Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, China.
School of Pharmacy, Gannan Medical University, Ganzhou, China.
Pharm Biol. 2023 Dec;61(1):938-948. doi: 10.1080/13880209.2023.2222773.
The antidiabetic effects of flavonoids have been reported, but it is still unclear whether 5,7,3',4',5'-pentamethoxyflavone, isolated from Benth. (Fabaceae), also exhibits such properties.
To isolate 5,7,3',4',5'-pentamethoxyflavone from using high-speed countercurrent chromatography and examine its potential in treating diabetic nephropathy.
The phytochemical constituents from the stems of were separated and purified with high-speed countercurrent chromatography; 5,7,3',4',5'-pentamethoxyflavone (PMF) was identified by mass spectrum, H-NMR, and C-NMR. After exposing mesangial cells to 30 mM glucose and either 5 μM or 10 μM PMF for 6 h, the levels of fibronectin (FN) and p-Smad2/3 were analyzed using Western blotting. Male Sprague-Dawley rats were injected intraperitoneally with 55 mg/kg streptozotocin to induce diabetes and then were randomized into three groups ( = 10): vehicle administration, low-dose (5 mg/kg) PMF, and high-dose (25 mg/kg) PMF by intragastric gavage for 3 months. A healthy group was included as the control.
Compared to the diabetic group, low-dose and high-dose PMF treatment decreased the phosphorylation of Smad2/3 by 0.54- and 0.52-fold, and the accumulation of FN decreased by 0.82- and 0.77-fold ; the phosphorylation of Smad2/3 was decreased by 0.39- and 0.37-fold, and the accumulation of FN decreased by 0.47- and 0.40-fold , respectively. Furthermore, PMF alleviated the glomerular basement membrane thickness and foot process fusion.
The findings suggest for the first time that PMF may be a promising treatment option for diabetic kidney fibrosis, which warrants additional clinical investigation.
黄酮类化合物具有抗糖尿病作用,但 5,7,3',4',5'-五甲氧基黄酮(PMF)是否也具有这种特性仍不清楚,这种化合物从 中分离得到。
用高速逆流色谱法从 中分离 5,7,3',4',5'-五甲氧基黄酮,并研究其在治疗糖尿病肾病中的潜力。
采用高速逆流色谱法分离纯化 茎中的化学成分;通过质谱、H-NMR 和 C-NMR 鉴定 5,7,3',4',5'-五甲氧基黄酮(PMF)。将系膜细胞暴露于 30mmol/L 葡萄糖和 5μM 或 10μM PMF 中 6h 后,用 Western blot 法检测纤维连接蛋白(FN)和 p-Smad2/3 的水平。雄性 Sprague-Dawley 大鼠腹腔注射 55mg/kg 链脲佐菌素诱导糖尿病,然后随机分为 3 组(每组 10 只): vehicle 组、PMF 低剂量(5mg/kg)组和 PMF 高剂量(25mg/kg)组,通过灌胃给药 3 个月。健康组作为对照组。
与糖尿病组相比,PMF 低剂量和高剂量组 Smad2/3 磷酸化分别降低 0.54-和 0.52 倍,FN 积累分别降低 0.82-和 0.77 倍;Smad2/3 磷酸化分别降低 0.39-和 0.37 倍,FN 积累分别降低 0.47-和 0.40 倍。此外,PMF 还减轻了肾小球基底膜厚度和足突融合。
研究结果首次表明,PMF 可能是治疗糖尿病肾病纤维化的一种有前途的治疗方法,值得进一步的临床研究。