and principal component analysis were conducted on 22 batches of samples. Fifteen components showed good linear relationships within their own ranges (r ≥ 0.999 5), whose average recoveries were 96.52%-99.02% with the RSDs of 0.57%-1.40%. The result obtained by HPLC-QAMS approximated those obtained by external standard method. Cluster analysis of 22 batches of samples was divided into four classes. Four principal components were extracted by principal component analysis, and the contribution rate reached 81.706%. This accurate and specific method can be used for the quality control of Xiao'er Kechuanling oral liquid.
Protoberberine alkaloids exhibit significant antitumor and angiogenesis-regulating activities, yet their specific effects on angiogenesis intervention and metabolic regulatory mechanisms remain systematically elucidated. In this study, ultra-high performance liquid chromatography coupled with quadrupole/orbitrap high-resolution mass spectrometry (UHPLC-Q Exactive Orbitrap HRMS) was employed to identify the chemical composition profiles of Coptidis Rhizoma and Corydalis yanhusuo. The anti-angiogenic effects of the major protoberberine-type alkaloid components were evaluated using the quail chorioallantoic membrane (qCAM) model and human umbilical vein endothelial cell (HUVEC) proliferation assays, while vascular endothelial growth factor receptor 2 (VEGFR2) mRNA levels were detected via qPCR experiments. Further analysis was conducted using desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) technology to examine the metabolic profile changes induced by the intervention of key anti-angiogenic components. The interaction between these components and critical angiogenesis targets was characterized by integrating network pharmacology with molecular docking technology, followed by a "structure-activity" analysis. A total of 13 alkaloid components were identified in Coptidis Rhizoma, and 17 alkaloid components were identified in Corydalis yanhusuo, with protoberberine-type alkaloids being the predominant type in both. Both the qCAM model and HUVEC experiments demonstrated that oxyberberine exhibited the most significant anti-angiogenic activity. These metabolic abnormalities characterized by suppressed energy and lipid metabolism, may inhibit angiogenesis by affecting cell membrane structure (phosphatidic acid, sphingomyelin, phosphatidylcholine), signal transduction (VEGFR2), oxidative stress, and inflammatory responses. Molecular docking and network pharmacology analyses demonstrated that C-8 oxidation enhances oxyberberine's binding affinity to EGFR and JAK2 through reduced binding energy and increased weak interactions, ultimately conferring superior anti-angiogenic efficacy compared to berberine. These findings systematically elucidate the structure-activity relationship and metabolic basis of protoberberine-type alkaloids in angiogenesis modulation, providing novel insights for anti-angiogenic drug development.
Carbon quantum dots (CDs) are a class of zero-dimensional carbon nanomaterials with remarkable fluorescent properties, consisting of carbon nanoparticles with dimensions below 10 nm. Due to its advantages of excellent optical properties, good water solubility and biocompatibility, it shows great potential in photothermal/photodynamic therapy of cancer. In recent years, carbon quantum dots prepared from traditional Chinese medicine as a carbon source have attracted extensive attention from scientists. In this study, we synthesized carbon quantum dots of five Chinese medicines, Ganoderma lucidum, Poria cocos, Dendrobium officinale, Coix lacryma, and Ginger, in one step by a conventional hydrothermal method, and screened out the Ganoderma lucidum CDs with the best fluorescence quantum yields and photothermal conversion properties. The results show that the Ganoderma lucidum CDs prepared in this study, with a particle size of (6.40 ± 1.31) nm, have good in vivo and in vitro fluorescence imaging properties, demonstrating certain tumor targeting properties. And they can generate photothermal/photodynamic synergy to efficiently kill pancreatic cancer cells under the mediation of near-infrared laser. The animal experiment has been approved by the Animal Ethics Committee of Guizhou University of Chinese Medicine (No. 20230022).
O-Methyltransferases (OMTs) are key enzymes involved in the methylation modification of benzylisoquinoline alkaloids (BIAs), and their functional studies contribute to elucidating the molecular mechanisms underlying BIA biosynthesis. In this study, a novel OMT gene was successfully cloned from Stephania cephalantha and subjected to bioinformatics analysis and in vitro functional characterization. The coding sequence (CDS) of ScOMT26 is 1 092 bp in length, encoding a protein of 363 amino acids with a molecular formula of C1827H2879N467O543S18, classified as a stable hydrophobic protein. In vitro enzymatic assays demonstrated that ScOMT26 catalyzes the methylation of the C4′-hydroxyl group of coclaurine to produce 4′-methylcoclaurine. The optimal reaction conditions were identified as pH 7.0 in 50 mmol·L-1 potassium phosphate buffer at 25 ℃. This study represents the first report of cloning and functional characterization of an OMT from S. cephalantha, providing critical insights into the role of OMT genes in the biosynthetic pathway of benzylisoquinoline alkaloids.
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.
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