This analysis reveals that IDHP reduces inflammation and oxidative stress in cardiomyocytes during sepsis, suggesting potential therapeutic applications.
Background: Sepsis-induced myocardial injury (SIMI) significantly contributes to sepsis-related mortality, yet effective therapies remain limited. This study investigated the cardioprotective potential of isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate (IDHP), a bioactive metabolite from Salvia miltiorrhiza, focusing on its mechanism via the GAS6/Axl signaling axis in lipopolysaccharide (LPS)-induced myocardial injury. Methods: Using an in vitro HL-1 cardiomyocyte model, IDHP’s cytotoxicity was assessed (0–20 μM). Cells were pretreated with IDHP (10 μM, optimal concentration) before LPS exposure. Inflammatory cytokines (IL-6/TNF-α/IL-1β/IL-18), chemokines (CCL2/CCR2, CCL25/CCR9), ROS levels (Nrf2 pathway), and apoptosis markers (Bax) were quantified. GAS6/Axl-AMPK signaling was evaluated via GAS6 knockout experiments. Results: IDHP (≤20 μM) showed no cytotoxicity. At 10 μM, it exhibited anti-inflammatory effects by reducing LPS-induced cytokine/chemokine release, demonstrated antioxidant activity through lowering ROS via Nrf2 activation, and exerted anti-apoptotic action by downregulating Bax. Mechanistically, IDHP restored GAS6/Axl-AMPK phosphorylation, an effect abolished in GAS6-knockout cells. Conclusions: IDHP mitigates LPS-induced cardiomyocyte injury by concurrently targeting inflammation, oxidative stress, and apoptosis via GAS6/Axl-AMPK signaling, proposing a novel therapeutic avenue for SIMI.
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Chen et al. (2025) studied this question.
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