Takata Takanobu, Motoo Yoshiharu
Division of Molecular and Genetic Biology, Department of Life Science, Medical Research Institute, Kanazawa Medical University, Uchinada 920-0293, Ishikawa, Japan.
Department of Medical Oncology and Kampo Medicines, Komatsu Sophia Hospital, Komatsu 923-0861, Ishikawa, Japan.
Metabolites. 2023 Jul 24;13(7):878. doi: 10.3390/metabo13070878.
Kampo medicines are Japanese traditional medicines developed from Chinese traditional medicines. The action mechanisms of the numerous known compounds have been studied for approximately 100 years; however, many remain unclear. While components are normally affected through digestion, absorption, and metabolism, in vitro oral, esophageal, and gastric epithelial cell models avoid these influences and, thus, represent superior assay systems for Kampo medicines. We focused on two areas of the strong performance of this assay system: intracellular and extracellular advanced glycation end-products (AGEs). AGEs are generated from glucose, fructose, and their metabolites, and promote lifestyle-related diseases such as diabetes and cancer. While current technology cannot analyze whole intracellular AGEs in cells in some organs, some AGEs can be generated for 1-2 days, and the turnover time of oral and gastric epithelial cells is 7-14 days. Therefore, we hypothesized that we could detect these rapidly generated intracellular AGEs in such cells. Extracellular AEGs (e.g., dietary or in the saliva) bind to the receptor for AGEs (RAGE) and the toll-like receptor 4 (TLR4) on the surface of the epithelial cells and can induce cytotoxicity such as inflammation. The analysis of Kampo medicine effects against intra/extracellular AGEs in vitro is a novel model.
汉方药是由中药发展而来的日本传统药物。众多已知化合物的作用机制已被研究了约100年；然而，许多机制仍不清楚。虽然成分通常通过消化、吸收和代谢受到影响，但体外口腔、食管和胃上皮细胞模型可避免这些影响，因此是汉方药的优质检测系统。我们关注该检测系统表现出色的两个领域：细胞内和细胞外晚期糖基化终产物（AGEs）。AGEs由葡萄糖、果糖及其代谢物产生，并促进糖尿病和癌症等与生活方式相关的疾病。虽然目前的技术无法分析某些器官细胞中的全部细胞内AGEs，但某些AGEs可在1 - 2天内产生，口腔和胃上皮细胞的更新时间为7 - 14天。因此，我们假设可以在这类细胞中检测到这些快速产生的细胞内AGEs。细胞外AEGs（如饮食中的或唾液中的）与上皮细胞表面的AGEs受体（RAGE）和Toll样受体4（TLR4）结合，并可诱导炎症等细胞毒性。体外分析汉方药对细胞内/外AGEs的影响是一种新型模型。
