School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
Int J Biol Macromol. 2023 Jun 15;240:124413. doi: 10.1016/j.ijbiomac.2023.124413. Epub 2023 Apr 12.
Acetic acid has been shown to be effective in chronic kidney disease (CKD). However, it is a low-molecular-weight compound that allows it to be absorbed in the upper digestive tract so that it cannot function in colon. To overcome these deficiencies, an acetate-releasing xylan derivative, xylan acetate ester (XylA), was synthesized and selected in this study for its potential in the treatment of CKD. IR, NMR and HPGPC were used to characterize the structure of XylA and its antinephritic effects was evaluated in vivo. The results showed that acetate was successfully grafted onto the C-2 and C-3 positions of xylan and with a molecular weight at 69157 Da. XylA treatments could relieve the symptoms of CKD in an adenine-induced chronic renal failure (CRF) model and an adriamycin-induced focal segmental glomerulosclerosis (FSGS) model in SD rats. Further study indicated that XylA could upregulate the short-chain fatty acids (SCFAs) in vitro and vivo. Nevertheless, the relative abundance of Phascolarctobacterium in colon was increased after XylA treatment. XylA could upregulate G-protein-coupled receptor 41 (GPR41) expression, inhibit glomerular cell apoptosis and promoting proliferation. Our study expands the application of xylan and provides a new idea for the treatment of CKD with acetic acid.
醋酸已被证明在慢性肾脏病(CKD)中有效。然而,它是一种低分子量化合物,可在消化道上部被吸收,因此无法在结肠中发挥作用。为了克服这些缺陷,本研究合成并选择了一种释放醋酸盐的木聚糖衍生物,即木聚糖醋酸酯(XylA),用于治疗 CKD。IR、NMR 和 HPGPC 用于表征 XylA 的结构,并在体内评估其抗肾炎作用。结果表明,醋酸成功地接枝到木聚糖的 C-2 和 C-3 位,分子量为 69157 Da。XylA 处理可缓解腺嘌呤诱导的慢性肾衰竭(CRF)模型和阿霉素诱导的局灶节段性肾小球硬化(FSGS)模型中 SD 大鼠的 CKD 症状。进一步的研究表明,XylA 可以在体外和体内上调短链脂肪酸(SCFAs)。然而,XylA 处理后结肠中的 Phascolarctobacterium 相对丰度增加。XylA 可以上调 G 蛋白偶联受体 41(GPR41)的表达,抑制肾小球细胞凋亡并促进增殖。我们的研究扩展了木聚糖的应用,并为醋酸治疗 CKD 提供了新的思路。