Volume 37, Issue 10, Page 18 (October 2006)

LESLIE S. BAUMANN, M.D.

DR. BAUMANN is director of cosmetic dermatology at the University of Miami. To respond to this column, or to suggest topics for future columns, write to Dr. Baumann at our editorial offices via e-mail at This e-mail address is being protected from spambots. You need JavaScript enabled to view it .

Several varieties of ginseng have been used in traditional medicine across the globe, particularly in Asia and Native America, for thousands of years. Panax ginseng C.A. Meyer, long an ingredient in traditional Chinese medicine, and Panax quinquefolius L., a North American ginseng, are among the most commonly cultivated and investigated forms of the plant. Ginseng is considered to be one of the most precious herbs in Asia and is used to treat various diseases (J. Korean Med. Sci. 2001;16 Suppl:S3–5; J. Korean Med. Sci. 2001;16 Suppl:S38–41).

The major active components of ginseng, the ginsenosides, are known to exhibit anti-inflammatory, antioxidant, antiaging, and anticancer activities (Am. Fam. Physician 2003;68:1539–42; Biochem. Biophys. Res. Commun. 2004;316:348–55; J. Invest. Dermatol. 2003;121:607–13). In addition, epidemiologic studies have shown that ginseng consumption reduces the risk of cancer (Carcinogenesis 2005;26:359–67), as the herb is characterized as conferring anticarcinogenic activity.

Overall, ginseng has been associated with therapeutic activity against an increasingly broad array of conditions.

Action Against Tumor Promotion

The ocotillol-type saponin majonoside-R2, derived from the rhizome and root of Panax vietnamensis (Vietnamese ginseng), has exhibited strong anti-tumor-promoting activity in two-stage carcinogenesis tests of mouse hepatic and skin tumors (Cancer Lett. 1999;147:11–6).

Various ginseng extracts and constituents have demonstrated anti-tumor-promoting characteristics in other two-stage carcinogenesis studies of mouse tumors. Panax notoginseng extract, for example, has exhibited such activity against mouse skin tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by a mycotoxin, fumonisin B1, as a non-12-O-tetradecanoylphorbol-13-acetate (non-TPA) type promoter, as well as against tumors induced by a nitric oxide donor and promoted by TPA (Biol. Pharm. Bull. 1999;22:1150–2).

In vitro and in vivo experiments have shown that the oral administration of white ginseng extracts also suppresses skin tumor promotion by TPA in DMBA-initiated CD-1 mice (J. Korean Med. Sci. 2001;16 Suppl:S66–9).

Red ginseng is reputed to have the capacity to enhance human immune function. It has been used in traditional medicine with various therapeutic effects. In traditional Chinese medicine, red ginseng has long been considered a tonic herb. In a two-stage mouse model, red ginseng extracts, the active components of processed P. ginseng, inhibited DMBA/Croton oil-induced skin papilloma, lowered the incidence of papilloma, prolonged the latent period of tumor development, and decreased tumor number per mouse in a dose-dependent manner. These extracts also inhibited the growth of transplantable mouse sarcoma S180 and melanoma B16 (J. Ethnopharmacol. 1998;60:71–8). Another study demonstrated the capacity of red ginseng extract to inhibit DMBA-induced skin papilloma (J. Cell Biochem. Suppl. 1997;27:7–11).

An in vivo mouse study examined the anti-tumor-promoting effects of IH-901 (20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol), an intestinal bacterial metabolite derived from protopanaxadiol-type saponins of P. ginseng.

Investigators found that pretreatment with the compound repressed TPA-induced ear edema in a dose-dependent manner, and epidermal NF-B DNA binding. TPA-induced expression of cyclooxygenase-2 (COX-2) and prostaglandin E(2) production were also inhibited by the topical application of IH-901 onto the shaved backs of female ICR mice. The researchers noted that the administration of IH-901 before each topical TPA application reduced the number of DMBA-induced skin papillomas. They concluded that this ginseng byproduct has anti-inflammatory effects that are potentially conducive to its antitumor activity (Carcinogenesis 2005;26:359–67).

In another study evaluating the effects of IH-901 (also known as compound K), investigators found that compound K-treated HaCaT cells upregulated the hyaluronan synthase 2 (HAS2) gene, with HAS2 mRNA elevated in a time- and dose-dependent fashion. Compound K increased hyaluronan production in HaCaT cells and, on hairless mouse skin, it augmented hyaluronan levels in the epidermis and papillary dermis.

The researchers concluded that topical compound K has the potential to prevent or reverse wrinkles, xerosis, and other symptoms associated with the age-related decline of hyaluronan levels in human skin (Biochem. Biophys. Res. Commun. 2004;316:348–55).

The methanol extract of heat-processed neoginseng (NGMe) also has exhibited significant antioxidant activity, scavenging superoxide produced by xanthine-xanthine oxidase or TPA in differentiated human promyelocytic leukemia (HL-60) cells. When investigators topically applied NGMe onto the shaved backs of female ICR mice 10 minutes before applying TPA, they found a significant reduction in DMBA-initiated skin papillomagenesis. The team observed similar findings in other experiments examining the effects of topical NGMe on mice.

