A Comprehensive Review of Natural Compounds for Wound Healing: Targeting Bioactivity Perspective

Abstract

Wound healing is a recovering process of damaged tissues by replacing dysfunctional injured cellular structures. Natural compounds for wound treatment have been widely used for centuries. Numerous published works provided reviews of natural compounds for wound healing applications, which separated the approaches based on different categories such as characteristics, bioactivities, and modes of action. However, current studies provide reviews of natural compounds that originated from only plants or animals. In this work, we provide a comprehensive review of natural compounds sourced from both plants and animals that target the different bioactivities of healing to promote wound resolution. The compounds were classified into four main groups (i.e., anti-inflammation, anti-oxidant, anti-bacterial, and collagen promotion), mostly studied in current literature from 1992 to 2022. Those compounds are listed in tables for readers to search for their origin, bioactivity, and targeting phases in wound healing. We also reviewed the trend in using natural compounds for wound healing.

Keywords: anti-bacterial; anti-inflammation; anti-oxidant; bioactivity; collagen promotion; natural compounds; targeting phase; wound healing.

Figure 1

Illustration of four phases in the wound healing process.

Figure 2

Summary of collected literature based on bioactivities of natural compounds used in wound healing.

Figure 3

The effect of lupeol cream on wound healing. Up and down arrows mean increasing and decreasing of concentration, respectively. Reproduced with permission from Beserra et al., “From Inflammation to Cutaneous Repair: Topical Applica-tion of Lupeol Improves Skin Wound Healing in Rats by Modulating the Cytokine Levels, NF-κB, Ki-67, Growth Factor Expression, and Distribution of Collagen Fibers”; published by MDPI, 2020 [58].

Figure 4

(A) Representative images of the wound treated with Bilirubin and (B) wound contraction after 19 days. Three asterisks (***) indicates p-value < 0.001. Reproduced with permission from Ram et al., “Bilirubin modulated cytokines, growth factors and angiogenesis to improve cutaneous wound healing process in diabetic rats”, published by Elsevier, 2016 [138].

Figure 5

Gallic acid regulates the expression of anti-oxidant genes. (A): SOD2, (B): CAT, (C): Gpx1. Asterisk (*) indicates p-value < 0.05. Reproduced with permission from Yang et al., “Gallic Acid Promotes Wound Healing in Normal and Hyperglucidic Conditions”, published by MDPI, 2016 [61].

Figure 6

Effect of resveratrol on wound healing. (A): Representative images of wound bed size from two groups. (B): Quantitation of wound bed sizes. Reproduced with permission from Zhou et al., “Resveratrol accelerates wound healing by attenuating oxidative stress-induced impairment of cell proliferation and migration”, published by Elsevier, 2021 [149].

Figure 7

Representative photomicrographs of the rat skin tissues in the control, drug-free chitosan-coated naringenin and chitosan-coated naringenin (CNNE) treated groups of abrasion model in albino Wistar rats. (A) Wound area before the treatment at day 0, (B) control group at day 14, (C) drug-free chitosan-coated naringenin formulation treated group at day 14, and (D) CNNE treated group at day 14. (I: inflammatory cells; B: blood vessels; K: keratinization; Star icon: granulated tissue). Reproduced with permission from Akrawi et al., “Development and Optimization of Naringenin-Loaded Chitosan-Coated Nanoemulsion for Topical Therapy in Wound Healing”, published by MDPI, 2020 [72].

Figure 8

Chemical structure of Chitin and Chitosan.