Panax ginseng suppresses endothelin-1-induced cardiomyocyte hypertrophy through inhibition of the local angiotensin II-AT1 receptor signaling axis.

Authors

Tomohiro Numata, Hideaki Tagashira, Kaori Sato-Numata, Ryo Takayama, Aoto Aoyama, Ayako Sakai, Ha Nam Tran, Hiroyuki Watanabe

Published in

Naunyn-Schmiedeberg's archives of pharmacology. Oct 20, 2026. Epub Oct 20, 2026.

Abstract

Panax ginseng (PG) is a traditional herbal medicine widely used for the treatment of cardiovascular disorders in East Asia. Although PG has been reported to attenuate cardiomyocyte hypertrophy, the molecular mechanisms underlying its cardioprotective effects remain incompletely understood. In this study, we investigated whether modulation of the endothelin-1 (ET-1)-angiotensin II (AngII) signaling axis contributes to the anti-hypertrophic action of PG. Neonatal rat ventricular myocytes (NRVMs) were used to evaluate ET-1-induced hypertrophy, and pharmacological experiments using receptor antagonists were performed to examine the signaling pathways involved. Extracellular AngII levels were quantified by ELISA, intracellular Ca²⁺ accumulation was assessed in AT_1AR-overexpressing NRVMs, and whole-cell patch-clamp recordings were performed in HEK293T cells co-expressing AT_1AR and TRPC6. PG significantly attenuated ET-1-induced cardiomyocyte hypertrophy without altering ET_AR or ET_BR expression. Pharmacological experiments with the ET_AR antagonist BQ-123 suggested that the anti-hypertrophic effect of PG could not be explained solely by direct inhibition of ET_AR signaling. PG markedly suppressed ET-1-induced extracellular AngII production, and interaction studies with losartan further implicated the AngII-AT_1AR pathway in the anti-hypertrophic action of PG. Moreover, PG inhibited AngII-induced intracellular Ca²⁺ accumulation in AT_1AR-overexpressing NRVMs and attenuated AngII-evoked TRPC6-mediated membrane currents without affecting basal channel activity. These findings demonstrate that PG suppresses ET-1-induced cardiomyocyte hypertrophy by inhibiting both ET-1-induced AngII production and downstream AT_1AR-dependent signaling, identifying suppression of the AngII-AT_1AR signaling axis as a key mechanism underlying its cardioprotective effects.

PMID:
42900370
Bibliographic data and abstract were imported from PubMed on 21 Oct 2026.

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