Chinese Medicine最新文献

Sepsis-induced acute lung injury (SALI) is characterized by a dysregulated inflammatory and immune response. As a key component of the innate immune system, macrophages play a vital role in SALI, in which a macrophage phenotype imbalance caused by an increase in M1 macrophages or a decrease in M2 macrophages is common. Despite significant advances in SALI research, effective drug therapies are still lacking. Therefore, the development of new treatments for SALI is urgently needed. An increasing number of studies suggest that natural products (NPs) can alleviate SALI by modulating macrophage polarization through various targets and pathways. This review examines the regulatory mechanisms of macrophage polarization and their involvement in the progression of SALI. It highlights how NPs mitigate macrophage imbalances to alleviate SALI, focusing on key signaling pathways such as PI3K/AKT, TLR4/NF-κB, JAK/STAT, IRF, HIF, NRF2, HMGB1, TREM2, PKM2, and exosome-mediated signaling. NPs influencing macrophage polarization are classified into five groups: terpenoids, polyphenols, alkaloids, flavonoids, and others. This work provides valuable insights into the therapeutic potential of NPs in targeting macrophage polarization to treat SALI.

Background: Polycystic ovary syndrome (PCOS) is a complex neuroendocrine disorder characterized by dysregulation of the hypothalamus. Both electroacupuncture (EA) and manual acupuncture (MA) have demonstrated therapeutic efficacy in the treatment of PCOS through improvements in hypothalamic function. However, the underlying mechanisms remain poorly understood. Gonadotropin-releasing hormone (GnRH) neurons are pivotal in regulating hypothalamic endocrine function, whereas tanycyte, a specialized glial cell type, potentially contribute to this process.

Methods: A dihydrotestosterone (DHT)-induced PCOS-like mouse model was used to investigate the effects of acupuncture. Tissue clearing and three-dimensional (3D) imaging were employed to visualize the hypothalamic GnRH neuronal network and assess postacupuncture modifications. Transcriptome sequencing was performed to identify changes in the gene profiles associated with EA and MA. Rax-CreER^T2 transgenic mice were utilized to investigate the molecular targets of EA in tanycytes.

Results: EA significantly alleviated neuroendocrine dysfunction in PCOS-like mice by restoring the density and coverage of GnRH axonal projections. MA displayed similar therapeutic effects but had less pronounced effects on GnRH axons. Transcriptome analysis revealed distinct mechanisms for these two approaches: EA primarily regulates neuroglial plasticity, whereas MA predominantly targets neurotransmitter regulation. Both EA and MA share a common therapeutic target in the integrin family. Functional studies in Rax-CreER^T2 transgenic mice confirmed that Itgb1 plays a critical role in maintaining the balance of hypothalamic GnRH-tanycyte unit during EA treatment.

Conclusions: EA exerts therapeutic effects on PCOS by targeting hypothalamic GnRH-tanycyte unit, with Itgb1 identified as a key factor. MA primarily functions through neurotransmitter regulation. These findings highlight potential hypothalamic targets and provide new insights into the distinct mechanisms of EA and MA.

Background: Steroid-resistant asthma (SRA) is a form of asthma resistant to corticosteroid therapy, which is characterized by the presence of neutrophil-predominant inflammatory response and neutrophil extracellular traps (NETs) formation. Hyssopus cuspidatus Boriss., a traditional Uyghur medicine, is known for its efficacy in treating inflammatory lung conditions such as asthma. However, the therapeutic impact and underlying mechanisms of Hyssopus cuspidatus Boriss.'s volatile oil (HVO) in SRA have not been fully elucidated.

Methods: This study established an ovalbumin/lipopolysaccharide (OVA/LPS)-induced SRA mice model to evaluate the therapeutic effect of HVO on SRA. UPLC-QE-Orbitrap-MS was applied to analyze the serum compositions of HVO. Network pharmacology and molecular docking were employed to uncover the complex mechanisms of HVO in treating SRA and predict potential effective compounds in HVO. Furthermore, in vivo studies in SRA mice and in vitro studies using HL-60 cells and bone marrow neutrophils were conducted to validate the mechanism.

