Jackass Bitters

Scientific Name(s): Neurolaena lobata (L.) R. Br. Family: Asteraceae (daises). 1 , 2 , 3

Common Name(s): Jackass bitters , tres puntas , Mano de lagarto , gavilana , capitana , contragavilana , inaciabi , zeb-a-pique , herbe-a-pique , cow-gall bitter 1 , 2 , 3 , 4

Uses

The plant species has numerous ethnomedicinal uses. Medical literature documents in vitro and animal studies on the plant's antibacterial, antimalarial, antiplasmodial, anthelminthic, and hypoglycemic activity, but there are no clinical trials to support its use for any indication.

Dosing

None validated by clinical data. Ethnomedicinal resources vary for dosage of an N. lobata leaf decoction in treating malaria, ranging from 3 glasses daily for 4 days to 1 glass daily before breakfast for 7 days.

Contraindications

Patients with known hypersensitivity reactions to any of the components of the plant species.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

None well documented.

Toxicology

Chemical analysis revealed the presence of pyrrolizidine alkaloids. No toxicity was observed with oral doses up to 5,000 mg/kg in mice.

Botany

The weedy herbaceous plant N. lobata grows in northwestern South America through Central America and into southern Mexico. The plant species also is found throughout the Caribbean islands. It grows 1 to 2 m tall and has alternate trilobed leaves. The yellow flowers grow in compact groups at the end of the branches. All portions of the plant have a bitter taste. When handled, the fresh leaves and stems stain the skin yellow. 3 , 4 , 5

History

The plant species has numerous ethnomedicinal uses. In Mesoamerica, the herb was used to treat several diseases, including cancer, diabetes, dysentery (amebiasis), and malaria. In Panama, an infusion of the leaves was used to treat diabetes, hypertension, and hepatic ailments. In the Panamanian province of Darian, it is used for malaria and as an insect repellent. In Caribbean folk medicine, the herb was used medicinally to treat skin diseases, gastric pain, ulcers, and as a general pain reliever. In Guatemala, the plant has been used to treat malaria, anemia, and nervous weakness. It also has been used as a tonic and an antipyretic. 2 , 3 , 5 , 6 , 7 , 8 , 9

Chemistry

The primary medicinal components, the sesquiterpene lactones, are found in the leaf. The germacranolide sesquiterpene lactones include neurolenins A, B, C, D, E, and F and lobatin A. The neurolenins are found in the leaves in high concentrations and may be involved with the plant's medicinal use in treating dysentery. The neurolenins are extremely bitter substances. The germacranolide sesquiterpene lactones possess the structural requirements for cytotoxic and anticancer activities; however, neurolenins A and B were inactive in an animal model against sarcoma-180. Examples of isolated furanoheliangolides from N. lobata include lobatins B and C. The sesquiterpene content also is associated with the plant's antimalarial activity and activity against insects. N. lobata plants of different geographical origin show some qualitative and quantitative variations in their sesquiterpene lactone content. Flavonoids, coumarins, thymols, mellilotic acid, iridoids, and alkaloids also have been identified. More than 12 flavonoids have been isolated. 3 , 4 , 5 , 7 , 10 , 11 , 12 , 13 , 14 , 15 , 16

Uses and Pharmacology

In vitro and animal studies of the plant's chemotherapeutic, GI, and hypoglycemic activity have been conducted.

Antiplasmodial activity

The antiplasmodial effects of the neurolenins are not primarily caused by direct cytotoxic actions but by another specific mechanism that is yet to be identified. The germacranolide sesquiterpene lactones (neurolenins) are highly active compared with the furanoheliangolides (lobatin B or C). Neurolenin C seems to be the most reactive. The activity appears to depend on an alpha, beta-unsaturated-ketone and a free hydroxyl group at C-8. 17

In vitro and animal data

Ethanol extracts from N. lobata inhibited growth of Leishmania mexicana promastigotes, Trypanosoma cruzi trypomastigotes and epimastigotes, and Trichomonas vaginalis trophozoites. Treatment with an N. lobata extract of 100 mg/kg showed a 65% inhibition against T. cruzi in mice, similar to the activity of the allopurinol control. Methanol extracts of N. lobata also reduced parasitemias in Plasmodium berghei -infected mice. The aqueous and chloroform extracts of N. lobata were active against Plasmodium vinckei pettieri 279 BY, with a LC 50 less than 200 mg/mL. 2 , 6 , 18 , 19

