Department of Bioengineering, Zunyi Medical University, Zhuhai Campus, Zhuhai, Guangdong, 519041, China.
Shanghai Animal Disease Control Center, Shanghai, 201103, China.
J Ethnopharmacol. 2021 Jan 30;265:113389. doi: 10.1016/j.jep.2020.113389. Epub 2020 Sep 11.
In traditional Chinese medicine (TCM) theory, "Qi" is classified as energetic essence supporting the life activities in human. "Blood" is categorized as nourishing essence and circulating in the body. "Blood" and "Qi" have an intimate relationship. Astragali Radix (AR; root of Astragalus membranaceus (Fisch.) Bge. Var. mongholicus (Bge.) Hsiao) has a broad spectrum of application for "Qi-Blood" enrichment. Astragaloside IV, a major saponin in AR, has therapeutic functions in erythropoietic, cardiovascular and immune systems. However, the efficacy of astragaloside IV in erythrophagocytosis has not been elucidated.
The possible functions of astragaloside IV in heme iron recycling during erythrophagocytosis in cultured macrophage were elucidated.
The translational and transcriptional expressions of heme recycling enzymes were determined after incubating of astragaloside IV for 24 h in cultured macrophage.
In astragaloside IV-treated macrophage, the expressions, both RNA and protein levels, of regulators of heme recycling, e.g. heme oxygenase-1 (HO-1), ferroportin (FPN), biliverdin reductase A and B (BVRA, BVRB), were markedly induced in dose-dependent manners. In parallel, the transcriptional activity of antioxidant response element, cloned within an expression vector as pARE-Luc and transfected in cultured macrophages, was markedly induced after a challenge with astragaloside IV in a dose-dependent manner. Moreover, the translocation of Nrf2, a transcriptional factor in regulating expression of heme recycling protein, was induced by astragaloside IV, leading to an enrichment at nucleus fraction.
Astragaloside IV shed lights in enhancing the expression of heme recycle proteins via Nrf2/ARE signaling pathway.
在传统中医（TCM）理论中，“气”被归类为支持人体生命活动的能量本质，“血”被归类为滋养本质并在体内循环。“血”和“气”之间有着密切的关系。黄芪（AR；膜荚黄芪（Fisch.）Bge. Var. 蒙古（Bge.）Hsiao 的根）广泛应用于“气血”补充。黄芪甲苷 IV 是 AR 的主要皂苷之一，具有在红细胞生成、心血管和免疫系统中的治疗功能。然而，黄芪甲苷 IV 在红细胞吞噬作用中的功效尚未阐明。
本研究的目的是阐明黄芪甲苷 IV 在培养的巨噬细胞红细胞吞噬过程中血红素铁循环利用中的可能作用。
在培养的巨噬细胞中孵育 24 小时后，测定黄芪甲苷 IV 对血红素循环利用酶的翻译和转录表达。
在黄芪甲苷 IV 处理的巨噬细胞中，血红素循环利用调节剂的表达（RNA 和蛋白质水平）均以剂量依赖性方式明显上调，例如血红素加氧酶-1（HO-1）、亚铁转运蛋白（FPN）、胆红素还原酶 A 和 B（BVRA、BVRB）。与此同时，抗氧化反应元件（ARE）的转录活性在转染培养巨噬细胞的表达载体 pARE-Luc 中明显被黄芪甲苷 IV 诱导，呈剂量依赖性方式。此外，NF-E2 相关因子 2（Nrf2），一种调节血红素循环蛋白表达的转录因子，被黄芪甲苷 IV 诱导易位，导致核部分富集。
黄芪甲苷 IV 通过 Nrf2/ARE 信号通路增强血红素回收蛋白的表达。
