School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.
Nuclear Medicine Department, Guangdong Provincial Peoples Hospital, Guangzhou, China.
Pharm Biol. 2023 Dec;61(1):427-436. doi: 10.1080/13880209.2023.2174145.
Sanziguben (SZGB) is an empirical prescription used in traditional Chinese medicine to treat diabetic nephropathy (DN). As an abundant and primarily effective component of SZGB, Sanziguben polysaccharides (SZP) can be digested by flora to generate biological activity.
Our study aimed to clarify the potential mechanism of SZP in improving chronic DN.
Male db/db mice were randomized into DN, SZP (500 mg/kg) and metformin (MET, 300 mg/kg) groups. Wild-type littermates served as the normal control (NC) group. The drug was orally administered for 8 weeks. Enzyme-linked immunosorbent assay was used to detect the inflammatory factors. Proteins related to inflammation were evaluated using western blotting and immunohistochemical examination. Gut microbiota was analysed using 16S rRNA sequencing.
SZP significantly reduced 24 h urine albumin ( < 0.05) of DN mice. Compared to DN group, SZP significantly decreased the homeostasis model assessment of insulin resistance index, serum creatinine and blood urea nitrogen levels (20.27 ± 3.50 vs. 33.64 ± 4.85, 19.22 ± 3.77 vs. 32.52 ± 3.05 μmol/L, 13.23 ± 1.42 vs. 16.27 ± 0.77 mmol/L, respectively), and mitigated renal damage. SZP also regulated gut microbiota and decreased the abundance of Gram-negative bacteria (Proteobacteria, and ). Subsequently, SZP reduced lipopolysaccharides levels (1.06- to 1.93-fold) of DN mice. Furthermore, SZP inhibited the expression levels of TLR4, phospho-NF-κB p65, NLRP3 proteins and interleukin (IL)-18 and IL-1β.
These results demonstrated that SZP improved intestinal flora disorder and inhibited the TLR4/NF-κB/NLRP3 pathway to alleviate DN.
三芪固本（SZGB）是一种用于治疗糖尿病肾病（DN）的中医经验方。作为 SZGB 的丰富且主要有效的成分之一，三芪固本多糖（SZP）可被菌群消化生成具有生物活性的物质。
本研究旨在阐明 SZP 改善慢性 DN 的潜在机制。
雄性 db/db 小鼠随机分为 DN 组、SZP（500mg/kg）组和二甲双胍（MET，300mg/kg）组。野生型同窝仔鼠作为正常对照组（NC 组）。药物灌胃 8 周。酶联免疫吸附试验检测炎症因子。Western blot 和免疫组化检测炎症相关蛋白。16S rRNA 测序分析肠道菌群。
SZP 显著降低了 DN 小鼠 24h 尿白蛋白（<0.05）。与 DN 组相比，SZP 显著降低了胰岛素抵抗指数、血清肌酐和血尿素氮水平（20.27±3.50 比 33.64±4.85，19.22±3.77 比 32.52±3.05μmol/L，13.23±1.42 比 16.27±0.77mmol/L），减轻了肾脏损伤。SZP 还调节了肠道菌群，降低了革兰氏阴性菌（变形菌门和厚壁菌门）的丰度。随后，SZP 降低了 DN 小鼠的内毒素水平（1.06-1.93 倍）。此外，SZP 抑制了 TLR4、磷酸化 NF-κB p65、NLRP3 蛋白和白细胞介素（IL）-18 和 IL-1β 的表达水平。
这些结果表明，SZP 通过改善肠道菌群紊乱，抑制 TLR4/NF-κB/NLRP3 通路，缓解了 DN。
