Chinese Medicine最新文献

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.

Background: Polycystic ovary syndrome (PCOS), a prevalent endocrine disorder, is characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. In light of the critical role of bile acids in metabolic regulation and the therapeutic potential of acupuncture for endocrine-metabolic disorders, this study aims to explore the effects of acupuncture on bile acid metabolism and insulin sensitivity in both PCOS patients and rat models.

Methods: 33 PCOS participants and 28 age/BMI-matched controls were enrolled in a clinical trial (NCT04193371). PCOS participants received 4 month acupuncture plus lifestyle (A&L) or a sham acupuncture plus lifestyle (SA&L) intervention followed by 4 month observation. Serum bile acids were profiled by LC-MS/MS. Multiple hormones and inflammatory markers were analyzed by enzyme-linked immunosorbent assay and insulin sensitivity was evaluated through oral glucose tolerance test and insulin tolerance test. A dihydrotestosterone -induced PCOS rat model was established and treated with acupuncture. The estrous cycle and ovarian morphology were assessed using HE staining, insulin resistance was evaluated and hormone levels were measured. Transcriptome profiling of hepatic tissues was conducted in a PCOS rat model to delineate molecular alterations associated with acupuncture intervention, with particular emphasis on genes involved in bile acid biosynthesis.

Results: The homeostasis assessment of insulin resistance (HbA1c, HOMA, AUC) of PCOS is significantly reduced after acupuncture compared to the pre-intervention (p < 0.05). Surprisingly, simultaneously ameliorated outcomes included the body mass index (BMI), sex hormone-binding globulin (SHBG), free androgen index (FAI) and anti-Müllerian hormone (AMH). The potency lasted for another 4 months, indicating the enduring effects of the acupuncture regimen. Metabolic improvements were associated with changes in specific bile acids (e.g., taurocholic acid, lithocholic acid). In PCOS rat models, acupuncture restored regular estrous cycles, reduced the incidence of ovarian cysts and improved the insulin resistant. Transcriptomic analysis of rat liver revealed that acupuncture significantly reversed the expression of genes associated with bile acid metabolism and the FXR signaling pathway.

Conclusions: Acupuncture therapy offers potential therapeutic benefits to PCOS women, with mechanisms involving the bile acid-FXR axis potentially contributing to improvements in insulin resistance and other disease-related symptoms.

Background: Aging is characterized by cellular senescence, inflammation, and physiological decline. Currently available antiaging therapies often have limitations due to their toxicity and off-target effects. However, natural compounds derived from Chinese herbal medicine, such as Rhapontigenin (Rhap), have shown potential as safer antiaging agents.

Purpose: This study aimed to evaluate the potential of Rhap to be used as an antiaging agent by investigating its effects on cellular senescence, physical function, immune modulation, and autophagy in both in vitro and in vivo aging models.

Methods: NIH3T3 and IMR90 cells were subjected to oxidative or genotoxic stress to induce senescence and then treated with Rhap. Senescence markers, cell viability, and autophagy-related protein levels were assessed. Aged mice were treated with Rhap for 8 weeks, and physical performance, immune modulation, and organ health were evaluated. Mechanistic studies were conducted to determine the role of Sirt1 in mediating the effects of Rhap.

Results: Rhap treatment significantly reduced cellular senescence marker (p16 and p21) levels and senescence-associated β-galactosidase (SA-β-Gal) activity in stressed cells. In aged mice, Rhap improved physical performance, such as grip strength and motor coordination, and reduced depressive-like behaviors. Rhap also decreased liver senescence, lipid accumulation, and fibrosis and increased immune function by reducing proinflammatory cytokine production and enhancing T-cell homeostasis. Mechanistically, Rhap upregulated Sirt1 and promoted autophagy, both of which contributed to its antiaging effects. Sirt1 knockdown attenuated the effects of Rhap on autophagy and senescence, indicating the importance of Sirt1 in mediating these beneficial effects.

Conclusion: Rhap is a promising candidate for mitigating age-related cellular and physiological decline by reducing cellular senescence, promoting autophagy, and modulating immune function. However, further work is needed to fully elucidate the precise molecular mechanisms of Rhap's action and its pharmacokinetic profile to assess its translational potential in humans.

