# Cinnamomum migao H.W. Li Ethanol-Water Extract Suppresses IL-6 Production in Cardiac Fibroblasts: Mechanisms Elucidated via UPLC-Q-TOF-MS, Network Pharmacology, and Experimental Assays

## TL;DR

This study identifies how an extract from Cinnamomum migao suppresses IL-6 in heart cells, potentially offering a new treatment for heart fibrosis.

## Contribution

The study reveals the active compounds and molecular mechanisms of Cinnamomum migao extract in inhibiting cardiac fibroblast IL-6 production.

## Key findings

- MG-EWE contains 173 compounds, with 14 core constituents targeting IL-6 synthesis via ADRB2 and MAPK9.
- Laurolitsine and Hecogenin inhibit CF proliferation, migration, and IL-6 expression through the ADRB2/JNK/c-Jun pathway.
- Experimental assays confirm MG-EWE's anti-fibrotic effects by suppressing ISO-induced CF transdifferentiation.

## Abstract

This study aims to elucidate the active components and underlying molecular mechanisms by which the ethanol-water extract of Cinnamomum migao H.W. Li (MG-EWE) inhibits cardiac fibroblast (CF) transdifferentiation and IL-6 production, providing insights into its anti-myocardial fibrosis effects. The chemical composition of MG-EWE was characterized using UPLC-Q-TOF-MS. Network pharmacology analysis identified active constituents and their mechanisms in inhibiting IL-6 production in CFs. An isoproterenol (ISO)-induced rat CF model was established to evaluate the effects of MG-EWE and its main monomers, Laurolitsine and Hecogenin, on cell proliferation, migration, collagen metabolism, IL-6 production, and key proteins in the ADRB2/JNK signaling pathway. A total of 173 compounds were identified in MG-EWE, with 14 core constituents regulating IL-6 synthesis via 16 key targets, including ADRB2 and MAPK9. Gene Ontology enrichment indicated that MG-EWE affects phosphorylation and the JNK signaling cascade. Molecular docking showed strong binding affinities between Laurolitsine, Hecogenin, and their targets ADRB2 and JNK. Experimentally, MG-EWE, Laurolitsine, and Hecogenin significantly inhibited ISO-induced CF proliferation, migration, and hydroxyproline synthesis, as well as the expression of p-ADRB2, p-JNK, p-c-Jun, and IL-6. MG-EWE inhibits CF transdifferentiation and IL-6 production via the ADRB2/JNK/c-Jun signaling axis, mediated by its constituents Laurolitsine and Hecogenin, highlighting its potential for drug development targeting myocardial fibrosis.