Wound Healing Properties of Natural Products: Mechanisms of Action

Abstract

A wound is the loss of the normal integrity, structure, and functions of the skin due to a physical, chemical, or mechanical agent. Wound repair consists of an orderly and complex process divided into four phases: coagulation, inflammation, proliferation, and remodeling. The potential of natural products in the treatment of wounds has been reported in numerous studies, emphasizing those with antioxidant, anti-inflammatory, and antimicrobial properties, e.g., alkaloids, saponins, terpenes, essential oils, and polyphenols from different plant sources, since these compounds can interact in the various stages of the wound healing process. This review addresses the most current in vitro and in vivo studies on the wound healing potential of natural products, as well as the main mechanisms involved in this activity. We observed sufficient evidence of the activity of these compounds in the treatment of wounds; however, we also found that there is no consensus on the effective concentrations in which the natural products exert this activity. For this reason, it is important to work on establishing optimal treatment doses, as well as an appropriate route of administration. In addition, more research should be carried out to discover the possible side effects and the behavior of natural products in clinical trials.

Keywords: anti-inflammatory; antimicrobial; antioxidant; cell migration; collagen; natural products; phenolic compounds; wound healing.

Figure 1

Wound healing process. (1) Hemostasis (coagulation); (2) inflammation (early/late inflammation); (3) proliferation (proliferation/migration/epithelialization/granulation); (4) remodeling (maturation/repair).

Figure 2

Chronic wound exhibit and persistent inflammation, an infection (biofilm), hyperproliferative epidermis, fibroblast senescence, elevated MMPs (metalloproteinases), impaired migration.

Figure 3

Example of the compounds from natural products evaluated for their in vitro wound healing effect.

Figure 4

Operations for obtaining and incorporating secondary metabolites in dermatological products. During the extraction, it is necessary to use green and innocuous solvents to extract large amounts of the compounds of interest. During its isolation and purification, column and thin-layer chromatography are recommended, as well as spectroscopic tools, to elucidate and monitor the compound of interest. Once the metabolite is isolated and purified, it is necessary to use biomaterials that protect it and, at the same time, be innocuous and biodegradable. It is worth mentioning that before their incorporation into pharmaceutical products, it is necessary to evaluate the biological, functional, and in vitro and in vivo tests. It is worth mentioning that the incorporation into the final product must be during operations that safeguard its bioactivity and stability.