Immune thrombocytopenia (ITP) is an acquired autoimmune hemorrhagic disorder with a substantial incidence globally across all age groups. Its pathogenesis involves the accelerated immune-mediated platelet destruction and impaired platelet production due to dysfunctional megakaryocyte maturation interactively. ITP is primarily treated by glucocorticoids and intravenous immunoglobulin in Western medicine conventionally. However, these therapies exhibit several limitations such as corticosteroid dependency, increased risk of infection, treatment resistance, and frequent relapse, despite its obvious efficacy in rapidly elevating platelet counts. In contrast, traditional Chinese medicine (TCM) attributes the pathogenesis of ITP (under "blood syndrome" or "purpura disease") to an imbalance in the fundamental TCM principle of "Yang transforming Qi and Yin constituting the body". By targeting both pathological platelet destruction and insufficient platelet production, TCM exerts multidimensional therapeutic effects in ITP, with clearly elucidated mechanisms demonstrated by active components from single herbs and compound formulations. The integration of TCM with Western medicine has shown promise in enhancing the therapeutic outcomes of the latter therapy while mitigating their side effects. Accordingly, the present study intends to systematically review the mechanisms of TCM in ITP, summarize recent research advances, analyze current challenges, and propose future research directions. This work is expected to provide potential foundation for further investigation and clinical application of TCM in ITP.

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease closely associated with metabolic dysregulation, exhibiting a complex and multifactorial pathogenesis. Recent studies demonstrate that impaired intestinal barrier function, intestinal immune barrier dysfunction, gut microbiota dysbiosis, and their associated metabolites collectively promote energy metabolism dysregulation and systemic inflammatory responses via the gut-liver axis. These interconnected processes represent key drivers in the pathogenesis and progression of NAFLD. Notably, Traditional Chinese Medicine (TCM) offers a promising therapeutic approach for NAFLD by holistically modulating intestinal barrier function, immune responses, and gut microbiota composition via multiple targets and pathways, thereby ameliorating gut dysbiosis and its downstream metabolic and inflammatory sequelae. This review systematically synthesizes the established relationship between NAFLD and intestinal barrier dysfunction. It critically evaluates current research progress on TCM interventions-including single herbs, bioactive constituents, and compound formulas-that target the intestinal barrier for NAFLD management. Key mechanistic insights into TCM efficacy are summarized, focusing on the repair of the intestinal mucosal barrier, modulation of bile acid metabolism and gut microbiota composition, and enhancement of intestinal immune barrier function. Future research should prioritize elucidating the specific molecular mechanisms underpinning TCM-mediated intestinal barrier regulation and strengthening clinical validation, ultimately advancing the scientific foundation for TCM-based NAFLD therapeutics.

Background: Postoperative pain develops after surgical operation. Inadequately managed postoperative pain is oftentimes associated with deterioration in life quality and delayed rehabilitation. Clinical studies confirmed analgesic effects of acupuncture on patients with postoperative pain. We hereby explored mechanisms underlying how acupuncture alleviates postoperative pain.

Methods: A mouse model of skin incision-induced pain was established to mimic postoperative pain condition. Electroacupuncture (EA) or sham EA was administered at ST36 and BL60 acupoints in model mice. A combination of RNA-Sequencing (RNA-Seq), immunostaining, biochemical assay, in vivo imaging and behavioral test were applied for mechanism investigations.

Results: 2/100 Hz EA intervention ameliorated mechanical allodynia and improved cumulative pain of incisional pain model mice. Sham EA exerted no obvious analgesic effect. Incisional pain model mice develop gait impairment, which was improved by EA intervention. RNA-Seq identified EA significantly reduced Il33 gene overexpression in the incised skin tissues of model mice. IL-33 was produced from keratinocytes upon skin incision. EA reduced IL-33 overproduction from keratinocytes, resulting in less macrophage infiltration and less ROS accumulation in the incised skin. Adoptive transfer of macrophages into the incised tissue abrogated the ameliorative effects of EA on macrophage infiltration as well as ROS accumulation in incised skin and further reversed EA-induced analgesia on incisional pain model mice. Additionally, EA intervention did not affect skin wound healing process.

Conclusion: These results demonstrate that EA ameliorates incisional pain via suppressing IL-33 overproduction in incised skin tissue. EA-induced suppression of IL-33 overproduction results in less macrophage infiltration and ROS accumulation that contribute to analgesia. Our work helps to support EA as an alternative and green therapy for postoperative pain management.