The property theory of Chinese medicine is a distinctive feature and essence of traditional Chinese medicine (TCM) theory, among which the five-flavor property theory serves as its core component. The five-flavor property theory originated from imagery thinking and was developed through deductive reasoning. It has a long history of formation, with complex and diverse content, and its systems and concepts vary greatly, lacking systematic sorting and analysis. For a long time, there has been a lack of modern research. Therefore, establishing an overall research approach and technical methods for modern research on the five-flavor property is of great significance for promoting modern research on TCM. With the support of the key project of the National Natural Science Foundation of China, this paper has established a systematic modern research approach and method for the five-flavor property of TCM. Based on specific research work, modern research approach and characterization methods were proposed from aspects such as the original semantics, functional attributes, relationship with meridians, separation of properties and effects, and compatibility rules. Finally, based on the basic understanding of the historical, dynamic and universal connections of the theory of five-flavor property, a research approach combining systems theory and reductionism and a research model of the "property-efficacy-component" ternary theory were proposed.

The theory of traditional Chinese medicine (TCM) is fundamentally grounded in a holistic perspective, wherein the properties and effects of crude drugs illustrate its action mechanisms at different levels. However, a notable discrepancy persists between the traditional theory of drug properties and modern research on drug efficacy, highlighting the need for interdisciplinary approaches to elucidate their scientific connections. This article reviews research approaches and case studies that utilize systems biology methods to analyze the core network and key modules of drug properties, as well as employ chemical biology techniques to elucidate the interaction mechanisms between active components and their targets. Herein, a chemobiological research paradigm integrating systems theory with reductionism was proposed, leveraging the unique advantages of TCM and its properties and effects. By integrating molecular probe tracing and identification, multi-omics analysis, network prediction, and dynamic regulatory network interpretation of drug properties, this approach overcomes the limitations of single-target or efficacy research and establishes a framework for mutual validation between "the whole" and "the part". The dual methodology serves as a critical entry point for tackling medical challenges, facilitating a transition from observing phenomena to uncovering essence and from dealing with ambiguity to achieving precision. This approach effectively illuminates the fundamental nature of the medicinal properties and pharmacodynamic effects. Simultaneously, by refining the evaluation system for TCM property theories and constructing a "properties-effects-compositions" correlation framework, the bottleneck in quality control of TCM can be effectively addressed, thereby highlighting the critical role of chemical biology in driving innovative research in TCM.

The "unclear substances and mechanisms" underlying the efficacy of Chinese material medica is a bottleneck limiting its modernization and internationalization. As the fundamental attribute that reflects the efficacy of Chinese material medica, the concept of "Five flavors" serves as the theoretical basis guiding its clinical application. Chemical biology, utilizing target fishing technology and molecular interaction analysis, has become a comprehensive approach to elucidate the targets and underlying molecular mechanisms of Chinese material medica. This review focuses on studies of the effective substances found in bitter-propertied Chinese material medica as an example to explore chemical biology strategies based on the flavors of Chinese material medica, providing a research perspective for interpreting effective substances through the lenses of the "Five flavors" theory.

The properties of traditional Chinese medicines (TCM) include five main aspects: four Qi, five flavors, ascending and descending, floating and sinking, and channel tropism and toxicity. Through processing, the properties can be enhanced, moderated, or altered to satisfy different clinical needs. Previous analyses of changes in the properties of traditional Chinese medicine caused by processing have mostly been based on traditional Chinese medicine theory; limited research has examined these changes using modern scientific methods. Using "traditional Chinese medicine processing chemical biology" as a guide, a strategy of "target identification-ligand fishing" is used to establish a chemical biology-driven platform to study the chemical basis, and direct target and molecular mechanism of differences in efficacy of traditional Chinese medicines caused by processing, so as to reveal the scientific connotation of the changes in the properties of traditional Chinese medicine processing. It would provide guidance to enrich processing theory, decipher the processing technique, develop the industry, and also to provide strong support to optimize the processing technology, establish decoction pieces quality standards, and ensure clinical efficacy. Ultimately, it helps to expand the paradigm of traditional Chinese medicine processing research in the new era.

Traditional Chinese medicine (TCM), as a treasure of traditional medicine, has complex and diverse active ingredients and mechanisms of action. For the purpose of thoroughly investigate the direct targets of active ingredients in traditional Chinese medicine, promote research into the efficacy mechanisms of TCM, and advance new drug development. This paper presents a review of new technologies that are widely used or have potential in the field of target discovery for active ingredients in TCM. It is intended to provide new perspectives and ideas for related fields. Currently, active ingredient target discovery technologies for TCM are mainly divided into labelling methods and non-labelling methods. Labelling methods identify and capture targets through the design of specific molecular probes, offering high sensitivity and specificity. The non-labelling method identifies targets by monitoring changes in biophysical properties such as target protein stability. It is simple, accurate, and does not require drug modification. Both approaches have their unique advantages, revealing the mechanisms of interaction between active components of traditional Chinese medicine and biomolecules from different perspectives. This provides scientific basis and innovative ideas for the study of the efficacy mechanisms of traditional Chinese medicine and the development of new drugs. This paper reviews the research achievements and methodological advances from February 2006 to January 2025, in the identification of active components in TCM, natural products research, and the application of proteomics technologies for target identification. The review focuses on research methodologies and application dimensions, aiming to supply traditional drug discovery approaches and provide insights for future studies in this field.

