Phytomedicine最新文献

Synovitis, a characteristic feature of inflammatory arthritis (IA), is often driven by an aberrant macrophage-mediated inflammatory response that promotes irreversible joint damage. The α7 nicotinic acetylcholine receptor (α7nAChR) is a key regulator of the cholinergic anti-inflammatory pathway. Despite its therapeutic potential, how α7nAChR coordinates macrophage metabolic reprogramming to resolve synovitis remains underexplored. This study aims to elucidate the therapeutic effects of Notopterol, a bioactive constituent derived from the rhizome of Notopterygium incisum Ting ex H.T. Chang, a traditional Chinese medicine known for its potent anti-inflammatory and antioxidant properties, in treating inflammatory arthritis and the molecular mechanisms by which α7nAChR modulates macrophage reprogramming in synovitis. An in vivo mouse model of IA was established through complete Freund's adjuvant (CFA)-induced, Notopterol administration significantly attenuated synovitis progression, reduced joint swelling, and enhanced mechanical pain thresholds as well as suppressed the production of pro-inflammatory cytokines (IL-1β, TNF-α, and IFN-γ) while promoting anti-inflammatory IL-4 secretion. Complementary in vitro models employing lipopolysaccharide (LPS)-stimulated macrophages demonstrated that Notopterol exerts anti-inflammatory effects, restores mitochondrial function while shifting energy metabolism towards oxidative phosphorylation, a transition mechanistically linked to M1/M2 polarisation. Mechanistically, Notopterol promotes a shift from glycolysis to oxidative phosphorylation in macrophages, restoring mitochondrial function and enhancing their polarizing capacity through α7nAChR activation, thus revealing this receptor's pivotal role in macrophage metabolic regulation. Furthermore, biophysical validation confirms the high-affinity binding of Notopterol to α7nAChR, supporting its therapeutic potential in anti-inflammatory treatment. These findings highlight the innovative prospect of targeting macrophage metabolic pathways as a novel strategy for treating inflammatory arthritis.

Background: New antiviral strategies are urgently needed, as evidenced by an increase in drug-resistant influenza A virus (IAV). Salvianolic acid C (Sal-C) is isolated from Salvia miltiorrhiza and possesses various pharmacological activities, such as anti-inflammatory and antioxidant. However, no studies on its anti-IAV activity have been reported yet.

Purpose: To investigate the anti-IAV effects of Sal-C through both in vitro and in vivo approaches and to elucidate its mechanisms of action.

Methods: The anti-IAV effects of Sal-C in vitro were determined by cytopathic effect (CPE) inhibition, western blot and viral plaque assays. Western blot analysis revealed that the compound significantly reduced the expression of critical viral proteins. Neuraminidase (NA) inhibition assays and signalling pathway experiments were used to investigate the mechanism of action of Sal-C. The in vivo activity of Sal-C was evaluated using a mouse pneumonia model.

Results: Sal-C can inhibit IAV proliferation in different cells and has low toxicity. Sal-C exerts its anti-IAV activity by interacting with NA and regulating phosphorylated-STAT3 (p-STAT3) and phosphorylated-AKT/phosphorylated-mTOR/phosphorylated-S6K (p-AKT/p-mTOR/p-S6K) activity. Sal-C treatment significantly improved mice survival, attenuated inflammatory symptoms, and reduced viral titers in IAV infected mice.

Conclusion: Sal-C exhibits significant anti-IAV activity in vitro and in vivo by acting on the viral protein NA and regulating host signalling pathways. Thus, Sal-C has potential for development as a novel anti-IAV agent.

Background: Rheumatoid arthritis (RA) is marked by chronic synovial inflammation and systemic immune dysregulation, in which oxidative stress and pyroptosis play critical pathogenic roles. Salvianolic acid B (SalB), a major polyphenolic compound derived from Salvia miltiorrhiza, exhibits potent antioxidant and anti-inflammatory activities that confer therapeutic benefits in RA.

Purpose: To clarify SalB's therapeutic potential and underlying mechanisms in RA.

