The kidney antifibrotic effects of 5,7,3′,4′,5′-pentamethoxyflavone from Bauhinia championii in streptozotocin-induced diabetic rats: in vivo and in vitro experiments

Abstract

Context

The antidiabetic effects of flavonoids have been reported, but it is still unclear whether 5,7,3′,4′,5′-pentamethoxyflavone, isolated from Bauhinia championii Benth. (Fabaceae), also exhibits such properties.

Objective

To isolate 5,7,3′,4′,5′-pentamethoxyflavone from B. championii using high-speed countercurrent chromatography and examine its potential in treating diabetic nephropathy.

Materials and methods

The phytochemical constituents from the stems of B. championii were separated and purified with high-speed countercurrent chromatography; 5,7,3′,4′,5′-pentamethoxyflavone (PMF) was identified by mass spectrum, ¹H-NMR, and ¹³C-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 (n = 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.

Results

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 in vitro; 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 in vivo, respectively. Furthermore, PMF alleviated the glomerular basement membrane thickness and foot process fusion.

Conclusion

The findings suggest for the first time that PMF may be a promising treatment option for diabetic kidney fibrosis, which warrants additional clinical investigation.

Keywords:

• Extracellular matrix
• diabetes mellitus
• renal fibrosis
• high-speed countercurrent chromatography

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by grants from the Jiangxi Provincial Natural Science Foundation (No. 20202ACBL216010, 20224BAB206045), The Open Project of Key Laboratory of Prevention and treatment of cardiovascular and cerebrovascular diseases, Ministry of Education (No. XN201915, XN201927), Science and Technology innovation team project of Gannan Medical University (No. TD201706), Collaborative Innovation Center for Gannan Oil-tea Camellia Industrial Development (No. YK201608), Scientific Research Fund of Jiangxi Provincial Education Department (GJJ2201432), Talents′ Start-up Fund of Gannan Medical University (No. QD202018).