Chemical proteomics is a technology widely used in the discovery of active ingredients in traditional Chinese medicine (TCM) and the identification of their targets, enabling the systematic elucidation of TCM's mechanisms of action. Its core lies in designing specific molecular probes to accurately identify target proteins of active TCM components, providing a theoretical basis for revealing pharmacodynamic material foundations and supporting new drug development. China is rich in herbal medicine resources, yet the specific mechanisms and "scientific validity" of TCM have long faced skepticism and criticism. Due to its high specificity and systematic approach, chemical proteomics has become a key tool in promoting the modernization of TCM research. This review summarizes studies from the past five years on identifying targets of active TCM ingredients using chemical proteomics, analyzing both label-based and label-free methods, and discusses the advantages and limitations of different identification strategies. The aim is to provide methodological references for target identification of active TCM components and contribute to the modernization of TCM research.

The clinical efficacy of Chinese medicines (CMs) fundamentally relies on their material basis, with active constituents serving not only as the cornerstone of CM's pharmacological activity, but also as a valuable resource for innovative drug research and development. However, the precise clinical application and internationalization of CMs have long been hindered by limited understanding of the molecular targets, modes of action, and pharmacological mechanisms underlying their functional components. Novel biochemical and biophysical approaches, in combination with recent advancements in mass spectrometry (MS)-based techniques, instrumentation, and data analysis pipelines, have significantly facilitated the identification of molecular targets and elucidation of pharmacological mechanisms of functional components in CMs. This review summarizes recent advances in the target identification of functional components in CMs and the characterization of small molecule-target protein interactions. We discuss the principles and technical aspects of small molecule-labeled and label-free target deconvoluted strategies leveraging biological mass spectrometry, providing a comparative analysis of their application scopes, strengths and limitations. This review article also addressed the recent progress made by the scholars in characterizing the interaction modes between functional components of CMs and target proteins, using biomass spectrometry and other cutting-edge technologies. The relevant research strategies, methodologies, and application cases are expected to provide a series of solutions and research models for the discovery of targets and in-depth elucidation of pharmacological mechanisms of CMs pharmacodynamic substances.

In the field of prevention and treatment of metabolic diseases, liver is the core metabolic organ, and its functional status has an important impact on the development of diseases and the selection of treatment strategies. In recent years, with the in-depth study of liver receptor molecules, asialoglycoprotein receptor 1 (ASGR1) has gradually attracted attention because of its role in glycoprotein recognition, lipid metabolism regulation, and immune regulation. Although studies have suggested that ASGR1 dysfunction is closely related to a variety of metabolic diseases, it is still controversial to directly use ASGR1 as a therapeutic target, and further studies are needed to explore the feasibility and efficacy of ASGR1 as a liver target. On the other hand, ASGR1-mediated liver-targeted delivery systems have shown clinical application potential in multiple drug development. This article systematically reviews the physiological functions of ASGR1 and its research progress in metabolic diseases, focusing on its molecular regulatory mechanisms and drug application prospects, in order to provide reference for the diagnosis and treatment strategies of liver-related metabolic diseases.

Epilepsy and its comorbidities affect the health of tens of millions of people, characterized by complex and poorly understood etiology. While anti-seizure medications (ASMs) remains the primary treatment approach, antiepileptic drugs face issues like drug resistance and severe side effects, highlighting an urgent need for novel drugs and therapeutic strategies. The gut microbiota plays a crucial role in the pathogenesis of central nervous system diseases. They can interact with the brain through the nervous, endocrine, immune and metabolic systems, thereby influencing the course of the disease. Some researches have indicated that gut microbiota-targeted interventions, such as the ketogenic diet (KD), fecal microbiota transplantation (FMT), and probiotics, demonstrate the significant potential in the treatment of epilepsy. However, there are still many unsolved mysteries regarding the role of gut bacteria in the onset and treatment of epilepsy. Investigating the regulatory role of the gut microbiota in epilepsy and its comorbidities holds great significance.

Alzheimer's disease (AD), a prevalent neurodegenerative disorder, significantly impairs patients' cognitive functions and quality of life, with no definitive cure currently available. Consequently, there is an urgent necessity to explore and develop promising novel drug molecules. Quinoline and isoquinoline derivatives have emerged as key candidates in AD research owing to their diverse pharmacological activities, particularly in inhibiting the aggregation of amyloid β-protein (Aβ), reducing the phosphorylation of tubulin-associated unit (Tau) proteins, modulating the cholinergic system, and exhibiting anti-inflammatory and antioxidant properties. This article provides an overview of the latest advancements in the study of quinoline and isoquinoline derivatives for AD, emphasizing their performance in both in vitro and in vivo biological evaluations. It further elucidates their mechanisms of action in combating Aβ accumulation, regulating Tau dephosphorylation, ameliorating cholinergic system imbalances, and suppressing neuroinflammatory responses, serving as a reference for further research into the application of quinoline and isoquinoline derivatives in AD treatment.

