1. Academic Validation
  2. Characterization of andrographolide-loaded exosome-like nanoparticles from Nauclea officinalis and their modulation of inflammatory and lipid metabolic pathologies in WRL68 cells

Characterization of andrographolide-loaded exosome-like nanoparticles from Nauclea officinalis and their modulation of inflammatory and lipid metabolic pathologies in WRL68 cells

  • Fitoterapia. 2026 Apr:190:107179. doi: 10.1016/j.fitote.2026.107179.
Yuxuan Peng 1 Vadim Demidchik 2 Yan Li 3 Donghai Zhou 4 Yaqin Lin 5 Jiaqi Liu 4 Jinfu Zuo 6 Xianglan Lei 7
Affiliations

Affiliations

  • 1 Department of Plant Cell Biology and Bioengineering, Faculty of Biology, Belarusian State University, 4 Independence Ave., 220030 Minsk, Belarus; Department of Veterinary Internal Medicine, Faculty of Veterinary Medicine, Huazhong Agricultural University, 1 Shizishan St., Hongshan District, 430070 Wuhan, China; Hainan College of Vocation and Technique, 95 Nanhai Ave., 570100 Haikou, China.
  • 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 Department of Veterinary Internal Medicine, Faculty of Veterinary Medicine, Huazhong Agricultural University, 1 Shizishan St., Hongshan District, 430070 Wuhan, China.
  • 5 Department of Genetics, Faculty of Biology, Belarusian State University, 4 Independence Ave., 220030 Minsk, Belarus.
  • 6 Hainan College of Vocation and Technique, 95 Nanhai Ave., 570100 Haikou, China. Electronic address: [email protected].
  • 7 Hainan College of Vocation and Technique, 95 Nanhai Ave., 570100 Haikou, China; Hainan College of Software Technology, No. 128, Fuhai Road, 571400 Qionghai, China. Electronic address: [email protected].
Abstract

Andrographolide (AG), a natural diterpenoid compound derived from Andrographis paniculata, exhibits potential against non-alcoholic steatohepatitis (NASH). However, its therapeutic utility is limited by poor solubility, short half-life, and low bioavailability. This study aimed to enhance AG's efficacy by encapsulating it into exosome-like nanoparticles (ELNs) isolated from Nauclea officinalis (N. officinalis, Rubiaceae family) and evaluating its anti-NASH activity in WRL68 cells. This study isolated Nauclea officinalis-derived ELNs (N-ELNs) via ultracentrifugation. Loganin, andrographolide, and asiatic acid were detected in N-ELNs using the HPLC method. RNA Sequencing and target gene analysis identified miRNAs in N-ELNs and their cross-kingdom targets in the human genome. AG-loaded N-ELNs (AG-N-ELNs) were prepared using a passive loading method and characterized by transmission electron microscopy, nanoparticle tracking analyzer, and high-performance liquid chromatography. Their effects were tested in free fatty acid (FFA)-exposed WRL68 cells. As for the results, AG suppressed Nuclear Factor kappa-B p50 (NF-κB p50) activation, downregulated NLRP3 expression, and reduced pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) in WRL68 cells. It also restored mitochondrial membrane potential and decreased Reactive Oxygen Species (ROS). N-ELNs targeted the ACC/ CPT1 axis to alleviate lipid deposition, reducing total Cholesterol and triglyceride levels. AG-N-ELNs outperformed both AG and N-ELNs individually, demonstrating superior anti-NASH activity through synergistic effects of AG's anti-inflammatory/antioxidant properties and N-ELNs' miRNA-mediated metabolic regulation. In conclusion, AG-N-ELNs effectively alleviate NASH-like pathological features in vitro through multi-target regulation, offering a promising strategy for NASH treatment. Further in vivo validation and formulation optimization are warranted.

Keywords

Andrographolide; Exosome-like nanoparticles; Fatty liver; Nauclea officinalis; Non-alcoholic steatohepatitis; WRL68 cells.

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