Chinese Medicine最新文献

Background: Fuzheng Jiedu Formula (FZJD) is a polyherbal prescription that is commonly used in the treatment of infectious diseases, particularly infectious pneumonia. However, the key molecular mechanisms underlying its empirical therapeutic effects have not yet been fully elucidated. This study aimed to assess the anti-pneumonia efficacy of FZJD and elucidate its underlying regulatory mechanisms. Furthermore, it aimed to identify the plasma-exposed phytochemicals that may contribute to these pharmacological effects.

Methods: A mouse model of Pseudomonas aeruginosa (PA-14) pneumonia was employed to evaluate the in vivo efficacy of FZJD. UPLC/Q-TOF-MS analyses were conducted to identify FZJD extracts and its plasma exposure components. Quantitative proteomics and non-targeted metabolomics combined with network pharmacology were used to map key molecular pathways. In parallel, in vitro assays conducted in macrophages and neutrophils evaluated the effects of FZJD's key active compounds on inflammation and NETs formation.

Results: Oral FZJD (10-40 g/kg) dose-dependently improved lung histopathology, limited macrophage and neutrophil infiltration, and lowered circulating TNF-α, IL-1β, and IL-6. Multi-omics integration analysis identified the NLRP3 signaling pathway and NETs formation as key dysregulated processes that were effectively reversed by FZJD treatment. Concordantly, lungs from treated mice showed lower p‑NF‑κB/NF‑κB, NLRP3, and cleaved caspase‑1, together with reduced cit‑H3/MPO and MPO-cfDNA complexes. Among 31 plasma-exposure constituents, saikosaponin A, prunasin, aloe-emodin, and glycyrrhizic acid emerged as multifunctional inhibitors that blocked NF-κB activation, curtailed NLRP3 assembly, and restrained NETosis in vitro. Pathway readouts supported actions on complementary axes (TLR4-IRAK1, STING1-IFN-β, FPR1-AKT, CASP8, and HDAC2-H3K9ac), providing a mechanistic basis for their collective protection against pneumonia.

Conclusions: FZJD mitigates acute pneumonia by dampening macrophage NLRP3 inflammasome activation while restraining neutrophil NETosis. The mechanistic study provides evidence supporting the traditional use of FZJD in the treatment of respiratory infections and underscores its potential as a host-directed therapy.

Background: In recent years, skin sunburn injury caused by UVB has become a growing concern. Although PNS have demonstrated potential in alleviating this condition, the precise mechanisms involved remain incompletely elucidated.

Purpose: This study was designed with three primary objectives. First, to apply network pharmacology-based predictive approaches to elucidate the mechanisms underlying PNS-mediated protection against UVB-induced skin sunburn injury. Second, to systematically analyze the chemical profile of PNS through UHPLC-Q-Orbitrap-MS/MS. Third, to conduct a comprehensive assessment of the pharmacodynamic properties of NGR1, a major bioactive constituent of PNS.

Methods: The chemical constituents of PNS were analyzed qualitatively and quantitatively using UHPLC and UHPLC-Q-Trap-MS/MS. Network pharmacology approaches were employed to identify the core molecular targets and potential mechanisms through which PNS alleviates UVB-induced sunburn injury. To evaluate the therapeutic effects of PNS and NGR1, an in vivo model was established using nude mice, while mechanistic studies were conducted in HaCaT cells to elucidate the underlying signaling pathways.

Results: A total of 16 primary saponins in PNS were successfully identified and quantified. Through network pharmacology analysis, 49 crucial molecular targets associated with PNS in the context of UVB-induced skin sunburn injury were revealed. Treatment with PNS and NGR1 ameliorated signs of photoaging via multiple mechanisms, including suppression of inflammatory responses, boosting antioxidant capacity, inhibition of the PI3K/AKT/mTOR signaling cascade, and regulation of proteins involved in maintaining cellular homeostasis. In HaCaT cells, PNS and NGR1 exert protective effects against apoptosis by modulating proteins associated with cellular homeostasis and autophagy. Both compounds counteracted the UVB-induced reduction in NAT10 expression. The degradation of NAT10, potentially mediated by the autophagy pathway involving key selective adaptors such as NBR1 and p62, may occur under both basal and UVB-exposed conditions.

Conclusion: PNS and NGR1 demonstrate promising therapeutic potential for the treatment of UVB-induced skin sunburn injury. Their capacity to mitigate photodamage via multiple mechanisms, such as inhibition of key signaling pathways, regulation of apoptosis and autophagy, and modulation of NAT10 expression, lays a strong foundation for future clinical studies on topical applications of PNS and NGR1, while also providing valuable insights into their preventive and curative effects.

Background: In obesity, excessive energy intake and the expansion of adipose tissue increase ROS generation, contributing to adipocyte dysfunction and inflammation, which leads to abnormal adipose tissue remodeling (ATR). Alpha lipoamide (ALM) is the neutral amide form of lipoic acid, a natural antioxidant extracted from plant-based foods such as asparagus, spinach, and broccoli. This work focuses on ALM's beneficial effects and mechanism in adipose tissue inflammation (ATI) and abnormal ATR in obesity.

