HAIR GROWTH–PROMOTING EFFECT OF L. ESCULENTUM EXTRACT 439 years, but can even start in later decades of life. The severity of hair loss in women is usu- ally much less than in men (30,31). Two U.S. FDA-approved pharmacotherapies, minoxidil and fi nasteride, are available for treatment of male pattern baldness. Oral fi nasteride, a competitive inhibitor of type 2, 5α-reductase, and topical minoxidil, an adenosine triphosphate–sensitive potassium channel opener, have been reported to stimulate the production of VEGF in cultured dermal papilla cells. These drugs are most useful in men with thinning and many minia- turized hairs. Generally, minoxidil is well tolerated with long-term daily use. Adverse events are pri- marily dermatologic and include irritant contact dermatitis, and less often, allergic con- tact dermatitis (12,13,30). Finasteride is also well tolerated with long-term daily use, except for slight adverse sexual effects (14). Therefore, there remains a demand for highly Figure 8. Draize skin irritation test on two male NZW rabbits 1—(A) through (D), 2—(E) through (H). Before exposure (A, E), immediate after exposure (B, F), 1 day after exposure (C, G), 3 days after exposure (D, H). Back of each rabbit was clipped free of hair and then divided into four sectors as follow after abrasion and application of hair tonic (upper left), after abrasion and no treatment as NC (upper right), no abrasion and application of hair tonic (lower left) and no abrasion and no treatment as NC (lower right), respectively. Figure 9. HPLC chromatograms of 3% LTS. (A) All-trans-lycopene and (B) cis-lycopene.

JOURNAL OF COSMETIC SCIENCE 440 effective pharmacotherapies for the treatment of male pattern baldness with excellent safety and effi cacy profi les. Thus, for many years, there have been numerous attempts to develop new agents capable of preventing and/or treating pattern baldness (25,31,32). It has been reported that the mechanism of hair loss is similar to that of prostate disease. Namely, the cause of prostate disease and hair loss is known to be an excess amount of DHT from testosterone by 5α-reductase (33–35). Further, 1 or 5 mg fi nasteride per day was prescribed for both symptoms (36). It has been recently reported that L. esculentum and lycopene is useful for the prevention and treatment of prostate disease (37,38). However, to our knowledge, it has not been determined if L. esculentum or lycopene is an effective treatment for hair loss. Therefore, in this study, we evaluated the potential hair growth–promoting activity and the expression of cell growth factors of crude L. esculentum extracts and isolated lycopene and test hair tonic containing LTS in C57BL/6 mice. Of the 3% (w/w) of EAE and SCE of L. esculentum and LTS, LTS exhibited hair growth–promoting potential similar to that of 3% minoxidil PC in our results (Figs 1 and 2). It has been reported that the dermal papilla cell-derived growth factors, such as VEGF, KGF, and IGF-I, and the root-sheath cell-derived growth factors, such as TGF-β, have chemotactic effects on the surrounding cells, which in turn lead to hair growth (6,7). To promote hair growth and to maintain anagen, it is essential that increased expression of anagen maintaining factor, such as IGF-1, bFGF, and VEGF, and decreased expression of cytokines promoting apoptosis, such as TGF-β and IL-1 (6,7). In our results, the mRNA expression of VEGF, TGF-β, KGF, and IGF-I in both of L. esculentum extract and LTS as isolated lycopene was higher than those of the PC, as well as the NC. Especially, in the LTS group, signifi cant increase in the expression of VEGF, KGF, and IGF-1 was observed (Fig. 3). However, as seen in Fig. 1, the treatment of both L. esculentum extracts and LTS obviously showed hair growth–promoting activity, but the expression of TGF-β genes in dorsal skin tissue of mice was not lower than PC and NC. Further research to elucidate the reason is needed. To examine the possibility of commercial applicability, a hair tonic product containing 3% LTS showed hair growth–promoting potential similar to that of the same product containing 3% minoxidil (Fig. 4). In this case, TGF-β mRNA expression was lower than that of the PC and NC, and KGF and IGF-I mRNA expression was higher than the con- trols (Fig. 6). Further studies to elucidate the reason are needed. After topical application onto the back skins of C57BL/6 mice daily up to 4 weeks, LTS induced earlier telogen-to-anagen conversion as compared to the vehicle-treated group. Histologic studies showed that LTS markedly increased the depth and size of hair follicles as compared with NC, showing rather slightly lower hair growth–promoting potential than that of PC. This result clearly supports that LTS induces early onset of anagen and stimulates hair growth (Fig. 7). A Draize skin irritation test was performed to confi rm the safety of the hair tonic product containing 3% LTS. No erythema, edema, or irritation was observed on abraded or intact back skin of male rabbits 24 or 72 h after treatment (Fig. 8). The results suggested that at moderate doses, humans can safely use the extracts. When the lycopene quantifi cation was performed (Fig. 9), the all-trans-lycopene and cis- lycopene content of 3% LTS was 3.63 μg/ml and 1.65 μg/ml, respectively, to elucidate