Solanum dulcamara L. (Bittersweet)

2015

Biology and Distribution

Solanum dulcamara L. (=Dulcamara flexuosa Moench) (), known as dogwood or bittersweet (Solanaceae), is a clambering or prostrate, perennial shrub which may grow to a height of 2 m (Hegi 1927). Its stem is angular and woody with the exception of the herbaceous top and ranges in diameter between 0.25 and 2 cm, rarely up to 5-6 cm. The leaves are alternate, long-stalked, sparsely pubescent on both sides, and quite variable in shape. The oval- to egg-shaped leaf blade is pointed at the tip. Its base, however, may also be cordate, arrow-shaped, or may consist of one or two lobes. Different leaf forms may be found on the same plant. The flowers emerge axillary in panicle-like loose clusters. The calyx bears five narrow teeth; the five joint petals are bright purple and their tips are somewhat reflexed when fully expanded. The five stamens have yellow anthers which form a conspicuous column. The fruit is a round- to egg-shaped berry, green when young and becoming bright red when mature. In Europe, the flowering season is May to September. It is distributed throughout Europe and is also a native to North Africa, West Asia, India, the USSR, China, and Japan. It is not clear whether its occurrence in North America is of native origin or whether it was introduced from Europe. Growth habitats of the plant are wet meadows, ditches, and poplar-alder forests, but it may also grow on dry and sandy soils, waste areas, between gravel or rubble, and in clefts of old walls. The variability in morphological appearance, habitat, and its wide distribution gave rise to the description of several subspecies and varieties. Their taxonomic significance and position, however, is not quite clear and is further complicated by the occurrence of chemovarieties.

Steroidal Alkaloid Patterns

The three chemovarieties of Solanum dulcamara contain either solasodine, soladulcidine, or tomatidenol glycosides () in leaves and stems ().

The difference in alkaloid composition is a genetically fixed character of the plant (). The differences in alkaloid composition are restricted to the chlorophyllous vegetative organs. Fruits and flowers always contain solasodine glycosides in amounts comparable to the content of the type-specific alkaloid (). Roots additionally contain the aglycones tomatidine and/or 15α-hydroxylated derivatives of solasodine, soladulcidine, tomatidenol, and tomatidine (). The steroidal alkaloids are always accompanied by the biosynthetically closely related neutral sapogenins diosgenin, tigogenin, and yamogenin, which are nitrogen-free oxygen-analogous compounds.

The geographical distribution of the chemovarieties indicates a spatial separation: the tomatidenol-producing taxa are found in the humid Atlantic climate of western Europe, the soladulcidine type occurs in drier continental climates (). Plants of the solasodine variety are comparatively rare. Along the boundary of the areals, populations of Solanum dulcamara exist which contain all three steroidal alkaloids ().

Medicinal Uses

Solanum dulcamara plays a role in folk medicine and as a drug of limited importance in Europe, China, and Japan. In European folk medicine, the dried stems are used separately or in combination with other drugs for the preparation of teas for “blood purification” (List and Horhammer 1979). The drug is used against bronchitis and asthma. Decoctions are applied externally to treat eczema, ulcers, and to improve healing of wounds.

In India, Solanum dulcamara (kakmachi, ruba-barik) k used for the treatment of tumors, warts, chronic rheumatism, and skin affections. Infusions made from the dried stem are credited with sedative and analgesic properties ().

In Chinese medicine, Solanum dulcamara is known under the name ku qie and infusions of the dried stem are used for similar purposes as in Europe and India, e.g., to treat asthma and rheumatism. Vinegar-marinated berries and decoctions of the root are applied externally to cancerous sores and other swellings (). Hsu () lists in his Materia Medica the drug Solani lyrati herba which is the entire dried plant of Solanum lyratum Thunb. (pai-mao-teng) or of Solanum dulcamara L. Therapeutical applications of the drug are used for malaria, jaundice, rheumatalgia, ascites, edema, furuncle, and erysipelas. Both Solanum species look very similar, and in the Index Kewensis of 1885 they are considered to be identical. In the Flora Reipublicae Popularis Sinicae of 1978 it is listed with the synonyms Solanum dulcamara L. var. pubescens Blume and Solanum dulcamara L. var. lyratum (Thunb.) Sieb et Zucc. ex Bonati in Lecte. A reassessment of its position, however, seems to be necessary.

Pharmacological and Biological Activities of Steroidal Alkaloids

Attention should be paid to the fact that the external application of herbal medicines containing steroidal alkaloids against skin disorders is common throughout all cultures. A patent application by Spencer et al. () shows that this application proves true in modern medical therapy. Steroidal alkaloids are considered to be the active compounds in the drug. As early as 1965, Kupchan et al. demonstrated a tumor-inhibiting activity of the glycoside P-solamarine. Cham et al. () report antitumor effects of the glycoalkaloid fraction of Solanum sodomaeum, which consists mostly of solasonine and solamargine. The experiments were performed with mice (Herston Whites) and with rats (Sprague Dawley) using Sarcoma 180 cells. Bahr and Hansel () found immunomodulating properties of the aglykone solasodine in an in vitro assay using spleen cell cultures. A patent application on preparations with antitumor activity of Solanum lyratum by a Japanese research group () indicates the interest and expectations set in this activity. Strong antiviral activity of the steroidal glycoalkaloids α-chaconine, α-solasonine, and α-tomatine was shown by Thome et al. () using herpes-simplex infection of in vitro cultured cells as a test system.

