The American journal of Chinese medicine最新文献

As cancer continues to pose a significant threat to human health, the search for effective therapeutic agents has become a critical focus in medical research. Cordyceps is a fungus used in traditional Chinese medicine (TCM) valued for its potential health benefits, which include boosting energy, supporting the immune system, and acting as an anti-oxidant. Cordycepin, also known as 3[Formula: see text]-deoxyadenosine, is a bioactive nucleoside derived from Cordyceps. This compound recently has garnered widespread attention for its potential anticancer properties. Through systematic integration of our prior experimental evidence with literature retrieval from PubMed, we confirmed its efficacy in inducing apoptosis, suppressing proliferation, and blocking metastasis across a broad range of cancer types. These effects are primarily attributed to its modulation of key signaling pathways, such as MAPK, AMPK, mTOR, and Wnt/[Formula: see text]-catenin, all of which play crucial roles in various malignant conditions. In addition, cordycepin's ability to modulate immune responses through the regulation of adenosine receptor (AR), and in particular the A3 adenosine receptor (A3AR), has gained attention as an innovative strategy for enhancing the effectiveness of immunotherapy. Recent advancements in improving cordycepin's biostability, bioavailability, and transport efficiency within the body system have further supported the clinical application of this compound in medical oncology. This review highlights key research findings and explores promising future directions with the aim of contributing to ongoing studies in cancer management.

Acute lung injury (ALI) can lead to severe respiratory system damage, characterized by extensive inflammation and lung tissue injury. Ophiopogonin D (OD), from Ophiopogon japonicus, has pharmacological effects such as anti-inflammatory and anti-oxidant, hypoglycemic, anti-aging, and immune regulation properties. This study attempts to identify the protective mechanism of OD against ALI by the inhibition of ferroptosis of macrophages. The tissue-specific expression of USP25 in patients with COVID-19 was evaluated using single-cell data from the China National GeneBank and the GSE147507 dataset from Gene Expression Omnibus (GEO). C57BL/6 mice, Murine bone marrow derived macrophages (BMDM) or RAW264.7 cells were induced by Lipopolysaccharide (LPS). OD prevented ALI, and reduced inflammation levels and oxidative stress in mice models. OD significantly decreased the number of monocyte/macrophages (CD11b [Formula: see text]Ly6G-cells) in the peritoneal cavity after ALI induction. OD-mitigated inflammation and oxidative stress of macrophages in the ALI model. OD-reduced ferroptosis of macrophages in a model of ALI through the inhibition of ROS-induced mitochondrial damage. USP25 is significantly expressed in macrophages in patients with COVID-19 using single-cell analysis. OD-suppressed Rac1/NOX1-derived ROS to reduce the mitochondrial damage of macrophages in a model of ALI by the induction of USP25 activity. OD-identified USP25 at 907-VAL and 975-ARG in an ALI model to suppress USP25 Ubiquitination. OD from Ophiopogon japonicus induces USP25 activity to reduce ferroptosis of macrophages in ALI by binding the Rac1 and Nox1 complex. Therefore, it can be concluded that OD may be a potential therapeutic drug for the treatment of ALI.

Non-small cell lung cancer (NSCLC) is a malignancy that faces serious resistance challenges in treatment. In this study, we identified Piperlongumine as a promising therapeutic candidate to overcome Osimertinib resistance in NSCLC. We systematically investigated the inhibitory effect of Piperlongumine on NSCLC cells and confirmed that it could effectively inhibit the in vitro kinase activity of wild-type (WT), exon 19 deletion, and L858R/T790M-mutated EGFR. We also found that Piperlongumine-induced intrinsic apoptosis by interfering with the EGFR signaling pathway, which was characterized by the down-regulation of the anti-apoptotic protein Mcl-1. Further mechanistic studies revealed that Piperlongumine-induced degradation of Mcl-1 was dependent on the Akt-GSK3β signaling pathway. Additionally, Piperlongumine-promoted interaction between Mcl-1 and β-TRCP, thereby enhancing β-TRCP-mediated ubiquitination and the degradation of Mcl-1. Furthermore, Piperlongumine significantly inhibited tumor growth in both Osimertinib-sensitive and resistant NSCLC xenograft models. These findings highlight the potential of Piperlongumine as an effective agent in overcoming EGFR-targeted therapy resistance and suggest new avenues for its clinical application in NSCLC treatment.

Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, posing a significant threat to human health. Recently, gambogic acid (GA) has garnered attention for its anticancer properties in GC. However, it remains unclear whether GA can regulate other forms of cell death beyond apoptosis. In this study, we found that GA inhibited proliferation and induced ferroptosis in GC cells. Western blot analysis was employed to assess ferroptosis and endoplasmic reticulum (ER) stress-related proteins, as well as forkhead box A2 (FOXA2) expression. Additionally, malondialdehyde (MDA) and glutathione (GSH) levels were measured following GA treatment, and quantitative real-time polymerase chain reaction (RT-qPCR) was used to evaluate miR-1291 expression. Our findings revealed that GA treatment elevated reactive oxygen species (ROS) levels and promoted intracellular Fe[Formula: see text], MDA, and GSH accumulation. Furthermore, GA upregulated SLC7A11 and ferritin expression while suppressing glutathione peroxidase 4 (GPX4) in AGS and HGC27 cells, suggesting its role in ferroptosis induction. Notably, GA increased miR-1291 levels and downregulated FOXA2 expression. Subsequent analyses showed FOXA2 as a direct target of miR-1291. Functional experiments involving miR-1291 and FOXA2 knockdown or overexpression further suggested that the miR-1291/FOXA2 axis mediates ferroptosis. Finally, tumor xenograft models showed that GA effectively inhibited tumor growth by inducing ferroptosis. In conclusion, our study provides compelling evidence that GA induces ferroptosis in GC through the miR-1291/FOXA2 axis, highlighting its potential as a novel therapeutic strategy and preventive target for gastric cancer treatment.

Bile acid metabolism mediated by gut microbiota is significantly related to immunity regulation that plays an important role in the development and treatment of inflammatory bowel disease (IBD). Our previous study has demonstrated that Panax notoginseng saponins (PNS) alleviate colitis due to the regulation of T helper 17/Regulatory T cells (Th17/Treg) balance via gut microbiota. However, the effects and mechanism of PNS on colitis pertinent to bile acid metabolism mediated by gut microbiota remain elusive. This study aims to investigate the anti-colitis mechanism of PNS by regulating the Th17/Treg balance pertinent to gut microbiota-bile acid metabolism. Results showed that PNS significantly decreased the relative abundance of Allobaculum, Dubosiella, Muribaculum, and Alistipes, and up-regulated the relative contents of conjugated bile acids, such as TCA and TCDCA. Fecal microbiota transplantation (FMT) showed that the gut microbiota remodeled by PNS had a regulatory effect on bile acid metabolism, and up-regulated the relative contents of TCA and TCDCA, which alleviated IBD and promoted Treg cell expression in vivo and in vitro. Taken together, PNS could reshape the profiling of gut microbiota to generate more TCA and TCDCA, which improve the balance of Th17/Treg to exert anti-IBD effects.

The growing global burden of metabolic syndrome (MetS), a key driver of multiple chronic diseases, highlights the limited treatment options for its multifactorial pathophysiology. Tanshi-Tiaoti Decoction (TTD), a Chinese herbal formula comprised of Citri Reticulatae Pericarpium (Tangerine peel), Coicis Semen (Raw coix seed/Job's tears), Raphani Semen (Radish seed), Nelumbinis Folium (Lotus leaf), Eckloniae/Laminariae thallus (Kelp), and Crataegi Fructus (Raw hawthorn fruit), demonstrates efficacy in the clinical management of MetS. However, its underlying molecular mechanisms remain incompletely elucidated. This study indicates that TTD restored gut microbiota homeostasis and bile acid (BA) profiles in high-fat diet (HFD)-induced MetS mice. TTD significantly attenuated body weight gain, fasting glucose levels, serum triglycerides, and hepatic steatosis. TTD corrected gut microbiota dysbiosis, most notably by reducing the Firmicutes/Bacteroidetes ratio. Fecal microbiota transplantation (FMT) validated the fact that the gut microbiome mediates TTD's therapeutic effects. TTD regulated BA biosynthesis through this microbial modulation, and thus specifically increased hyodeoxycholic acid (HDCA). HDCA, which has been identified as the signature BA during TTD treatment, phenocopied TTD's therapeutic effects against MetS by both activating the BA receptor TGR5 and subsequently promoting beige adipocyte browning. Collectively, TTD ameliorates MetS by reshaping microbial-mediated BA pools, and in particular elevates HDCA levels to thereby activate TGR5 and induce beige adipocyte browning. These findings support TTD as a promising herbal-based therapeutic strategy for the treatment of MetS.

