Chinese Medicine最新文献

Background: Zhen-Wu-Tang (ZWT), a classic herbal formula from Treatise on Febrile and Miscellaneous Diseases, is commonly used for heart and kidney-related diseases. Despite its widespread application, research on the active components of ZWT and their mechanisms in heart-kidney cross-organ regulation remains underexplored.

Aim of the study: This study aimed to elucidate the therapeutic mechanisms of ZWT in uremic cardiomyopathy (UC) focusing on its modulation of the heart-kidney inflammatory axis.

Materials and methods: A UC model was established via 5/6 nephrectomy in mice, followed by 8 weeks of ZWT treatment. Functional assessments included serum creatinine, blood urea nitrogen, cardiac ejection fraction, and left ventricular metrics. Proteomic analysis using Olink technology exerts its therapeutic effects by suppressing systemic inflammation. UHPLC-Q/TOF-MS were employed to identify prototype components and blood-entering components in ZWT. Cellular experiments using a three-step co-culture system were conducted to evaluate the regulatory effects of ZWT active components on HK-2 and AC16 cells and to explore their underlying molecular mechanisms.

Results: ZWT significantly improved renal and cardiac functions. Proteomics revealed ZWT suppressed pro-inflammatory cytokines TNFα, IL-6, IL-1β and chemokines. The bioactive constituents of ZWT, including benzoylaconine, paeoniflorin, and atractylenolide III, inhibited NF-κB activation, thereby reducing CCL2 synthesis and subsequent macrophage recruitment via the CCR2 axis. This attenuated systemic inflammation and cardiomyocyte injury.

Conclusions: ZWT exerts therapeutic effects on UC by targeting the kidney-heart inflammatory axis and suppressing CCL2/CCR2-mediated macrophage activation. This study provides new insights into the molecular mechanisms underlying ZWT's efficacy in treating heart-kidney disorders.

Background: Fuzheng Huayu formula (FZHY) has been extensively applied in clinical for liver fibrosis treatment in China, its therapeutic potential in cholestatic liver injury remains underexplored.

Objective: To evaluate the protective effects and underlying mechanisms of FZHY against chronic cholestatic liver injury.

Methods: The therapeutic effect of FZHY was initially validated in a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced murine model of chronic cholestasis. Subsequent mechanistic investigations were conducted through comparative analyses in peroxisome proliferator-activated receptor α gene knockout (Pparα^-/-) mice subjected to DDC challenge.

Results: FZHY significantly ameliorated chronic cholestatic liver injury phenotypes in DDC-induced mice, as evidenced by bile acids (BAs) accumulation, inflammation, ductular reaction and biliary fibrosis was remarkably reduced after treatment with FZHY. Transcriptome sequencing analysis revealed that the effect of FZHY on chronic cholestatic liver injury was closely associated with activating PPAR signaling pathway and suppressing nuclear factor kappa-B (NF-κB) signaling. Further research found FZHY did not only enhance the total hepatic content of PPARα protein, but also increased its nuclear to cytoplasmic ratio that was reduced by DDC inducing. Additionally, FZHY suppressed hepatic phosphorylation of IκBα and NF-κB. The therapeutic effect of FZHY in treating DDC-induced mice with chronic cholestatic liver injury is similar to that of fenofibrate, a PPARα agonist. Crucially, genetic ablation of Pparα substantially abrogated the hepatoprotective and anti-fibrotic effects of FZHY in DDC-induced mice.

Conclusions: The present study underscores FZHY regulated BAs metabolism and alleviated hepatic inflammation and fibrosis by upregulating PPARa in DDC-induced mice. Our study provides novel insights that FZHY might be a promising drug for chronic cholestatic liver injury.

Background: Jianpi Qingre Tongluo Prescription [also named Huangqin Qingrechubi Capsule (HQC)] is an empirical prescription for the treatment of gouty arthritis (GA) with excellent clinical efficacy. Mechanistically, HQC suppresses inflammation and lipid metabolism imbalance in GA by regulating long non-coding RNA H19 (lncRNA H19). Nevertheless, the detailed mechanism requires further investigation.