Protein arginine methylation is an important post-translational modification and epigenetic regulation mechanism. In mammalian cells, protein arginine methyltransferases (PRMTs) catalyze the methylation of protein arginine residues. Eleven PRMTs have been found in mammals and plants to date. PRMTs catalyze the transfer of methyl groups from S-adenosyl-L-methionine to the guanidinium nitrogen atom of arginine residues in substrates to produce arginine methylated proteins, thus playing key roles in the control of many biological processes such as DNA damage repair, RNA splicing processing, transcription, translation, cell signal transduction, cell cycle regulation, protein-protein interactions, protein-nucleic acid interactions. Dysregulation of protein arginine methylation mediated by PRMTs is closely related to the occurrence and development of cancer. Therefore, the development of anticancer drugs targeting PRMTs has also become a research hotspot in the field of cancer treatment. This paper reviews the role and molecular mechanisms of PRMTs in the pathological process of colorectal cancer, and introduces the research progress of small molecule drugs targeting PRMTs in colorectal cancer therapy, aiming to provide a theoretical basis and important clues for the development of small molecule drugs isolating from natural products and targeting at PRMTs in colorectal cancer treatment.

Proteostasis is the fundamental process by which cells maintain their normal functions. It involves maintaining the dynamic equilibrium of protein synthesis, folding, transport, and degradation. Disruption of proteostasis leads to the accumulation of misfolded proteins and a deficiency of functional proteins, triggering a pathological cascade—a hallmark of various diseases. Traditional drug development primarily focuses on inhibiting the activity of disease-causing proteins. However, many proteins are considered "undruggable" due to the absence of well-defined binding sites or functional redundancy. Recently, the targeted protein degradation (TPD) has provided a novel therapeutic strategy for traditionally undruggable targets. In this review, we systematically analyze how TPD overcomes the limitations of undruggable targets by remodeling the proteostatic network, covering the classification of protein degradation technologies, molecular mechanisms, and disease applications. Furthermore, we explore the clinical translation potential of TPD technologies, providing novel therapeutic strategies and theoretical frameworks for complex diseases.

The association rule analysis is a model that describes the correlation between two or more things. The Apriori algorithm is a classic method of association rule analysis used to discover frequent item sets from large-scale datasets. In this review, the Apriori algorithm was used to analyze the usage rules of excipients from 28 formulations of commercially available orally disintegrating tablets (ODTs) and 77 formulations of ODTs collected from literatures. Statistical analyses were conducted on the usage frequency of excipients, preparation processes, and tablet weight of the ODTs. Meanwhile, the influence of mannitol on the taste of ODTs was explored. The results show that commercially available ODTs focus on the addition of flavoring and taste-masking agents as well as colorants to improve compliance. ODTs in literatures focus on adding glidants and flavoring agents to improve the quality of ODTs. Powder direct compression is currently the mainstream process for preparing ODTs. Mannitol, microcrystalline cellulose, and magnesium stearate are the core excipients for the composition of ODTs prepared by this method. Crospovidone is the most commonly used super-disintegrating agent, and aspartame is the most commonly used flavoring agent. Moreover, mannitol can improve the taste of ODTs to a certain extent and reduce the addition of sweeteners. Finally, the development of excipients for ODTs was prospected. Through statistics, analysis and induction, this review aims to provide references for the formulation design of ODTs as well as application and development of excipients for ODTs.

Plant-derived extracellular vesicles are a kind of nanoscale vesicles with lipid bilayer membrane structure actively secreted by plant cells. As important media for intercellular communication in plants, extracellular vesicles are rich in a variety of biologically active molecules, including nucleic acids, proteins and lipids, and play key roles in intercellular material transport and information transmission. Due to excellent biocompatibility, low immunogenicity and natural cross-species delivery ability, plant-derived extracellular vesicles have become an ideal choice for new drug delivery carriers, which can efficiently load nucleic acid drugs, protein preparations and hydrophobic drug molecules. In recent years, with the rapid development of nanomedicine technology, the application of plant-derived extracellular vesicles in targeted drug delivery systems has made significant progress. This review systematically summarizes the separation and purification technology, stability, targeting, drug loading strategy of plant-derived extracellular vesicles and their latest application results as drug delivery carriers, in order to provide theoretical reference for related research.

Analyzing the molecular mechanisms of classic traditional Chinese medicine (TCM) formulas is essential for interpreting TCM principles through modern scientific frameworks, and serves as a cornerstone for establishing dominant disease categories of TCM. However, the lack of correlation with disease progression characteristics and clinical efficacy has become a scientific issue in this field that requires urgent resolution. To address this issue, this paper employs the classic formulas "Yuquan Pill" and "Xiaoke Prescription" for the treatment of "Xiaoke", a dominant disease in TCM, as a demonstration. Adhering to an "originating from clinic-returning to clinic" strategy, omics integrated with generative artificial intelligence is employed to identify active molecules and their biological associations in the formula, thereby uncovering integrated feature PANEL of disease progression and outcomes. This approach bridges the "clinical-basic" gap, enabling the characterization of emergent pharmacodynamic features that arise from metabolic network oscillations and chaotic dynamics. It reveals the synergistic principles of active molecules and their biological mechanisms in classic formulas. Returning to clinical practice, the focus is on validating the active molecules and discovering novel multi-component formulas with superior efficacy to that of classical formulas. This approach establishes a new paradigm for clearly elucidating and comprehensively clarifying the complex active molecules in classic TCM formulas.