Toxic effects of steroidal alkaloids on livestock and man were repeatedly reported and experimentally confirmed. A teratogenic activity was assigned to these compounds (). In laboratory experiments, a single dose of solasodine (1.2 g/kg) given to pregnant hamsters produced spina bifida, exen-cephaly, and cranial bleb. Tomatidine and diosgenin were not teratogenic (). Steroidal alkaloids bearing a basic nitrogen atom in ring F, shared or unshared with ring E, with bonding capabilities in α-position to the steroid plane may be teratogenic ().

Glycoalkaloids are long known to be inhibitors of acetylcholin-esterase (). In this investigation, α-chaconine and α-solanine were the strongest inhibitors, tomatine was already less active, and solasonine and solamargine only showed a weak inhibitory activity. The aglycones were basically inactive.

Beside the pharmacological effects listed, steroidal alkaloids possess a number of additional biological activities such as antifungal, moluscicidal, and insecticidal properties. All these effects are most likely based on the saponin-like structure, in particular of the glycoalkaloids which will allow strong interactions with membranes, thus inflicting membrane damage (). The membrane-disrupting properties of solasonine and solamargine were studied thoroughly in artificially prepared phosphatidylcholine/cholesterol liposomes ().

In the 1960s, tomatine gained interest as an externally applied antimycotic in the USA, but it did not prove to be effective (). Wolters investigated the antifungal activities of aqueous leaf and fruit extracts (), isolated steroidal alkaloids (), and neutral saponins () from Solanum dulcamara and studied structure activity relationships. Steroidal alkaloids inhibited the growth of a number of different fungi. Against some fungi the aglycones were more active than-the glycosides, but generally the spirosolanole glycosides were more active than the respective aglycones. The aglycones soladulcidine, solasodine, tomatidine, and A5-tomatidenol showed some differences in their spectrum of activity. Compared to the steroidal alkaloids, the corresponding O-analogous neutral steroid sapogenins exhibited a similar spectrum of activity, but were less active when the minimal inhibitory activity was compared. A recent screening of the antifungal activity of a number of steroidal alkaloids showed strong differences between their biological activity. Minor changes in the side chain strongly affect the activity (). The mode of action is still insufficiently elucidated, but complex formation with membrane sterols plays an important role in it (). Structure activity studies, however, do not correlate with the sterol-binding activity (). When investigating the effect of steroidal alkaloids (including solasodine) on cholesterol biosynthesis, Kusano et al. () measured a significant inhibition of the enzymatic conversion of dihydrolanosterol into cholesterol. They discuss an inhibition of sterol synthesis as a possible mechanism for fungitoxicity.

A role as a disease-resistance factor of plants is discussed for the steroidal alkaloids. The data available, however, lead to the conclusion that they are not key factors in the defence against fungal attacks ().

Field Production

The growing interest in plants containing solasodine for commercial solasodine production led to the exploitation of many Solanum species in this respect. Various aspects of steroidal alkaloid production of Solanum laciniatum and Solanum aviculare in the field and in vitro were reviewed by Macek (). Also see site for Solanum glaucophyllum. Solasodine (and the C-22 epimer tomatidenol) can easily be converted to key intermediates for the synthesis of corticosteroids and contraceptive hormones. Mathe et al. () suggested the cultivation of the tomatidenol/solasodine variety of Solanum dulcamara in temperate climates as an alternative to the subtropical species Solanum aviculare/Solanum laciniatum or Solanum khasianum. Solanum dulcamara is easily cultivated and produces tomatidenol in yields (15-45 kg/ha) comparable to or even better than the subtropical species under the same conditions in Hungary.

The importance of Solanum dulcamara as a source of steroidal alkaloids for the production of steroid hormones is limited. Only the tomatidenol and solasodine varieties may be of some interest; in general, the yield will not compare to the one obtainable with some other Solanum species, e.g., Solanum laciniatum. If its steroidal alkaloid production could be boosted by any specific manipulation, Solanum dulcamara may become more attractive for commercial growing due to its other qualities, fair cold hardiness, good growth on poor soils and perennial life cycle. These properties may also be valuable for breeding efforts aiming at the production of hybrid Solanum with unique qualities. Here, Solanum dulcamara may be of particular interest, as it shows a high potential for plant regeneration. The most fascinating aspects in working with S. dulcamara, however, are not in the application, but concern basic research questions. The developmentally regulated biosynthesis of steroidal alkaloids in Solanum dulcamara represents an exciting system for studies on differential gene expression in secondary metabolism.

 

Selections from the book: “Medicinal and Aromatic Plants IV”, 1993.