Chinese Medicine最新文献

Background: Cerebral ischemia/reperfusion injury (CI/RI) remains a critical barrier to effective ischemic stroke (IS) treatment. While mitophagy activation has been shown to attenuate apoptosis and pyroptosis, thereby ameliorating CI/RI, the therapeutic potential of natural compounds targeting this pathway remains underexplored. Penthorum chinense Pursh (PCP), a traditional hepatoprotective herb, contains Thonningianin A (TA), a bioactive compound with reported autophagic properties. However, the role and mechanisms of TA in CI/RI mitigation remain unclear.

Methods: In vivo, a middle cerebral artery occlusion/reperfusion (MCAO/R) rat model was established to evaluate TA's neuroprotective effects via TTC staining, Longa neurological scoring, and immunofluorescence staining. In vitro, oxygen-glucose deprivation/reoxygenation (OGD/R)-treated HT22 and BV2 cells were used to assess TA's impact on cell viability (MTT, Hoechst/PI staining), mitochondrial oxidative stress (DHE, TMRM, JC-1, Mito-Tracker staining and Western blot), apoptosis (flow cytometry, immunofluorescence staining, Hochest and PI staining and Western blot), and pyroptosis (EthD-2/YO-PRO-1 staining and Western blot). Autophagy and mitophagy modulation was investigated using rapamycin (Rap), 3-MA (autophagy inhibitor), CCCP (mitophagy inducer), and AC220 (mitophagy inhibitor) in EGFP-LC3-U87 and mCherry-GFP-FIS1-293T cells. Co-localization immunofluorescence and Western blotting were employed to validate PINK1/Parkin pathway involvement.

Results: TA administration significantly improved neurological function, reduced cerebral infarct volume, and attenuated neuronal damage in MCAO/R rats. In vitro, TA suppressed OGD/R-induced mitochondrial oxidative stress and apoptosis in HT22 cells while mitigating pyroptosis in BV2 microglia. Mechanistically, TA activated PINK1/Parkin-dependent mitophagy, as evidenced by enhanced LC3-II/I ratio, and increased mitochondrial-autophagosome co-localization. Crucially, TA's anti-apoptotic and anti-pyroptotic effects were abolished upon mitophagy inhibition. These findings were corroborated in the MCAO/R model, where TA upregulated PINK1/Parkin signaling and mitigated cell damage.

Conclusion: This study identifies TA as a novel natural agent alleviating CI/RI by activating PINK1/Parkin-mediated mitophagy, thereby concurrently suppressing apoptosis and pyroptosis. These findings provide the first elucidating the molecular mechanis underlying TA's potential as a therapeutic candidate for IS.

Background: Traditional Chinese Medicines (TCM) has long relied on bioactive compounds derived from natural sources, but conventional extraction and separation methods often involve violate/hazardous organic solvents, posing environmental and health risks. Deep Eutectic Solvents (DESs) have emerged as a sustainable alternative, offering tunable physicochemical properties, biodegradability, and enhanced extraction efficiency for TCM constituents such as alkaloids, flavonoids, and polysaccharides.

Methods: This review comprehensively summarizes the synergistic integration of DESs with TCM, highlighting their applications in green extraction, purification, and stabilization of bioactive compounds. It investigates a series of separation techniques, including liquid/solid-liquid (micro) extraction, chromatographic systems and others, where DESs enhance efficiency and recyclability. Environmental-Health-Safety (EHS) analyses, such as life cycle assessments and related tools, are also discussed.

Results: DESs demonstrate superior performance in preserving heat-sensitive compounds, improving solubility, and enabling selective extraction as well as isolation while aligning with green chemistry principles. However, challenges such as high viscosity, scalability, and toxicological assessments remain. Despite these limitations, DESs show significant eco-friendly potential, and future opportunities in policy support and AI-driven design could further advance their role in modernizing TCM for safer, more efficient, and sustainable therapeutic development.

