Chelidonium majus / Stinkende gouwe

De Stinkende gouwe heeft met zijn felgeel- en in de wortels oranje gekleurde melksap en met zijn rijkdom aan alkaloïden steeds de aandacht getrokken zowel vanwege zijn ge­neeskrachtige als zijn giftige werking. De plant is van oudsher aanbevolen voor vele ziekten en later meer specifiek voor zijn spasmolytische werking te vergelijken met andere papaverachtigen
De Stinkende gouwe  is  inderdaad licht giftig, maar omdat ze ook branderig scherp van smaak is met een langdurige nawerking, zijn vergiftigingen van mensen en grote herbivo­ren zeldzaam. Bij de enkele gevallen werd vooral sterke irritatie van de slijmvliezen van mond, maag en darmen waargenomen.

De opgaven over het totale gehalte aan alkaloïden variëren sterk. Het gehalte van de bo­vengrondse plantendelen bedraagt circa 0,3% (drooggewicht) en 1-2% voor de wortels. De samenstelling van het alkaloïdenmengsel is afhankelijk van de groeiplaats. De voornaamste alkaloïden zijn naast protopine en berberine, het spasmolytische chelidonine en de beide verbindingen die de gele kleur aan het melksap geven: chelerythtine en vooral in de wortels sanguinarine. 
Chelerythrine en sanguinarine hebben een vrij sterk antibacteriële werking over een breed spectrum van organismen. In veel geval­len wordt de groei geremd bij een concentra­tie van 12,5 mg/l (Mitscher et al., 1978). San­guinarine is met het oog op mogelijke medische toepassingen wat meer uitgebreid farmacologisch onderzocht met overwegend gebruik van geïsoleerde organen en intrave­neuze of subcutane injectie. 

Inhoudsstoffen
 Benzylisoquinoline type (0.01-1%): with at least three subgroups,
 Benzophenanthridines: chelerythrine, chelidonine, sanguinarine, isochelidonine
 Protoberberines: berberine, coptisine, dihydrocoptisine, stylopine
 Protopine

 Acids: chelidonic, malic, citric, caffeic (0.4%) ferulic (0.02%), p-coumaric (0.06%), gentisic and phydroxybenzoic
acids
 Hydroxycinnamic acid derivates: (-)-2-(E)-caffeoyl-D-glyceric acid, (-)-4-(E)-caffeoyl-Lthreonic
acid, (-)-(2)-(E)-coffeoyl threonic acid lactone, (+)-(E)-caffeoyl-L-malic acid
 Others: a saponine, carotenoids, a phytocytostatin (chelidocystatin), sparteine and flavonoids.

Samenvatting van EMA monografie
Chelidonium extracts have a well documented antiviral activity with perspective. Herpes simplex, polio as well as several adenoviruses are affected. There is even an in vivo anti-Influenza activity.
Protoberberine was found active against reverse transcriptase of RNA-tumour viruses. Antimicrobial activity was mostly tested with separate compounds of Chelidonium. The same results were obtainedfor the anti-tumoral activity.
Choleretic activity seems to be linked to the totality of the components. Furthermore in different  experimental models there are indications for anti-inflammatory and analgesic properties.
The alkaloids of Chelidonium seem to be intensively metabolised. A high volume of distribution should be taken into consideration. Although the acute toxicology of the total extract is low, some alkaloids such as sanguinarine induced DNA damage in bone marrow cells. The same can be stated for the cytotoxicity. There is only one clinical study with the total extract in patients with epigastric complaints, whereas
there are warnings against possible hepatotoxicity of Chelidonium containing preparations. These warnings were translated into registration restrictions in Germany.

A risk-benefit analysis can be made for the herbal preparations containing Chelidonium. The herbal substance is described in the European Pharmacopoeia with a minimum of 0.6% of total alkaloids. The herbal substance as well as the alkaloids can be characterised without too much difficulty. Adulteration of the herbal substance is no point of concern.
Although voluntary intoxications with the herbal substance and preparations thereof are not reported, there is a concern with regard to possible hepatotoxicity. Indications for genotoxicity or foetotoxicity are known for single alkaloids of Chelidonium, not for the total extracts. Chelidonium preparations are used for epigastric discomfort and superficial warts. These conditions are not serious and other herbal as well as conventional medicines exist for internal use. Warts are mostly treated with preparations containing several plants which complicate the characterisation of mono preparations in the monograph. The fresh latex is traditionally used in folk medicine and cannot be considered in an industrial context. Patients with liver diseases should be considered as patients at risk and should not take Chelidonium containing preparations. Although the herbal substance has a long standing use in Europe, the risk-benefit balance can be considered as negative and the use of Chelidonium containing
preparations should be restricted as type of patients and daily intake of alkaloids is concerned. 