Purpose: This study further explored the mechanism of HQC in suppressing inflammation and improving lipid metabolism via lncRNA H19 in GA.

Methods: A rat model of GA was established to analyze the effects of HQC on joint injury, inflammation, and lipid metabolism in GA. Subsequently, network pharmacology was employed to identify the key pathway involved in the effects of HQC on inflammation and lipid metabolism in GA. Based on clinical and animal experimental observations, a co-culture model of GA-peripheral blood mononuclear cells and GA-fibroblast-like synoviocytes was constructed to validate the mechanism of HQC in regulating GA-related inflammation and lipid metabolism from the perspective of N6-methyladenosine (m6A) modification of lncRNA H19.

Results: HQC alleviated joint injury and improved the abnormal levels of inflammatory factors (hs-CRP, IL-4, IL-1β, and TNF-α) and lipid metabolites (TC, TG, lipoprotein, adiponectin, leptin, visfatin, and resistin) in GA rats. The IL-17 pathway was identified as an important node in HQC's effects on improving inflammation and lipid metabolism in GA. Alterations of lncRNA H19 and the IL-17 pathway were observed in GA patients and rats, which were closely correlated with inflammation and lipid metabolites. Cellular experiments revealed that high expression of lncRNA H19, attributed to ALKBH5/FTO-mediated demethylation, facilitated inflammation and lipid metabolism imbalance in GA via activating the IL-17 pathway. HQC could repress inflammation and improve lipid metabolism in GA through inhibiting the IL-17 pathway by increasing ALKBH5/FTO-mediated m6A modification of lncRNA H19; these effects might be achieved by Carthamidin.

Conclusion: HQC inhibited inflammation and improved lipid metabolism in GA via inactivation of the IL-17 pathway by regulating m6A modification of lncRNA H19. Our findings further support the great potential of HQC as a candidate drug for GA treatment.

Triptolide, a bioactive triepoxide diterpenoid extracted from Tripterygium wilfordii Hook. f., has demonstrated broad pharmacological activities and significant toxicities. Mechanistically, triptolide has exerted therapeutic effects by regulating programmed cell death (PCD) through multiple pathways; however, its toxic reactions have been closely associated with this process. This review systematically summarizes the molecular mechanisms by which triptolide regulated various forms of PCD and its application progress in disease treatment, including apoptosis, autophagy, pyroptosis, ferroptosis, cuproptosis, necroptosis, and PANoptosis. A plethora of extant studies have revealed that triptolide exerted a regulatory effect on the PCD networks by intervening in multiple important signaling pathways and their key signaling nodes. Nevertheless, due to its poor target specificity, triptolide has resulted in multi-organ toxicities, which has in turn limited its clinical translation. Nano-delivery systems have explored as a potential strategy to mitigate the toxicity and improve the efficacy of triptolide by enhancing its tissue targeting (Specific nanocarriers can increase LD₅₀ from 0.48 to 0.88 mg/kg). Furthermore, key pharmacodynamic evidences from triptolide's current clinical studies are limited, necessitating the elucidation of precise target sites and the advancement of standardized clinical trials. This review systematically integrates the pleiotropic pharmacological activities and multiple-organ toxicities of triptolide from a PCD perspective, providing novel insights and theoretical references for overcoming its clinical translation barriers.

Background: Ulcerative colitis (UC), a chronic-relapsing inflammatory disease with rising prevalence worldwide, is primarily driven by intestinal epithelial barrier dysfunction resulting from gut microbial dysbiosis and metabolic disturbances. Daikenchuto (DKT), a traditional Chinese medicine formulation, is commonly used for digestive disorders. Although DKT has demonstrated therapeutic potential for gut inflammation by modulating gut microbiota, its therapeutic effects on chronic ulcerative colitis (CUC) and the related mechanisms remain elusive.

