Chinese Medicine最新文献

Background: Paclitaxel-induced peripheral neuropathy (PIPN) is prevalent among patients receiving paclitaxel chemotherapy, which results in sensory abnormality as well as neuropathic pain. Conventional medications lack effectiveness on PIPN. Clinical trials identified beneficial effects of acupuncture on PIPN among patients receiving chemotherapy. Here we explored the mechanisms underlying how acupuncture might alleviate PIPN.

Methods: A mouse model of PIPN was established by repeated paclitaxel application. Electroacupuncture (EA) was applied at ST36 and BL60 acupoints of model mice. Immunostaining, flow cytometry, behavioral assay, in vivo imaging were utilized for effects determination and mechanism exploration.

Results: EA ameliorated mechanical and cold pain hypersensitivities, reduced sensory neuron damage and improved loss in intra-epidermal nerve fibers (IENFs) in model mice. Macrophages infiltration were detected in DRG and sciatic nerve of model mice, which was reduced by EA. EA affected M1-like pro-inflammatory macrophage infiltration in DRG, whereas it did not affect M2-like macrophages. DRG neurons released chemoattractant CCL2 that recruited macrophages via CCR2 to DRG. EA reduced CCL2 overproduction by DRG neurons and reduced macrophage infiltration. Blocking CCR2 mimicked EA's anti-allodynic effect, whereas exogenously applying recombinant CCL2 reversed the ameliorative effect of EA on macrophage infiltration and abolished EA's anti-allodynia on model mice. EA ameliorated other signs of PIPN, including sensory neuron damage, sciatic nerve morphology impairment and IENFs loss. In mice inoculated with breast cancer cells, EA didn't affect paclitaxel-induced antitumor effect.

Conclusions: These findings suggest EA alleviates PIPN by reducing CCL2/CCR2 mediated-pro-inflammatory macrophage infiltration into sensory ganglia as well as the sciatic nerve. Our study supports EA could be used as a potential non-pharmacological therapy for PIPN.

Network pharmacology plays a pivotal role in systems biology, bridging the gap between traditional Chinese medicine (TCM) theory and contemporary pharmacological research. Network pharmacology enables researchers to construct multilayered networks that systematically elucidate TCM's multi-component, multi-target mechanisms of action. This review summarizes key databases commonly used in network pharmacology, including those focused on herbs, components, diseases, and dedicated platforms for network pharmacology analysis. Additionally, we explore the growing use of network pharmacology in TCM, citing literature from Web of Science, PubMed, and CNKI over the past two decades with keywords like "network pharmacology", "TCM network pharmacology", and "herb network pharmacology". The application of network pharmacology in TCM is widespread, covering areas such as identifying the material basis of TCM efficacy, unraveling mechanisms of action, and evaluating toxicity, safety, and novel drug development. However, challenges remain, such as the lack of standardized data collection across databases and insufficient consideration of processed herbs in research. Questions also persist regarding the reliability of study outcomes. This review aims to offer valuable insights and reference points to guide future research in precision TCM network pharmacology.

Background: The individualized prediction and discrimination of precancerous lesions of gastric cancer (PLGC) is critical for the early prevention of gastric cancer (GC). However, accurate non-invasive methods for distinguishing between PLGC and GC are currently lacking. This study therefore aimed to develop a risk prediction model by machine learning and deep learning techniques to aid the early diagnosis of GC.

Methods: In this study, a total of 2229 subjects were recruited from nine tertiary hospitals between October 2022 and November 2023. We designed a comprehensive questionnaire, identified statistically significant factors, and created a web-based column chart. Then, a risk prediction model was subsequently developed by machine learning techniques. In addition, a tongue image-based risk prediction model was established by deep learning algorithms.

Results: Based on logistic regression analysis, a dynamic web-based nomogram was developed and it is freely accessible at: https://yz6677.shinyapps.io/GC67/ . Then, the prediction model was established using ten different machine learning algorithms and the Random Forest (RF) model achieved the highest accuracy at 85.65%. According with the predictive results, the top 10 key risk factors were age, traditional Chinese medicine (TCM) constitution type, tongue coating color, tongue color, irregular meals, pickled food, greasy fur, over-hot eating habit, anxiety and sleep onset latency. These factors are all significant risk indicators for the progression of PLGC patients to GC patients. Subsequently, the Swin Transformer architecture was used to develop a tongue image-based model for predicting the risk for progression of PLGC. The verification set showed an accuracy of 73.33% and an area under curve (AUC) greater than 0.8 across all models.

Conclusions: Our study developed machine learning and deep learning-based models for predicting the risk for progression of PLGC to GC, which will offer the assistance to determine the high-risk patients from PLGC and improve the early diagnosis of GC.

