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image of Lingguizhugan Decoction Attenuates Angiotensin II-Induced Cardiac Hypertrophy Through the LITAF Signaling Pathway

Abstract

Objective

Lingguizhugan Decoction (LGZGD), a traditional Chinese herbal prescription with recognized efficacy in heart failure, has an unclear mechanism against cardiac hypertrophy. This study investigated its protective effects against angiotensin II (Ang II)-induced cardiac hypertrophy and the role of the LITAF signaling pathway.

Methods

An mouse model of cardiac hypertrophy was established continuous Ang II infusion. LGZGD was administered, and its effects on cardiac function, hypertrophy markers, and pathway proteins were evaluated using echocardiography, histopathology, and molecular techniques. , H9c2 cardiomyocytes were treated with Ang II to induce hypertrophy; LGZGD-containing serum was applied to assess the impacts on cell size, hypertrophic markers, and signaling pathways. LITAF expression in H9c2 cells was silenced siRNA to validate its role in LGZGD-mediated anti-hypertrophy.

Results

LGZGD improved cardiac function, reduced cardiomyocyte size, and downregulated hypertrophic markers. It also upregulated LITAF protein expression and suppressed the phosphorylation of ASK1, JNK1/2, and p38 MAPK. LGZGD-containing serum inhibited Ang II-induced H9c2 hypertrophy activating LITAF and inhibiting the ASK1–JNK/p38 pathway. LITAF silencing reversed these anti-hypertrophic effects, confirming its pivotal role in mediating LGZGD's protective action.

Discussion

LGZGD alleviates cardiac hypertrophy by activating LITAF and inhibiting the ASK1-JNK/p38 pathway, identifying key therapeutic targets of this formula. These findings advance understanding of LITAF’s non-inflammatory cardiovascular protective roles and provide insights into multi-target strategies for cardiac hypertrophy.

Conclusion

LGZGD attenuates Ang II-induced cardiac hypertrophy by activating the LITAF pathway and inhibiting the ASK1-JNK/p38 signaling cascade.

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2026-01-12
2026-01-29

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Lingguizhugan Decoction Attenuates Angiotensin II-Induced Cardiac Hypertrophy Through the LITAF Signaling Pathway
Bentham Science Publishers ; https://doi.org/10.2174/0113862073421853251128081254
/content/journals/cchts/10.2174/0113862073421853251128081254
/content/journals/cchts/10.2174/0113862073421853251128081254
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  • Article Type:     Research Article
Keywords: cardiac hypertrophy ; ASK1-JNK/p38 pathway ; LITAF ; heart failure ; Lingguizhugan decoction ; angiotensin II

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