Atropa belladonna

Atropa belladonna L., commonly known as deadly nightshade, or belladonna belongs to the family Solanaceae. Atropa is a small genus native throughout middle and southern Europe and extending to central and western Asia up to the Himalayas. A. belladonna L., the economically most important species, is an erect perennial herb which may grow up to 5 ft in height. It has purple flowers (to distinguish it from the yellow-flowered A acuminata) and black berries with many small seeds. This plant grows in damp or shady places, mainly in the mountains, and is attacked by various species of Gonocephalum, Agrotis, and Archips, which cause defoliation.

It is generally propagated through seed in the nurseries, and later transferred to the field. The leaves (folium belladonnae) are mainly used as a source for medicinal drugs, mainly atropine (dl-hyoscyamine), with scopolamine as a minor component.

Preparations of belladonna are known to have been used for many centuries. During the time of the Roman Empire and in the Middle Ages this plant was frequently used to produce marked dilatation of the pupils. Tropane alkaloids have been used in domestic medicine, for example, for inducing sleep and for toothache. Some of them have hallusinogenic effects. A. belladonna is known as a highly toxic species, and it has been employed as a poison since early classic times.

Tropane alkaloids are the most important naturally occurring antimuscarinic drugs found especially in some solanaceous genera (Atropa, Anisodus, Datura, Duboisia, and Hyoscyamus). This class of drugs inhibits the action of acetylcholine on autonomic effectors innervated by postganglionic cholinergic nerves as well as on smooth muscles that lack cholinergic innervation. Since they antagonize the muscarinic action of acetylcholine they are known as antimuscarinic agents. The best-known member of this class of drugs is dl-hyoscyamine. Parasympathetic neuroeffector junctions in different organs are not all equally sensitive to these drugs. With small doses salivary and bronchial secretion and sweating are depressed. With large doses the pupil dilates and vagal effects on the heart are blocked so that the heart beat rate is increased.

The main pharmacological uses of hyoscyamine are as premedication for anesthesia, in gastrointestinal disorders, and in ophthalmology. Scopolamine prevents motion sickness, although some side effects are common (drowsiness and dry mouth). Many semi-synthetic and a large number of synthetic antimuscarinic compounds have been prepared with the objective of depressing gastric secretion without antimuscarinic effects on other organs. The new drugs have, however, few advantages over the naturally occurring alkaloids and their derivatives. Atropine is an effective medicine against some choline esterase inhibiting nerve gases.

Because of the immense importance of this plant as a source of medicines, there has been active research, employing biotechnological methods, to improve the yield of tropane alkaloids. Therefore in this chapter various aspects of tissue culture, micropropagation of plants, cryopreservation of cell cultures, and the in vitro production of tropane alkaloids are summarized.

Atropa belladonna, a medicinal plant with a rich source of some tropane alkaloids has been extensively studied in vitro. Complete plants have been regenerated from callus cultures, excised anthers, and the isolated protoplasts. These plants showed somaclonal variation. Protoplast fusion has resulted in somatic hybrids with Datura and Nicotiana spp. The isolated protoplasts and pollen embryos cryopreserved in liquid nitrogen retained their morphogenetic potential. Genetic transformation of excised roots with Agrobacterium rhizogenes caused increased production of tropanes with hairy roots. Callus and suspension cultures of A. belladonna have been used as model systems of differentiation and nitrogen metabolism.

At present, tissue cultures of A. belladonna give much lower yields of medicinally important alkaloids than the intact plants grown in the field. Hairy root cultures are, however, a quite promising system, but the costs may be too high compared to leaf material harvested from out-of-door plantations. A. belladonna is able to produce the main alkaloids also under greenhouse conditions in winter, but extra light, heating, and watering increase the price considerably.

Better understanding of the regulation of the biosynthesis of tropane alkaloids in A. belladonna is needed for biotechnological applications. Unfortunately, the enzymes are poorly known and many of the alkaloid precursors are not commercially available and some of them are rather labile. Both induction and repression mechanism(s) of different steps in the biosynthetic pathway ought to be studied using different types of aseptic cultures.

Medicinal and Aromatic Plants III (1991)