Harpagoside (HPG) is an iridoid compound derived from Scrophularia ningpoensis Hemsl. This study aimed to investigate the therapeutic effect of HPG on metabolic dysfunction-associated steatohepatitis (MASH) and elucidate its underlying mechanisms. MASH was induced in mice using a methionine-choline-deficient diet (MCD). The efficacy of HPG in improving MASH was assessed through serum biochemical indexes, liver pathological changes, oxidative stress markers, and inflammatory responses (this experiment was approved by the Laboratory Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine, with approval number PZSHUTCM2305180005). To further explore the mechanism of action, Western blot (WB), quantitative real-time polymerase chain reaction (qPCR), and in vitro cell models were employed. The results demonstrated that HPG (30 and 60 mg·kg^-1) significantly mitigated liver damage (P < 0.05, P < 0.001), reduced hepatic lipid accumulation (P < 0.05, P < 0.001), lowered the elevated non-alcoholic fatty liver disease (NAFLD) activity score (NAS) (P < 0.05, P < 0.01, P < 0.001), alleviated hepatic oxidative stress injury, and suppressed hepatic inflammation in MCD-induced MASH mice (P < 0.05, P < 0.01, P < 0.001). WB and qPCR analyses revealed that HPG promoted the nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2) in the livers of MCD-fed mice and in AML-12 cells (P < 0.05). Additionally, it reduced the nuclear accumulation of nuclear factor kappa B (NF-κB) in the livers of MCD-fed mice and in THP-1 cells (P < 0.05). Collectively, these findings suggest that HPG improves MASH through alleviating liver oxidative and inflammatory injury by activating Nrf2 antioxidant signaling pathway and inhibiting NF-κB inflammatory signaling pathway.

Skin aging is a complex pathological process mediated by a combination of endogenous metabolic dysregulation and exogenous ultraviolet (UV) radiation, with oxidative stress due to excessive accumulation of reactive oxygen species (ROS) as the central driver. Rare ginsenoside Rh1 is a natural compound with antioxidant and anti-inflammatory properties, but its mechanism of action in UV-induced skin photoaging remains unclear. This study aims to investigate the protective effect of Rh1 against UV-induced skin aging and the underlying molecular mechanisms. All animal experiments were approved by the Animal Ethics Committee of West China Hospital, Sichuan University (approval number: 20241230001). To evaluate the anti-photoaging effect of Rh1, we established photoaging models in BALB/c mice and human dermal fibroblasts (HDF). In vivo experiments showed that Rh1 (25 and 50 μmol·L^-1) significantly alleviated UV-induced skin thickening, erythema, and moisture loss, reduced the expression of pro-apoptotic protein Bax, and up-regulated anti-apoptotic protein Bcl-2. In vitro experiments indicated that Rh1 (12.5, 25, and 50 μmol·L^-1) reduced UVB (UV wavelength 280-320 nm)-induced ROS accumulation, oxidative damage, and the proportion of senescence-associated β-galactosidase (SA-β-Gal) positive cells. Mechanistic studies demonstrated that Rh1 promotes nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation by activating sirtuin 3 (Sirt3), thereby upregulating downstream heme oxygenase-1 (HO-1) expression. Sirt3 siRNA experiments confirmed that gene silencing can blocks Rh1 from activating the Nrf2/HO-1 pathway, weakening its ability to inhibit ROS production and delay cellular aging. In summary, Rh1 alleviates UV-induced oxidative damage and skin aging through the Sirt3/Nrf2/HO-1 signaling axis, providing a new strategy for the development of anti-photoaging drugs targeting the antioxidant pathway.

α6/α3β2β3 nicotinic acetylcholine receptors (nAChRs) subtype is widely expressed in mesolimbic dopaminergic pathway and other regions, which plays a vital role in modulating the release of multiple neurotransmitters and drug reward mechanisms. It has become a potential therapeutic target for the treatment of various neuropsychiatric disorders and drug addiction. However, most ligands identified with high affinity and selectivity targeting α6/α3β2β3 subtype showed limited subtype discrimination against the closely related α3β2 subtype. Furthermore, the molecular mechanisms underlying ligands interact with α6/α3β2β3 nAChR remain absent. In this study, the related approaches of site-directed mutagenesis of receptor, in vitro transcription and electrophysiological assay were utilized to establish the drug screening models of wild-type α6/α3β2β3 nAChR and its α6/α3 subunit single-point mutants. The effects led by single amino acid substitution to the function of α6/α3β2β3 nAChR were also evaluated. The animal experimental protocol involved in this study has been approved by the Ethics Committee of Guangxi University (Approval No: GXU-2023-0249). As the results showed, the half maximal effective concentration (EC₅₀) for ACh activating α6/α3β2β3 nAChR was 18.5 μmol·L^-1. All 7 single-point mutations of α6/α3 subunit resulted in increase of the agonist sensitivity, while the EC₅₀ of ACh towards mutants α6/α3[V112E]β2β3、α6/α3[T147S]β2β3、α6/α3[E152K]β2β3 nAChR decreased to the greatest extent (EC₅₀s were 3.5, 4.4, and 2.0 μmol·L^-1, respectively, which were 0.1-0.2-fold relative to that of the wild-type receptor). These results established models for the research of structure-function relationship of α6/α3β2β3 nAChRs and molecular mechanism of ligand-receptor specific binding, as well as provided theoretical foundation for the design and optimization of selective drug leads targeting α6/α3β2β3 nAChRs.

