The potential application of natural products in cutaneous wound healing: A review of preclinical evidence

Abstract

Under normal circumstances, wound healing can be summarized as three processes. These include inflammation, proliferation, and remodeling. The vast majority of wounds heal rapidly; however, a large percentage of nonhealing wounds have still not been studied significantly. The factors affecting wound nonhealing are complex and diverse, and identifying an effective solution from nature becomes a key goal of research. This study aimed to highlight and review the mechanisms and targets of natural products (NPs) for treating nonhealing wounds. The results of relevant studies have shown that the effects of NPs are associated with PI3K-AKT, P38MAPK, fibroblast growth factor, MAPK, and ERK signaling pathways and involve tumor growth factor (TNF), vascular endothelial growth factor, TNF-α, interleukin-1β, and expression of other cytokines and proteins. The 25 NPs that contribute to wound healing were systematically summarized by an inductive collation of the six major classes of compounds, including saponins, polyphenols, flavonoids, anthraquinones, polysaccharides, and others, which will further direct the attention to the active components of NPs and provide research ideas for further development of new products for wound healing.

Keywords: inflammation; natural products; proliferation; remodeling; skin; wound healing.

FIGURE 1

Diagram of the mechanisms of wound formation and healing. Inflammatory phase: after platelets perform initial hemostasis and release chemokines recruiting neutrophils, fibroblasts. Conversion of monocytes into macrophages engulfs necrotic tissue, decomposes bacterial products, and helps the wound to enter the proliferative phase. Proliferative phase: angiogenesis, granulation tissue regeneration, attachment of fibroblasts onto the wound. Remodeling phase: fibroblasts and myofibroblasts continuously differentiate to form tight cross links.

FIGURE 2

Diagram of natural product antimicrobial mechanisms. Five natural products of oleuropein, aloin, chamomile, honey, Resina Draconis promote wound healing by antibacterial, antiviral mechanisms.

FIGURE 3

Diagram of the mechanisms of action of natural products to promote angiogenesis. Astragaloside IV, asiaticoside, gallic acid, apigenin, quercetin, hesperdin, bleilia striata polysaccharide, astragalus polysaccharide, snail mucins, angular sinensis ethanol extract, Simmondsia chinensis, the above 11 natural products play a positive role in wound healing by promoting angiogenesis.

FIGURE 4

Diagram of the mechanisms by which natural products promote wound re epithelialization. Ginscnoside Rb1, lupeol, curcumin, ferulic acid, Flammulina velutipes, Ganoderma lucidum polysaccharides, the above six natural products release IL-1, TNF - α and EGF by keratinocytes to promotes wound re epithelialization.

FIGURE 5

Diagram of the chemical formula structure of natural products.