Natural Products Targeting Myocardial Fibrosis: Pharmacological Basis, Molecular Mechanisms and Translational Barriers

Figures

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  Figure 1. Natural products attenuate myocardial fibrosis through multitarget modulation of inflammatory responses, oxidative stress, autophagy, metabolic homeostasis, fibroblast-to-myofibroblast transition, and TGF-β/Smad signaling. These coordinated regulatory effects suppress fibroblast activation and extracellular matrix accumulation, thereby mitigating adverse cardiac remodeling.

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  Figure 2. This figure illustrates the anti-inflammatory pathways. Icariside II, Corydalis hendersonii Hemsl., stevioside, celastrol, phloretin, and muscone are mapped to key inflammatory and profibrotic signaling axes, including NF-κB, JAK2/STAT3, TGF-β/Smad, and NLRP3/caspase-1 pathways. By suppressing cytokine release and inflammasome activation, these natural products may contribute to reduced collagen deposition and improved cardiac function.

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  Figure 3. This figure illustrates the antioxidant mechanisms by which natural products modulate myocardial fibrosis. Tanshinone IIA, geniposide, salidroside, puerarin, mangiferin, naringenin, and baicalein are mapped to key redox-related processes, including ROS suppression, Keap1/Nrf2 pathway activation, mitochondrial protection, endoplasmic reticulum stress inhibition, and GSH restoration. Collectively, these effects contribute to decreased collagen I/III and α-SMA expression, thereby attenuating myocardial fibrotic remodeling.

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  Figure 4. This figure summarizes the regulatory mechanisms by which natural products inhibit endothelial-to-mesenchymal transition-associated profibrotic remodeling. Puerarin, apigenin, ginsenoside Rb1, and diosgenin are mapped to key signaling axes, including PPARγ/TGF-β/Smad2, GTPBP4, macrophage-derived IGFBP2, and GR/IL-6 pathways. Collectively, these effects contribute to the maintenance of endothelial identity and the suppression of collagen deposition, thereby limiting myocardial fibrotic progression.

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  Figure 5. This figure illustrates the regulatory mechanisms by which natural products modulate cardiac fibroblast activation and differentiation. Salvianolic acid B, curcumin, higenamine, oxymatrine, emodin, palmatine, EGCG, and quercetin converge on key profibrotic signaling axes, including Smad, p38, STAT3, NF-κB, MTA3, and SIRT3/TGF-β/Smad pathways. Collectively, these effects contribute to the inhibition of fibroblast proliferation, myofibroblast transdifferentiation, collagen synthesis, and extracellular matrix accumulation, thereby attenuating myocardial fibrotic remodeling.

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  Figure 6. This figure illustrates the autophagy-associated regulatory mechanisms by which natural products attenuate myocardial fibrosis. Luteolin, quercetin, puerarin, Chikusetsusaponin IVa, crocetin, and chlorogenic acid are mapped to key autophagy-related signaling pathways and processes, including JNK/c-Jun/miR-221, miR-223-3p/FOXO3, autophagy–lysosomal pathway regulation, AMPK/mTOR/ULK1 signaling, autolysosome formation, and PINK1/Parkin-mediated mitophagy. Collectively, these effects underscore the restoration of autophagic flux, rather than a simple increase in LC3 expression, as the central mechanistic interpretation of autophagy-mediated antifibrotic activity.