Can Topical Use of Ginseng or Ginsenosides Accelerate Wound Healing?

Skin is the first line of protection against the external environment, including pathogenic microorganisms and toxins. Injuries that disrupt the skin barrier are an emergency to which the body responds with immune responses and repair mechanisms, which induce inflammation and oxidative stress. ¹ Wounds result from various causes such as physical cutting, allergens, reactive oxygen species, and cytokines in atopic dermatitis, vascular diseases, and neuropathy. ² Numerous plant-based preparations have been used to treat skin for cancer prevention, antiaging effects, and wound healing ¹ and more. Among them, mulberry leaves have been shown to be effective against early stage cutaneous wound healing ³ and red ginseng oil has been shown to potentially protect against chemically induced skin cancer. ⁴ In this issue of the Journal, Shin et al. ⁵ extends the skin protection through botanical treatments, and ginseng Rb1 ginsenoside in particular, to wound repair through a sphingosine-1-phosphate (S1P)-mediated pathway.

Wound repair is facilitated by several steps: matrix metalloproteinase (MMP)-mediated proteolysis to degrade adhesion molecules, keratocyte migration, and angiogenesis. The activation of MMPs is involved in extracellular signal-regulated kinases (ERK)-1 and nuclear factor (NF)-κB signaling. The wound healing process is reported to be facilitated, at least in the early stages, by transforming growth factor (TGF)-β1 → ERK-1 → NF-κB signaling. ^{2,6 –8} Proteolysis by MMPs promotes keratocyte migration and in this process, sphingolipid signaling, one of the lipid modulators used to restore the epidermal barrier, is known to be involved. Wounding potentiates S1P, a sphingolipid metabolite, which activates ERK-1 and NF-κB signaling, thereby increasing the expression of MMPs. Thus, S1P signaling plays an important role in keratocyte migration to promote the wound healing process. Previous studies have revealed that alternative therapies, including phytochemicals, promote wound healing by activating TGF-β1 → ERK → NF-κB signaling. ^6,9,10 This article demonstrated that S1P was a signal molecule to activate the signaling and Rb1, a major ginsenoside of ginseng, promoted the production of S1P and stimulated the TGF-β1 → ERK → NF-κB signaling to enhance the wound healing.

This research suggests a topical efficacy, which is somewhat novel since most herbal medicines have been used orally. We often hear the quote: “let food be thy medicine” and that reflects the mission of this journal. However, this is rarely applied to the topical use of foods as medicines, but the use of food ingredients as topical treatments is certainly a compelling concept. There remains more work to determine if ginsenoside Rb1 is safe and effective for promoting wound healing in humans. Also, there is evidence that suppressing NF-κB signaling may be beneficial for wound healing, ¹¹ the opposite of what was seen in the study by Shin et al. ⁵ This may be due to the known complications of timing, since inflammation is needed in the early stages of wound healing, but detrimental at later stages. ¹¹ The understanding of the mechanism of ginsenoside Rb1 in wound healing is further complicated since the method described by Shin et al. involves activating NF-κB, a proinflammatory action, but ginsenosides, including RB1, are well-known anti-inflammatory molecules. ¹² Therefore, it is possible that it can be inflammatory in response to some signals and anti-inflammatory under different conditions. Therefore, human trials are needed with carefully monitored time courses to demonstrate the wound healing properties of ginsenoside RB1 at different stages of the wound healing process in people.