Dali Traditional Chinese Medicine Hospital

Asthma, a chronic inflammatory respiratory disease with significant global health burden, faces limitations in current therapies, necessitating novel therapeutic strategies. The plant Geranium wilfordii Maxim. (GWM), a traditional Chinese herbal medicine with diverse pharmacological activities and clinical applications, has been traditionally used in the treatment of rheumatism, numbness, infectious diseases, dermatosis, tumors and other disease by the Bai, Miao, Yi minority people of Southwest China for generations. Earlier research in our lab also demonstrated that GWM exhibits anti-asthmatic activity, but the mechanism of action remains unclear. To investigate the anti-asthmatic mechanisms of GWM by identifying compounds and elucidating key molecular targets involved in immune cell regulation through integrated computational and experimental approaches. We employed UPLC-QE-Orbitrap-MS to identify active compounds. Network pharmacology and machine learning analyses were conducted to identify key hub genes, followed by validation through Mendelian randomization analysis, molecular docking, and animal models. Immune infiltration and single-cell RNA sequencing analyses using publicly available Gene Expression Omnibus (GEO) datasets, combined with mediation Mendelian randomization (MR), were performed to elucidate the underlying cellular mechanisms. A total of 43 compounds were identified in GWM. Network pharmacology and machine learning prioritized NOTCH2, HDAC2, and MAPK1 as hub targets, validated using MR and molecular docking. Subsequent in vivo experiments validated the regulatory effects of GWM on the expression levels of these hub genes and demonstrated its therapeutic efficacy in asthma. Further analysis showed that GWM regulation of these hub genes may subsequently affect the activity of CD4+ T cells and regulatory T cells, potentially contributing to its therapeutic effects against asthma. This study provides novel evidence for the potential therapeutic activity of GWM in asthma. By targeting key hub genes such as NOTCH2, HDAC2, and MAPK1, GWM may modulate immune cell activity, thereby contributing to its anti-asthmatic effects.

Acetaminophen (APAP) overdose is a major global cause of drug-induced liver injury (DILI), and the rising incidence of APAP-induced hepatotoxicity has raised substantial concern in the medical community, highlighting an urgent need for effective therapeutic approaches. Coptidis Rhizoma alkaloids (CRAs) have shown hepatoprotective effects in multiple hepatic disease models. This study aimed to investigate the therapeutic efficacy and the underlying mechanisms of CRA in acetaminophen (APAP)-induced acute liver injury. After identifying 18 alkaloid components in CRA, we employed an integrated strategy of untargeted metabolomics and network pharmacological analysis to investigate the underlying mechanisms. The potential mechanisms were subsequently validated through histopathological examination and molecular biology assays. Our results showed that CRA exerted dose-dependent protection against APAP-induced liver injury in vitro and in vivo. This protective effect was mediated by enhanced hepatic glutathione (GSH) biosynthesis via increased intracellular cysteine (Cys) availability. In the mouse model, hepatic Cys and GSH levels were increased by 2.2-fold and 1.8-fold, respectively, relative to the model group, which consequently attenuated oxidative stress damage. Furthermore, CRA suppressed APAP-induced activation of ERK and NF-κB, reducing the phosphorylation levels by 39.2% and 38.0%, respectively. Accordingly, it also downregulated the subsequent expression of inflammatory mediators in the TNF signaling pathway. These findings provide crucial mechanistic insights into the hepatoprotective role of CRA against APAP-induced toxicity, establishing a valuable foundation for developing novel therapeutic or preventive strategies for APAP-induced liver injury.

Glioma, the most common primary malignant tumor of the central nervous system, still brings a dismal prognosis, even after stringent standard therapies. This study investigates the RNA epitranscriptomic regulatory mechanism of curcumin analog EF24 in inducing ferroptosis to counter glioma. Both in vitro and in vivo experiments demonstrated that EF24 induces significant ferroptosis and effectively suppresses the growth and metastasis of glioma. Mechanistically, EF24 specifically downregulates the m6A methyltransferase METTL3, a core component of the RNA methylation machinery. More specific, METTL3 recruits an m6A reader YTHDF1 to catalyze methylation at the 3’-UTR region of NRF2 mRNA, forming an m6A-YTHDF1-NRF2 translational enhancement complex that activates downstream antioxidant gene GPX4 expression. EF24 disrupts this complex through suppressing NRF2 mRNA stability and impairing its protein translation, ultimately depleting GPX4 and triggering ferroptosis cascades. For the first time, our study proposes an epitranscriptomic axis of METTL3/YTHDF1/NRF2/GPX4 as a regulator of ferroptosis in glioma, which may be targeted to design an effective and safe therapeutic strategy.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12964-025-02583-4.

Electroacupuncture (EA) accelerates repair of peripheral nerve injury. The aim of this study was to explore how EA regulates energy metabolism by examining its effects on glucose transport and mitochondrial dynamic balance in a rat model of sciatic nerve injury. In experiment 1, expression of glucose transporter (GLUT)4 was measured in n = 16 rats at 1, 3, 5 and 7 days following EA to identify the optimal glucose uptake time. In experiment 2, n = 32 rats were randomly divided into the following four groups: Normal, Injury, EA and ES (electrical stimulation). Three days after sciatic nerve injury modeling, micro-positron emission tomography/computed tomography (PET/CT) was performed to observe glucose uptake in the sciatic nerve and surrounding tissues. After 1 week, we measured nerve conduction velocity and expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), mitofusin (Mfn)1/2 and dynamin-related protein (Drp)1 in the sciatic nerve (by Western blotting) and observed pathological changes in the sciatic nerve and gastrocnemius. Protein expression levels of GLUT4, Mfn1/2 and Drp1 were significantly higher in the EA group, and histopathological changes were improved, compared with other groups. Glucose uptake by micro-PET/CT in the target area in the EA group was significantly higher than that in the other groups. Furthermore, nerve conduction velocity and NGF/BDNF expression was significantly higher in the EA group compared with the other three groups. EA accelerated the repair and regeneration of the injured sciatic nerve, activated glucose transport and improved mitochondrial dynamic balance, in a rat model.