Objective: Electroacupuncture has been shown to play a neuroprotective role following ischemic stroke, but the underlying mechanism remains poorly understood. Ferroptosis has been shown to play a key role in the injury process. In the present study, we wanted to explore whether electroacupuncture could inhibit ferroptosis by promoting nuclear factor erythroid-2-related factor 2 (Nrf2) nuclear translocation.

Methods: The ischemic stroke model was established by middle cerebral artery occlusion/reperfusion (MCAO/R) in adult rats. These rats have been randomly divided into the EA + MCAO/R group, the MCAO/R group, the EA + MCAO/R + Brusatol group (the inhibitor of Nrf2), and the EA + MCAO/R + DMSO group, and the Sham group. The EA + MCAO/R group, EA + MCAO/R + Brusatol group, and the EA + MCAO/R + DMSO group received EA intervention 24 h after modeling for 7 consecutive days. The behavioral function was evaluated by Neurologic severity score (NSS), Garcia score, Foot-fault Test, and Rotarod Test. The infarct volume was detected by TTC staining, and the neuronal damage was observed by Nissl staining. The levels of Fe²⁺, reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured by ELISA. The immunofluorescence and Western blotting were used to detect the expression of Total Nrf2, p-Nrf2, Nuclear Nrf2, and Cytoplasmic Nrf2, and the essential ferroptosis proteins, including glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11) and ferritin heavy chain 1 (FTH1). The mitochondria were observed by transmission electron microscopy (TEM).

Results: Electroacupuncture improved neurological deficits in rats model of MCAO/R, decreased the brain infarct volume, alleviated neuronal damage, inhibited the Fe²⁺, ROS, and MDA accumulation, increased SOD levels, increased the expression of GPX4, SLC7A11 and FTH1, and rescued injured mitochondria. Especially, we found that the electroacupuncture up-regulated the expression of Nrf2, and promoted phosphorylation of Nrf2 and nuclear translocation, However, Nrf2 inhibitor Brusatol reversed the neuroprotective effect of electroacupuncture.

Conclusion: Electroacupuncture can alleviate cerebral I/R injury-induced ferroptosis by promoting Nrf2 nuclear translocation. It is expected that these data will provide novel insights into the mechanisms of electroacupuncture protecting against cerebral I/R injury and potential targets underlying ferroptosis in the stroke.

Background: Cell membrane chromatography (CMC) is a biochromatography with a dual function of recognition and separation, offering a distinct advantage in screening bioactive compounds from Chinese medicines (CMs). Yindan Xinnaotong soft capsule (YD), a CM formulation, has been widely utilized in the treatment of cardiovascular disease. However, a comprehensive mapping of the myocardial protective active compounds remains elusive.

Purpose: To establish a stable and efficient 2D H9c2/CMC-RPLC-MS system, and to utilize it for screening the active compounds of YD that are associated with myocardial protection.

Methods: An imidazole-modified silica gel exhibiting high modification efficiency and protein binding capacity was synthesized to enhance the longevity and efficiency of H9c2/CMC. Subsequently, the potentially bioactive compounds of YD were screened by integrating the 2D H9c2/CMC-RPLC-MS system with a high-content component knockout strategy. Additionally, an RNA-seq approach was employed to predict the targets and mechanisms of YD and the active compounds for myocardial protection.

Results: The developed imidazole-modified H9c2/CMC exhibits remarkable selectivity, specificity, stability, and reproducibility. Following three rounds of screening, a total of 24 potential myocardial protective compounds were identified, comprising 8 flavonoids, 8 phenolic acids, 4 saponins, and 4 tanshinones. Bioinformatic analysis utilizing RNA-seq indicated that the FOXO signaling pathway, with FOXO3 identified as a key target, plays a significant role in the cardioprotective effects of YD. Furthermore, all 24 screened compounds exhibit strong binding affinities with FOXO3 evaluated by molecular docking.

Conclusion: A highly stable and efficient 2D imidazole-modified H9c2/CMC-RPLC-MS system was developed, allowing for the screening of potentially active compounds from YD. Through the integration of the bioinformatic analysis, the pharmacodynamic foundation of YD for myocardial protection has been comprehensively characterized.

Background: Jianwei Xiaoshi oral liquid (JWXS), a classical traditional prescription comprising various edible medicinal plants, has demonstrated significant efficacy in treating paediatric indigestion. It originates from Jianpi Pill, which is developed in the Ming Dynasty and nourishes the spleen and regulates gastrointestinal function. However, the specific molecular mechanisms involved remain unclear.

