**Salograviolide A: A Plant-Derived Sesquiterpene Lactone with Promising Anti-Inflammatory and Anticancer Effects**

Isabelle Fakhoury and Hala Gali-Muhtasib *American University of Beirut Lebanon* 

#### **1. Introduction**

368 Advances in Cancer Therapy

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> Natural products are chemical substances produced by living organisms of the Biota superdomain, namely plants, animals, fungi and bacteria (G. & C. Merriam Co., 1913). Up to 80% of all drugs discovered prior to 1981 and 50% of all approved drugs between the years 1994 and 2007 are of natural product origin (Harvey, 2008). The contribution of natural products derived from plants, particularly to the well-being of mankind, extends very far back in history. Some of the most famous findings supportive of this fact come from the Middle East region and include documented medical papyri of ancient Egyptians dating back to ca. 1,850 B.C., as well as recent studies revealing their use of medicinal herbs dispensed in grape wine ca. 3,150 B.C. (McGovern et al., 2009). Incidentally, the oldest evidence for the use of herbal medicine to be so far discovered dates back to the prehistoric Neanderthal man who lived also in the Middle East region around 60,000 years ago (Solecki, 1971).

> Several world heritages of medicinal plants have also inspired and greatly contributed to the development of modern medicine (Azaizeh et al., 2008). Indeed some of the early drugs were derived from plants. Morphine, for instance, was the first pharmacologically active pure compound to be extracted from a plant over 200 years ago (Jesse et al., 2009). Clinical, pharmacological, and chemical studies have since then led to the identification of a lengthy list of drugs derived from plants covering a wide range of diseases from diabetes, malaria, microbial infections, osteoporosis to inflammation and cancer.

> The story of the discovery of plants exhibiting anticancer properties in particular, began almost fifty years ago. With the increase in cancer incidences, there has been an increase of interest in screening for anti-tumor agents from diverse sources including plants. For that purpose, in 1960 the National Cancer Institute (NCI) launched a large-scale screening of 35,000 sample plants. The program resulted among others, in the discovery in 1967 of the best-selling anticancer drug today; Taxol (Cragg, 1998). This breakthrough boosted cancer researchers all over the world and especially those in regions with high diversity to explore the indigenous plants' active ingredients efficacy against cancer. Considering that more than 60% of anticancer drugs available for clinical use today are derived from natural products including plants (Balunas et al., 2005; Newman and Cragg, 2007), one cannot deny that there has been a successful contribution of plants to the fight against cancer (reviewed in Gali-Muhtasib and Bakkar, 2002; Darwiche et al., 2007).

Salograviolide A: A Plant-Derived Sesquiterpene

different species and summarized some of them in Table 1.

Lactone with Promising Anti-Inflammatory and Anticancer Effects 371

introduced to North America around the late 1800's and can now be found all around the world. *Centaurea* extracts have also been used in traditional medicine for their effects as stimulants, diuretics, analgesics, anti-rheumatics, anti-microbial, anti-diabetics and antiinflammatory (refer to www.ibsar.org). Anecdotally; the genus' name is a dedication to the centaur Chiron who, according to Greek mythology, had discovered the curative properties of these medicinal plants (Nehmeh, 1977). Scientists eventually investigated the medicinal properties traditionally attributed to the *Centaurea* genus and isolated a multitude of SLs in addition to other various types of compounds such as alkaloids, lignans, acetylenes and flavonoids. When entering on PubMed the search terms "Centaurea and sesquiterpene lactones", and adding to them the hits from the search "Centaurea and cancer", 46 results get displayed. We investigated the number, nature and biological activity of SLs in the

 *Artemisia annua Tanacetum parthenium Thapsia garganica* 

Artemisinin Parthenolide Thapsigargin

Rignanese, Mr. Peter Griffee and Mr. Paul Drobot, respectively.

Fig. 1. Illustration of the sesquiterpene lactones that have reached clinical trials, namely thapsigargin extracted from *Thapsia garganica*, artemisinin from *Artemisia annua* L., and parthenolide from *Tanacetum parthenium*. The plants pictures are courtesy of Mr. Luigi

Table 1 indicates that there are at least 89 SLs in 10 *Centaurea* species. As expected, the amount of the SLs as well as their nature is species-specific. Also, the activities of the represented SLs cover most of those attributed to the plants in traditional medicine. Aside

Lebanon falls within the Levantine Uplands center of diversity. Compared to other Mediterranean countries, it stands second after Turkey in its floristic diversity with 2600 plant species distributed around its humble 10452 km2 (Nehmeh, 1977). About 311 plants corresponding to 12% of the total plant species are endemic to Lebanon and have been used in part by Lebanese folk medicine practitioners and Lebanese people for preventive and therapeutic purposes (Nehmeh, 1977). As members of the Nature Conservation Center for Sustainable Futures (IBSAR), we have been leading research over the past 10 years for the understanding and evaluation of Lebanese indigenous plant properties against various conditions, especially cancer. The following chapter aims at retracing our adventure with "Salograviolide A" (Sal A), and bringing to light this peculiar molecule that exhibits both anti-inflammatory and anticancer effects.
