The American journal of Chinese medicine最新文献

Cistanche deserticola polysaccharides (CDPS) exhibit a range of pharmacological activities, most notably in immune modulation, anti-oxidation, and gut microbiota regulation. Emerging evidence suggests that restoring gut microbial and metabolic homeostasis may decelerate the progression of Alzheimer's disease (AD). However, the specific in vivo effects and underlying mechanisms of CDPS in the context of AD remain incompletely understood. In this study, we employed behavioral tests, 16S rRNA high-throughput sequencing, and time-resolved metabolomic analyses to comprehensively evaluate the therapeutic efficacy of CDPS. CDPS administration significantly ameliorated cognitive impairment, suppressed pro-inflammatory cytokine expression, and reduced A[Formula: see text] deposition and Tau hyperphosphorylation in the brains of APP/PS1 Tg mice. These effects were associated with CDPS-induced modulation of gut microbial composition - especially the Firmicutes/Bacteroidetes ratio - and regulation of D-Proline and Histidine metabolism. Further in vitro and in vivo validation confirmed that D-Proline and Histidine, key CDPS-associated metabolites, protected against A[Formula: see text]-induced apoptosis and oxidative stress. Notably, the cognitive benefits of CDPS were markedly weakened under conditions of gut microbiota disruption or immune suppression, which highlights the importance of microbial and immune system integrity in mediating its therapeutic effects. Collectively, these findings highlight gut microbial and metabolic disturbances as critical contributors to AD pathogenesis, and support CDPS as a promising multi-target therapeutic strategy. The integration of longitudinal microbiota and metabolomic profiling offers novel mechanistic insights into the neuroprotective actions of CDPS in AD.

Chrysin, a naturally occurring flavonoid and FDA-approved dietary supplement, is ubiquitously present in fruits, vegetables, and mushrooms. Emerging evidence highlights its broad-spectrum therapeutic potential against diverse pathologies, including inflammation, cancers, organ injuries, metabolic dysfunctions, and neuropathic pain. Nevertheless, critical gaps persist in understanding its physicochemical properties, pharmacokinetic profile, and precise molecular mechanisms, and there remains only limited systematic evaluation of advanced drug delivery systems and structural modification strategies. This review comprehensively synthesizes cutting-edge advances in understanding chrysin's natural sources, physicochemical characteristics, pharmacological activities, pharmacokinetic features, innovative drug delivery systems, and chemical modifications. Through a rigorous analysis of peer-reviewed literature, we reveal that chrysin exerts its therapeutic effects predominantly by modulating key signaling pathways such as JAK/STAT3, NF-κB, and FOXM1/β-catenin. Despite a poor oral bioavailability, next-generation nano-platforms have demonstrated remarkable efficacy in enhancing bioavailability and targeted delivery, while structure-optimized derivatives further amplify their therapeutic index. By integrating current knowledge, this work not only provides a holistic overview of chrysin as a multifunctional bioactive compound but also identifies pressing challenges. Targeted research in these areas is imperative to unlock the full translational potential of chrysin for clinical applications.

Ginkgo biloba L., an ancient medicinal tree with origins tracing back over 280 million years, holds a unique place in both traditional and modern therapeutic systems. Widely used in East Asian ethnomedicine, and increasingly validated by pharmacological research, it serves as a rich source of bioactive compounds like terpene trilactones (ginkgolides, bilobalide), flavonoids (quercetin, kaempferol), alkaloids, proanthocyanidins, alkyl phenols, and organic/phenolic acids. This review provides a critical synthesis of Ginkgo biloba's traditional uses, phytochemical constituents, and pharmacological activities, and highlights its anti-oxidant, anti-inflammatory, anticancer, neuroprotective, and vasoprotective properties. In addition, recent advances in the structural transformation and semi-synthetic modification of ginkgolides are presented to offer insights into their structure-activity relationships. Beyond therapeutic roles, Ginkgo biloba exhibits notable potential in non-pharmaceutical domains, which include its use as a natural colorant and photoprotective agent in cosmetics, and as a bio-based material in textile dyeing. Through a systematic examination of peer-reviewed literature, this review underscores Ginkgo biloba's multifaceted value as a promising botanical resource for both medicinal and industrial innovation.

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.

Among the spectrum of digestive system cancers, hepatocellular carcinoma (HCC) poses a particularly formidable challenge due to its poor prognosis. Geniposide, an iridoid glucoside extracted from the fruit of Gardenia jasminoides Ellis, exhibits a diverse array of biological activities. The goal of this study is to delineate the specific roles and underlying mechanisms of geniposide on the progression of HCC. Cell viability, apoptosis and migration of Huh7 and HepG2 cells were, respectively, assessed via CCK-8, flow cytometry and trans-well assays. The level of reactive oxygen species (ROS) was assessed with a dihydroethidium (DHE) probe. The measurement of mitochondrial membrane potential (MMP) was conducted using JC-1 staining. Ferroptosis-related markers were evaluated by Western Blot assay. Transcriptome sequencing was performed in HCC cells both treated and untreated with geniposide. In vivo experiments were applied with the subcutaneous xenograft tumor model. In vitro experiments revealed that geniposide exerted a concentration-dependent suppression on cell viability and migration, concurrently eliciting apoptosis in HCC cells. Ferroptosis was identified as the main form of geniposide-induced cell death in HCC. Geniposide promoted the iron ions levels, ROS accumulation, and the expression of ferroptosis markers, which were partially reversed by the addition of deferoxamine (DFO, ferroptosis inhibitor). Intersection analysis was applied between upregulated genes of HCC cells and ferroptosis-related genes. DUOX1 was proven to be involved in geniposide-mediated roles in HCC. In vivo experiments further clarified the suppressive effects of geniposide on tumors. Geniposide treatment increased intracellular iron ions and induced ferroptosis in HCC. Geniposide attenuated tumor progression and oxidative stress via DUOX1-mediated ferroptosis.

Ischemic Stroke (IS) is a severe neurological disease with high mortality rates worldwide, involving a complex cascade reaction in which the ubiquitination process of nuclear factor kappa B (NF-[Formula: see text]B) pathway has been proposed as a therapeutic target for IS on account of the fact that NF-[Formula: see text]B can be suppressed by the Ubiquitin-Proteasome System (UPS). This review systematically discusses the epidemiology of IS, the NF-[Formula: see text]B signaling pathway, and the anti-inflammatory and anti-apoptotic effects that TCM monomers and formulations exert by regulating the ubiquitination process of the NF-[Formula: see text]B signaling pathway. We initially offer an overview of the incidence and treatment of IS, following which the canonical pathway and non-canonical pathway of NF-[Formula: see text]B are introduced. Next, the ubiquitination mechanisms of NF-[Formula: see text]B when using traditional Chinese medicine (TCM) to treat IS were highlighted. We also discussed the involvement of MyD88, an upstream protein, in the herb-based treatment of IS. Finally, we proposed future research directions for screening advantageous herbal components. Given previous research, we anticipate that TCM drugs will present promising candidates for IS treatment in clinical medicine.