Gentian

Scientific Name(s): Gentiana lutea L. and other species including Gentiana acaulis L. and Gentiana scabra Bunge. Family: Gentianaceae (gentians)

Common Name(s): Gentian (common: European pale, stemless, yellow, or wild gentian), bitter root , bitterwort , felwort , gall weed , gentiana , Radix Gentianae Lutea .

Uses

No clinical trials support traditional use of gentian to stimulate appetite, improve digestion, or treat GI complaints. Gentian has also been used as an emmenagogue and to treat wounds, sore throat, arthritic inflammation, and jaundice.

Dosing

Infusions, decoctions, and macerations of gentian roots and rhizomes have been used as a bitter digestive tonic in doses of 1 to 4 g/day. There are no clinical studies to substantiate this dosage recommendation.

Contraindications

Contraindicated in gastric or duodenal ulcer and hypertension.

Pregnancy/Lactation

Documented adverse effects. Avoid use.

Interactions

None well documented.

Adverse Reactions

The extract may cause headache, nausea, and vomiting.

Toxicology

Mutagenicity has been demonstrated for methanolic extracts in Salmonella assays. Acute veratrum alkaloid poisoning has been reported due to accidental contamination of gentian preparations by veratrum.

Botany

Native to the mountains of central and southern Europe, G. lutea is a perennial herb that grows to 1.8 m with erect stems and smooth, oval leaves. The plant produces a cluster of fragrant orange-yellow flowers. The roots and rhizomes are nearly cylindrical, sometimes branched, varying in thickness from 5 to 40 mm. The root and rhizome portions are longitudinally wrinkled. The color of the rhizomes, ranging from dark brown to light tan, appears to be related to the content of bitter principles, because the darker roots have a more persistent, bitter taste. The roots and rhizomes of G. lutea are used medicinally. 1 , 2 , 3

G. acaulis is a smaller herb with a basal rosette of lance-shaped leaves and generally grows to 10 cm in height. It is native to the European Alps at 914 to 1,524 m above sea level. The entire G. acaulis plant is used medicinally. Numerous species of gentian native to China are used in Chinese traditional medicine. Radix Gentianae Scabrae (known as Chinese or Japanese gentian) is indigenous to Korea, China, and Japan, and contains chemical constituents similar to these of G. lutea . 2

History

The gentians have been used for centuries as bitters to stimulate the appetite, improve digestion, and treat a variety of GI complaints (eg, diarrhea, heartburn, stomach ache, vomiting). Stemless gentian usually is consumed as a tea or alcoholic extract, such as Angostura bitters. The extracts are used in a variety of foods, cosmetics, and some antismoking products. The plant has been used externally to treat wounds and internally to treat sore throat, arthritic inflammation, and jaundice. Despite the name, the dye gentian violet is not derived from this plant. 2 , 4 , 5

Chemistry

The most characteristic aspect of gentian is its bitter taste imparted by a number of iridoid glycosides, primarily amarogentin, gentiopicrin (about 1.5% in fresh roots), gentiopicroside, and swertiamarin. The speed of drying of the roots affects their properties as medicinal bitters. Slow drying permits enzymatic hydrolysis of gentiopicrin into gentiogenin and glucose, therefore reducing bitterness. Gentian extract is used as a bitter in concentrations of approximately 0.02% in nonalcoholic beverages. The iridoids have been analyzed by thin-layer chromatography, micellar electrokinetic capillary chromatography, and high-performance liquid chromatography mass spectrometry. 6 , 7 , 8

In addition to iridoids, the roots contain xanthones and triterpenes. 9 , 10 , 11 The reported pyridine alkaloids gentianine and gentialutine are thought to be artifacts of basic extraction derived from the iridoids. Stemless gentian also contains the xanthone glycoside gentiacauloside. The flowers and leaves of G. lutea contain iridoids, flavonoids, and xanthones. 12

Uses and Pharmacology

Quality clinical trials evaluating the effect of gentian or its chemical constituents are lacking. 2

Analgesic/anti-inflammatory
Animal data

Gentianine and gentiopicroside have been shown to exert a measurable anti-inflammatory and analgesic effect in animals. Extracts of G. lutea were active in carageenan-induced rat paw edema, xylol-induced mouse ear edema, and cotton-pellet granulatoma models. In addition, the extracts were active in several wound-healing models. 13 , 14 , 15

Clinical data

Clinical trials are lacking.

Antimicrobial

Radix Gentianae Lutea and gentian extracts have been shown to exert antibacterial, antifungal, and antiprotozoal effects in vitro. 2

Methanolic extracts of the flowers and leaves of G. lutea demonstrated a wide range of activity against gram-positive and gram-negative bacteria and yeasts. Isolated chemical constituents mangiferin, isogentisin, and gentiopicrin also demonstrated activity. 16 , 17 Activity against Helicobacter pylori has been demonstrated in vitro. 18 , 19 Amarogentin and 2 other iridoids inhibited topoisomerase I of Leishmania . 20

Animal data

The roots of G. lutea have been used as an anthelmintic in ethnoveterinary medicine. 19

Clinical data

Clinical trials are lacking.