To explore the protective effect of benzoylpaeoniflorin (BP), an active component of Paeonia lactiflora, on cerebral ischemic reperfusion injury (CIRI) in rats and its molecular mechanism, middle cerebral artery occlusion and reperfusion (MCAO/R) model was established, and oxygen-glucose deprivation/recovery (OGD/R) model was established by using rat adrenal pheochromocytoma nerve cells (PC12) to carry out experimental research. The results show that BP can significantly improve the neuronal apoptosis induced by CIRI, reduce the area of cerebral infarction, the neuronal damage in hippocampus, the loss of Nissl bodies and the mitochondrial damage. Western blot results showed that BP could significantly down-regulate the expression of pro-apoptosis proteins (Caspase3, Bax) and up-regulate the expression of anti-apoptosis protein (Bcl-2). qRT-PCR showed that BP down-regulated the gene expression levels of pro-inflammatory factors (TNF-α, IL-1β, IL-6) and pro-apoptosis proteins (Caspase3, Bax), and up-regulated the expression level of anti-apoptosis protein (Bcl-2). Transcriptome analysis showed that the differential genes regulated by BP were mainly concentrated in TNF signaling pathway, rheumatoid arthritis, IL-17 signaling pathway and so on. To sum up, BP can reduce inflammatory reaction and oxidative stress, inhibit neuronal apoptosis, and alleviate the nerve injury of CIRI in rats, which provides experimental basis for the clinical application of BP in the treatment of ischemic stroke. All experimental procedures were approved by the Experimental Animal Ethics Committee of Zhejiang Chinese Medical University (approval number: 20241209-15).

This study aims to observe the effects of Guben Fangxiao Decoction (GBFXD) on inhibit ferroptosis of airway epithelial cells by regulating iron metabolism, thereby playing a role in the prevention and treatment of the asthma remission. The animal experiments have been approved by the Ethics Committee of the Animal Experiment Center of Nanjing University of Chinese Medicine (approval number: 202401A044). Female Balb/c mice were randomly divided into control group, model group, GBFXD low-, medium-, and high-dose groups [12, 24, 36 g·kg^-1 (crude drug)], and montelukast sodium group (2.6 mg·kg^-1). Except for the control group, the other groups of mice were used to establish a mouse model of the remission period of asthma with ovalbumin. Hematoxylin-eosin staining (HE) of the lung tissue of mice was observed and the inflammation score was conducted; the levels of interleukin 33 (IL-33), tumor necrosis factor-α (TNF-α), and high mobility histone B1 (HMGB1) in the lung tissue were detected by enzyme-linked immunosorbent assay (ELISA); the expression of solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), and long-chain acyl-CoA synthase 4 (ACSL4) in the lung tissue was observed by immunohistochemistry; the content of lipid peroxides (LPO) and ferrous ions (Fe²⁺) in the lung tissue was detected. The protein expression levels of SLC7A11, GPX4, ACSL4, transferrin receptor 1 (TFR1), ferritin heavy chain 1 (FTH1), nuclear receptor co-activator 4 (NCOA4), and ferroportin 1 (FPN1) in 16HBE of each group were detected by Western blot; the expression of Fe²⁺ in 16HBE of each group was detected. The results of HE staining of lung tissue showed that GBFXD could reduce inflammatory infiltration in the periairway region of mice (P < 0.05). The results of ELISA showed that GBFXD down-regulated the levels of IL-33, TNF-α and HMGB1 in lung tissue of mice (P < 0.05). Immunohistochemical results showed that GBFXD could up-regulate the expression of SLC7A11 and GPX4 in the lung tissue of mice, and down-regulate the expression of ACSL4 (P < 0.05). Biochemical results showed that GBFXD treatment reduced LPO accumulation in lung tissue of mice and Fe²⁺ accumulation in lung tissue and 16HBE cells (P < 0.05). Western blot results showed that GBFXD up-regulated the expressions of SLC7A11, GPX4, FTH1, FPN1 in 16HBE cells, and down-regulated the expressions of ACSL4, TFR1 and NCOA4 in 16HBE cells (P < 0.05). These results suggest that GBFXD can inhibit ferroptosis of airway epithelial cells, reduce airway epithelial damage, alleviate airway inflammation, and prevent and treat the remission period of asthma. Its mechanism of inhibiting ferroptosis may be related to the regulation of iron metabolism-related protein expression and the reduction of Fe²⁺ accumulation.

Gastric cancer is a leading global malignancy with high incidence and mortality rates, highlighting the urgent need for novel therapeutic agents. As a natural product in the traditional Chinese medicine Arnebiae Radix, the anti-gastric cancer effects of β,β-dimethylacrylalkannin (β,β-DAL) have not been reported. This study aimed to evaluate the in vitro anti-gastric cancer effects of β,β-DAL and elucidate its underlying mechanisms. Through CCK-8 assay, colony formation experiment, and EdU staining, we demonstrated that β,β-DAL significantly suppressed the proliferation of human gastric cancer AGS and HGC-27 cells in a dose-dependent manner, with 48-hour IC₅₀ values of approximately 0.28 and 0.15 μmol·L^-1, respectively. RNA sequencing analysis indicated that the anti-gastric cancer effect of β,β-DAL is associated with the regulation of ferroptosis. Flow cytometry analysis revealed that β,β-DAL upregulated the ROS levels in AGS and HGC-27 cells. In addition, β,β-DAL increased the level of lipid peroxidation in AGS and HGC-27 cells, and the ferroptosis inhibitor ferrostatin-1 reduced their sensitivity to β,β-DAL. Western blot analysis showed that β,β-DAL downregulated the protein expression of stearoyl-CoA desaturase 1 (SCD1) and nuclear factor erythroid 2-related factor 2 (Nrf2), as well as inhibited the ratio of SCD1 to acyl-CoA synthetase long-chain family member 4 (ACSL4) in human gastric cancer AGS and HGC-27 cells. In summary, β,β-DAL may exert anti-gastric cancer effects by inducing ferroptosis in human gastric cancer cells through upregulating ROS levels, increasing intracellular lipid peroxidation, and inhibiting the antioxidant SCD1/Nrf2 pathway. This study provides a candidate drug for gastric cancer treatment and lays the groundwork for further research into the anti-gastric cancer effects of β,β-DAL.

