Natural products for the treatment of hypertrophic scars: Preclinical and clinical studies

Abstract

Hypertrophic scarring (HS) is a complication of wound healing that causes physiological and psychological distress in patients. However, the possible mechanism underlying HS is not fully understood, and there is no gold standard for its treatment. Natural products are more effective, economical, convenient, and safe than existing drugs, and they have a wide application prospect. However, there is a lack of literature on this topic, so we reviewed in vivo, in vitro, and clinical studies and screened natural products showing beneficial effects on HS that can become potential therapeutic agents for HS to fill in the gaps in the field. In addition, we discussed the drug delivery systems related to these natural products and their mechanisms in the treatment of HS. Generally speaking, natural products inhibit inflammation, myofibroblast activation, angiogenesis, and collagen accumulation by targeting interleukins, tumor necrosis factor-α, vascular endothelial growth factors, platelet-derived growth factors, and matrix metalloproteinases, so as to play an anti-HS effects of natural products are attributed to their anti-inflammatory, anti-proliferative, anti-angiogenesis, and pro-apoptotic (enhancing apoptosis and autophagy) roles, thus treating HS. We also screened the potential therapeutic targets of these natural compounds for HS through network pharmacology and constructed a protein-protein interaction (PPI) network, which may provide clues for the pharmacological mechanism of natural products in treating this disease and the development and application of drugs.

Keywords: Drug discovery; Hypertrophic scars; Mechanisms; Natural products; Traditional Chinese medicine.

Fig. 1

Diagram of the histological features of hypertrophic scars. The formation process of HS involve several cytokines, mediators, cells, and matrix molecules. HS histologically exhibits abundant blood vessels, numerous mesenchymal cells, thickened epidermal cell layer, ECM deposition, and infiltration of lymphocytes, macrophages, and mast cells.

Fig. 2

Mechanism diagram of natural products acting on hypertrophic scars. Natural products exert various effects such as anti-inflammation, anti-proliferation, inhibition of angiogenesis and pro-apoptotic effects through multiple targets in the wound healing stage, explaining their potential for prevention and treatment of hypertrophic scars.

Fig. 3

Structural formulae of natural products with HS therapeutic effects.

Fig. 4

The natural product-target network predicted by network pharmacology. The figure was constructed by Cytoscape 3.6.1. Green circles represent the natural products and the different colored circles represent the targets. The size of the circle representing each node is determined based on the value of betweenness centrality. The color transition from yellow to red indicates the increasing value of betweenness centrality of the targets in the process of HS treatment.

Fig. 5

The PPI network. The figure was constructed by Cytoscape 3.6.1. The size of the circle representing each node is determined based on the value of betweenness centrality. AHR, AKT1, MTOR, PTGS2, HIF1A, and JUN emerge as the pivotal targets within the network.