Demethylzeylasteral serum concentration was proved as Tripterygium Glycosides effects Biomarker on diabetic nephropathy treatment

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MAO

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YONGHUI

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ZHAO BAN zbyule@139.com BEIJING HOSPITAL Nephrology BEIJING

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Introduction

Diabetic nephropathy (DN) represents the most prevalent and severe microvascular complication associated with diabetes. Along with DN mechanism developing, inflammation were regarded as critical process in its development. Due to tripterygium glycosides (TWP) anti-inflammation effects, it was adapted as DN symptoms releasing treatment. Considering TWP significant pharmacokinetic variability, solid effect marker was required for TWP further clinical applications.

Methods

Based on TWP active compounds and serum migration components identifications, network pharmacology analysis were carried out to find the compound (Demethylzeylasteral) related to TWP anti-DN effects. The prediction of TWP DN symptoms releasing effects based on demethylzeylasteral serum concentration was validated by a DN cohort treated with TWP.

Results

Effective constituents of Tripterygium Glycosides tables detected with HRMS

Regeol C, Demethylzeylasteral, and Triptonoditerpenic acid were found in serum samples. A further confirm was carried out with standards.

Demethylzeylasteral was identified as a primary active ingredient of TWP effects on diabetic nephropathy relieving using network pharmacology

Regeol C, Demethylzeylasteral, and Triptonoditerpenic acid identified in TWPs treated patients serum were selected as potential active ingredients to perform confirmatory network pharmacology analysis.

Demethylzeylasteral serum concentration associated with patients’ urine protein concentrations

The undulated concentration of demethylzeylasteral in serum may be attributed to TWP pharmacokinetic variability. This indicated dynamic adjustment of TWP dosage was necessary in clinical practice.

Demethylzeylasteral serum concentration was selected as a potential marker for TWP symptoms releasing effects. When urine protein levels decreased by 50%, the demethylzeylasteral serum concentration's cutoff value was determined to be 78 ng/ml, resulting in an AUC of 0.7857.

Conclusions

This study revealed a connection between the serum concentration of demethylzeylasteral and its impact on alleviating symptoms of diabetic nephropathy in patients receiving TWP treatment which could facilitate TWP further clinical application.

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