Methods: To elucidate the material base of JWXS and its underlying mechanism in treating dyspepsia, the UHPLC-Q-Orbitrap HRMS method and network pharmacology were utilized. This was followed by pharmacological experiments, transcriptomics analyses and gut microbiota studies to further investigate the effects of JWXS on dyspepsia.

Results: A total of 105 compounds, mainly flavonoids, alkaloids, organic acids and cyclic peptides, were identified. According to the five principles of generic drug properties, 43 candidate compounds were screened out. Their efficacy was verified through gastric emptying and intestinal propulsion experiments. Transcriptomic analysis revealed that JWXS primarily alleviated dyspepsia symptoms by regulating the secretion of 8 key proteins in the pancreatic secretion pathway. The differences in the gut microbiota, as identified through 16S rRNA and ITS2 sequencing, were subsequently more pronounced than those observed in the bacterial microbiota of the model group. In total, 15 differential bacteria and 16 differential fungi were identified. Targeted metabolomics analysis of SCFAs revealed a significant decrease in valeric acid (VA), acetic acid (AA), and isovaleric acid (IVA) levels in the model group, which were restored to the corresponding levels after the administration of JWXS. Correlation analysis revealed that VA, AA, and IVA were positively correlated with Lactobacillus and Bacteroides, and negatively correlated with Aspergillus and Candida. This further suggested that JWXS might alleviate symptoms of indigestion by regulating the composition of the microbiota, increasing the variety and quantity of beneficial bacteria, reducing fungal contamination, and further increasing the levels of SCFAs in the body.

Conclusion: JWXS improved functional dyspepsia in immature rats via a mechanism involving the regulation of the secretion of 8 key proteins in the pancreatic secretion pathway and the amelioration of flora disorders.

Background: This research aims to explore the anti-obesity potential of Wu-Mei-Wan (WMW), particularly its effects on adipose tissue regulation in obese mice induced by a high-fat diet (HFD). The study focuses on understanding the role of heat shock factor 1 (HSF1) in mediating these effects.

Methods: HFD-induced obese mice were treated with WMW. Body weight, food intake, and histopathological analysis of adipose tissue were conducted. Brown adipose tissue (BAT) activity was evaluated using Positron Emission Tomography, and ultrastructural changes were examined via transmission electron microscopy. Proteomic analysis identified targets of WMW in obesity treatment. HSF1 expression was inhibited to confirm its role. Molecular docking studied interactions between WMW and HSF1. Short-chain fatty acids (SCFAs) in the intestines were measured to determine if WMW's effects on HSF1 are mediated through SCFAs. Protein expression was assessed using western blot, immunohistochemistry, immunofluorescence and RT-qPCR were employed to detect the mRNA levels. Statistical analyses included t-tests, ANOVA, and non-parametric tests like the Mann-Whitney U test or Kruskal-Wallis test.

Results: WMW significantly mitigates the adverse effects of a HFD on body weight and glucose metabolism in obese mice. Both low-dose WMW and high-dose WMW treatments led to reduced weight gain and improved glucose tolerance, with low-dose WMW showing more pronounced effects. WMW also reversed structural damage in BAT, enhancing mitochondrial integrity and thermogenic function, particularly at the low dose. Additionally, WMW treatment promoted the browning of WAT, evidenced by increased expression of key thermogenic proteins such as UCP1 and PGC-1α. The increase in HSF1 expression in both BAT and WAT, observed with WMW treatment, was crucial for these beneficial effects, as inhibition of HSF1 negated the positive outcomes. Furthermore, WMW treatment led to elevated levels of short-chain fatty acids SCFAs in the intestines, which are associated with increased HSF1 expression.

Conclusions: WMW represents a potent therapeutic strategy for obesity, promoting metabolic health and beneficial modulation of adipose tissue through an HSF1-dependent pathway.

Background: Magnolia kobus DC (MO), as a plant medicine, has been reported to have various physiological activities, including neuroprotective, anti-inflammatory, and anti-diabetic effects. However, vascular protective effects of MO remain incompletely understood. In this study, we evaluated the vascular protective effect of MO against ferroptosis in a carotid artery ligation (CAL)-induced neointimal hyperplasia mouse model and in aortic thoracic smooth muscle A7r5 cells.

Methods: This study was conducted to estimate the vascular protective effects of MO by systematically measuring histopathological analysis and western blot analysis in CAL animal model. In vitro protective effects of MO were evaluated by estimating cell viability, reactive oxygen species (ROS) content, glutathione (GSH) levels, lipid peroxidation, mitochondrial morphological change, cell proliferation, migration, western blot analysis, and qRT-PCR against erastin (Era)-induced A7r5 cells.