Methods: The anti-inflammatory effect of ALM was evaluated by ELISA, flow cytometry, Western blots, and immunofluorescence assays. The binding affinity of ALM to SIRT3 deacetylase was evaluated through cellular thermal shift assay (CETSA) and molecular docking. The adipose tissue-targeting alpha lipoamide nanoemulsion (ALM-NE) was validated using small animal live imaging. Adipose tissue inflammation was evaluated by histological analysis and immunohistochemical staining in both high-fat diet (HFD) and LPS plus ATP-induced inflammation models in mice.

Results: ALM suppressed the activation of NLRP3 inflammasome via enhancing SIRT3-mediated autophagy. Co-immunoprecipitation revealed that ALM blunted mitochondrial damage through SIRT3-mediated SOD2 deacetylation and FUNDC1-mediated mitophagy activation, resulting in ROS reduction and NLRP3 inflammasome inactivation. Moreover, ALM mitigates inflammatory crosstalk between macrophages and adipocytes in an in vitro co-culture model. Finally, we established an adipose tissue-targeting ALM-NE, which alleviated ATI in LPS and ATP-induced acute inflammation in mice and inhibited abnormal ATR in high-fat diet-induced obese mice.

Conclusion: In summary, ALM attenuates inflammatory crosstalk between M1 macrophages and adipocytes by enhancing SIRT3-mediated mitophagy and suppressing NLRP3 inflammasome activation, thereby alleviating adipose tissue inflammation and pathological remodeling in obesity. Thus, ALM has the capacity to become a therapeutic candidate for treating obesity and its associated metabolic disorders.

Shi Zheng (Dampness syndrome) is a prevalent condition in traditional Chinese medicine (TCM) syndrome caused by the humid environment (external dampness) or metabolic imbalance (internal dampness) and characterized by sense of heaviness in the body and numbness in the limbs. Most Shi Zheng patients suffer from metabolic disorders and inflammation, and they were diagnosed as the diseases such as rheumatoid arthritis, gouty arthritis, nonalcoholic fatty liver disease or type 2 diabetes mellitus by modern medicine, and they are prone to complications or recurrent episodes despite long-term medication. Chinese medicine formulas (CMFs) and their effective compounds have shown promising results in treating these diseases, with high cure rates and a low incidence of adverse events. However, modern science has yet to establish a clear understanding of the underlying mechanisms between Shi Zheng, related diseases, and CMFs, probably because of the extremely abstract concept of TCM syndrome. Therefore, this review aims to provide an overview of the characteristics of Shi Zheng and the effects of CMFs and active compounds in TCMs on typical diseases associated with Shi Zheng to clarify the concrete connection between TCM symptoms and modern diseases, thereby to bridge the gap between TCM syndrome concepts and modern medicine.

Acute Myocardial Infarction (AMI) is one of the leading causes of global mortality, posing a severe threat to human health. Currently, the clinical management of AMI remains a major challenge, and its pathological mechanisms lack systematic elucidation. Neutrophils, as key effector cells in the pathogenesis of AMI, have emerged as a highly promising therapeutic target. This review comprehensively summarizes the origin, subtypes, stage-specific roles, and mechanistic contributions of neutrophils in AMI. Furthermore, it explores how active components of traditional Chinese medicine (TCM) modulate neutrophil function through multi-target interventions, exerting therapeutic effects in anti-inflammation, anti-fibrosis, and pro-angiogenesis. Recent advances highlight significant progress in neutrophil-targeted therapies, including novel drug development, nanoparticle-based delivery systems, and multi-omics biomarker discovery, offering new avenues for precision medicine in AMI. Although translational challenges persist, enhanced collaboration between basic research and clinical applications may unlock innovative treatment strategies for AMI patients.

Mylabris, a traditional Chinese medicine (TCM), is derived from the dried forms of Mylabris phalerata Pallas or Mylabris cichorii Linnaeus. It was recorded in Shennong Bencaojing in Han Dynasty and used for the treatment of psoriasis, facial paralysis, amenorrhea, and carbuncle. As a key component in antitumor formulations, Mylabris contains numerous bioactive compounds, including organic acids, terpenoids, amino acids and their conjugates, metal complexes, cantharimide dimers and peptides and proteins. Traditionally, Mylabris has been employed in the treatment of malaria, suppurative infectious diseases, and lymph node tuberculosis. Pharmacological studies have demonstrated its antitumor, anti-inflammatory, leukocytosis-inducing, and immune function-enhancing activities, as well as its pest resistance and skin blistering effects. Clinical prescriptions containing Mylabris have been used in the treatment of cancer and skin diseases. However, strong penetration and rapid absorption in all tissues contribute to multi-organ toxicity on the liver, kidney, heart, nerves and reproduction and gastrointestinal systems. Therefore, traditional processing methods and targeted drug delivery systems have been designed for increasing efficacy and decreasing toxicity. Here, we provide a comprehensive overview of Mylabris in terms of entomology, active ingredients, traditional use, pharmacology, clinical application, pharmacokinetics, toxicity, and detoxification strategies to provide a rational application in the future.