Depression is a widespread mental disorder with profound effects on both physical and psychological health. Aberrant signal transduction contributes to depression by impairing neuronal function, reducing synaptic plasticity, and disrupting neurotransmitter transmission. Aberrant signal transduction can impair neuronal function, reduce synaptic plasticity, and disrupt neurotransmitter transmission, thereby contributing to the development of depression. Xiao-Yao-San (XYS), a traditional Chinese medicine (TCM) formula, has been extensively employed in the treatment of depression, with a broad therapeutic profile. This review aims to critically assess current scientific evidence on the antidepressant effects of XYS, focusing on its modulation of key signaling pathways. The goal is to provide a more robust mechanistic foundation for XYS-based therapies and offer insights for developing novel antidepressants that target signaling pathways. We systematically searched PubMed, Web of Science, ScienceDirect, CNKI, and Wanfang databases from inception to May 1, 2025, using relevant terms to identify studies on XYS and its active components, particularly those elucidating its regulation of signaling pathways involved in depression. XYS and its active ingredients modulate several crucial signaling pathways implicated in depression, including the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), NOD-like receptor family pyrin domain containing 3 (NLRP3), nuclear factor-kappa B (NF-κB), and mitogen-activated protein kinase (MAPK) pathways. The antidepressant effects of XYS are primarily mediated through anti-inflammatory actions, improved hippocampal architecture, suppression of neuronal and mitochondrial apoptosis, reduction of oxidative stress, and enhancement of synaptic plasticity. Despite current limitations, this review identifies future research directions focusing on unexplored and cross-linked signalling pathways, which may support the development of signalling-targeted antidepressant agents based on XYS.

Bronchiectasis is a complex and heterogeneous disease with various etiologies and clinical manifestations. While Western medicine (WM) primarily focuses on infection control, symptom management, and airway clearance techniques, traditional Chinese medicine (TCM) adopts a holistic strategy aimed at systemic regulation and immune modulation through herbal formulae and acupuncture. The integration of TCM and WM offers a comprehensive therapeutic framework that targets both clinical manifestations and the underlying pathophysiology. This review systematically outlines current WM treatment strategies, such as antibiotic therapy, anti-inflammatory drugs, and surgical interventions. The TCM treatment principles, including individualized syndrome differentiation and treatment, specific TCM formulae, and acupuncture therapies, are detailed. This study further synthesizes clinical evidence demonstrating that integrated TCM-WM therapy not only significantly alleviates symptoms and improves lung function but also enhances immune regulation and quality of life. This combined strategy not only improves clinical outcomes but also enhances patients' quality of life, which provides a more personalized and multidimensional paradigm to manage bronchiectasis. Future research should focus on optimizing integrated protocols, rigorous randomized controlled trials, and exploring novel therapeutic targets to consolidate the evidence base for this synergistic model.

Background: Metabolic dysfunction-associated steatohepatitis (MASH) has emerged as the primary contributor to the increasing incidence and mortality rates linked to cirrhosis and hepatocellular carcinoma globally, while the availability of clinical treatment drugs remains severely limited. Ecliptasaponin A (EA), naturally isolated from Ecliptae Herba, possesses multiple biological activities. However, the effects of EA on MASH remain unclear.

Purpose: This study aimed to explore the roles of EA in MASH and its engaged mechanisms.

Methods: Two established NASH animal models, non-obese MASH induced by methionine-choline-deficient (MCD) dietary administration and obese MASH developed through high-fat/high-cholesterol (HFHC) feeding were employed to assess EA's therapeutic effects in vivo. RNA-seq analysis was conducted to uncover EA's molecular mechanisms. Complementary in vitro investigations utilized LPS-treated BMDMs and THP1 cells, and TGF-β1-activated LX-2 hepatic stellate cells to systematically examine EA's cellular-level impacts and regulatory pathways.

Results: Oral administration of EA demonstrated dose-responsive therapeutic effects against MCD/HFHC-induced MASH. The compound effectively attenuated hepatic steatosis, inflammatory responses, and fibrotic progression in experimental models through dual modulation of NLRP3 and YAP signaling pathways. Mechanistic studies revealed EA specifically suppressed NLRP3 inflammasome activation in BMDMs without affecting AIM2 or NLRC4 inflammasomes, effectively blocking cytokine secretion, pyroptotic cell death, caspase-1 activation, and inflammasome complex formation. Molecular interactions analysis confirmed EA directly binds to NLRP3, disrupting inflammasome assembly. In LX-2 cells, EA suppressed TGF-β1-induced COL1A1 and α-SMA expression while reducing YAP protein levels. Genetic silencing or pharmacological inhibition of YAP failed to potentiate EA's anti-fibrotic effects on α-SMA suppression, Collagen I expression, or YAP-regulated gene transcription. Molecular docking and SPR showed that EZ could directly bind to NLRP3 and YAP.

Conclusion: These findings reveal novel perspectives on the natural compound Ecliptasaponin A, demonstrating its dual-targeting capability against both NLRP3 inflammasome activation and YAP signaling cascades. This discovery highlights its potential as a promising therapeutic agent for mitigating MASH.