Diabetic kidney disease is one of the most significant comorbidities of diabetic patients, and has become the second cause of end-stage renal disease. Current clinical management programs have difficulty in reducing morbidity and poor prognosis, and thus new treatment options and concepts need to be developed. Traditional Chinese medicine formulae and Chinese patent medicines contain a variety of medicinal flavors, laying the material foundation for the multi-target, multi-level therapeutic features. This study describes the main pathologic features of DKD as well as its pathogenesis. Additionally, the categorization of TCM according to its different therapeutic mechanisms is discussed, and the signaling pathways targeted and corresponding biological effects are described in detail. For example, TCM formulae can alleviate oxidative stress through pathways such as Nrf2 and NOX4, can inhibit the development of inflammation through pathways such as TGF-β and NF-κB, and can ameliorate DKD by inhibiting endoplasmic reticulum stress and apoptosis. Moreover, it highlights the superior efficacy of the combined application of TCM formulae and Western medicine over Western medicine alone, which can compensate for the shortcomings of existing DKD treatment methods to a certain extent. TCM formulae and CPMs are promising candidates for the auxiliary treatment of DK, however, the lack of clarity regarding the active ingredients intensifies the difficulty of integrating TCM formulae and CPMs into clinical practice. Further research is warranted to explore the material basis and molecular mechanisms of action of TCM formulae against DKD.

Inflammation is a pathological process implicated in a wide range of diseases, and is orchestrated by complex regulatory networks at both transcriptional and post-transcriptional levels. A growing body of evidence supports the understanding that numerous natural compounds exhibit robust anti-inflammatory activity, structural diversity, low toxicity, and minimal side effects. These qualities make them promising leads for therapeutic development. Within the framework of Traditional Chinese Medicine (TCM), which has been extensively applied in the management of chronic conditions, specific herbal remedies, such as Paeonia lactiflora for rheumatoid arthritis, and Angelica sinensis and Codonopsis pilosula for cardiovascular regulation, have clinically relevant efficacy. In recent years, bioactive peptides (BAPs) derived from Chinese medicinal herbs, including peptides from Cordyceps sinensis and Panax ginseng, have drawn considerable international attention for their anti-inflammatory potential. This review delineates the principal methodologies for the extraction, isolation, and purification of anti-inflammatory peptides derived from medicinal herbs, highlights recent advances in their therapeutic application for inflammatory disorders, critically assesses existing barriers to clinical translation, and outlines future research priorities.

Notoginsenoside R1 (NGR1), a natural triterpenoid saponin, is extracted from Panax notoginseng, and has cardiovascular and cerebrovascular protective effects due to anti-inflammatory, anti-oxidant, and anti-apoptotic properties. Previous research has suggested a protective role for NGR1 in myocardial ischemia/reperfusion (MI/R) injury. However, the potential mechanisms involved have not been fully elucidated. Thus, the objective of our study was to validate the protective role of NGR1 in MI/R injury and to investigate its underlying mechanisms. Results showed that, in mice, NGR1 substantially improved heart function, reduced infarct area, and inhibited cardiomyocyte apoptosis. Mechanistically, network pharmacological predictions suggested that NGR1 could inhibit apoptosis by activating the Wnt signaling pathway. Experimentally, the protective effects of NGR1 in inhibiting cardiomyocyte apoptosis, improving cardiac function, and reducing infarct size were significantly attenuated with the use of the Wnt signaling inhibitor XAV-939. Collectively, our investigation demonstrated that NGR1 improves myocardial injury triggered by ischemia/reperfusion (I/R) by enhancing Wnt/[Formula: see text]-catenin pathway activity, which in turn suppresses apoptosis.

The aim of this study was to evaluate the therapeutic effect of puerarin (PUE) on alcoholic liver disease (ALD) and elucidate the potential mechanism from the perspective of lipolysis and hepatic steatosis. Assessment of PUE efficacy against ALD was performed using serum biochemical parameters and the histological examination of liver and adipose tissue via Hematoxylin and eosin (H&E) staining. The potential mechanisms underlying the amelioration of ALD by PUE were investigated using Western blotting (WB) analysis and immunofluorescence (IHC) staining. We demonstrated that PUE attenuated steatosis in ALD by alleviating ethanol-induced liver damage and lipid accumulation, suppressing the expression of lipid synthesis genes, upregulating the expression of lipid metabolism genes, and reducing lipolysis by inhibiting adipose triglyceride lipase (ATGL) activation and the phosphorylation of hormone-sensitive lipase (HSL). In conclusion, PUE ameliorates ALD by inhibiting the sympathetic outflow-mediated activation of key lipolysis enzymes ATGL and HSL. These findings provide a solid theoretical foundation for the potential application of PUE in the clinical treatment of ALD.