Ye Sun

Ethnopharmacological relevance: Jingfang Baidu San (JF) is a classic traditional Chinese medicine（TCM）formula that has been widely used in clinical practice for hundreds of years. While its efficacy in treating Feng Han (wind-cold, FH) common cold has garnered increasing attention, its underlying mechanism of action remain incompletely understood.Aim: This study aimed to evaluate the therapeutic effect of JF on wind-cold common cold and to elucidate its molecular mechanism.Methods: A common FH model in mice was established by exposing them to continuous wind and cold stimulation for 7 days. The therapeutic efficacy of intragastric administration of JF was first evaluated by detecting behavioral changes, body weight, anal temperature, and energy metabolism, followed by histopathological examination of lung tissues via hematoxylin-eosin (HE) staining. To investigate the underlying mechanisms, we performed lungtranscriptomic analysis sequencing to identify key regulatory network. Subsequently, the expression of inflammatory cytokines in serum and lung tissues was detected by using enzyme-linked immunosorbent assay (ELISA), and the expression of key proteins was analyzed by immunofluorescence, immunohistochemistry and Western blotting.Results: JF significantly alleviated symptoms, as evidenced by increased body weight, improved energy metabolism, and amelioration of behavioral impairments such as listlessness and cough. Histologically, JF markedly attenuated lung pathological damage and reduced the levels of inflammatory factors (including IL-6, IL-1β, and TNF-α) in serum and lung tissues. Mechanistically, T transcriptome sequencing and in vivo analyses revealedthat JF restored M1/M2 macrophage immune homeostasis by upregulating the expression of Dectin-1 (Clec7a). This upregulation led to the inhibitionof the NF-κB/TGF-β signaling pathway, which subsequently reduced the expression of macrophage-derived matrix-remodeling factors (MMP12/19), downregulated the expression of collagen Col1a1 and Col3a1, pro-fibrotic factor SPP1, and decreased the neutrophil marker Elane, collectively improving pulmonary tissue matrix remodeling and inflammatory infiltration.Conclusion: Our findings demonstrate that JF alleviates lung injury in FH common cold by upregulating the expression of Dectin-1 in macrophages to restore M1/M2 macrophage immune homeostasis, thereby inhibiting the NF-κB/TGF-β signaling pathway and improving lung tissue matrix remodeling and inflammatory infiltration. This study provides novel mechanistic insights into the therapeutic action of JF in the treatment of the common FH cold and supports its clinical application.

Ethnopharmacological relevanceArtemisia capillaris Thunb. is a traditional Chinese medicinal herb commonly used in clinical practice for chronic alcoholic liver disease (CALD). Scoparone, a natural coumarin isolated from Artemisia capillaris Thunb., has emerged as a promising candidate for CALD intervention, yet its mechanism remains unclear.Aim of the studyThis study systematically investigated scoparone’s molecular mechanisms on CALD via multi-omics combined with targeted validation.Materials and methodsUsing the national institute on alcohol abuse and alcoholism (NIAAA) animal model. The NIAAA-established CALD mouse model (chronic ethanol feeding + acute binge, mimicking acute-on-chronic liver injury) was diagnosed via classic clinical methods (liver function biomarkers + histopathology). Post-validation, scoparone exhibited significant efficacy across different doses. Metabolomics and transcriptomics analyzed urine/tissue samples, with integrated analysis identifying core hubs. While, primary hepatocytes were cultured and treated with scoparone. Potential targets were validated via gene knockdown, CETSA, CHX chase and ubiquitination assays. Seahorse XF mito stress test assessed CALD-related mitochondrial damage to establish the interrelationships among various elements.ResultsScoparone normalized serum biochemical indices and liver pathology to near-healthy levels. Urinary metabolomics identified 9 biomarkers, and liver transcriptomics detected 3665 differentially expressed genes, with integrated analysis showing enrichment in the phenylalanine pathway (phenylpyruvate/phenylalanine co-regulated by TAT and AST). In vitro, primary hepatocytes were cultured with 100 mmol/L ethanol ±25 μmol/L scoparone; CETSA and CHX chase assays confirmed scoparone enhances TAT stability via direct binding and inhibiting the Ubiquitin-Proteasome pathway. Seahorse analysis showed TAT knockdown-induced hepatocyte apoptosis, oxidative stress, lipid accumulation, and mitochondrial damage were reversed by scoparone or TAT activity restoration.ConclusionsThis study first reveals scoparone’s novel mechanism in treating CALD: it directly binds tyrosine aminotransferase (TAT), stabilizes its activity by inhibiting Ubiquitin-Proteasome-mediated degradation, restores TAT’s regulation of phenylalanine to prevent tyrosinemia and associated liver injury or jaundice, and normalizes tyrosine regulation to recover mitochondrial tricarboxylic acid cycle-related pyruvate, reversing oxidative stress and mitochondrial dysfunction.This study validates scoparone as a potential CALD therapeutic and provides robust preclinical data for TAT-targeted therapy.