Hepatic effects
Animal data

In rats, intragastric and intraduodenal administration of gentian extracts stimulated bile production 2 , 21 and showed a protective effect on the liver against chemical insults. 21

Clinical data

In an uncontrolled study, stimulation of gall bladder secretions was increased by gentian. 2

GI tract

Bitter substances ingested before meals are reputed to improve the appetite and aid digestion by stimulating the flow of gastric juices and bile. However, because gentian is most often consumed in alcoholic beverages, it is difficult to distinguish the effects of gentian from those of alcohol.

Animal data

Ethanol extracts of the roots and rhizomes of G. lutea have increased gastric secretions in rats and sheep. 2

Clinical data

In 2 uncontrolled clinical studies, stimulation of gastric secretions was increased and GI symptoms (eg, abdominal pain, constipation, dyspepsia, heartburn) were reduced. 2

Other uses

Gentian extracts have hydroxy radical scavenging activity 22 , 23 and exert a protective effect against ketoconazole-induced testicular damage in rats, assumed to be due to antioxidant effects. 24 Gentiopicroside and the essential oil of G. lutea relax smooth muscle in isolated animal trachea and ileum. 2 , 25 Gentian extracts prolong swimming endurance in mice. 26

Dosage

The pharmacokinetics and tissue distribution of gentiopicroside after oral and parenteral administration have been studied in mice. It was rapidly absorbed with low bioavailability and rapidly cleared. 27 , 28

Infusions, decoctions, and macerations of gentian roots and rhizomes have been used as a bitter digestive tonic in doses of 1 to 4 g/day. There are no clinical studies to substantiate this dosage recommendation. 2

Pregnancy/Lactation

Mutagenic activity has been demonstrated in assays, and G. lutea has been traditionally used as an emmenagogue. Avoid use in pregnancy and lactation. 2

Interactions

Case reports are lacking; however, hemostatic activity has been demonstrated in vitro for extracts of G. lutea , 29 and isogentisin and several other compounds from gentian inhibited monoamine oxidase. 30 , 31 If substantiated in a clinical setting, these properties may have implications for coadministration of anticoagulant or antidepressant medicines.

Adverse Reactions

The extract is usually taken in very small doses that do not appear to cause adverse effects; however, it may cause GI irritation, resulting in nausea and vomiting and, rarely, headache. 2 Radix Gentianae Lutea is contraindicated in GI or duodenal ulcer. Classical texts include hypertension as a contraindication, but the reasons are difficult to substantiate. 2

Toxicology

Mutagenicity has been demonstrated for methanolic extracts in Salmonella assays. 2

The highly toxic white hellebore ( Veratrum album L.) often grows in close proximity to gentian. Cases of acute veratrum alkaloid poisoning have been reported due to accidental contamination of gentian preparations by veratrum. 32 , 33