Abstract Introduction Degeneration of bone microarchitecture and decreased bone mineral density are hallmarks of osteoporosis, a prevalent skeletal disorder. The promise of natural compounds derived from medicinal plants as safe and efficient treatments has drawn attention due to the drawbacks and adverse effects of existing pharmaceutical medicines. Therefore, knowledge of medicinal plants and phytochemicals with antiosteoporosis potential is crucial. Thus, this article’s goal was to compile the mechanisms and efficacy of medicinal plants and their many types of phytochemicals in the fight against osteoporosis. Content This article reviews current studies on natural substances with anti-osteoporosis properties, discussing their mechanisms such as regulating bone resorption, preventing osteoclastogenesis, encouraging osteoblast differentiation, and reducing inflammatory processes from sources like ScienceDirect, Google Scholar and PubMed. Summary Flavonoids, polyphenols, alkaloids, terpenoids, and vitamins are naturally occurring compounds with promising anti-osteoporotic properties. They inhibit NF-κB, PI3K/Akt, MAPK, and Wnt/β-catenin pathways, regulating bone turnover and inhibiting resorption. Some phytochemicals also protect bones with antioxidant and anti-inflammatory properties. However, challenges remain in translating these findings into clinical practice. Outlook By finding natural products that help fight osteoporosis, this review seeks to increase therapy choices, especially for older persons with osteoporosis. These therapies may lessen health issues, enhance wellbeing, and provide an affordable substitute for pricey prescription drugs. People with chronic illnesses may find natural products attractive since they may have fewer adverse effects than synthetic medications.

BackgroundNeutrophil extracellular traps (NETs) contribute significantly to osteoarthritis (OA) pathogenesis; however, the precise molecular interactions remain unclear. This study aimed to identify key NET-associated genes and their correlated metabolites and microbiota in OA through an integrated multi-omics approach.MethodsInitially, transcriptomic datasets were screened to identify NET-related genes implicated in OA. A rat OA model was established, and the expression of key genes was validated using RT-qPCR, histological analysis, and immunohistochemistry. TIMP1 was selected for further exploration via in vivo gene silencing. Subsequently, transcriptomics, metabolomics, and 16S rRNA sequencing were performed on serum, cartilage, and fecal samples from experimental animals. Differentially expressed genes (DEGs), microbiota, and metabolites associated with TIMP1 were identified through integrated bioinformatics analyses. Correlation analyses across omics data layers were conducted to pinpoint biomarkers, key metabolites, and microbial taxa.ResultsITGB1, ITGB2, MMP9, and TIMP1 emerged as key NET-associated genes, with TIMP1 being selected as the primary target. TIMP1 silencing significantly alleviated inflammatory responses and cartilage degradation in OA rats. Multi-omics analyses identified 6 biomarkers, 9 key metabolites (e.g., FAHFAs, 12-HETE, MTA, xanthosine), and 1 key microbial genus (Muribaculaceae) strongly correlated with TIMP1 expression. These molecular entities were enriched in pathways related to lipid metabolism, nucleotide turnover, immune regulation, and gut-joint crosstalk.ConclusionTIMP1 acts as a pivotal regulator in OA, influencing inflammation, cartilage remodeling, metabolic pathways, and gut microbiota composition. This study provides novel mechanistic insights and potential therapeutic targets for OA.

The enone is a widely occurring structural unit and functional motif in natural products. Its synthesis at specific positions on the lanostane skeleton represents a hallmark feature of type I ganoderic acids (GAs), a class of triterpenoids fromGanoderma lucidumrenowned for their potent pharmacological properties. However, the current knowledge on their biosynthesis is limited to the notion that type I GA serves as the direct precursor of type II GAs, another class of bioactive Ganoderma triterpenoids. Here, we report a groundbreaking discovery: a multifunctional cytochrome CYP512A13, which directly catalyzes the conversion of the carbon–carbon conjugated double bond on the lanostane skeleton, the hallmark feature of type II GA, into an enone. This transformation is facilitated by a water channel and the C15 hydroxyl group of the substrate, representing an exceptionally rare mechanism in enone biosynthesis. Beyond this remarkable activity, CYP512A13 demonstrates catalytic promiscuity, hydroxylating additional carbon positions on the same substrate to generate unreported type II GAs. By integrating computational modeling with experimental validation, we elucidated the catalytic mechanism of CYP512A13, revealing its dual capability to produce both enone-containing type I GAs and type II GAs. Leveraging these insights, we employed rational design to engineer CYP512A13, achieving selective production of these distinct GA classes. Our findings not only uncover a critical biosynthetic route for the interconversion of GA types but also significantly expand the synthetic biology toolkit, enabling the efficient biosynthesis of high-value Ganoderma triterpenoids.

Glioma, the most common primary malignant tumor of the central nervous system, still brings a dismal prognosis, even after stringent standard therapies. This study investigates the RNA epitranscriptomic regulatory mechanism of curcumin analog EF24 in