Astragali radix (AR) is a traditional Chinese herbal medicine derived from the roots of Astragalus membranaceus and A. mongholicus. AR exhibits a wide range of pharmacological activities, such as cardioprotective, hypoglycemic, antitumor, antiviral, and multi-organ restorative effects. Nearly 400 bioactive compounds have been identified in AR by phytochemical investigations, with astragalus polysaccharides (APS), astragalosides (I–IV), formononetin (FMN), and calycosin (CA) established as principal bioactive constituents. These components exhibit multifunctional mechanisms encompassing antioxidative stress, apoptotic suppression, autophagy regulation, anti-inflammation, and immune regulation, thereby exerting significant protective effects on critical organ systems such as the cardiovascular, renal, neural, hepatic, gastrointestinal, and immune systems. This review synthesized research over the past three decades, elucidating the organ protective mechanisms of AR through phytochemical profiling. Key findings demonstrated that FMN-mediated Nrf2 pathway activation could attenuate reactive oxygen species (ROS) generation, while astragaloside IV (AS-IV) could suppress endoplasmic reticulum stress by inactivating the PERK/ATF6/CHOP axis to ameliorate apoptosis. Additionally, comprehensive safety assessment and pharmacokinetic analysis also substantiated favorable bioavailability and toxicological profiles. To sum up, these findings provide a comprehensive theoretical basis and offer innovative strategies for preventing and treating complex diseases associated with multi-organ dysfunction, thereby facilitating future clinical applications.

Metabolomics, a promising field in the realm of omics, focuses on the investigation of alterations and patterns in the composition and abundance of metabolites generated by organisms under perturbation, directly linking measurable chemical reactions with biological events. Its research philosophy aligns harmoniously with the holistic perspective and syndrome differentiation and treatment principles of traditional Chinese medicine (TCM). Consequently, metabolomics has garnered unparalleled attention and has been widely applied in various fields of TCM research such as disease diagnosis, effective constituents and mechanism related with efficacy. In recent years, nuclear magnetic resonance (NMR)-based metabolomics, a non-destructive testing technique, has played a crucial role in metabolomics research, owing to its exceptional repeatability, stability, and advantages in qualitative and quantitative aspects. Through reviewing relevant literature in recent years, this article provides a comprehensive analysis of the fundamental principles of NMR metabolomics technology and its utilization in TCM. Additionally, it examines the challenges encountered in this field and explores potential future development trends, aiming to offer substantial support for further investigations in the realm of TCM metabolomics.

Ferulic acid (FA), a hydroxycinnamic acid derivative, is a key bioactive component in traditional medicinal plants including Angelica sinensis and Asafoetida. Accumulating evidence supports its therapeutic efficacy in inflammatory disorders, such as rheumatoid arthritis (RA) and ulcerative colitis (UC). FA exerts anti-inflammatory effects through (1) the regulation of inflammatory cytokine levels; (2) modulation of signaling pathways such as nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and janus kinase/signal transducer and activator of transcription (JAK/STAT); (3) amelioration of oxidative stress; and (4) regulation of immune cell homeostasis. At the pharmacokinetic level, studies show that FA is rapidly absorbed but exhibits low bioavailability, mainly due to the influence of metabolic pathways and food matrix characteristics. This review systematically summarizes the literature on the anti-inflammatory effects of FA, covering molecular mechanisms, pharmacokinetic characteristics, and application scenarios. Preclinical studies show that FA has low toxicity and good safety, demonstrating potential for development as a novel anti-inflammatory drug. However, its clinical translation is hindered by bottlenecks such as low bioavailability and insufficient human clinical data. Future research should prioritize developing novel drug delivery systems and conducting large-scale clinical trials to facilitate its clinical translation.

Rhein is a natural active ingredient in traditional Chinese medicine that has attracted much attention due to its wide range of pharmacological activities. However, its clinical application is limited by low water solubility, poor oral absorption, and potential toxicity to the liver and kidneys. Recently, advanced extraction and synthesis techniques have made it possible to develop derivatives of rhein, which have better pharmacological properties and lower toxicity. This article comprehensively summarizes the biological activity and action mechanism of rhein. Notably, we found that TGF-β1 is the target of rhein improving tissue fibrosis, while NF-κB is the main target of its anti-inflammatory effect. Additionally, we reviewed the current research status of the pharmacokinetics, toxicology, structural optimization, and potential drug applications of rhein and found that the coupling and combination therapy of rhein and other active ingredients exhibit a synergistic effect, significantly enhancing therapeutic efficacy. Finally, we emphasize the necessity of further studying rhein’s pharmacological mechanisms, toxicology, and development of analogs, aiming to lay the foundation for its widespread clinical application as a natural product and elucidate its prospects in modern medicine.

Colorectal cancer (CRC) is common Cancer as well as the third leading cause of mortality around the world; its exact molecular mechanism remains elusive. Although CRC risk is significantly correlated with genetic factors, the pathophysiology of CRC is also influenced by external and internal exposures and their interactions with genetic factors. The field of CRC research has recently benefited from significant advances through Omics technologies for screening biomarkers, including genes, transcripts, proteins, metabolites, microbiome, and lipidome unbiasedly. A promising application of omics technologies could enable new biomarkers to be found for the screening and diagnosis of CRC. Single-omics technologies cannot fully understand the molecular mechanisms of CRC. Therefore, this review article aims to summarize the multi-omics studies of Colorectal cancer, including genomics, transcriptomics, proteomics, microbiomics, metabolomics, and lipidomics that may shed new light on the discovery of novel biomarkers. It can contribute to identifying and validating new CRC biomarkers and better understanding colorectal carcinogenesis. Discovering biomarkers through multi-omics technologies could be difficult but valuable for disease genotyping and phenotyping. That can provide a better knowledge of CRC prognosis, diagnosis, and treatments.