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Ursolic acid (UA) and oleanolic acid (OA), isolated from Glechoma hederacea, inhibited Epstein-Barr virus activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) in mouse skin. The inhibitory effects were evaluated for 20 weeks. Continuous application of UA and OA (41 nmol of each) before TPA-treatment (4.1 nmol) delayed the formation of papillomas in mouse skin and reduced the rate (%) of papilloma bearing mice. Both UA and OA exhibited remarkable inhibitory activity against tumor promotion, which is comparable to the known tumor inhibitor, retinoic acid (RA). Compared to either RA or OA, ursolic acid inhibited tumor more effectively after a single application before initial TPA-treatment as shown in Figure 1. This suggests that the role of tumor inhibition by UA differs from that of either RA or OA. It is suggested that pretreatment of skin with UA may inhibit the first dramatic cellular event in tumor promotion caused by TPA17.

Topical application of ursolic acid derived from rosemary extract inhibited TPA-induced tumor initiation and promotion, inflammation, and ornithine decarboxylase activity in mouse skin. Ursolic acid exhibited strong anti-inflammatory activity. It is even more active than of 1 or 2 mmol of ursolic acid along with 5 nmol of TPA for TPA for 20 weeks inhibited the formation of skin tumors per mouse by 45 or 61% respectively.

Lower doses (0.1 or 0.3 mmol) of ursolic acid had a similar inhibitory effect as the higher doses. Twice weekly topical application of 0.1, 0.3, 1, or 2 mmol of ursolic acid along with 5 nmol TPA for 8,12, and 18 weeks reduced the number of skin tumors per mouse by 52-86%, 49-63%, and 44-61%, respectively18.

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Each point represents the mean + SE from 30 mice pper group.
* means statistically different from TPA control group (p<0.05)

Ursolic acid and its isomer, oleanolic acid have been recommended for skin cancer therapy in Japan19. Topical cosmetic preparations containing ursolic acid/ oleanolic acid have been patented in Japan for the prevention of topical skin cancer20. An ursolic acid/ oleanolic acid ointment inhibited 7,12-dimethylbenz [a] anthracene (DMBA)-induced skin cancer in mice. Reportedly, 0% and 3% of mice developed cancer in 15 weeks and 30 weeks, respectively compared to 50% and 90% for the control mice20.
    

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