Methods: The main components of DKT were tentatively identified using ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS), and the therapeutic effects of DKT were evaluated in the mouse models of acute colitis (AC) and CUC induced using dextran sulfate sodium. The models were validated based on alterations in the disease activity index (DAI), colonic inflammatory status, and intestinal barrier integrity. The impact of DKT on the dysbiosis of gut microbiota was evaluated using the 16S rRNA gene and metagenomic sequencing. Targeted metabolomics was conducted to quantify shifts in short-chain fatty acids and tryptophan (Trp) metabolites. To further elucidate the underlying mechanisms of DKT, key pathways were analyzed using Western blotting, immunohistochemistry, and real-time quantitative polymerase chain reaction.

Results: The principal constituents of DKT were tentatively identified. DKT administration significantly alleviated the symptoms of AC and CUC, reduced inflammation, and maintained intestinal barrier function. Furthermore, DKT modulated the structure and abundance of gut microbiota. Metagenomic sequencing analysis demonstrated that DKT significantly enriched the relative abundance of Ligilactobacillus murinus, Lactobacillus taiwanensis, and Lactobacillus johnsonii. Moreover, Trp metabolism and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathways might be the therapeutic mechanisms of DKT. Targeted metabolomics confirmed that Trp/indole was the major pathway during the therapeutic process of DKT on CUC. Further mechanistic studies demonstrated that activation of the aryl hydrocarbon receptor (AhR) signaling enhanced proliferation in the colonic crypts by stimulating IL-22 secretion and promoting STAT3 phosphorylation.

Conclusions: DKT alleviated AC and CUC in mouse models by modulating gut microbiota, restoring Trp metabolism, and activating the AhR/IL-22/STAT3 signaling pathway. These findings provide a basis for the clinical application of DKT in UC patients.

Background: Pulmonary hypertension (PH) is a severe pulmonary vascular disease lacking early diagnostic biomarker and effective therapeutics. Osthole has capability to alleviate pulmonary vascular remodeling targeting by decadienyl-L-carnitin (C10:2) in PH rats. We sought to explore the novel functional mechanism of C10:2 in cell proliferation, apoptosis, extracellular matrix remodeling, and energy biosynthesis of pulmonary vascular remodeling as well as new inventional mechanism of osthole.

Methods: Animal and cell models of PH were established using monocrotaline (MCT) and platelet-derived growth factor-BB (PDGF-BB). C10:2 biosynthesis was manipulated through the administration of exogenous C10:2 and etomoxir. Markers of pyroptosis and pulmonary vascular remodeling, as well as components of the C10:2/HSP47/NLRP3 axis, were evaluated using western blotting, ELISA, and biochemical assays.

Results: Osthole inhibited cell pyroptosis and alleviated pulmonary vascular remodeling by suppressing the expression of NLRP3, GSDMD, Caspase-1, IL-1β, IL-18, and C10:2 in PH rats. Additionally, C10:2 levels were positively correlated with the progression of pulmonary vascular remodeling in a time-dependent manner. C10:2, similar to PDGF-BB, promoted the proliferation of pulmonary arterial smooth muscle cells (PASMCs), accelerated extracellular matrix remodeling, inhibited apoptosis, activated AMPKα-1, and increased ROS accumulation, ultimately leading to mitochondrial dysfunction in PASMCs. Osthole attenuated C10:2-induced pulmonary vascular remodeling by downregulating proliferation markers (PCNA, cyclin A, CDK2), modulating apoptosis markers (Caspase-3, Bax, Bcl-2), inhibiting migration-related proteins (MMP2, MMP9, TGF-β), and reducing AMPKα-1 and ROS overaccumulation as well as HSP47 expression. Collectively, our findings reveal a novel role for C10:2 in accelerating pulmonary vascular remodeling by promoting proliferation, apoptosis resistance, extracellular matrix remodeling, and mitochondrial dysfunction through NLRP3 inflammasome activation. Mechanistically, osthole significantly inhibited pyroptosis and mitigated pulmonary vascular remodeling via the C10:2/HSP47/NLRP3 axis.