Bibliography

1. Gentiana lutea L. USDA, NRCS. 2010. The PLANTS Database ( http://plants.usda.gov , July 2010). National Plant Data Center, Baton Rouge, LA 70874-4490 USA.
2. Radix Gentianae Luteae . In: WHO Monographs on Selected Medicinal Plants . Vol 13. Geneva, Switzerland: World Health Organization; 1999.
3. Meyer JE. The Herbalist . Hammond, IN: Hammond Book Co; 1934.
4. Leung AY. Encyclopedia of Common Natural Ingredients Used in Food, Drugs, and Cosmetics . 2nd ed. New York, NY: J Wiley; 1996.
5. DerMarderosian A, Liberti L. Natural Product Medicine . Philadelphia, PA: GF Stickley Co; 1988.
6. Bricout J. Identification and determination of the bitter constituents of Gentiana lutea roots [in French]. Phytochemistry . 1974;13(12):2819-2823.
7. Glatz Z, Pospisilova J, Musil P. Determination of gentiopicroside in extracts of Centaurium erythreae and Gentiana lutea by micellar electrokinetic capillary chromatography. J Liq Chromatogr Relat Technol . 2000;23(12):1831-1839.
8. Szucs Z, Danos B, Nyiredy S. Comparative analysis of the underground parts of Gentiana species by HPLC with diode-array and mass spectrometric detection. Chromatographia . 2002;56(1):S19-S23.
9. Hayashi T, Yamagishi T. Two xanthone glycosides from Gentiana lutea . Phytochemistry . 1988;27(11):3696-3699.
10. Toriumi Y, Kakuda R, Kikuchi M, Yaoita Y, Kikuchi M. New triterpenoids from Gentiana lutea . Chem Pharm Bull (Tokyo) . 2003;51(1):89-91.
11. Kakuda R, Machida K, Yaoita Y, Kikuchi M, Kikuchi M. Studies on the constituents of Gentiana species. II. A new triterpenoid, and (S)-(+)- and (R)-(−)-gentiolactones from Gentiana lutea . Chem Pharm Bull (Tokyo) . 2003;51(7):885-887.
12. Menkovic N, Savikin-Fodulovic, Savin K. Chemical composition and seasonal variations in the amount of secondary compounds in Gentiana lutea leaves and flowers. Planta Med . 2000;66(2):178-180.
13. Mathew A, Taranalli AD, Torgal SS. Evaluation of anti-inflammatory and wound healing activity of Gentiana lutea rhizome extract in animals. Pharm Biol . 2004;42(1):8-12.
14. Ozturk N, Korkmaz S, Ozturk Y, Baser KH. Effects of gentiopicroside, sweroside and swertiamarine, secoiridoids from gentian ( Gentiana lutea ssp. symphyandra), on cultured chicken embryonic fibroblasts. Planta Med . 2006;72(4):289-294.
15. Chen L, Liu JC, Zhang XN, et al. Down-regulation of NR2B receptors partially contributes to analgesic effects of Gentiopicroside in persistent inflammatory pain. Neuropharmacology . 2008;54(8):1175-1181.
16. Savikin K, Menkovic N, Zdunic G, Stevic T, Radanovic D, Jankovic T. Antimicrobial activity of Gentiana lutea L. extracts. Z Naturforsch C . 2009;64(5-6):339-342.
17. Weckesser S, Engel K, Simon-Haarhaus B, Wittmer A, Pelz K, Schempp CM. Screening of plant extracts for antimicrobial activity against bacteria and yeasts with dermatological relevance. Phytomedicine . 2007;14(7-8):508-516.
18. Mahady GB, Pendland SL, Stoia A, et al. In vitro susceptibility of Helicobacter pylori to botanical extracts used traditionally for the treatment of gastrointestinal disorders. Phytother Res . 2005;19(11):988-991.
19. Lans C, Turner N, Khan T, Brauer G. Ethnoveterinary medicines used to treat endoparasites and stomach problems in pigs and pets in British Columbia, Canada. Vet Parasitol . 2007;148(3-4):325-340.
20. Ray S, Majumder HK, Chakravarty AK, Mukhopadhyay S, Gil RR, Cordell GA. Amarogentin, a naturally occurring secoiridoid glycoside and a newly recognized inhibitor of topoisomerase I from Leishmania donovani . J Nat Prod . 1996;59(1):27-29.
21. Liu ZW, Chen C, Jin R, Shi G, Song C, Hu Z. Studies on liver-protecting and bile secretion-promoting effects of gentiopicroside. Zhong Cao Yao . 2002;33:47-50.
22. Calliste CA, Trouillas P, Allais DP, Simon A, Duroux JL. Free radical scavenging activities measured by electron spin resonance spectroscopy and B16 cell antiproliferative behaviors of seven plants. J Agric Food Chem . 2001;49(7):3321-3327.
23. Kusar A, Zupancic A, Sentjurc M, Baricevic D. Free radical scavenging activities of yellow gentian ( Gentiana lutea L.) measured by electron spin resonance. Hum Exp Toxicol . 2006;25(10):599-604.
24. Amin A. Ketoconazole-induced testicular damage in rats reduced by Gentiana extract. Exp Toxicol Pathol . 2008;59(6):377-384.
25. Rojas A, Bah M, Rojas JI, Gutiérrez DM. Smooth muscle relaxing activity of gentiopicroside isolated from Gentiana spathacea . Planta Med . 2000;66(8):765-767.
26. Öztürk N, Baser KH, Aydin S, Öztürk Y, Calis I. Effects of Gentiana lutea ssp. symphyandra on the central nervous system in mice. Phytother Res . 2002;16(7):627-631.
27. Wang CH, Wang ZT, Bligh SW, White KN, White CJ. Pharmacokinetics and tissue distribution of gentiopicroside following oral and intravenous administration in mice. Eur J Drug Metab Pharmacokinet . 2004;29(3):199-203.
28. Wang CH, Cheng XM, He YQ, et al. Pharmacokinetic behavior of gentiopicroside from decoction of Radix Gentianae, Gentiana macrophylla after oral administration in rats: a pharmacokinetic comparison with gentiopicroside after oral and intravenous administration alone. Arch Pharm Res . 2007;30(9):1149-1154.
29. Bakuridze AD, Nikolaev SM, Tsagarenshvili NT, Kurdiani NG, Mikaia GA. Influence of Gentiana lutea L extract on blood coagulation [in Russian]. Georgian Med News . 2009;(172-173):89-91.
30. Suzuki O, Katsumata Y, Oya M. Inhibition of monoamine oxidase by isogentisin and its 3-O-glucoside. Biochem Pharmacol . 1978;27(16):2075-2078.
31. Haraguchi H, Tanaka Y, Kabbash A, Fujioka T, Ishizu T, Yagi A. Monoamine oxidase inhibitors from Gentiana lutea . Phytochemistry . 2004;65(15):2255-2260.
32. Garnier R, Carlier P, Hoffelt J, Savidan A. Acute dietary poisoning by white hellebore ( Veratrum album L.). Clinical and analytical data. A propos of 5 cases [in French]. Ann Med Interne (Paris) . 1985;136(2):125-128.
33. Rauber-Lüthy C, Halbsguth U, Kupferschmidt H, et al. Low-dose exposure to Veratrum album in children causes mild effects—a case series. Clin Toxicol (Phila). 2010;48(3):234-237.

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