Antibacterial activity
In vitro data

Topical application of neurolenin C and D from N. lobata inhibited the growth of Streptococcus mutans cultures. The minimum inhibitory concentration (MIC) was greater than 100 mcg/mL after 24 hours; the control antibiotic was penicillin V, which exhibited a MIC of 40 mcg/mL. 20

Anthelminthic activity
In vitro data

Ethanol extract from N. lobata leaves had macro- and micro-filaricidal activity against the Brugia pahangi worm. The effect on motility of adult worms was in a concentration- and time-dependent manner. Higher concentrations induced mortality of the microfilariae. 21

Other pharmacologic activity

Hypoglycemic activity was demonstrated in normoglycemic and hyperglycemic mice. A significant lowering of blood glucose ( P < 0.05) was found with an ethanolic extract of N. lobata 500 mg/kg after 1, 2, and 4 hours in normoglycemic mice. An ethanolic extract of N. lobata 250 mg/kg lowered blood glucose levels ( P < 0.01) in alloxan-diabetic mice within 4 hours. 22

Hexane, chloroform, and aqueous fractions of a hydroalcoholic extract of N. lobata aerial parts reduced gastric lesion formation 48%, 70%, and 52%, respectively. The hexane, chloroform, and aqueous fractions (41%, 57%, and 51%, respectively) also reduced gastric lesions induced by a combination of indomethacin and bethanechol, and reduced ulcers induced by hydrochloride/ethanol solution 77%, 86%, and 83%, respectively ( P < 0.05). The mechanism of action may be associated with mucus production and prostaglandin synthesis. 23

Aqueous extracts of N. lobata decreased spontaneous motor activity and muscle tone in mice. Analgesic and diuretic activity also have been shown in animal models. 8 , 24 , 25

Extracts of the branches, leaves, and stems of N. lobata had moderate neutralization activity at doses up to 4 mg per mouse against the hemorrhagic effect of Bothrops atrox snake venom of from Antioquia and Chocó, northwestern Colombia. 26

Dosage

None has been validated by clinical data. Ethnomedicinal resources vary for dosage of an N. lobata leaf decoction in treating malaria, ranging from 3 glasses daily for 4 days to 1 glass daily before breakfast for 7 days. 9 , 19

Pregnancy/Lactation

Avoid use during pregnancy and lactation because of lack of clinical studies. 17

Interactions

None validated by clinical data. The herb has the potential to produce additive effects in patients also taking analgesics, diuretics, or antimalarial medications.

Adverse Reactions

None well documented.

Toxicology

Chemical analysis revealed the presence of pyrrolizidine alkaloids; however, toxic necine pyrrolizidines were not present. No toxicity was observed with oral doses up to 5,000 mg/kg in mice. 8 , 17