Conclusion: Our study identifies a novel function of C10:2 in promoting pyroptosis and accelerating pulmonary vascular remodeling through activation of the HSP47/NLRP3 axis. Furthermore, we demonstrate that osthole effectively inhibits C10:2/HSP47/NLRP3 axis-induced pyroptosis, thereby alleviating pulmonary vascular remodeling. These findings suggest that C10:2 may serve as a potential biomarker for PH diagnosis and provide a foundation for the development of novel anti-PH therapeutic strategies.

Ferroptosis is a novel iron-dependent form of programmed cell death characterized by the accumulation of lipid peroxides. Its mechanism involves the disruption of iron metabolism, imbalances in the antioxidant system, and lipid peroxidation. As a leading global cause of death, cancer treatment often faces challenges such as drug resistance and adverse side effects. Traditional Chinese medicine (TCM), as a complementary and alternative therapy, demonstrates significant potential in tumor treatment due to its multi-targeted and multi-pathway regulatory advantages. Recent studies reveal that numerous natural products in Chinese herbal medicines can inhibit tumor growth by inducing ferroptosis. This review systematically elucidates the core molecular mechanisms of ferroptosis, encompassing iron metabolism, lipid peroxidation, and various regulatory pathways. It highlights the research progress on how natural products from TCM induce ferroptosis by regulating key targets in lung cancer, breast cancer, colorectal cancer, gastric cancer, and liver cancer. This review aims to provide a reference for the development of anticancer drugs based on TCM.

Introduction: Müller cell pyroptosis and immune inflammation-induced retinal ganglion cell (RGC) damage are the core pathological markers and potential therapeutic targets for neurodegeneration in early diabetic retinopathy (DR). Qiming Granules (QMG)-recommended by the traditional Chinese medicine guidelines for DR owing to their multi-target immunomodulatory, antioxidant, and microvascular protective effects. This study aimed to clarify the protective effect of QMG on early DR neurodegeneration, reveal their neuroprotective mechanism by regulating the P2X7R/NLRP3 pathway to inhibit Müller cell pyroptosis and immune inflammation, identify the chemical components of QMG and its absorbed components in rat plasma, study the effects of major absorbed components on inhibiting Müller cells pyroptosis and immune inflammatory response, and investigate the potential pharmacodynamic substances of QMG.

Methods: An in vivo DR neurodegeneration model was established. HE staining, transmission electron microscopy, WB, and ELISA were used for detecting RGC apoptosis, histomorphological changes, P2X7R/NLRP3 expression, and pyroptosis pathway proteins. An in vitro high-glucose-induced Müller cell pyroptosis model was constructed. After activating or inhibiting P2X7R, lactate dehydrogenase levels were measured; moreover, ELISA, WB, and immunofluorescence were performed to examine cell membrane damage, inflammatory factor release, and pyroptosis pathway protein expression. UPLC-Q-Orbitrap HRMS was utilized to characterize the chemical and blood-entering profiles of QMG, aiming to evaluate the inhibitory effects of its main blood components on high glucose-induced Müller cell pyroptosis.

Results: QG inhibited RGC apoptosis, the P2X7R/NLRP3 pathway, and retinal cell pyroptosis in DR neurodegeneration model rats. In vitro, QMG reduced membrane rupture and pyroptosis pathway protein expression in Müller cells by suppressing the P2X7R/NLRP3 pathway, ultimately inhibiting Müller cell pyroptosis and immune-inflammatory responses. Nine of the 70 compounds identified in QMG were absorbed into the bloodstream. The main absorbed components, astragaloside IV and puerarin, effectively mitigated high glucose-induced Müller cell pyroptosis, with astragaloside IV exhibiting a more pronounced effect.

Conclusions: QMG mitigated Müller cell pyroptosis and inflammatory responses by regulating the P2X7R/NLRP3 pathway, thereby inhibiting early neurodegeneration in DR. Astragaloside IV and puerarin absorbed into systemic circulation, significantly attenuated high glucose-induced pyroptosis, and suppressed immunoinflammatory responses in Müller cells.