Results: HVO could significantly ameliorate OVA/LPS-induced SRA symptoms, including airway hyperresponsiveness, airway inflammation, mucus overproduction and airway remodeling. 41 prototype compounds, 65 Phase I metabolites and 50 Phase II metabolites were identified in serum-containing HVO. The integration of network pharmacology with experimental validation revealed that HVO can inhibit the formation of NETs by targeting neutrophil elastase, thereby exerting a therapeutic influence on SRA. Meanwhile, molecular docking results showed that 3-methoxy-4-hydroxy mandelonitrile, 1,2,3,4-tetrahydro-1,5,7-trimethyl-naphthalene, cis-calamenene and aristol-1(10)-en-9-yl isovalerate may be the therapeutic compounds of HVO in treating SRA.

Conclusion: These findings suggest that HVO is a promising therapeutic candidate for neutrophil-dominant SRA by targeting NETs formation.

Background: Mitophagy is closely related to the regulation of retinal ganglion cell (RGC) structure and function. Our previous study suggested that long noncoding RNAs (lncRNAs) can cause damage to myopic RGCs. However, whether electroacupuncture (EA) treatment can delay myopia progression through lncRNA-mediated mitophagy in RGCs is currently unknown. This study aimed to investigate the effect of EA on lncRNA-mediated mitophagy in myopic RGCs.

Methods: Our study investigated the modulatory effect of EA on mitophagy in RGCs of guinea pigs with form-deprived myopia (FDM). RNA sequencing was performed to further analyze the expression profiles of lncRNAs and mRNAs in RGCs of guinea pigs with FDM after EA treatment, and the related competing endogenous RNA (ceRNA) network was constructed. Importantly, PINK1, a mitophagy-related gene, was included in the core ceRNA network to explore the relationship between lncRNAs and mitophagy in myopic RGCs regulated by EA. We also collected eyeballs from myopic and highly myopic adults to further verify the mechanistic results.

Results: This study demonstrated that EA treatment delayed the reduction in refraction and increase in axial length and alleviated RGC damage in guinea pigs with FDM. We further found that EA could induce mitophagy in guinea pig RGCs with FDM by promoting the mitophagy-related PINK1/Parkin signaling pathway. Moreover, mitophagy is inhibited in the retina of highly myopic adults. RNA sequencing revealed that 599 lncRNAs and 455 mRNAs were differentially expressed in guinea pig RGCs with FDM after EA treatment. A core ceRNA network was constructed by incorporating PINK1 and verified by related molecular experiments, and we found that EA treatment may induce mitophagy and attenuated RGC injury in guinea pigs with FDM by sponging miR-342-5p through lncRNA-XR_002789763.1 to activate the PINK1/Parkin signaling pathway and promote Mfn2 ubiquitination.

Conclusion: EA treatment might regulate lncRNA-XR_002789763.1/miR-342-5p axis and activate the mitophagy-related PINK1/Parkin signaling pathway, and promote Mfn2 ubiquitination, thereby alleviating RGC damage and delaying myopia progression.

Background: Cutaneous hypertrophic scar is a fibro-proliferative hard-curing disease. Recent studies have proved that antagonists of angiotensin II type 1 receptor (AT₁R) and agonists of type 2 receptor (AT₂R) were able to relieve hypertrophic scar. Therefore, establishing new methods to pursue dual-target lead compounds from Chinese herbs is in much demand for treating scar.

Methods: To this end, we immobilized AT₁R or AT₂R onto the surface of silica gel from cell lysates through a specific covalent bond by bioorthogonal chemistry. The columns containing immobilized AT₁R or AT₂R were jointly utilized to pursue potential bioactive compounds simultaneously binding to AT₁R and AT₂R from the extract of Rhei Radix et Rhizoma. Their functions on AT₁R and AT₂R expressions were investigated by in vitro and in vivo experiments.