Bibliography

1. Arvigo R . Herbal alternatives to antibiotics . Nat Pharm . 1999;3:1, 8-9.
2. Caceres A , Lopez B , Gonzalez S , Berger I , Tada I , Maki J . Plants used in Guatemala for the treatment of protozoal infections. I. Screening of activity to bacteria, fungi and American trypanosomes of 13 native plants . J Ethnopharmacol . 1998;62:195-202.
3. Borges-del-Castillo J , Manresa-Ferrero MT , Rodríguez-Lius F , Vázquez-Bueno P , Gupta MP , Joseph-Nathan P . Panama flora. II. New sesquiterpene lactones From Neurolaena lobata . J Nat Prod . 1982;45:762-765.
4. Manchand PS , Blount JF . Chemical constituents of tropical plants. 11. Stereostructures of neurolenins A and B, novel germacranolide sesquiterpenes from Neurolaena lobata (L.) R. Br . J Org Chem . 1978;43:4352-4354.
5. Passreiter CM , Wendisch D , Gondol D . Sesquiterpene lactones from Neurolaena lobata . Phytochemistry . 1995;39:133-137.
6. Franssen FF , Smeijsters LJ , Berger I , Medinilla Aldana BE . In vivo and in vitro antiplasmodial activities of some plants traditionally used in Guatemala against malaria . Antimicrob Agents Chemother . 1997;41:1500-1503.
7. Passreiter CM , Isman MB . Antifeedant bioactivity of sesquiterpene lactones from Neurolaena lobata and their antagonism by γ-aminobutyric acid . Biochem System Ecol . 1997;25:371-377.
8. Gracioso JS , Paulo MQ , Hiruma Lima CA , Souza Brito AR . Antinociceptive effect in mice of a hydroalcoholic extract of Neurolaena lobata (L.) R. Br. and its organic fractions . J Pharm Pharmacol . 1998;50:1425-1429.
9. Giron LM , Freire V , Alonzo A , Caceres A . Ethnobotanical survey of the medicinal flora used by the Caribs of Guatemala . J Ethnopharmacol . 1991;34:173-187.
10. Bohimann F , Natu AA , Kerr K . Naturally occurring terpene derivatives. Part 185. Thymol derivatives from Neurolaena species . Phytochemistry . 1979;18:489-490.
11. Kerr KM , Mabry TJ , Yoser S . 6-Hydroxy- and 6-methoxyflavonoids from Neurolaena lobata and N. macrocephala . Phytochemistry . 1981;20:791-794.
12. Castro O , Barrios M , Chinchilla M , Guerrero O . Chemical and biological evaluation of the effect of plant extracts against Plasmodium berghei [in Spanish]. Rev Biol Trop . 1996;44:361-367.
13. Todorova MN , Ognyanov IV , Navas H . Sesquiterpene lactones in Neurolaena lobata from Costa Rica . Biochem Syst Ecol . 1997;25:267-268.
14. Passreiter CM , Medinilla A , Beatriz E . Variability of sesquiterpene lactones in Neurolaena lobata of different origin . Planta Medica . 1998;64:427-430.
15. Passreiter CM , Sandoval-Ramirez J , Wright CW . Sesquiterpene lactones from Neurolaena oaxacana . J Nat Prod . 1999;62:1093-1095.
16. Passreiter CM . Pyrrolizidine alkaloids from Neurolaena lobata . Biochem Syst Ecol . 1998;26:839-843.
17. Francois G , Passreiter CM , Woerdenbag HJ , Van Looveren M . Antiplasmodial activities and cytotoxic effects of aqueous extracts and sesquiterpene lactones from Neurolaena lobata . Planta Med . 1996;62:126-129.
18. Berger I , Passreiter CM , Caceres A , Kubelka W . Antiprotozoal activity of Neurolaena lobata . Phytother Res . 2001;15:327-330.
19. Berger I , Barrientos AC , Caceres A , et al. Plants used in Guatemala for the treatment of protozoal infections: II. Activity of extracts and fractions of five Guatemalan plants against Trypanosoma cruzi . J Ethnopharmacol . 1998;62:107-115.
20. Lentz DL , Clark AM , Hufford CD , et al. Antimicrobial properties of Honduran medicinal plants . J Ethnopharmacol . 1998;63:253-263.
21. Fujimaki Y , Kamachi T , Yanagi T , Caceres A , Maki J , Aoki Y . Macrofilaricidal and microfilaricidal effects of Neurolaena lobata , a Guatemalan medicinal plant, on Brugia pahangi . J Helminthol . 2005;79:23-28.
22. Gupta MP , Solis NG , Avella ME , Sanchez C . Hypoglycemic activity of Neurolaena lobata (L.) R. Br . J Ethnopharmacol . 1984;10:323-327.
23. Gracioso JS , Hiruma-Lima CA , Souza Brito AR . Antiulcerogenic effect of a hydroalcoholic extract and its organic fractions of Neurolaena lobata (L.) R.Br . Phytomedicine . 2000;7:283-289.
24. Morales C , Gomez-Serranillos MP , Iglesias I , Villar AM , Caceres A . Preliminary screening of five ethnomedicinal plants of Guatemala . Farmaco . 2001;56:523-526.
25. Morales Cifuentes C , Gomez-Serranillos MP , Iglesias I , et al. Neuropharmacological profile of ethnomedicinal plants of Guatemala . J Ethnopharmacol . 2001;76:223-228.
26. Otero R , Nunez V , Barona J , et al. Snakebites and ethnobotany in the northwest region of Colombia. Part III: neutralization of the haemorrhagic effect of Bothrops atrox venom . J Ethnopharmacol . 2000;73:233-241.

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