**4.** *Cynara cardunculus* **L. other traditional and industrial applications: the biopharmaceutical potential**

Traditionally, infusions of artichoke and wild cardoon leaves have been used since the fourth century B.C. [150], based on well accepted health benefits, regarding liver protection [151] and stimulating bile flow from the gallbladder (choleretic action) [150, 152, 153]. Artichoke leaves and seed extracts are also consumed to protect toward atherosclerosis, arterial hypertension and hyperuricemia [11, 154]. Wild cardoon leaves are popular in folk medicine, given to their cardiotonic, antihemorrhodial, and antidiabetic actions [155] mainly due to the biological effects of the secondary compounds. Among the different *C. cardunculus* physiological comparts, leaves appeared to accumulate a wide range of compounds with known biological activities [31, 36, 37, 156].

In order to pull out compounds of interest from *C. cardunculus* leaves, extraction processes must be done and optimized. Divided in conventional and non-conventional, extraction methodologies applied to *C. cardunculus* are commonly conventional, as batch and Soxhlet extraction [31, 36, 37, 156, 157], while application of non-convention extraction methodologies, as ultrasound, microwave, supercritic fluid or ionic liquid solutions, are still very scarce [158].

With interesting biological activities, the study of cynaropicrin extraction, a sesquiterpene lactone, found for the first time by Ramos et al. [31] in *C. cardunculus* leaves with a Soxhlet extraction, is an important step for the recovery of this added value compound. Some studies are recently appearing, applying new and non-conventional methodologies for cynaropicrin extraction from *C. cardunculus* leaves, such as ultrasound assisted extraction, where an increase of 36% on cynaropicrin concentration was achieved as well a reduction on energetic costs [159, 160]. *C. cardunculus* biological potential is tremendous, but the challenge is to transfer this knowledge to industry, toward new value chains, being crucial the cost reduction of extraction/purification processes ensuring safety, and end products functionality.

The lignocellulosic fraction, especially of cultivated cardoon, over the years has demonstrated a great potential as solid biofuel. The first research on *C. cardunculus* potential as an energy crop was carried out in the 1980s [161]. Currently research within energy and cardoon is wide, with several reports which highlight different possibilities: solid biofuel [14, 162], liquid biofuel (seed oil [29], biodiesel [163] and bioethanol [22, 164, 165]), and biogas production [20, 24]. Clearly, within energy production, *C. cardunculus* represents a high potential as an alternative to fossil materials.
