In situ visualization of the cellular uptake and sub-cellular distribution of mussel oligosaccharides
10.1016/j.jpha.2023.12.022
- Author:
Yu ZHENJIE
1
;
Shao HUARONG
;
Shao XINTIAN
;
Yu LINYAN
;
Gao YANAN
;
Ren YOUXIAO
;
Liu FEI
;
Meng CAICAI
;
Ling PEIXUE
;
Chen QIXIN
Author Information
1. Key Laboratory for Biotechnology Drugs of National Health Commission,School of Pharmaceutical Sciences & Institute of Materia Medica,Medical Science and Technology Innovation Center,Shandong First Medical University & Shandong Academy of Medical Sciences,Jinan,250117,China
- Keywords:
Cellular imaging;
Fluorescence labeling;
Mussel oligosaccharide;
Lipid metabolism
- From:
Journal of Pharmaceutical Analysis
2024;14(6):840-850
- CountryChina
- Language:Chinese
-
Abstract:
Unlike chemosynthetic drugs designed for specific molecular and disease targets,active small-molecule natural products typically have a wide range of bioactivities and multiple targets,necessitating extensive screening and development.To address this issue,we propose a strategy for the direct in situ micro-dynamic examination of potential drug candidates to rapidly identify their effects and mechanisms of action.As a proof-of-concept,we investigated the behavior of mussel oligosaccharide(MOS-1)by tracking the subcellular dynamics of fluorescently labeled MOS-1 in cultured cells.We recorded the entire dynamic process of the localization of fluorescein isothiocyanate(FITC)-MOS-1 to the lysosomes and visualized the distribution of the drug within the cell.Remarkably,lysosomes containing FITC-MOS-1 actively recruited lipid droplets,leading to fusion events and increased cellular lipid consumption.These drug behaviors confirmed MOS-1 is a candidate for the treatment of lipid-related diseases.Furthermore,in a high-fat HepG2 cell model and in high-fat diet-fed apolipoprotein E(ApoE)-/-mice,MOS-1 significantly promoted triglyceride degradation,reduced lipid droplet accumulation,lowered serum triglyceride levels,and mitigated liver damage and steatosis.Overall,our work supports the prioritization of in situ visual monitoring of drug location and distribution in subcellular compartments during the drug development phase,as this methodology contributes to the rapid identification of drug indications.Collectively,this methodology is significant for the screening and development of selective small-molecule drugs,and is expected to expedite the identification of candidate molecules with me-dicinal effects.
