Bittersweet nightshade is a member of the same family as the potato and tomato. This plant is found widely throughout Europe, Asia, the US, and Canada. Bittersweet nightshade is a vine-like perennial that can grow to a height of approximately 3 m. It has alternating heart-shaped oval leaves that usually have 2 small ear-like segments at their bases. Its star-shaped flowers bloom from April to September; the flowers are pinkish-purple with bright yellow stamens. The flowers produce green berries that turn bright red when mature.
History
The Latin name dulcamara refers to the flavor of the berries, which are first bitter, then unpleasantly sweet. Bittersweet nightshade has been used to treat cancers, tumors, and warts since ancient times as far back as Galen (AD 180) 1 and was recorded in Culpeper's Complete Herbal in 1681. 2 Although the plant has long been recognized as being highly toxic, 3 it has been used as an external remedy for skin abrasions. Its use to treat felons (inflammations around nail beds) may be the source of the name felonwort . The plant has been investigated for possible antirheumatic, diuretic, narcotic, and sedative activity, but these actions are linked to the toxicity of the plant, and therefore, have not been successfully exploited.
Chemistry
Chemical investigations into the composition of bittersweet have identified a number of alkaloids in the leaves and fruit. There are several varieties of the plant that possess different alkaloid profiles. They occur primarily as glycosides of the 3 spirosolane alkaloids tomatidenol, soladulcidine, and solasodine, although the free alkaloids are sometimes also detected. Alpha-, beta-, and gamma-solamarine are glycosides of tomatidenol, 4 , 5 while soladulcines A and B are derived from soladulcidine, 6 and solasonine 7 and solamargine 8 are glyosides of solasodine. Green and yellowing fruits contain a higher percentage of the glycoalkaloids than ripe fruits. 9 Other compounds isolated from the plant include saponins such as soladulcosides A and B, 10 free sterols such as tigogenin, 11 and lycopene.
Uses and Pharmacology
Bittersweet has been used as a traditional external remedy for skin abrasions and inflammation. The stems were approved by the German Commission E for external use as supportive therapy in chronic eczema. 12
Animal/Clinical data
Research reveals no published animal or clinical data regarding the use of bittersweet as an external remedy.
Dosage
There is no clinical evidence to guide dosage of bittersweet nightshade. Traditional use of the stem was at a dosage of 1 to 3 g/day, usually given as a decoction or infusion in 250 mL of water.
Pregnancy/Lactation
Administration of mature, unripe fruit to pregnant hamsters on day 8 of gestation resulted in a significant increase in craniofacial malformations over controls. The malformations included exencephaly, encephalocele, and occasional cebocephaly, cleft palate, or cleft lip. The dose used (7.5 g/kg by gavage) also induced significant maternal toxicity. However, the 2 effects were considered distinct because purified alkaloids (eg, solasodine) caused fetal damage without maternal toxicity. S. dulcamara was 10-fold more potent than the other species of Solanum studied, based on alkaloid content. The saponins present in the fruit may enhance absorption of the glycoalkaloids. 13
Interactions
None well documented.
Adverse Reactions
No data.
Toxicology
The FDA classifies bittersweet as an unsafe poisonous herb because of the presence of the toxic spirosolane glycoalkaloids. Like saponin, the glycoalkaloids cause hemolytic and hemorrhagic damage to the GI tract. Such poisoning is often confused with bacterial gastroenteritis, with symptoms appearing only after a latent period of several hours following ingestion. A weak effect on cardiovascular function has been documented. 14 Toxic effects on both pregnant and nonpregnant mice have been found. 15
Symptoms of spirosolane alkaloid poisoning include the following: circulatory and respiratory depression, convulsions, cyanosis, death, diarrhea, dilated pupils, headache, paralysis, scratchy throat, shock, speech difficulties, stomachache, subnormal temperature, vertigo, and vomiting. Adults appear to be relatively resistant to the toxicity of spirosolanes, but fatal intoxications are more common in children. Emesis, fluid replacement, and supportive care, such as that used for gastroenteritis, should be administered. Despite this typically aggressive therapy, the results of one study in mice fed ripened fruit suggested that because no GI or neurologic toxicity was observed, aggressive treatment of children who ingest ripened berries may not be necessary. 15 Nevertheless, these investigators found significant neurologic and pathologic GI toxicity when mice were fed unripened fruit, indicating that poisoning with this plant should be considered a critical situation. Other investigators have confirmed the pathologic changes in the GI tract (glandular mucosal necrosis and necrosis of the small intestine) in hamsters fed ground bittersweet fruit. 13
Despite its history of obvious toxicity and teratogenicity, bittersweet nightshade continues to appear as a component of homeopathic 16 and herbal medicine, in the latter case appearing as biological immune response modifier (BIRM) from an Ecuadorian source used in alternative cancer treatment. 17
Bibliography
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2. Culpeper, N. Amara bulcis, Culpeper's Complete Herbal. Available at: http://www.bibliomania.com/2/1/66/113/20916/1.html . Accessed August 24, 2004.
3. Lowe H. Poisoning by bittersweet ( Solanum dulcamara ). Analyst . 1929;54:153.
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6. Lee YY, Hashimoto F, Yahara S, Toshihiro N, Yoshida N. Steroidal glycosides from Solanum dulcamara . Chem Pharm Bull . 1994;42:707.
7. Briggs LH, Vining LC. Solanum alkaloids. Part X. The mode of linkage in the trisaccharide moiety of solanine and solasonine. J Chem Soc . 1953;2809.
8. Briggs LH, Cambie RC, Hyslop DM. Solanum alkaloids. Part XVII. The sugar unit of solamargine. J Chem Soc . 1975;2455.
9. Sander H. Solanum dulcamara. VII. Biosynthesis of spirosolanol glycosides in the ripening fruit. Planta Med . 1963;11:23.
10. Yamashita T, Matsumoto T, Yahara S, Yoshida N, Nohara T. Structures of two new steroidal glycosides, soladulcosides A and B from Solanum dulcamara . Chem Pharm Bull . 1991;39:1626-1628.
11. Marker RE, Wagner RB, Ulshafer PR, Wittbecker EL, Goldsmith DP, Ruof CH. Sterols. CLVII. Sapogenins. 69. Isolation and structures of thirteen new steroidal sapogenins. New sources for known sapogenins. J Am Chem Soc . 1943;65:1199.
12. Blumenthal M, ed. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicine . Austin, TX: American Botanical Council; 1998:232.
13. Keeler RF, Baker DC, Gaffield W. Studies on Spirosolane-containing Solanum species and induction of congenital craniofacial malformations. Toxicon . 1990;28:873-874.
14. Krayer O, Briggs LH. Studies on solanum alkaloids: II. The anti-accelerator cardiac action of solasodine and some of its derivatives. Br J Pharmacol . 1950;5:517-525.
15. Friedman M, Henika PR, Mackey BE. Effect of feeding solanidine, solasodine and tomatidine to non-pregnant and pregnant mice. Food Chem Toxicol . 2003;41:61-71.
16. Jaggi R, Wurgler U, Grandjean F, Weiser M. Dual inhibition of 5-lipoxygenase/cyclooxygenase by a reconstituted homeopathic remedy; possible explanation for clinical efficacy and favourable gastrointestinal tolerability. Inflamm Res . 2004;53:150-157.
17. Dandekar DS, Lokeshwar VB, Cevallos-Arellano E, Soloway MS, Lokeshwar BL. An orally active Amazonian plant extract (BIRM) inhibits prostate cancer growth and metastasis. Cancer Chemother Pharmacol . 2003;52:59-66.