**3. Role of ginsenosides in wound healing**

The principal active constituent of ginseng is a saponin called ginsenosides. Ginsenosides are found exclusively in the *Panax* species (ginseng); thus, they are also known as panaxosides. Nearly, 150 naturally occurring ginsenosides have been isolated from the roots, leaves, stems, fruits and flower heads of ginseng plant [38]. Ginsenosides are often divided into the Rb1 group (characterized by the presence of protopanaxadiols: Rb1, Rb2, Rc and Rd) and the Rg1 group (protopanaxatriols: Rg1, Re, Rf and Rg2). The remaining non-saponin components of ginseng are polysaccharides, polyacetylenes, peptides and amino acids. *P. ginseng* component, Rb1 (G-Rb1) has been studied extensively. It has been found to possess anti-inflammatory, antioxidant and antimicrobial activity. G-Rb1 has also been found to enhance protein synthesis, neovascularization or angiogenesis and immunostimulation [39]. There have been inconsistent reports on effects of G-Rb1 on dermal cell activities. This might be due to substantial variances in responses to G-Rb1 in numerous cell lines being tested. An *in vitro* study revealed that G-Rb1 had no cytotoxic effect on human keratinocyte (HaCaT) multiplication [19]. However, another study confirmed that G-Rb1 improved the viability of human retinal pigment epithelial cells [40, 41]. An *in vivo* study showed that G-Rb1 inhibits the chemoinvasion of endothelial cells during neovascularization [31]. However, another study showed that G-Rb1 increases the number of blood vessels in burn wound areas of mice [42]. Schwann cell proliferation is significantly inhibited at 1 mg/ml, whereas 10 μg/ml of G-Rb1 induces proliferation [40]. The effect of G-Rb1 on collagen synthesis is also uncertain. One study revealed that G-Rb1 enhances collagen production in HaCaT cells [42]; however, G-Rb1 reduced collagen levels in normal rat renal tubular epithelial cells (NRK-52E) [43]. Similarly, the effects of G-Rb1 on cell function have been varied. Hence, the efficacy of G-Rb1 on human dermal fibroblasts has not been confirmed. Lee et al. [44] treated cultured human dermal fibroblasts with one of six concentrations of *P. ginseng*: 0, 1, 10, 100 ng/ml and 1 and 10 μg/ml. Cell proliferation was determined 3 days posttreatment using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide

assay. The collagen type I carboxy-terminal propeptide method was used to evaluate collagen synthesis. It was found that *P. ginseng* stimulated human dermal fibroblast proliferation and collagen synthesis at an optimal concentration of 10 ng/ml. This study, reported that G-Rb1 had significant positive effects on dermal fibroblast proliferation and collagen synthesis, which are essential factors during wound healing. *P. ginseng* generally is well tolerated. Although mild and reversible adverse effects of *P. ginseng* have been reported in cases where it was administered orally, including capsules, liquids or powders [45–49].