Results: Aloe-emodin and emodin were identified as the potential bioactive compounds binding to both of the two receptors, thereby improving the appearance and pathomorphology of hypertrophic scar. They blocked the AT₁R pathway to down-regulate the expression of transforming growth factor-β1 (TGF-β1) and stimulate matrix metalloproteinase-1 (MMP-1) expression. As such, the expression of collagen I/III reduced. Conversely, the bindings of the two compounds to AT₂R reduced the production of nuclear factor-кB1 (NF-кB1), whereby the generation of interleukin-6 (IL-6) was blocked.

Conclusion: We reasoned that aloe-emodin and emodin had the potential to become dual-target candidates against hypertrophic scar through the regulation of AT₁R and AT₂R signaling pathways. It showed considerable potential to become a universal strategy for pursuing multi-target bioactive compounds from Chinese herbs by the utilization of diverse immobilized receptors in a desired order.

Background: Bear bile powder (BBP), a unique animal-derived medicine with anti-inflammatory and antioxidant effects, is used in Shexiang Tongxin dropping pills (STDP), which is applied to treat cardiovascular diseases, including acute myocardial infarction (AMI). The efficacy and compatibility mechanisms of action of BBP in STDP against cardiovascular diseases remain unclear. This study aimed to investigate the compatibility effects of BBP in STDP in rats with AMI.

Methods: We investigated the compatibility effects of BBP in STDP in rats with AMI. Non-targeted metabonomics, 16S rRNA analysis, RNA sequencing, and network pharmacology were performed to explore the underlying mechanisms.

Results: The combination of BBP and CF (STDP without BBP) significantly reduced AMI-induced infarction size, pathological alterations of cardiac tissues, and serum lactate dehydrogenase and creatine kinase levels in rats, compared with CF or BBP treatment alone. Gut microbiota and metabonomics results revealed that the combination treatment could upregulate the relative abundance of Lactobacillus and downregulate that of Helicobacter, Bilophila, and Butyricimonas, thereby rebalancing the gut microbiota dysbiosis induced by AMI. Consequently, the intestinal metabolite levels of oleoylcholine, glutamylalanine, isokobusone, and hemorphin-4 were altered. However, treatment with CF or BBP alone has a weaker effect on these bacteria. Additionally, the combination treatment induced a 62.34% gene reversion rate compared with 55.56% for BBP and 30.20% for CF treatment alone. Modulation of endothelin 1 and growth factor receptor-bound protein 2 was identified as a key synergistic mechanism underlying the anti-AMI effects of BBP in STDP.

Conclusion: This research provides a scientific explanation of the compatibility of BBP in STDP. Our findings suggested that combination treatment with CF and BBP synergistically attenuates AMI by altering gene expression, gut microbiota, and intestinal metabolite profiles.

Objective: Cinnamic acid (CA) is a bioactive compound isolated from cinnamon. It has been demonstrated to ameliorate inflammation and metabolic diseases, which are associated with endothelial dysfunction. This study was aimed to study the potential protective effects of CA against diabetes-associated endothelial dysfunction and its underlying mechanisms.

Methods: High-fat diet (HFD) with 60 kcal% fat was used to induce obesity/diabetes in C57BL/6 mice for 12 weeks. These diet-induced obese (DIO) mice were orally administered with CA at 20 or 40 mg/kg/day, pioglitazone (PIO) at 20 mg/kg/day or same volume of vehicle during the last 4 weeks. Isolated mouse aortic segments and primary culture rat aortic endothelial cells (RAECs) were induced with high glucose (HG) to mimic hyperglycemia and co-treated with different concentrations of CA.

