Ginsenoside Rb1 improves human nonalcoholic fatty liver disease with liver organoids-on-a-chip

• Published in: Engineered regeneration Vol. 5; no. 3; pp. 283 - 294
• Main Authors: Wang, Hui, Zhu, Yue, Shi, Pengcheng, Li, Xiangyang, Bu, Qingyun, Li, Yachun, You, Xiaoyan, Zhao, Guoping
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.09.2024; KeAi Communications Co., Ltd
• Subjects: Biological activity evaluation; Ginsenoside Rb1; Microfluidic platform; Nonalcoholic fatty liver; Organoid; Microfluidic platform; Organoid; Ginsenoside Rb1; Nonalcoholic fatty liver; Biological activity evaluation
• ISSN: 2666-1381; 2666-1381
• DOI: 10.1016/j.engreg.2024.06.002

•The liver organoids-on-a-chip platform could recapitulate key features of human liver physiology.•Free fatty acid-induced liver organoids displayed typical pathological characteristics similar to those observed in patients with non-alcoholic fatty liver disease (NAFLD).•Ginsenoside Rb1 improved lipid accumulation, oxidative stress, lipid peroxidation, inflammation and fibrosis in NAFLD treatment. Non-alcoholic fatty liver disease (NAFLD), a type of liver disease for which no treatment is currently approved, remains a major concern worldwide. It is manifested as simple hepatocyte steatosis and can develop into inflammation, fibrosis, cirrhosis and liver cancer in severe cases. However, due to the lack of appropriate in vitro drug testing platforms, an in-depth understanding of the therapeutic activity of ginsenoside Rb1 in NAFLD remains challenging. Here, we proposed a NAFLD model on a liver organoids (LOs)-on-a-chip platform to evaluate the therapeutic effect of ginsenoside Rb1 in a dynamic, multi-condition and high-throughput manner. This platform allowed us to reshape certain features such as multicellular types and liver-specific functions of the physiology of the human-relative liver. Free fatty acids (FFAs)-induced LOs displayed typical pathological characteristics of NAFLD progression, including steatosis, oxidative stress, lipid peroxidation, inflammation and fibrosis. With ginsenoside Rb1 intervention, these pathological features can be significantly improved, which may provide new insights into the potential mechanisms of NAFLD progression and treatment and suggest the clinical implications for humans. The proposed system enables the formation, differentiation, and function of LOs to serve as a scalable, high-throughput and sensitive drug testing model, to potentially expedite the NAFLD drug discovery. [Display omitted]