Wu Jian-Sheng, Chu Pei-Yi, Hsu Wei-Yu, Chuang Ta-Hsien, Yu Ying-Chun, Pan Yi-Cheng, Lin Yi-Ting, Tang Chih-Hsin, Lee Chia-Lin, Wu Yang-Chang
Graduate Institute of Biomedical Sciences, China Medical University, Taichung, 0402, Taiwan; Department of Ophthalmology, Changhua Christian Hospital, Changhua, 50006, Taiwan.
Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung, 40447, Taiwan; Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan; Master Program of Pharmaceutical Manufacture, College of Pharmacy, China Medical University, Taichung, 40402, Taiwan.
J Ethnopharmacol. 2025 Feb 11;341:119328. doi: 10.1016/j.jep.2025.119328. Epub 2025 Jan 9.
Kochiae Fructus, the ripe fruit of Kochia scoparia, is a traditional Chinese medicine commonly used to treat eye discomforts and vision problems. Although Kochiae Fructus is mentioned in many classical Chinese medical texts, its protective effects and the roles of its active phytochemicals in eye treatment still lack scientific exploration.
This study aimed to clarify the protective effects and identify the active fractions and compounds of Kochiae Fructus against oxidative stress-induced retinal pigment epithelium (RPE) cell death.
Liquid-liquid partitioning was employed to prepare active fractions. Silica gel, RP-18, and Sephadex™ LH-20 gels were used as stationary phases to purify the compounds through column chromatography. Cell models were established by treating ARPE-19 (RPE cell line) with hydrogen peroxide (H₂O₂) and tert-butyl hydroperoxide (TBHP), respectively.
The methanol aqueous fraction from ethyl acetate-soluble extract (KSEM) alleviated oxidant-induced RPE cell death in a dose-dependent manner and activated the Nrf2/HO-1 pathway, a critical defense mechanism against oxidative damage. The isolated flavonols in fraction KSEM, hyperoside, quercetin, and kaempferol, reduced oxidant-induced cell mortality, with quercetin showing the strongest effect. Moreover, combination treatment revealed that hyperoside and kaempferol synergistically enhanced the protective effects of quercetin, making the combined treatment more efficient than quercetin alone.
The protective effects of Kochiae Fructus against oxidative damage in RPE cell was validated with the KSEM fraction. The compound quercetin was identified as the important contributor. However, the synergistic effect of the hyperoside, quercetin, and kaempferol mixture may play a dominant role in the protective action of Kochiae Fructus. Overall, these findings highlight the potential of Kochiae Fructus and its flavonol mixture as a basis for developing treatments targeting ocular diseases associated with oxidative damage in retina.
地肤子，即地肤的成熟果实，是一种常用于治疗眼部不适和视力问题的传统中药。尽管许多中国古典医学典籍中都提到了地肤子，但其保护作用及其活性植物化学成分在眼部治疗中的作用仍缺乏科学探索。
本研究旨在阐明地肤子对氧化应激诱导的视网膜色素上皮（RPE）细胞死亡的保护作用，并确定其活性成分和化合物。
采用液液分配法制备活性成分。以硅胶、RP - 18和葡聚糖凝胶LH - 20为固定相，通过柱色谱法纯化化合物。分别用过氧化氢（H₂O₂）和叔丁基过氧化氢（TBHP）处理ARPE - 19（RPE细胞系）建立细胞模型。
乙酸乙酯可溶提取物的甲醇水相部分（KSEM）以剂量依赖的方式减轻了氧化剂诱导的RPE细胞死亡，并激活了Nrf2/HO - 1通路，这是一种对抗氧化损伤的关键防御机制。KSEM部分中分离出的黄酮醇，金丝桃苷、槲皮素和山奈酚，降低了氧化剂诱导的细胞死亡率，其中槲皮素的效果最强。此外，联合处理表明金丝桃苷和山奈酚协同增强了槲皮素的保护作用，使联合处理比单独使用槲皮素更有效。
KSEM部分验证了地肤子对RPE细胞氧化损伤的保护作用。确定化合物槲皮素是重要贡献者。然而，金丝桃苷、槲皮素和山奈酚混合物的协同作用可能在地肤子的保护作用中起主导作用。总体而言，这些发现突出了地肤子及其黄酮醇混合物作为开发针对视网膜氧化损伤相关眼部疾病治疗方法基础的潜力。