Background: Hypericum perforatum L. (Guan Ye Jin Si Tao, GYJST), commonly known as St. John's wort, is a widely distributed medicinal plant across Europe and Asia. Preclinical studies have identified its therapeutic potential in both neurological and metabolic disorders. However, its impact on metabolic-associated fatty liver disease (MAFLD) remains unclear. This study comprehensively investigated the therapeutic effects of GYJST on MAFLD through both in vivo and in vitro experiments. Utilizing a multi-omics approach, the research elucidated the regulatory mechanisms of GYJST on ferroptosis, focusing on oxidative stress, lipid metabolism, and inflammatory response modulation. The findings provide valuable insights into the potential therapeutic applications of GYJST in managing MAFLD.

Materials and methods: Liver assessments were systematically conducted to evaluate the therapeutic effects of GYJST on HFD-induced mice and PA-induced AML12 cells. Comprehensive histological analyses, including H&E, Masson, Sirius Red, Oil Red O, and F4/80 staining, were performed to assess the impact of GYJST on liver pathology. To elucidate the underlying mechanisms of GYJST, a multi-omics approach was employed, integrating network pharmacology, transcriptomics, proteomics, and metabolomics. Additionally, RT-qPCR, western blotting, and immunofluorescence techniques were utilized to validate the effects of GYJST.

Results: GYJST effectively protects against liver injury by mitigating inflammation, oxidative stress, and lipid metabolism dysregulation. A total of 90 major compounds in GYJST were tentatively identified. Network pharmacology analysis revealed its multi-target, multi-pathway mechanisms of action. Integrative transcriptomic, metabolomic, and proteomic analyses consistently highlighted pathways associated with inflammatory responses, oxidative stress, and lipid metabolism. Mechanistically, GYJST suppresses systemic inflammation via the NF-κB/COX-2 signaling axis and alleviates oxidative stress and lipid accumulation through the Nrf2/PPARα/g pathway. Additionally, GYJST plays a crucial role in inhibiting ferroptosis, partly through Nrf2-mediated mechanisms.

Conclusion: GYJST exerts multi-target therapeutic effects against MAFLD by concurrently regulating ferroptosis, oxidative stress, lipid metabolism, and inflammation through interconnected mechanisms. These findings establish GYJST as a promising multi-target therapeutic candidate for MAFLD treatment.

Non-clinical pharmacology of traditional Chinese medicine (TCM) formulae plays a crucial role in elucidating their therapeutic mechanisms. With the integration of cutting-edge disciplines such as systems biology, big data, and artificial intelligence, the research depth and breadth in this field continue to expand. However, technical standards for non-clinical pharmacology research on TCM formulae have not yet been established. To address this, technical guidelines for non-clinical pharmacology research of TCM formulae were formed, aiming to scientifically standardize research content, elevate research quality, and facilitate the mutual translation between clinical and basic research. Guided by integrative pharmacology of TCM and driven by clinical value, these guidelines employ multi-dimensional qualitative pharmacokinetics (PK) and pharmacodynamics (PD) studies alongside quantitative "PK-PD" studies of key components. This approach enables the transition from panoramic description to precise mechanistic research, establishing a complete evidence chain system for the effectiveness of TCM formulae and demonstrating their holistic action characteristics of "multi-component, multi-pathway, multi-target". Meanwhile, the guidelines emphasize that animal models for TCM research should ensure stability and reproducibility. Additionally, pharmacodynamic evaluation is characterized by its measurability and quantifiability. The mechanisms of action at the molecular level should be in-depth and interpretable. These aspects collectively provide guidance for basic non-clinical pharmacology research on TCM formulae and the development of new TCM drugs. The formulation of these guidelines leveraged the research strengths of the drafting units' teams, incorporated literature review findings, and achieved consensus through extensive discussions among multidisciplinary experts. Broad expert opinions from universities, research institutes, and enterprises engaged in new drug development were solicited, ensuring the guidelines' practicality, standardization, scientific rigor, and feasibility.

As an important class of bioactive components in TCM, saponins exhibit various significant pharmacological effects. Therefore, investigating the impacts of processing on the chemical components and action mechanisms of saponin-rich TCMs is of great importance. This review aims to summarize the effects of different processing methods on saponin components in TCMs and the chemical transformations of saponins during processing, while also prospecting future research directions. A bibliographic investigation was performed by examining the available data on saponin-rich TCMs from globally accepted scientific databases and search engines (Pubmed, Scopus and Web of Science, SciFinder and Google Scholar). Different processing methods cause distinct saponin changes, significantly affecting their physicochemical properties and pharmacological effects. Understanding these effects and transformations is crucial for developing targeted saponin preparations, aiding clinical use of such TCMs and mechanism research.