Background: Metabolic dysfunction-associated steatohepatitis (MASH) is a severe progressive subtype of metabolic-related fatty liver disease that is defined by hepatic steatosis, hepatocyte damage, inflammation, and fibrosis. Alisol F 24-acetate (ALI), a triterpene derived from Rhizoma Alismatis, has anti-inflammatory and antioxidant properties. This study aimed to evaluate the therapeutic effects of ALI in a mouse model of MASH, RAW264.7 cells, and bone marrow-derived macrophages (BMDMs).

Methods: Levels of serum biochemicals, pathological changes in the liver, pyroptosis, and expression of the Kelch-like ECH-associated protein 1(KEAP1)/Nuclear factor E2-related factor 2 (NRF2) pathway were assessed in mice fed a methionine-choline-deficient (MCD) diet with different doses of ALI. Lipopolysaccharide (LPS)-stimulated RAW264.7 cells and BMDMs were used to ascertain the potential mechanisms of ALI on macrophage polarization.

Results: We found that ALI supplementation in MCD-fed mice decreased liver pathology, lipid accumulation, inflammation, and fibrosis. Moreover, ALI could attenuate M1 polarization, promote M2 polarization, suppress pyroptosis, and reduce oxidative stress levels via the KEAP1/NRF2 signaling pathway in tissue samples. ALI also suppressed LPS-induced RAW264.7 cells and BMDMs pyroptosis by inhibiting NLRP3 activation and reducing the level of reactive oxygen species. Molecular docking results suggested that ALI could bind with KEAP1. Overexpressing Keap1 weakened the effects of ALI on pyroptosis and affirmed a role associated with KEAP1/NRF2 pathways in macrophage.

Conclusion: Our findings suggest that ALI suppressed macrophage pyroptosis by targeting KEAP1/NRF2 interactions, providing reliable data on the protective mechanism of natural antioxidants against MASH.

Traditional Chinese Medicine (TCM), characterized by multi-component and multi-target pharmacological effects, boasts millennia of clinical application. The complexity of its pharmacological material basis extends beyond individual chemical components to include physical structures formed among constituents. Supramolecular chemistry offers a new perspective for elucidating this basis. This review systematically summarizes recent advances in supramolecular self-assemblies within TCM, focusing on molecular formation mechanisms, key chemical component characteristics driving assembly, their roles in decoctions, and the supramolecular basis for "efficacy enhancement and toxicity reduction" in compatibility theory. The biomedical applications of supramolecular self‑assemblies in TCM are also reviewed. Ultimately, this work aims to offer new insights into TCM's material basis, clarify compatibility mechanisms, advance the supramolecular interpretation of TCM theories, and provide perspectives for TCM modernization and drug development.

Background: Metabolic-associated fatty liver disease (MAFLD) is a common metabolic disease with complex pathogenesis and lack of effective treatment. Si-Ni-San (SNS), a traditional Chinese medicine, has emerged as a promising candidate for MAFLD treatment. However, the protective mechanism remains unclear.

Methods: C57BL/6N mice were fed with high-fat diet (HFD) for 12 weeks to establish MAFLD mouse model. Concurrently, oleic acid-induced HepG2 cells were used in vitro as a cellular model for MAFLD. The effects of SNS and the positive drug obeticholic acid on hepatic lipid droplets deposition in MAFLD mice and cell models were evaluated. The expression levels of farnesoid X receptor (FXR) and glycerol 3-phosphate acyltransferase 4 (GPAT4) were detected by western blot. The siRNA and dual-luciferase reporter assay were used to detect the interaction between FXR and GPAT4. High-performance liquid chromatography (HPLC) was used to identify the active components in the SNS aqueous solution, and their binding affinities to targets were detected through molecular docking, molecular dynamics simulations, and surface plasmon resonance (SPR).

Results: The active ingredients of SNS were identified by HPLC. SNS ameliorated hepatic lipid droplets deposition in both mouse and cellular models of MAFLD. SNS up-regulated the expression of FXR and down-regulated the expression of GPAT4 in hepatic tissues, thereby modulating proteins involved in hepatic lipolysis and lipophagy. FXR reduced lipid droplets accumulation by inhibiting GPAT4. The dual-luciferase reporter assay confirmed that FXR transcriptionally regulated and inhibited GPAT4 expression. Furthermore, molecular docking and molecular dynamics simulations predicted potential interactions between the active components of SNS and the FXR and GPAT4 proteins, with the binding affinity for FXR being subsequently confirmed through SPR analysis.

