Peng Yuxuan, Demidchik Vadim, Li Yan, Lei Xianglan, Lin Yaqin, Zhang Yixin, Zhou Donghai
Department of Veterinary Internal Medicine, Faculty of Veterinary Medicine, Huazhong Agricultural University, 1 Shizishan St., Hongshan District, 430070 Wuhan, China; Department of Plant Cell Biology and Bioengineering, Faculty of Biology, Belarusian State University, 4 Independence Ave., 220030 Minsk, Belarus; Hainan College of Vocation and Technique, 95 Nanhai Ave., 570100 Haikou, China.
Institute of Experimental Botany, National Academy of Sciences of Belarus, 27 Botanichskaya St., 220072 Minsk, Belarus; International Research Centre for Environmental Membrane Biology and Department of Horticulture, Foshan University, Foshan, China.
Cell Signal. 2025 Jul 20;135:112014. doi: 10.1016/j.cellsig.2025.112014.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by relapsing colon inflammation. Side effects and drug resistance limit current therapies. Andrographolide (AG), an NF-κB pathway inhibitor, shows promise in UC treatment but suffers from poor oral bioavailability. In this study, Paederia scandens-derived exosome-like nanoparticles (P-ELNs) were used as a delivery system to enhance the therapeutic efficacy of AG in UC. P-ELNs were extracted from Paederia scandens leaves and characterized for size, zeta potential, and morphology using transmission electron microscopy (TEM) and nanoparticle tracking analysis. AG was loaded into P-ELNs (AG-P-ELNs), and the complex was characterized for encapsulation efficiency using high-performance liquid chromatography (HPLC). The anti-inflammatory effects of AG, P-ELN, and the AG-P-ELNs complex were assessed in LPS-stimulated RAW264.7 macrophages (in vitro) and in a dextran sulphate sodium (DSS)-induced colitis mouse model (in vivo). According to the results, AG-P-ELNs demonstrated a high encapsulation efficiency of 38.64 % and a stable dispersion system with a zeta potential of -38.55 mV, indicating good colloidal stability. In vitro, AG-P-ELNs significantly reduced the production of pro-inflammatory cytokines IL-1β, IL-6, IL-18 and TNF-α, promoting M1 macrophage polarized to M2. In vivo, AG-P-ELN treatment ameliorated DSS-induced colitis, normalized colon length, and mitigated inflammatory cell infiltration. The AG-P-ELN group showed the lowest NF-κB, NLRP3, and iNOS expression, suggesting a synergistic therapeutic effect in modulating macrophage polarization and inflammation. P-ELNs effectively enhance the bioavailability and therapeutic efficacy of AG in treating UC by improving its solubility, stability, and cellular uptake while modulating macrophage polarization and inflammation. This study provides a novel approach for the delivery of AG and highlights the potential of plant-derived nanoparticles in inflammatory bowel disease management.
溃疡性结肠炎（UC）是一种以结肠炎症反复发作为特征的慢性炎症性肠病。副作用和耐药性限制了当前的治疗方法。穿心莲内酯（AG）作为一种核因子κB（NF-κB）信号通路抑制剂，在UC治疗中显示出前景，但口服生物利用度较差。在本研究中，鸡矢藤来源的类外泌体纳米颗粒（P-ELNs）被用作递送系统，以提高AG在UC治疗中的疗效。P-ELNs从鸡矢藤叶片中提取，并使用透射电子显微镜（TEM）和纳米颗粒跟踪分析对其大小、zeta电位和形态进行表征。将AG载入P-ELNs（AG-P-ELNs），并使用高效液相色谱（HPLC）对该复合物的包封率进行表征。在脂多糖（LPS）刺激的RAW264.7巨噬细胞（体外）和葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠模型（体内）中评估AG、P-ELN和AG-P-ELNs复合物的抗炎作用。结果显示，AG-P-ELNs表现出38.64%的高包封率和zeta电位为-38.55 mV的稳定分散体系，表明具有良好的胶体稳定性。在体外，AG-P-ELNs显著降低促炎细胞因子白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、白细胞介素-18（IL-18）和肿瘤坏死因子-α（TNF-α）的产生，促进M1巨噬细胞向M2极化。在体内，AG-P-ELN治疗改善了DSS诱导的结肠炎，使结肠长度恢复正常，并减轻了炎症细胞浸润。AG-P-ELN组显示出最低的NF-κB、NLRP3和诱导型一氧化氮合酶（iNOS）表达，表明在调节巨噬细胞极化和炎症方面具有协同治疗作用。P-ELNs通过提高AG的溶解度、稳定性和细胞摄取，同时调节巨噬细胞极化和炎症，有效提高了AG治疗UC的生物利用度和疗效。本研究为AG的递送提供了一种新方法，并突出了植物来源纳米颗粒在炎症性肠病管理中的潜力。