The study aims to investigate the interventional effect of peroxydehydrotumulosic acid (PHA) in Poria cocos on allergic asthma mice, and to investigate its mechanism of action based on metabolomics. Male BALB/c mice were randomly divided into normal group (CON), model group (M), positive drug montelukastna group (Y, 1.3 mg·kg^-1), PHA low-dose group (PHA-L, 15 mg·kg^-1), and PHA high-dose group (PHA-H, 30 mg·kg^-1). The mouse model of allergic asthma was established by intraperitoneal injection of ovalbumin (OVA) and aluminium hydroxide adjuvant for sensitisation and OVA nebulisation for excitation. The corresponding drugs were given by gavage 30 min before modelling, and the drugs were administered for 7 consecutive days. 24 h after the last administration of the drugs, the mice were tested for cough and asthma indexes, lung function and lung coefficient, the mice were stained with hematoxylin-eosin (HE) to observe the pathological changes of the lung histology, and the mice were stained with Masson to observe the level of collagen fibre deposition, and the levels of inflammatory factors in the serum and alveolar lavage fluid of the mice were measured by enzyme-linked immunosorbent assay (ELISA) and flow cytometry to determine the levels of inflammatory factors in the mice. Apoptotic cell levels in lung tissue and Th17 and Tregs cell levels in blood were detected by flow cytometry, and small molecule metabolites were analysed by liquid-liquid mass spectrometry (LC-MS) in serum samples of mice of different treatment groups. The metabolic pathway enrichment analysis was used to investigate the biometabolic pathways involved in the characterised metabolites. The results indicated a comparison with group M, PHA significantly improved lung function, reduced lung coefficient, attenuated lung histopathological damage and collagen fibre deposition, significantly down-regulated the levels of interleukin 4 (IL4), immunoglobulin E (IgE), interleukin 17A (IL17A) in blood and tumor necrosis factor-α (TNF-α) in alveolar lavage fluid, inhibited apoptosis and the generation of Th17 cells, and increased the level of Tregs cells in lung tissue. Metabolomics analysis of endogenous substances in the M and PHA groups separated significantly, and 63 differential metabolites were screened, mainly involving arachidonic acid metabolism, retinol metabolism, biosynthesis of phenylalanine, tryptophan, and tyrosine, glycerophospholipid metabolism, and tyrosine metabolism. PHA can improve the pathological state of mice with asthma by inhibiting the production of inflammatory factors IL4 and IL17A, hindering the recruitment of inflammatory cells, and regulating some differential metabolites and metabolic pathway disorders. The animal experiment was approved and supervised by the Animal Ethics Committee of Henan University of Traditional Chinese Medicine (ethics number: DWLL2018080003).

This study evaluated the effects of Shanyu Pills on the skeletal muscle mass, motor function, and metabolites of the gastrocnemius muscle in sarcopenia mice, aiming to explore the scientific essence of Shanyu Pills in treating sarcopenia. All animal experiments were approved by the Experimental Animal Ethics Committee of Fujian University of Traditional Chinese Medicine (approval No.: FJTCM IACUC 2022123). Eight-month-old rapidly aging mice SAMP8 (senescence accelerated mouse prone/8, SAMP8) were used as the animal model for sarcopenia. The biological effects of Shanyu Pills in improving the skeletal muscle mass and motor function of mice with sarcopenia were evaluated by evaluating of the degree of senescence of mice, muscle volume of the hindlimbs, grip strength, hanging net duration time, rotarod performance time, free movement assessment, biochemical indicators of spleen deficiency, and histopathology of gastrocnemius muscle tissue. The metabolites in the gastrocnemius muscle of mice were analyzed using LC-MS/MS. Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) was used to screen out the differential metabolites among different comparison groups. The differential metabolites were analyzed for metabolic pathway enrichment using the MetaboAnalyst 6.0 database and the "Compound-Reaction-Enzyme-Gene" network of the differential metabolites was constructed using Cytoscape 3.10.0 software. The results showed that Shanyu Pills could significantly reduce the degree of senescence of sarcopenia mice; increase the muscle volume of the hindlimbs, grip strength, hanging net duration time, rotarod performance time, free movement assessment; improve the biochemical indicators of spleen deficiency; and alleviate the phenomenon of gastrocnemius muscle fiber atrophy. The non-targeted metabolomics analysis of the gastrocnemius muscle showed that Shanyu Pills mainly affected 14 differential metabolites such as arachidonic acid, leukotriene A4, carnosine, methylimidazoleacetic acid. The potential target metabolic pathways enriched were the arachidonic acid metabolic pathway. In summary, Shanyu Pills can effectively improve the skeletal muscle mass and motor function of sarcopenia mice, and its mechanism may be closely related to the regulation of arachidonic acid metabolism.

