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Bittersweet Nightshade

Scientific Name(s): Solanum dulcamara L.
Common Name(s): Bitter nightshade, Bittersweet, Bittersweet nightshade, Blue nightshade, Deadly nightshade, Dulcamara, Fellen, Felonwort, Fever twig, Mortal, Scarlet berry, Snake berry, Staff vine, Violet-bloom, Woody nightshade

Clinical Overview

Use

Bittersweet nightshade has been used as a traditional external remedy for skin abrasions and inflammation. Limited studies have been conducted in diabetic rodents with equivocal findings; however, studies are limited by the plant’s toxicity.

Dosing

Traditional use of the stem has been at a dosage of 1 to 3 g/day, usually given as a decoction or infusion in 250 mL of water.

Contraindications

Contraindications have not yet been identified.

Pregnancy/Lactation

Avoid use. Documented teratogenic effects of the glycoalkaloids in animals.

Interactions

None well documented.

Adverse Reactions

Dilated pupils and GI effects (diarrhea, nausea, and vomiting) have been reported.

Toxicology

The plant is toxic. Ingestion of unripened berries should be considered a medical emergency. Symptoms may be delayed for several hours.

Botany

Bittersweet nightshade is a member of the same family as the potato, tomato, and belladona. 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.Duke 2003, USDA 2016

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)Kupchan 1965 and was recorded in Culpeper's Complete Herbal in 1681.Culpeper 2004 Although the plant has long been recognized as being highly toxicLowe 1929 it has been used as an external remedy for skin abrasions and inflammation. The stems were approved by the German Commission E Mongraphs for external use as supportive therapy in chronic eczema.Blumenthal 1998

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, and reviews have been published.Duke 2017, Heretsch 2015, Milner 2011 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 while soladulcines A and B are derived from soladulcidine and solasonine and solamargine are glyosides of solasodine. Green and yellowing fruits contain a higher percentage of the glycoalkaloids than ripe fruits. Other compounds isolated from the plant include saponins such as soladulcosides A and B free sterols such as tigogenin and lycopene.Duke 2017, Heretsch 2015, Milner 2011

Uses and Pharmacology

Diabetes

Animal data

Limited studies in rodents have evaluated the antihyperglycemic effects of methanol bittersweet plant extracts, with equivocal findings.Nwachukwu 2010, Sabudak 2015 One study reported high mortality rates.Sabudak 2015

Clinical data

Research reveals no clinical data regarding the use of bittersweet in diabetes.

Dosing

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.Duke 2003

Pregnancy / Lactation

Contraindicated in pregnancy and during lactation.Duke 2003

Toxic effects on both pregnant and nonpregnant mice have been found.Friedman 2003

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.Keeler 1990

Interactions

None well documented.

Adverse Reactions

Dilated pupils and GI effects (diarrhea, nausea, and vomiting) have been reported.Duke 2003

Toxicology

Both the immature and ripened fruit are toxic,Evens 2012 with a lethal dosage is estimated to be 200 berries.Duke 2003 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.Duke 2003, Krayer 1950 Toxic effects on both pregnant and nonpregnant mice have been found.Friedman 2003

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.Friedman 2003 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.Keeler 1990

Despite its history of obvious toxicity and teratogenicity, bittersweet nightshade continues to appear as a component of homeopathicJaggi 2004 and herbal medicine, in the latter case appearing as biological immune response modifier (BIRM) from an Ecuadorian source used in alternative cancer treatment.Dandekar 2003

References

Blumenthal M, ed. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicine. Austin, TX: American Botanical Council; 1998:232.
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.
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;52:59-66.12734674
Duke J. Handbook of Biologically Active Phytochemicals and Their Activities. Boca Raton, FL: CRC Press, Inc.; 1992. http://www.ars-grin.gov/duke/. Accessed 2017.
Duke JA. Handbook of Medicinal Herbs. 2nd ed. Boca Raton, FL: CRC Press; 2003.
Evens ZN, Stellpflug SJ. Holiday plants with toxic misconceptions. West J Emerg Med. 2012;13(6):538-542.23359840
Friedman M, Henika PR, Mackey BE. Effect of feeding solanidine, solasodine and tomatidine to non-pregnant and pregnant mice. Food Chem Toxicol. 2003;41(1):61-71.12453729
Heretsch P, Giannis A. The Veratrum and Solanum alkaloids. Alkaloids Chem Biol. 2015;74:201-232.25845062
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;53:150-157.15060721
Keeler RF, Baker DC, Gaffield W. Studies on Spirosolane-containing Solanum species and induction of congenital craniofacial malformations. Toxicon. 1990;28:873-874.2080514
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;5:517-525.14801459
Kupchan SM, Barboutis SJ, Knox JR, Cam CA. Beta-solamarine: tumor inhibitor isolated from Solanum dulcamara. Science. 1965;150:1827-1828.5859731
Lowe H. Poisoning by bittersweet (Solanum dulcamara). Analyst. 1929;54:153.
Milner SE, Brunton NP, Jones PW, et al. Bioactivities of glycoalkaloids and their aglycones from Solanum species. J Agric Food Chem. 2011;59(8):3454-3484.21401040
Nwachukwu DC, Okwuosa CN, Achukwu PU, Azubike N, Eze GE. Investigation of the anti-hyperglycaemic effect of the leaf extracts of Solanum dulcamara in diabetic rats. Indian J Novel Drug Deliv. 2010;2(4):138-143.
Sabudak T, Kaya O, Cukurova E. A new biflavonoid from Solanum dulcamara L. and investigation of anti-hyperglycaemic activity of its fruit extract. Nat Prod Res. 2015;29(4):308-314.25230855
Solanum dulcamara. USDA, NRCS. 2016. The PLANTS Database (http://plants.usda.gov, December 2016). National Plant Data Center, Baton Rouge, LA 70874-4490 USA.

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