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.
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.
ã Sabinsa Corporation 2000-2001