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  2. Paederia scandens-derived exosome-like nanoparticles as a delivery system for andrographolide to treat ulcerative colitis

Paederia scandens-derived exosome-like nanoparticles as a delivery system for andrographolide to treat ulcerative colitis

  • Cell Signal. 2025 Nov:135:112014. doi: 10.1016/j.cellsig.2025.112014.
Yuxuan Peng 1 Vadim Demidchik 2 Yan Li 3 Xianglan Lei 4 Yaqin Lin 5 Yixin Zhang 6 Donghai Zhou 7
Affiliations

Affiliations

  • 1 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. Electronic address: archer6947@outlook.com.
  • 2 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.
  • 3 International Sakharov Environmental Institute, Belarusian State University, 15 Botanichskaya St., 220030, Minsk, Belarus.
  • 4 Hainan College of Vocation and Technique, 95 Nanhai Ave., 570100 Haikou, China.
  • 5 Department of Genetics, Faculty of Biology, Belarusian State University, 4 Independence Ave., 220030, Minsk, Belarus.
  • 6 Department of Human and Animal Physiology, Faculty of Biology, Belarusian State University, 4 Independence Ave., 220030 Minsk, Belarus.
  • 7 Department of Veterinary Internal Medicine, Faculty of Veterinary Medicine, Huazhong Agricultural University, 1 Shizishan St., Hongshan District, 430070 Wuhan, China. Electronic address: bigdefoot@163.com.
Abstract

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.

Keywords

Andrographolide; Inflammation; Macrophage polarization; Plant-derived exosome-like nanoparticles; Ulcerative colitis.

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