Chinese Medicine最新文献

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.

Background: Promoting intestinal barrier repair and epithelial regeneration is a core therapeutic objective in managing ulcerative colitis (UC). Intestinal stem cell (ISC) differentiation is pivotal in sustaining epithelial renewal and mucosal homeostasis. Huangqin decoction (HQD), a classical herbal formulation comprising Scutellaria baicalensis, Ziziphus jujuba, Paeonia lactiflora, and Glycyrrhiza uralensis, is clinically used for inflammatory bowel disease. Nevertheless, how HQD precisely regulates ISC differentiation to promote UC repair remains unclear.

Purpose: This research sought to assess whether HQD ameliorates UC by concurrently modulating the gut microbiome, tryptophan metabolism, aryl hydrocarbon receptor (AhR) activation, and ISC differentiation.

Methods: Mice developed colitis after drinking water with a 3.5% (w/v) concentration of dextran sulfate sodium. We evaluated HQD effects on colon length, weight trajectory, disease activity index score, histological damage, and colonic inflammatory mediator abundance. Metagenomic sequencing resolved microbiota restructuring, while UPLC-MS/MS quantified fecal tryptophan metabolites such as indole derivatives. AhR pathway activity (AhR, CYP1A1), its downstream cytokine IL-22, and ISC fate were mapped by combining immunofluorescence, ELISA, Western blot, and RT-qPCR, probing Lgr5 for stem-cell identity and MUC2, LYZ, and ChgA for lineage-specific differentiation. The involvement of AhR and gut microbiota was investigated using AhR inhibitors and broad-spectrum antibiotics.

Results: High-dose HQD significantly alleviated colitis symptoms, reduced colon damage, and corrected gut dysbiosis. HQD increased the abundance of related bacteria that elevated colonic levels of indole-3-propionic acid, indole-3-acetamide, and tryptamine, acting as AhR ligands that upregulate AhR and its downstream targets CYP1A1 and IL-22. Crucially, HQD promoted a shift in expression from the ISC marker Lgr5 toward differentiation markers MUC2, LYZ, and ChgA, indicating enhanced ISC differentiation and improved barrier function. These effects were effectively blocked by AhR inhibition or antibiotic treatment.

Conclusion: HQD restores intestinal mucosal integrity and attenuates colonic inflammation by modulating gut microbiota composition, increasing microbial tryptophan metabolites with AhR-agonist activity, activating the AhR signaling pathway, and promoting ISC differentiation into functional epithelial cells. This work reveals a novel "microbiota-tryptophan metabolism-AhR-ISC differentiation" axis underlying HQD's therapeutic efficacy in UC.

Gastric cancer (GC) is the second most frequently diagnosed malignancy, as well as the second most common cause of cancer-related deaths in China. Drug resistance is a major factor that limits the efficacy of GC chemotherapy. Given the increased resistance of GC cells to ferroptosis, activating the ferroptotic pathways has emerged as a promising therapeutic strategy against GC. This review summarizes the pathways involved in ferroptosis resistance in GC cells and the mechanisms underlying the therapeutic effects of herbal formulae and their bioactive compounds, with particular emphasis on ferroptosis. Multiple signaling pathways are implicated in regulating ferroptosis in GC cells, including the Wnt/β-catenin, PI3K/AKT/mTOR, TGF-β1/Smad, NF-κB, and Hippo pathways. According to previous clinical trials, traditional Chinese medicine (TCM) formulations can prolong the survival or increase survival chances in patients with GC, and reduce adverse reactions, thereby improving the quality of life. Finally, preclinical studies have shown TCMs and their bioactive compounds can ameliorate GC progression by triggering ferroptosis. Despite these beneficial effects on patients with GC, the underlying molecular mechanisms of TCM in GC have not been fully elucidated yet, and there are also some crucial shortcomings in the current studies. Therefore, further clinical trials and experimental studies are required to deepen our understanding of the mechanisms for activating ferroptosis in GC cells through TCM.

Background: Sheng-Xian-Tang (SXT), a traditional Chinese medicine, ameliorates doxorubicin (DOX)-induced chronic heart failure (CHF), yet its molecular mechanisms remain elusive.

Objective: To elucidate SXT's cardioprotective mechanisms against DOX-induced CHF.

Methods: In vivo, cardioprotection was evaluated via echocardiography, oxidative stress assays, and histopathology. Integrated metabolomic and 16S rRNA sequencing identified metabolic disruptions. Serum pharmacochemistry analysis identified hepatic bioactive compounds targeting phenylalanine hydroxylase (PAH). Molecular docking, CETSA, SPR, and enzyme activity assay validated neomangiferin-PAH interactions.

Results: SXT dose-dependently improved DOX-induced cardiac dysfunction in rats. Metabolomic and microbiome analyses confirmed phenylalanine metabolic disorder in the CHF rats. DOX exposure elevated phenylalanine levels in plasma, urine, and heart, reducing hepatic PAH expression and function while inducing ectopic phenylalanine catabolism in the heart. Phenylalanine administration exacerbated the cardiac abnormalities, whereas SXT effectively prevented attenuated DOX-induced cardiac toxicity. CETSA and SPR revealed a strong binding of neomangiferin to PAH, stabilizing its interaction with cofactor BH₄ and preventing DOX-induced PAH inhibition.

Conclusions: SXT mitigated DOX-induced CHF through hepatic PAH modulation. Neomangiferin could enhance PAH stability via competitive binding. Targeting PAH-phenylalanine metabolism emerged as a novel therapeutic strategy for DOX-induced cardiac dysfunction.