Targeting type II diabetes with plant terpenes: the new and promising antidiabetic therapeutics

Over the past three decades, the number of people with diabetes mellitus has more than doubled globally, making it one of the most important public health challenges to all nations. Type 2 diabetes mellitus (T2DM) and prediabetes are increasingly observed among children, adolescents and younger adults. The causes of the epidemic of T2DM are embedded in a very complex group of genetic and epigenetic systems interacting within an equally complex societal framework that determines behavior and environmental influences. This complexity is reflected in the diverse topics discussed in this Review. In the past few years considerable emphasis has been placed on the effect of the intrauterine environment in the epidemic of T2DM, particularly in the early onset of T2DM and obesity. Prevention of T2DM is a 'whole-of-life' task and requires an integrated approach operating from the origin of the disease. Future research is necessary to better understand the potential role of remaining factors, such as genetic predisposition and maternal environment, to help shape prevention programs. The potential effect on global diabetes surveillance of using HbA(1c) rather than glucose values in the diagnosis of T2DM is also discussed.

Natural product and natural product-derived compounds that are being evaluated in clinical trials or are in registration (as at 31st December 2007) have been reviewed, as well as natural product-derived compounds for which clinical trials have been halted or discontinued since 2005. Also discussed are natural product-derived drugs launched since 2005, new natural product templates and late-stage development candidates.

Today cancer treatment is not only a question of eliminating cancer cells by induction of cell death. New therapeutic strategies also include targeting the tumour microenvironment, avoiding angiogenesis, modulating the immune response or the chronic inflammation that is often associated with cancer. Furthermore, the induction of redifferentiation of dedifferentiated cancer cells is an interesting aspect in developing new therapy strategies. Plants provide a broad spectrum of potential drug substances for cancer therapy with multifaceted effects and targets. Pentacyclic triterpenes are one group of promising secondary plant metabolites. This review summarizes the potential of triterpenes belonging to the lupane, oleanane or ursane group, to treat cancer by different modes of action. Since Pisha et al. reported in 1995 that betulinic acid is a highly promising anticancer drug after inducing apoptosis in melanoma cell lines in vitro and in vivo, experimental work focused on the apoptosis inducing mechanisms of betulinic acid and other triterpenes. The antitumour effects were subsequently confirmed in a series of cancer cell lines from other origins, for example breast, colon, lung and neuroblastoma. In addition, in the last decade many studies have shown further effects that justify the expectation that triterpenes are useful to treat cancer by several modes of action. Thus, triterpene acids are known mainly for their antiangiogenic effects as well as their differentiation inducing effects. In particular, lupane-type triterpenes, such as betulin, betulinic acid and lupeol, display anti-inflammatory activities which often accompany immune modulation. Triterpene acids as well as triterpene monoalcohols and diols also show an antioxidative potential. The pharmacological potential of triterpenes of the lupane, oleanane or ursane type for cancer treatment seems high; although up to now no clinical trial has been published using these triterpenes in cancer therapy. They provide a multitarget potential for coping with new cancer strategies. Whether this is an effective approach for cancer treatment has to be proven. Because various triterpenes are an increasingly promising group of plant metabolites, the utilisation of different plants as their sources is of interest. Parts of plants, for example birch bark, rosemary leaves, apple peel and mistletoe shoots are rich in triterpenes and provide different triterpene compositions. Georg Thieme Verlag KG Stuttgart. New York.