Results: MO intake significantly improved neointimal formation, inhibited ferroptosis and vascular smooth muscle cell (VSMC) phenotypes, and ameliorated the antioxidant system of carotid artery tissues. In addition, MO treatment effectively ameliorated Era-induced ferroptotic cytotoxicity, including cellular death, ROS production, and cell migration status. MO treatment also suppressed proliferation and migration in Era-induced A7r5 cells. MO considerably regulated Era-induced abnormal mechanisms related to ferroptotic changes, VSMC phenotype switching, and the ROS scavenging system in A7r5 cells.

Conclusion: MO has the potential for use as a functional food supplement, nutraceutical, or medicinal food, with protective effects on vascular health by regulating ferroptosis and VSMC phenotypic switching.

Background: With extended gefitinib treatment, the therapeutic effect in some non-small cell lung cancer (NSCLC) patients declined with the development of drug resistance. Aidi injection (ADI) is utilized in various cancers as a traditional Chinese medicine prescription. This study explores the molecular mechanism by which ADI, when combined with gefitinib, attenuates gefitinib resistance in PC9GR NSCLC cells.

Methods: In vitro and in vivo pharmacological experiments were conducted in PC9GR cells and NSG mice with PC9GR cell-derived tumors, respectively. The molecular mechanism of ADI was further studied using whole-transcriptome sequencing technology. Bioinformatics and molecular biology methods were employed to validate the critical targets of ADI.

Results: Firstly, ADI treatment alone and combined with gefitinib significantly inhibited the proliferation, migration, and invasion of PC9GR cells. Then, whole-transcriptome sequencing and bioinformatics analysis revealed that PLAT is a key target for the increased efficacy of ADI combined with gefitinib. Additionally, ADI downregulates the expression of PLAT, TNC, ITGB3, p-AKT, p-PI3K, and p-FAK. ADI inhibits the migration and invasion of PC9GR cells by regulating the PLAT/FAK/AKT pathway.

Conclusions: Aidi injection inhibits the migration and invasion of gefitinib-resistant lung adenocarcinoma cells by regulating the PLAT/FAK/AKT pathway. This study provides essential evidence for elucidating the mechanism of ADI in synergistic therapy for lung cancer.

Background: Lovastatin, the main lipid-lowering component in red yeast rice, is a golden anti-lipid drug, but its long-term application is continuously challenged by potential skeletal muscle atrophy. Daidzein, an isoflavone derived from soybeans and many Chinese medicines, shows therapeutic potential in treating muscle-related diseases and metabolic disorders. However, whether daidzein can improve lovastatin-induced muscle atrophy and the specific mechanism needs to further study.

Methods: Lovastatin-induced mice and zebrafish muscle atrophy models were used to validate the protective effect of daidzein in vivo. And the lovastatin-induced C2C12 myotube atrophy model was employed to validate the therapeutic efficacy and investigate the specific mechanism of daidzein in vitro. We combined specific siRNA targeting FOXO3a and AMPK-selective inhibitor, agonist to elucidate AMPK/FOXO3a-dependent muscle-protective mechanism of daidzein. The anti-atrophy effects of daidzein through blockage of abnormal activation of AMPK/FOXO3a was presented in Immunofluorescence, H&E staining, Western blot, qRT-PCR. Serum creatine kinase level was detected by ELISA and we used mouse muscle grip instrument to detect the strength of mouse muscles.

Results: In this study, we demonstrated that daidzein could dose-dependently alleviate lovastatin-induced mice skeletal muscle atrophy, reduce serum creatine kinase, and improve muscle grip strength in mice. Mechanistically, daidzein inhibited lovastatin-induced FOXO3a phosphorylation caused by AMPK activation, thereby inhibiting FOXO3a nuclear translocation to restrain the expression of muscle-related proteins Atrogin-1 and MuRF-1. In C2C12 myotube, administration of AMPK-selective inhibitor Compound C recapitulated the therapeutic effects of daidzein against lovastatin-induced myotubes atrophy, while the anti-atrophy effects of daidzein were lost in the presence of AMPK-selective agonist MK-3903. In lovastatin-induced mice muscle atrophy models, Compound C elicited similar anti-atrophy effects as daidzein, but this effect was not potentiated when it was applied in combination with daidzein, suggesting that daidzein exerted therapeutic efficacy dependent on blockage of AMPK activity.

Conclusions: Our study identified daidzein as an effective component that ameliorated lovastatin-induced skeletal muscle atrophy through blockage of abnormal activation of AMPK/FOXO3a and transcriptional activation of genes encoding downstream muscle-related proteins. Our results also highlighted the therapeutic potential by regulating the AMPK/FOXO3a axis in management of statin-induced myotoxicity.