What question did this study set out to answer?

The study aims to investigate how Ling-Gui-Zhu-Gan decoction mitigates doxorubicin-induced cardiotoxicity and its underlying mechanisms.

April 10, 2026

Ling-Gui-Zhu-Gan decoction decreases doxorubicin-induced cardiotoxicity by regulating inflammation via the cGAS-STING pathway

Key Result

Ling-Gui-Zhu-Gan decoction protected against doxorubicin-induced cardiotoxicity by improving cardiac function and reducing inflammation and mitochondrial damage via the cGAS-STING pathway.

Key Points

The study aims to investigate how Ling-Gui-Zhu-Gan decoction mitigates doxorubicin-induced cardiotoxicity and its underlying mechanisms.
Administered Ling-Gui-Zhu-Gan decoction in varying doses to C57 male mice for 4 weeks.
Evaluated cardiac function via ejection fraction and fractional shortening measurements.
Assessed inflammatory markers and oxidative stress levels in myocardium and HL-1 cells.
Analyzed expressions of cGAS, STING, Nrf2, and other relevant proteins.
Ling-Gui-Zhu-Gan decoction reduced inflammatory cell infiltration and myocardial collagen deposition.
Significant improvements were observed in ejection fraction and fractional shortening.
Mitochondrial damage and oxidative stress were decreased in HL-1 cells, along with reductions in NLRP3 and Caspase-1 expressions.

Structured PICO

Does Ling-Gui-Zhu-Gan decoction reduce doxorubicin-induced cardiotoxicity in preclinical models?

Population

C57 male mice and HL-1 cells with doxorubicin (DOX)-induced cardiotoxicity

Intervention

Ling-Gui-Zhu-Gan decoction (LGZGD) at doses of 2.15 g/kg, 4.29 g/kg, and 8.58 g/kg administered daily by gavage for 4 weeks

Comparator

Doxorubicin-induced cardiotoxicity model without LGZGD treatment

Outcome

Echocardiographic parameters (EF, FS, LVIDs, LVIDd), histological changes (inflammatory cell infiltration, collagen deposition), and molecular markers of the cGAS-STING pathway and oxidative stresssurrogate

Ling-Gui-Zhu-Gan decoction ameliorates doxorubicin-induced cardiotoxicity in preclinical models by regulating inflammation via the cGAS-STING pathway.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Recent evidence has shown that the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway mediated by nuclear factor E2-related factor 2 (Nrf2) contributes to the pathogenesis of doxorubicin (DOX)-induced cardiotoxicity. Ling-Gui-Zhu-Gan decoction (LGZGD) ameliorated DOX-cardiotoxicity in cardiomyocytes in our previously studies. In this study, the therapeutic effects of LGZGD protect against DOX-induced cardiotoxicity in C57 male mice and HL-1 cells, and the underlying mechanisms were investigated. LGZGD-L (2.15 g/kg), LGZGD-M (4.29 g/kg) and LGZGD-H (8.58 g/kg) were administered daily in C57 male mice by gavage starting with the first intraperitoneal injection of DOX modeling for 4 weeks. LGZGD reduced the inflammatory cell infiltration, collagen of myocardial tissue, and collagen fiber deposition, increased ejection fraction (EF) and fractional shortening (FS), decreased left ventricular internal dimension in end-systole (LVIDs) and left ventricular internal dimension in end-diastole (LVIDd), and reduced mitochondrial damage. LGZGD also decreased creatine kinase (CK) and malondialdehyde (MDA) activities, and increased the content of superoxide dismutase (SOD), increased the Nrf2 expressions, and reduce expressions of cGAS, STING, nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain- containing receptor 3 (NLRP3), cysteine aspartate protease-1 (Caspase-1), gasdermin D (GSDMD) and GSDMD-N-terminal domain (GSDMD-N). In HL-1 cells, LGZGD suppressed DOX-induced oxidative stress injury and the mitochondrial membrane potential. LGZGD inhibited dynamin-relatedprotein 1 (DRP1), an increased optic atrophy 1 (OPA1) and Nrf2 expressions, as evidenced by decreased NLRP3, Caspase1, and GSDMD gene and protein expressions. In summary, we reveal a novel aspect of the cardiovascular protective effect of LGZGD, regulating the cGAS-STING pathway.

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