The chemical constituents of 50% acetone extract of the dried roots bark of Paeonia suffruticosa Andr. (Moutan Cortex) were isolated and purified using various column chromatographic methods, yielding 16 compounds. According to their physiochemical properties and spectral data, the structures of the isolated compounds were further identified as suffruticoside N (1), 1, 1′-[(1R)-2, 2′-dihydroxy-6, 6′-dimethoxy[1, 1′-biphenyl]-3, 3′-diyl]bis[ethanone] (2), 5-(1, 2-dihydroxy-1-methylethyl)-4-methylbicyclo[3.1.0]hexan-2-one (3), 4-(1, 2-dihydroxy-1-methylethyl)-1-cyclohexene-1-carboxylic acid (4), teutenone A (5), dihydroactinidiolide (6), cadina-4, 11-dien-14-oic acid (7), adenosine (8), uridine (9), methyl palmitate (10), 1-(3-hydroxy-4-methoxyphenyl)ethanone (11), 2, 4-dihydroxyacetophenone (12), methyl gallate (13), 2, 3-dihydroxybenzoic acid (14), benzoic acid (15), and pinoresinol (16). Compound 1 was a new biphenyl compound. Compounds 2 and 3 were two new natural products, and compounds 4 and 5 were firstly isolated from Moutan Cortex. Additionally, in preliminary vitro bioassays, all the isolated compounds were tested their inhibitory effects on acetylcholinesterase (AChE). As a result, compound 2 exhibited a moderate AChE with IC₅₀ value of 15.7 ± 2.5 μmol·L^-1.

Thirteen compounds were isolated from the Lycii Cortex by macroporous resin column chromatography, gel column chromatography and semi-preparative high performance liquid chromatography. The structures of the isolated compounds were identified by ultraviolet spectroscopy, infrared spectroscopy, nuclear magnetic resonance spectroscopy and mass spectrometry as solavetivone A (1), solavetivone B (2), 9-hydroxy-3-methoxy-6H-pyrido [1, 2-a] pyrazin-6-one (3), 5, 5′-di(2-ethyl-hexyloxy)-5, 5′-bifuran (4), bis(2-ethylhexyl) phthalate (5), scopoletin (6), periplogenin (7), 3β, 5β-dihydroxy-14-en-card-20(22)-enolide (8), (7R, 8S)-4-hydroxy-3, 5′-dimethoxy-4′, 7-epoxy-8, 3′-neoligna-9, 9′-diol-4-O-β-D-glucopyranosyl-(1→4)-β-D-glucopy-ranoside (9), 2-carbomethoxy 3-prenyl-1, 4-naphtho hydroquinone-1, 4-di-O-β-glucoside (10), 4-hydroxy-3-methoxyphenyl-β-D-xylopyranosyl (1→6)-O-β-D-glucopyranoside (11), syringic acid (12), vanillic acid (13). Compounds 1 and 2 were new sesquiterpene glycosides with solavetivone skeleton. Compounds 4, 8-10 were isolated from Solanaceae for the first time. The bioactive screening results indicate that compounds 1 and 2 do not exhibit inhibitory effects on NO production; however, they demonstrate weak inhibitory activity against α-glucosidase.

The chemical components of the patchouli oil were isolated and purified by silica gel column chromatography, preparative thin layer chromatography and semi-preparative HPLC. Then, the structures of the obtained compounds were identified by HR-MS, IR, and NMR. The absolute configurations of the novel compounds were determined by single-crystal X-ray diffraction analysis and calculation of ECD. Finally, two novel spirocyclic sesquiterpenoids were obtained from patchouli oil and identified as spiroaxanol A (1) and spirojatamone A (2), respectively.

This study employs homogeneous time-resolved fluoroimmunoassay to quantitatively determine the concentration of cyclic adenosine monophosphate (cAMP) within LHCGR(-Ex10)-CRE-luc-HEK293 cells, utilizing a competitive immunoassay method. The research sets forth an in vitro biological activity assessment methodology for luteinizing hormone (LH). Key parameters of the methodology are optimized, and the relative accuracy, intermediate precision, linearity, and range are validated. The optimized experimental conditions are defined as follows: an initial concentration of 200 nmol·mL^-1, a seven-fold gradient dilution, a cell density of 24 000 cells·well^-1, and a duration of incubation of 30 min. The findings indicate that the method exhibits excellent linearity across a relative potency range of 64% to 156%, high relative accuracy, and satisfactory intermediate precision. The successful establishment and validation of a homogeneous time-resolved fluoroimmunoassay for the evaluation of LH biological activity is reported. This methodology is applicable for the assessment of biological activity and quality control of recombinant LH-like drugs, as well as for the differentiation of recombinant LH.

An integrated method based on UPLC-Q-Orbitrap-HRMS and ICP-MS was developed for the simultaneous characterization of chemical constituents and inorganic elements in brown sugar hand-crafted in the Ailao Mountain. After water extraction and ethanol precipitation, thirty metabolites were identified by UPLC-Q-Orbitrap-HRMS, including 10 amino acids and their derivatives, 8 sugars and derivatives, 4 organic acids, 3 aldehydes and 5 other organic compounds. ICP-MS quantified the elemental profiles of three independent batches, revealing high levels of the macro-elements K, Mg and Ca, along with nutritionally relevant amounts of the trace elements Fe, Zn, Cu, Se, Co, Mn and Cr. Fingerprinting, elemental correlation analysis and health-risk assessment were subsequently performed. Estimated daily exposure per kg body weight (Exp), hazard index (HI) and margin of exposure (MOE) indicated that all batches conformed to the heavy-metal limits set by the Chinese Pharmacopoeia (2025 edition), and the overall health risk from toxic elements is negligible. By integrating comprehensive chemical profiling with precise elemental quantification, the study establishes a dual-dimension quality evaluation system that provides robust data and technical support for constructing a quality profile of Ailao Mountain brown sugar and for elucidating the relationship between its chemical composition and nutritional functions.

