Of these compounds, the researchers found that cimigenol-3,15-dione showed the greatest potency and, in a subsequent two-stage DMBA/TPA carcinogenesis assay, reduced, at 20 weeks, the number of papillomas per mouse to 48% of controls. Both cimigenol and cimigenol-3,15-dione were also nearly as potent as epigallocatechin gallate, a primary constituent of green tea, in terms of anti-tumor initiation activity, as demonstrated in a two-stage carcinogenesis assay of mouse skin tumors induced by peroxynitrite (initiator) and TPA (promoter).
The investigators concluded that these two triterpenoids amply demonstrate anti-tumor promotion as well as anti-tumor initiation and warrant consideration as significant cancer chemopreventive agents (Bioorg. Med. Chem. 2005;13:1403–8).
Protection Against UV
Four triterpenoids isolated from the stems of Styrax japonica were recently found to significantly inhibit matrix metalloproteinase-1 (MMP-1) in primary human skin fibroblasts induced by UV radiation. This finding is significant given the association between the upregulation of MMPs and chronic skin damage (Biol. Pharm. Bull. 2005;28:2003–6).
Previously, some of the same investigators studied the effects of 3,23-dihydroxy-20(29)-lupen-27-oic acid, a triterpenoid derived from Tiarella polyphylla, on the regulation of MMP-1 and type 1 procollagen in UV irradiation of cultured old-age human dermal fibroblasts. The triterpenoid dose-dependently induced regulation of type 1 procollagen and diminished regulation of MMP-1 at the protein level (Arch. Pharm. Res. 2004;27:1060–4).
Other Pharmacologic Actions
Triterpenoids also have been found in Boswellia serrata, an herb used in traditional medicine to treat inflammatory and arthritic conditions (and discussed in this column in November 2006, p. 17).
In a study published in 2000, the primary components and derivatives of Boswellia markedly inhibited TPA-induced increases in skin inflammation, epidermal proliferation, the number of epidermal cell layers, and tumor promotion in DMBA-initiated mice. DNA synthesis in human leukemia HL-60 cells was also shown to be inhibited by the addition of various forms of boswellic acid. The investigators suggest that such findings demonstrate the anticarcinogenic and antitumor properties of the major constituents, including triterpenoids, of this herb (Biofactors 2000;13:225–30).
The anti-inflammatory activity of several triterpenoids suggests the potential for numerous additional medical applications. A study evaluating the mechanism of anti-inflammatory activity displayed by triterpenoids on edema induced in mouse ears and paws, as well as rat skin, revealed that the inhibition of protein kinase C may play a crucial role in facilitating the anti-inflammatory activity of this class of compounds (Eur. J. Pharmacol. 2000;410:69–81).
In another study, several triterpene constituents of Vochysia pacifica Cuatrec, a South American tree used by traditional communities to treat inflammation, skin sores, asthma, and pulmonary congestion, were found to exert mild inhibitory activity on the intracellular target for new anti-inflammatory medications, namely the cAMP phosphodiesterase 4 isozyme (PDE4) (Phytother. Res. 2005;19:75–7).
Some triterpenoids have been documented as irritating (J. Asian Nat. Prod. Res. 2003;5:35–41) and others as toxic, which is not unexpected as these compounds comprise the primary constituent class in the volatile oils of plants. Given the breadth of this biochemical class, it is expected that some members would be toxic and others safe and beneficial to human health, such as the triterpenoid saponin glycyrrhizin, derived from licorice root (and featured in this column in March 2007, p. 24, and April 2007, p. 30). Triterpenoid saponins, or sapogenins, are used in some emulsifiers, including some Estée Lauder products, for their capacity to confer antifungal, anti-inflammatory, antimicrobial, and adaptogenic activity.
Conclusion
As we continue to explore botanical sources for medical and cosmetic purposes, we will learn more about the numerous triterpenoids found in plants. This class of biochemical compounds typically receives less attention than polyphenols in discussions of the most potent herbal ingredients used in dermatology, but the considerable potential of triterpenoids to be used in a broad range of cutaneous applications is gradually becoming appreciated.