UPLC-Q-TOF/MS, Network Pharmacology, and Experimental Validation Reveal the Mechanisms of Shuangbai Tablet Against Albuminuria.

INTRODUCTION

Shuangbai Tablet (SBT), a traditional Chinese medicine, has demonstrated efficacy in reducing albuminuria. This study aimed to investigate the therapeutic mechanisms underlying its antialbuminuric effects.

METHODS

The phytochemicals of SBT were analyzed by UPLC-Q-TOF/MS. Subsequently, we crossvalidated the identified phytochemicals and predicted the potential targets of SBT for albuminuria by network pharmacology and molecular docking analysis. Albuminuric male Wistar rats were induced by a single tailvein injection of Adriamycin (ADR, 5 mg/kg) and orally administered SBT for 8 weeks. Then, 24-hour Urine Protein (24 h-UTP) and serum albumin were assessed, along with changes in renal function, systemic lipid metabolism, and serum COX-2 levels. Renal histopathology was evaluated by H&E staining, while the renal expressions of VEGFR-1, VEGFA, HIF-1α, NF-κB p65, ACTN-4, and podocin were assessed by immunohistochemistry and western blotting.

RESULTS

Nine core active phytochemicals of SBT targeting HIF-1α and VEGFA were identified for albuminuria treatment. Molecular docking predicted favorable binding affinities between these phytochemicals and both HIF-1α and VEGFA. In ADR-treated rats, SBT significantly reduced proteinuria (24 h-UTP: 245.1 (95% CI, 174.9 to 315.3) mg/24 h in the middle-dose SBT group vs. 585.2 (95% CI, 460.0 to 710.4) mg/24 h in the ADR group; p < 0.0001), reversed hypoalbuminemia (ALB: 24.44 (95% CI, 17.62 to 31.25) g/L vs. 9.70 (95% CI, 4.94 to 14.46) g/L; p < 0.05), ameliorated renal dysfunction and lipid metabolic disturbances, and suppressed serum COX-2 levels. Histopathological analysis showed ameliorated renal injury. SBT stabilized the decreased expressions of renal VEGFR-1, VEGFA, HIF-1α, ACTN-4, and podocin, while suppressing NF-κB p65expression.

DISCUSSION: Further functional characterization studies are warranted to validate the pharmacological effects of SBT on albuminuria.

CONCLUSION

SBT can alleviate albuminuria, inflammation, and renal injury, associated with the stabilization of HIF-1α and VEGFA expressions.