# Zhen-Wu-Tang ameliorates uremic cardiomyopathy via targeting the kidney–heart inflammatory axis and suppressing CCL2/CCR2-mediated macrophage activation

## TL;DR

Zhen-Wu-Tang improves heart and kidney function in uremic cardiomyopathy by reducing inflammation and macrophage activation.

## Contribution

The study identifies how Zhen-Wu-Tang targets the kidney-heart inflammatory axis and suppresses CCL2/CCR2 signaling in uremic cardiomyopathy.

## Key findings

- Zhen-Wu-Tang significantly improves renal and cardiac function in a mouse model of uremic cardiomyopathy.
- Active components of Zhen-Wu-Tang inhibit NF-κB activation and reduce CCL2-mediated macrophage recruitment.
- Proteomic analysis shows Zhen-Wu-Tang suppresses pro-inflammatory cytokines like TNFα, IL-6, and IL-1β.

## Abstract

Zhen-Wu-Tang (ZWT), a classic herbal formula from Treatise on Febrile and Miscellaneous Diseases, is commonly used for heart and kidney-related diseases. Despite its widespread application, research on the active components of ZWT and their mechanisms in heart–kidney cross-organ regulation remains underexplored.

This study aimed to elucidate the therapeutic mechanisms of ZWT in uremic cardiomyopathy (UC) focusing on its modulation of the heart–kidney inflammatory axis.

A UC model was established via 5/6 nephrectomy in mice, followed by 8 weeks of ZWT treatment. Functional assessments included serum creatinine, blood urea nitrogen, cardiac ejection fraction, and left ventricular metrics. Proteomic analysis using Olink technology exerts its therapeutic effects by suppressing systemic inflammation. UHPLC-Q/TOF–MS were employed to identify prototype components and blood-entering components in ZWT. Cellular experiments using a three-step co-culture system were conducted to evaluate the regulatory effects of ZWT active components on HK-2 and AC16 cells and to explore their underlying molecular mechanisms.

ZWT significantly improved renal and cardiac functions. Proteomics revealed ZWT suppressed pro-inflammatory cytokines TNFα, IL-6, IL-1β and chemokines. The bioactive constituents of ZWT, including benzoylaconine, paeoniflorin, and atractylenolide III, inhibited NF-κB activation, thereby reducing CCL2 synthesis and subsequent macrophage recruitment via the CCR2 axis. This attenuated systemic inflammation and cardiomyocyte injury.

ZWT exerts therapeutic effects on UC by targeting the kidney-heart inflammatory axis and suppressing CCL2/CCR2-mediated macrophage activation. This study provides new insights into the molecular mechanisms underlying ZWT's efficacy in treating heart–kidney disorders.

The online version contains supplementary material available at 10.1186/s13020-026-01376-2.

This study reveals the dual cardiorenal protective effects of ZWT in uremic cardiomyopathy.A total of 45 major compounds and 34 blood-entering components are identified in ZWT using UHPLC-Q/TOF–MS analysis.The cardiorenal protective effects of ZWT are mediated through targeting the kidney-heart inflammatory axis and suppressing CCL2/CCR2-mediated macrophage activation.

This study reveals the dual cardiorenal protective effects of ZWT in uremic cardiomyopathy.

A total of 45 major compounds and 34 blood-entering components are identified in ZWT using UHPLC-Q/TOF–MS analysis.

The cardiorenal protective effects of ZWT are mediated through targeting the kidney-heart inflammatory axis and suppressing CCL2/CCR2-mediated macrophage activation.

The online version contains supplementary material available at 10.1186/s13020-026-01376-2.