Conclusion: This study provided a new mechanistic exploration for FXR in improving MAFLD and broadened the research direction on the mechanisms by which SNS reduced hepatic lipid droplets deposition. It also offers a molecular dynamics basis for subsequent studies on how active components in SNS exert their effects through binding to FXR.

Background: Anxiety disorders-including generalized anxiety disorder, posttraumatic stress disorder, and social anxiety disorder-are highly prevalent psychiatric conditions that impose substantial clinical and social burdens. Preclinical and clinical studies have shown that electroacupuncture (EA) can effectively alleviate anxiety-like behaviors; however, the specific neural circuits and molecular mechanisms underlying EA's therapeutic effects remain incompletely elucidated.

Methods: We first assessed the impacts of EA at four classical acupoints-Zusanli (ST36), Neiguan (PC6), Tianshu (ST25), and Baihui (GV20)-delivered with distinct stimulation waveforms on anxiety-like behaviors in conventionally housed mice, using the elevated plus maze and open field test paradigms. To identify the neural circuit underlying the behavioral effects of Baihui (GV20) EA, we employed pseudorabies virus expressing enhanced green fluorescent protein (PRV-EGFP) for retrograde tracing from Baihui (GV20) and quantified c-Fos expression across the whole brain as a marker of neuronal activation. ELISA was utilized to measure plasma oxytocin (OXT) levels following EA at Baihui (GV20). Furthermore, a selective pharmacological antagonist of the oxytocin receptor (OXT-R) was administered to verify the critical role of OXT signaling in mediating the anxiolytic benefits of Baihui (GV20) EA.

Results: EA at GV20 using intermittent electrical wave stimulation exhibited the most robust anxiolytic effects compared to EA at other acupoints or alternative stimulation parameters. Retrograde virus tracing from GV20 revealed a direct neuronal connection between the PVN and the GV20 acupoint region. Further experiments showed that GV20 EA significantly increased the activation of OXT-synthesizing neurons in the PVN and elevated peripheral OXT concentrations in mouse plasma. Critically, intraperitoneal injection of an OXTR antagonist completely abrogated the anxiolytic effects of GV20 EA, confirming that OXT signaling is indispensable for this therapeutic action.

Conclusions: Intermittent 1.5 mA EA at Baihui (GV20) mitigates anxiety-like behavior in mice via a PVN-derived, OXT-dependent pathway. This work clarifies the anatomical and molecular mechanisms underlying EA-mediated anxiety relief and provides a basis for further exploring functional connections between specific acupoints and brain regions.

Single herbal medicines (SHMs) possess distinct advantages in regulating lipid metabolism, particularly through modulating the composition and function of the gut microbiota. Compared with herbal formulas, SHMs are characterized by traceable active components, clear pharmacological targets, and greater reproducibility. However, their intrinsic cold/hot properties must not be overlooked, as inappropriate or prolonged use may disturb the body's holistic balance and pose health risks. Therefore, it is essential to systematically classify lipid-lowering SHMs according to their cold/hot properties and establish a "medicinal properties-microbiota" framework to guide personalized treatment strategies for hyperlipidemia. We searched PubMed, Web of Science, EMBASE, the Cochrane Library, the Chinese Biomedical Literature Database, and CNKI for studies published up to August 2025. Studies reporting lipid-lowering effects of SHMs through gut microbiota regulation were screened and analyzed. Fifty-seven SHMs were included, comprising 24 cold/cool-property, 20 warm/heat-property, and 13 neutral-property medicines. These SHMs improved lipid metabolism mainly by modulating the gut microbial composition and metabolites such as short-chain fatty acids (SCFAs), lipopolysaccharides (LPS), bile acids (BAs), and trimethylamine N-oxide (TMAO). Shared microbiota changes included a reduced Firmicutes/Bacteroidetes ratio and increased abundance of Akkermansia, Lactobacillus, Ruminococcaceae, and Clostridium. A new pattern has been identified: cold/cool-property SHMs mainly targeted environmentally adaptive microbial taxa, warm/heat-property SHMs enriched Akkermansia muciniphila and promoted SCFA production, whereas neutral-property SHMs exerted broad-spectrum regulation to maintain microbial homeostasis. In summary, SHMs regulate lipid metabolism through multiple microbiota-related pathways, and the effects are closely associated with their cold/hot properties. The classification of SHMs according to the four natures provides a theoretical basis for personalized treatment and may guide the safe and effective use of SHMs for the treatment of dyslipidemia.