Methods: The anti-RA effects of SalB were assessed in adjuvant-induced arthritis (AIA) rats and RA fibroblast-like synoviocytes (RA-FLS). Bioinformatics analysis was performed to identify the crucial regulatory pathways. The involvement of the Keap1-Nrf2 pathway and its downstream ROS-NLRP3-pyroptosis axis was examined using in vitro and in vivo approaches.

Results: SalB alleviated synovial inflammation, pannus formation, and joint damage in AIA rats. In RA-FLS, it suppressed tumor necrosis factor-α-induced proliferation, migration, invasion, and cytoskeletal remodeling. SalB enhanced Nrf2 nuclear translocation and upregulated the antioxidant enzymes NQO1 and HO-1, thereby reducing ROS accumulation and preventing ROS-dependent activation of the NLRP3 inflammasome. Consequently, cleavage of Caspase-1 and GSDMD and the release of IL-18 and IL-1β were diminished, alleviating pyroptosis and inflammation. Notably, pharmacological inhibition of Nrf2 by ML385 significantly attenuated the effects of SalB in vitro. Mechanistically, various experimental approaches, including cellular thermal shift assays, molecular docking, and mutational analyses, confirmed that SalB directly binds to Keap1 at Arg415 and disrupts its inhibitory interaction with Nrf2.

Conclusions: SalB alleviates RA by mitigating oxidative stress and pyroptosis through Keap1-Nrf2/ROS/NLRP3 signaling. This study provides a solid mechanistic basis for SalB's future therapeutic research in RA.

Background: Coronary microvascular dysfunction (CMD) is a common cardiac disease that impairs patients' life quality substantially. Traditional Chinese medicine (TCM) demonstrates distinctive therapeutic potential in the management of CMD.

Purpose: This study aimed to analyze the chemical profile and blood-absorved constituents of Liqi Huatan Huoxue (LQHTHX) formula, and to evaluate its therapeutic effects on CMD through both in vivo and in vitro experiments.

Study design: Liquid chromatography-mass spectrometry (LC-MS) was employed to characterize the chemical composition of LQHTHX. The therapeutic efficacy of LQHTHX was assessed in a sodium laurate-induced CMD rat model and a hypoxia-induced primary cardiac microvascular endothelial cells (CMECs) model.

Methods: The chemical composition and the blood-absorved components of LQHTHX were identified by LC-MS. and,the effect of LQHTHX treatment was assessed in CMD rat model cardiac tissues, including collagen deposition, inflammation, and apoptosis. A hypoxia-induced CMEC injury model was established to investigate the effects of LQHTHX on cell viability, proliferation, mitochondrial function, migration, and apoptosis.

Results: The results suggested that nobiletin, corydaline, and isosinensetin in LQHTHX could enter the bloodstream. LQHTHX reduced collagen deposition, alleviated inflammation, and inhibited apoptosis in the cardiac tissues of CMD rats. Moreover, LQHTHX enhanced cell viability and proliferation, mitigated mitochondrial dysfunction, promoted cell migration, and suppressed apoptosis in hypoxia-induced CMECs. These protective effects were potentially mediated by up-regulation of NRG-1 and activation of the PI3K/AKT pathway.

Conclusion: This study offers new insights into complementary therapeutic strategies for CMD and provides a reference for development of natural product-based interventions.

Focal adhesion kinase (FAK) is an attractive therapeutic target overexpressed in numerous cancers. Despite extensive efforts, no FAK inhibitor has reached the market. Here, we identified poliumoside (Pol), a compound from Chinese herbs, as a novel FAK inhibitor through high-throughput virtual screening. Pol exhibited potent anti-proliferative and anti-metastatic activities both in vitro and in vivo. Mechanistically, Pol directly binds to His89 of FAK, thereby inhibiting its autophosphorylation at Y397. This inhibition led to the downregulation of the ERK-c-Myc axis, reduced transcription of IL-6, and consequent suppression of the JAK3-STAT3 signaling pathway. Our findings establish Pol as a promising FAK-targeting agent, exerting its anti-tumor effects in a FAK-dependent manner.