Results: In DIO mice, four-week administration of CA, particularly at 40 mg/kg/day, diminished the body weights, blood pressure, fasting blood glucose and plasma lipid levels, and ameliorated endothelium-dependent relaxations (EDRs) and oxidative stress in aortas. The beneficial effects of CA were comparable to the positive control group, PIO. Western blotting results indicated that CA treatment upregulated the expression of peroxisome proliferator-activated receptor delta (PPARδ), and activated nuclear factor erythroid 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) and AMP-activated protein kinase (AMPK)/ protein kinase B (Akt)/ endothelial nitric oxide synthase (eNOS) signaling pathways in mouse aortas in vivo and ex vivo. HG stimulation impaired EDRs in mouse aortas and inhibited nitric oxide (NO) production but elevated reactive oxygen species (ROS) levels in RAECs. CA reversed these impairments. Importantly, PPARδ antagonist GSK0660 abolished the vasoprotective effects of CA. Molecular docking analysis suggested a high likelihood of mutual binding between CA and PPARδ.

Conclusion: CA protects against endothelial dysfunction and oxidative stress in diabetes and obesity by targeting PPARδ through Nrf2/HO-1 and Akt/eNOS signaling pathways.

Background: The treatment options to delay the progression of diabetic nephropathy (DN), a key contributor to chronic kidney disease (CKD), are urgently needed. Previous studies reported that traditional Chinese medicine Panax notoginseng (PNG) exerted beneficial effects on DN. However, the renoprotective effects of Notoginsenoside R2 (NR2), an active component of PNG, on DN have not been investigated. This study aimed to assess the therapeutic potential of NR2 in DN and explore its underlying mechanisms.

Methods: In vivo models were developed using db/db mice, while in vitro models utilized HK-2 cells exposed to high glucose and palmitic acid (HGPA). Online databases and Cytoscape software were employed to predict the potential targets of NR2. The expression of associated proteins was measured using immunohistochemistry and western blot. Lipid accumulation, oxidative stress levels, mitochondrial function and cell apoptosis were also assessed. Small interfering RNA was used in in vitro experiments to examine the effect of c-Src.

Results: NR2 ameliorated albuminuria, renal function and renal pathology in db/db mice. The activation of c-Src was suppressed in db/db mice and in HK-2 cells exposed to HGPA. NR2 inhibited JNK/STAT1 phosphorylation and CD36 overexpression. NR2 also ameliorated lipid accumulation, oxidative stress, mitochondrial dysfunction and cell apoptosis in vivo and in vitro. By inhibiting c-Src, HK-2 cells exposed to HGPA experienced less lipid deposition and mitochondrial damage, indicating the renoprotective effects of NR2 were correlated with the inhibition of c-Src.

Conclusion: NR2 ameliorated mitochondrial dysfunction and delayed the progression of DN partly through suppression of c-Src. The protective effects of NR2 might be related to a reduction in lipid accumulation.

Background: Dilated cardiomyopathy (DCM) stands as one of the most prevalent and severe causes of heart failure. Inflammation plays a pivotal role throughout the progression of DCM to heart failure, while age acts as a natural predisposing factor for all cardiovascular diseases. These two factors often interact, contributing to cardiac fibrosis, which is both a common manifestation and a pathogenic driver of adverse remodeling in DCM-induced heart failure.

Method: Bulk RNA-seq, single-cell RNA-seq, Mendelian randomization analysis, animal model construction, and BMP6 knockdown were utilized to identify and validate potential specific markers and targets for intervention in DCM heart failure.

Results: We found that DCM hearts exhibit pronounced inflammatory cell infiltration and fibrosis. Both bulk RNA-seq and single-cell RNA-seq analyses revealed aberrant BMP6 expression specifically in fibroblasts. The ROC curve underscores the high specificity of BMP6 in relation to DCM, while Mendelian randomization analysis further confirms BMP6 as a protective factor against DCM. Notably, BMP6 knockdown led to a decrease in SMAD6 expression and a marked elevation in COL1A1 expression levels, indicating its antifibrotic role.

Conclusion: BMP6 emerges as a promising biomarker for DCM, and its functional role in exerting an antifibrotic effect underscores its potential as a therapeutic target.