Thapsia garganica L.

Thapsia garganica L., Apiaceae, called Derias by the Arabs, is an ancient medicinal plant that contains thapsigargins as the active constituents. Thapsigargins are highly oxygenated sesquiterpene lactones with three or four ester groups, a specific stereochemistry, with a ds-annulated lactone ring and possessing unique biological activities. The first known thapsigargin was trilobolid III isolated from Laser trilobum (L.) Borkh.. However, the biological activities were not recognized until the isolation of thapsigargin I and thapsigargicin II from T garganica (), a perennial herb growing on stony, sandy fields, and along roadsides in the Mediterranean area. The resin from roots of T garganica has been known since ancient times to cause a vigorous contact dermatitis and has been used in folk medicine until recently, especially by the Arabs of northern Africa. Radix Thapsiae and Resina Thapsiae have been recorded in several pharmacopoeias, most recently in the 1937 edition of the French Pharmacopoeia. The resin has been reported to be used against pulmonary diseases, catarrhs, and in the form of a medicinal plaster in the treatment of rheumatic pains.

Since the isolation of thapsigargins from T garganica, analogous compounds have been isolated from other Thapsia species as well, and 16 thapsigargins have been identified so far. All compounds were shown to induce an energy- and Ca2 + -dependent histamine release from rat peritoneal mast cells. For thapsigargin, an EC50 value of 15 nM was determined. In addition to mast cells, all tested cells of the immune system were found to be activated by thapsigargin. Intensive research has revealed that thapsigargin is a selective inhibitor of Ca2 + -ATPases in the endo- and sarcoplasmic reticulum in animal cells. The often found correlation between skin irritation and cocarcinogenesis applies for thapsigargin also, as it was shown to be a non-TPA-type tumor promotor.

Distribution and Importance

The genus Thapsia includes, according to Flora Europaea, three species, T. garganica, T. maxima Miller, and T. villosa L. However, chemotaxonomic investigations of Thapsia species have revealed distinct interas well as intraspecific variations, indicating a more complex deviation. Thus, .T transtagana Brot. is to be regarded as a separate species, not as a synonym of T. garganica (). T. maxima consists of two morphological types and T villosa includes at least five different types, some of which are polyploids. A new species, T. gymnesica Rossello & Pujadas, was recorded in 1991.

All Thapsia species are distributed in the Mediterranean area and on the Iberian Peninsula. T. garganica has the widest distribution, growing in Libya, Tunesia, Algeria, Greece, Italy, and Spain, especially on the Balearic Island, Ibiza. T. transtagana is found in Portugal, Spain, and Morocco, T maxima in Spain and Portugal, T villosa in France, Spain, Portugal, and northwest Africa, while T. gymnesica has been found only on the Balearic Islands, Mallorca and Minorca.

Thapsigargins are present only in some species, T. garganica, T. transtagana, T. gymnesica, and two polyploid types of T. villosa, with 44 and 66 chromosomes, respectively. Up to now thapsigargin has been detected only in T. garganica. However, it might also be present in T. gymnesica, as detected by TLC and HPLC.

Since thapsigargin became commercially available in 1989, it has developed into a most important tool for studying cell activation, tumor promotion, and calcium homeostasis.

Access to thapsigargin and its analogues is only possible by isolation from roots and fruits of wild-growing plants, as synthesis is not yet possible, and no cultivation has, to our knowledge, been undertaken.

Thapsia fruits are difficult to germinate and the plants develop very slowly to a flowering state, where isolation of thapsigargins is profitable. Germination has been achieved in this laboratory after 1-2 months, when placed in Petri dishes on wet filter paper and kept under alternate temperatures, 4 and 25 °C, in 1-week periods.

Thapsia garganica L.: Conclusion

Neither calli nor suspension cultures of Thapsia species produce thapsigargins spontaneously, and attempts to induce synthesis of thapsigargins by elicitation or to establish genetically transformed root culture systems were not successful. However, in vitro cultures of T. garganica proved to possess the capacity to synthesize thapsigargins, when embryogenic cultures developed into more differentiated stages, like the cotyledonary stage or regenerated roots and shoots; nortrilobolid III and trilobolid IV were detected.

Selections from the book: “Medicinal and Aromatic Plants IX” (1996).