Rheumatoid arthritis (RA) is a disease that seriously affects human health, and the existing treatments have the disadvantages of high side effects, drug resistance and poor effectiveness. In this study, we proposed a new anti-RA strategy based on the cross-linked hydrogel "acupuncture + swelling" dual stimulation of acupoints, and investigated the efficacy of brucine hydrogel microneedles targeting for RA in mice. All animal experimental procedures were approved by the Guizhou University of Traditional Chinese Medicine Laboratory Animal Ethics Committee (No: 20230179) and conducted in accordance with its guidelines. A mouse model of collagen-induced arthritis (CIA) was established, and the efficacy was investigated by using the swelling of the paw, spleen and thymus indices, histopathological sections of the ankle joints, serum levels of inflammatory factors and synovial tissue proteins, and it was found that the acupoint microneedling group and the acupoint + non-acupoint microneedling group could significantly decrease the swelling of the paw in the mouse model of CIA, reduce the swelling of the immune organs of the mice, reduce the levels of serum inflammatory factors, and improve the efficacy of CIA. Inflammatory factor content, improve the pathological state of synovial membrane and cartilage tissue of ankle joint and down-regulate the expression level of related inflammatory proteins in CIA mice, which has the effect of alleviating rheumatoid arthritis. The therapeutic strategy of brucine hydrogel microneedles based on "acupuncture + swelling" to stimulate the Zusanli (ST36) acupoint can significantly treat rheumatoid arthritis, which provides an important scientific basis for the subsequent development and utilisation of acupoint microneedles transdermal drug delivery system.

This study developed hyaluronic acid (HA)-modified, ginsenoside Rg₃-loaded hollow mesoporous MnO₂ nanoparticles (HMR@HA) and evaluated their characterization, in vitro release, and anti-triple-negative breast cancer efficacy. Hollow mesoporous MnO₂ nanoparticles (HM) were synthesized by template method. HMR nanoparticles were prepared by loading ginsenoside Rg₃, and then targeted HMR@HA system was constructed through HA modification. Laser particle size analysis, transmission electron microscopy (TEM), and Fourier transform infrared spectroscopy (FTIR) were used to characterize the samples. High-performance liquid chromatography (HPLC) quantified Rg₃ loading capacity and assessed HMR@HA's in vitro release profile. We evaluated the uptake capacity of 4T1 cells for nanoparticles and the in vitro antitumor activity of nanoparticles. The experimental results indicate that the optimal preparation parameters are: the mass ratio of drug to carrier of 5∶1, the stirring time of 12 h, and the drug concentration of 10 mg·mL^-1. The obtained HMR@HA exhibits the uniform hollow structure with a particle size of 216.3 ± 1.3 nm and the loading capacity is (42.42 ± 2.55)%. The release curve shows pH dependence, and the cumulative release gradually increases as the pH decreases. The results showed that HMR@HA was efficiently taken up by 4T1 cells and significantly inhibited the proliferation and migration of cancer cells. Active oxygen and mitochondrial membrane potential detection showed that HMR@HA can promote tumor cell apoptosis. HMR@HA has a high drug loading capacity and pH-sensitive drug release properties. Compared with ginsenoside Rg₃, it significantly enhances antitumor activity and induces apoptosis, providing an effective treatment strategy for triple-negative breast cancer.

Lipid nanoparticles (LNP) are highly promising gene delivery platform due to their high safety, good stability, and excellent nucleic acid encapsulation efficiency. However, current clinical gene therapy primarily relies on invasive administration routes. The development of compliant, non-invasive delivery routes, such as oral administration, is crucial. Nevertheless, creating gastric acid-resistant oral gene delivery vectors faces a critical bottleneck that nucleic acid therapeutics are highly susceptible to degradation in the harsh acidic environment (pH 1.5-4.5) of the gastrointestinal tract. To address this, we constructed a cholesterol-enriched hybrid system (RLSC/OMVC) based on an amphiphilic cationic lipopeptide (RLS) and Escherichia coli outer membrane vesicles (OMV). This system demonstrates efficient gene delivery capability under both neutral and acidic conditions, along with excellent in vitro biocompatibility. The study characterized the physicochemical properties of different formulations (RLS, RLSC, OMV, and OMVC). In vitro cell transfection experiments showed that the gene delivery efficiency of RLSC/OMVC under acidic condition (pH 4.5) was significantly increased by nearly 3-fold compared with Lipofectamine 2000. Furthermore, transmission electron microscopy observation, particle size/zeta potential analysis, and gel electrophoresis experiments revealed the mechanism by which OMV and cholesterol synergistically protect plasmid DNA from acidic degradation in conjunction with lipid peptide. The developed RLSC/OMVC hybrid system boasts integrated advantages of exceptional acid resistance, high-efficiency gene delivery, and good biocompatibility. This work provides an innovative strategy for oral gene therapy.