Many of the same researchers have also demonstrated that a topically applied ginsenoside, Rg3, inhibited TPA-induced epidermal ornithine decarboxylase activity and skin tumor promotion in mice. The ginsenoside also imparted several other benefits, such as inhibition of TPA-stimulated NF-B and extracellular-regulated protein kinase; and as a pretreatment, it suppressed the expression of COX-2 in TPA-stimulated mouse skin (J. Korean Med. Sci. 2001;16 Suppl:S38–41).

In a study of the anti-inflammatory effects on mice of several ginsenosides derived from P. ginseng, including Rb1, Rc, Re, Rg1, and Rg3, topical application of each derivative ameliorated TPA-induced ear edema and, in TPA-treated dorsal skin, inhibited COX-2 expression and NF-B activation. Rg3 was identified as the most effective compound in the study (Ann. N.Y. Acad. Sci. 2002;973:396–401).

In a more extensive study of Rg3 conducted by one of the authors of the aforementioned study and others, the ginsenoside, produced from heat-processed ginseng, was used to pretreat the dorsal skin of female ICR mice.

The results showed that Rg3 suppressed TPA-induced ornithine decarboxylase activity and DMBA-initiated papilloma formation. Rg3 pretreatment also eliminated COX-2 expression in TPA-stimulated mouse skin and inhibited TPA-induced activation of NF-B in both mouse skin and cultured HL-60 cells. Activator protein-1 (AP-1), which is instrumental in c-jun and c-fos oncogenic activation, was also inhibited. The authors suggested the downregulation of NF-B and AP-1 as possible pathways to achieving the anti-tumor-promoting activity associated with Rg3 (Mutat. Res. 2003;523–524:75–85).

Other Actions

Investigators studying the protective activity of the ginsenoside F1 found significant reductions in UVB-induced cell death in human HaCaT keratinocytes. They also found that F1, an enzymatically modified derivative of Rg1, protected HaCaT cells from UVB-induced apoptosis and poly (ADP-ribose) polymerase cleavage (J. Invest. Dermatol. 2003;121:607–13).

Researchers investigating the wound healing potential of ginseng found that the ginsenoside Rb2 stimulated epidermal cell proliferation in a dose-dependent manner in raft culture. Rb2 also enhanced the expression of protein factors associated with cell proliferation, such as epidermal growth factor, fibronectin, keratin 5/14, and collagenase I, also in a dose-dependent manner (Arch. Pharm. Res. 2002;25:71–6).

The promotion of hair growth has also recently been linked to some forms of ginseng. In an assay using mouse vibrissal follicles in organ culture, researchers found that a 70% methanol extract of red ginseng exhibited greater hair growth-promoting activity than did white ginseng (Phytother. Res. 2003;17:797–800).

In an earlier study of the water fraction of P. ginseng, investigators administered ginseng prior to whole-body doses of gamma radiation to adult N:GP(s) mice with hair follicles synchronously in the middle of the hair growth cycle.

The results of that study showed that ginseng strongly facilitated hair follicle recovery via combined effects on proliferation and apoptosis of hair follicle cells (In Vivo 1998;12:219–22).

P. ginseng has also been used in traditional Chinese medicine for enhancing sexual pleasure. It is believed that the herb's antioxidant properties improve nitric oxide synthesis in the endothelium of several organs, including the corpora cavernosa. The popular root is also thought to improve the acetylcholine-induced, transmural nerve stimulation-activated relaxation linked to elevated tissue cyclic guanosine monophosphate. Such effects would explain ginseng's reputation for possessing aphrodisiac properties (Clin. Auton. Res. 2001;11:303–7).

Another study evaluated radix ginseng (RG), which is the dried root of P. ginseng C.A. Meyer, and radix trichosanthis (RT), a traditional Chinese medicine extracted from the root of Trichosanthis kirilowii maxim. Researchers investigating the in vitro effects of these herbs on B16 melanoma cells found few effects from treatment with RG alone, but treatment with RG and RT together significantly inhibited melanogenesis. The authors suggested that this combination has potential as a depigmenting or whitening agent for the skin (Biol. Pharm. Bull. 2003;26:849–53).

Finally, ginseng may also confer antipruritic effects as a component of byakko-ka-ninjin-to (BN), a traditional Chinese medicine.

This herbal mixture, which contains ginseng, gypsum, anemarrhena root, licorice, and rice, was studied for its effects on an NC mouse model of atopic dermatitis. Orally administered BN significantly inhibited scratching frequency and reduced skin temperature by 1.97° C, which is noteworthy given the known relationship between cooling skin and inhibiting human itch. The researchers concluded that ginseng-containing BN exerts an inhibitory effect on pruritus, and offers potential as an antipruritic agent for the treatment of atopic dermatitis (Phytother. Res. 2000;14:192–4).

Conclusion

Ginseng is included as a minor ingredient, often amid a cocktail of botanical components, in numerous readily available skin products.

The characteristics of ginseng likely to translate into dermatologic applications pertain to the plant's anti-inflammatory, antioxidant, and anticarcinogenic capacity. The recent and impressive literature amassed on this popular herb suggests that its broad and potent healing capacities may be used to treat a wide range of conditions. More research is warranted, of course, and much remains to be learned before we see frequent direct use of this botanical as a first-line therapy in the dermatologic armamentarium.

PII: S0037-6337(06)71589-3

doi:10.1016/S0037-6337(06)71589-3

© 2006 Elsevier Inc. All rights reserved.