Chelidonium majus
How It Works

Greater celandine, like other members of the Papaveraceae (poppy) family, contains alkaloids as its major constituents. These include chelidoxanthine, chelidonine, and coptisine. Greater celandine extracts have been shown to stimulate production of bile and pancreatic digestive enzymes in human studies.11
Animal and test tube studies have shown that the alkaloids and whole plant extract can relieve gallbladder spasms and stimulate an under-active gallbladder.12 , 13 Test tube and animal studies have also shown celandine extracts and purified alkaloids to have anti-inflammatory, anti-cancer and antimicrobial properties.14 , 15 , 16 They have also shown greater celandine’s ability to protect animal livers from toxic substances.17 , 18
A double-blind trial found that a standardized extract of greater celandine could relieve symptoms of indigestion (such as abdominal cramping, sensation of fullness, and nausea) significantly better than a placebo.19 The trial used an extract standardized to 4 mg of chelidonine per capsule and gave 1–2 tablets three times daily for six weeks. An earlier, preliminary trial also found the same extract reduced symptoms in people with indigestion.20
Preliminary reports from Russia and China have reported that a tincture of greater celandine applied topically was useful for warts.21 However, these results have not yet been confirmed by double-blind clinical trials.
Several reports describe Eastern European clinical trials using semi-synthetic derivatives of greater celandine alkaloids for people with cancer.22 This injectable product goes by the name Ukrain®. The findings on this drug cannot be applied to greater celandine because the alkaloids have been modified from their original form.

How to Use It
One explanation for the variable results obtained from using greater celandine is improperly prepared, dried extracts.23 Drying extracts quickly at high temperature is necessary to preserve the alkaloids.24 Extracts standardized to a content of 4 mg chelidonine per capsule are recommended to be taken three times per day.25 Alternatively, one may mix 1–3 ml tincture into water and sip slowly 10–30 minutes before eating. Topical applications should consist of either concentrated tinctures or the fresh yellow latex. Herbalists and doctors recommend applying fresh latex once per day to warts and allowing it to dry in place.26

Side Effects
Use of fresh plant products may cause stomach upset.27 Topical use has been associated with intense itching and a rash in one case.28 Greater celandine should be avoided during pregnancy and in children under age 12.29 A recent report of ten women in Germany suffering from acute hepatitis following supplementation with a standardized extract of greater celandine (dosage was not given) suggest this herb should be avoided by people with hepatitis or impaired liver function. Greater celandine should be used cautiously and under the supervision of a healthcare professional until more is understood about its potential liver toxicity.30

References
1. Weiss RF. Herbal Medicine. Gothenburg, Sweden: Ab Arcanum and Beaconsfield, UK: Beaconsfield Publishers Ltd, 1985, 84–8.
2. Duke JA. CRC Handbook of Medicinal Herbs. Boca Raton, FL: CRC Press, 1985, 113.
3. Mességué M. Of Men and Plants. New York: Macmillian Co, 1973.
4. Duke JA. CRC Handbook of Medicinal Herbs. Boca Raton, FL: CRC Press, 1985, 113.
5. Stickel F, Pöschl G, Seitz HK, Waldherr R, Hahn EG, Schuppan D. Acute hepatitis induced by Greater Celandine (Chelidonium majus). Scand J Gastroenterol 2003;38:565–68.
6. Schulz V, Hänsel R, Tyler VE. Rational Phytotherapy: A Physician’s Guide to Herbal Medicine. 3rd ed, Berlin: Springer, 1998, 168–73.
7. Blumenthal M, Busse WR, Goldberg A, et al. (eds). The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Austin: American Botanical Council and Boston: Integrative Medicine Communications, 1998, 425–6.
8. Ritter R, Schatton WFH, et al. Clinical trial on standardized celandine extract in patients with functional epigastric complaints: Results of placebo-controlled double-blind trial. Comp Ther Med 1993;1:189–93.
9. Benninger J, Schneider HT, Schuppan D, et al. Acute hepatitis induced by greater celandine (Chelidonium majus). Gastroenterol 1999;117:1234–7.
10. Weiss RF. Herbal Medicine. Gothenberg, Sweden: Ab Arcanum, 1988, 337.
11. Baumann JC. Effect of Chelidonium, Curcuma, absinth and Carduus marianus on the bile and pancreatic secretion in liver diseases. Med Monatsschr 1975;29:173–80 [in German].
12. Hiller KO, Ghorbani M, Schilcher H. Antispasmodic and relaxant activity of chelidonine, protopine, coptisine, and Chelidonium majus extracts on isolated guinea-pig ileum. Planta Med 1998;64:758–60 [letter].
13. Hriscu A, Galesanu MR, Moisa L. Cholecystokinetic action of an alkaloid extract of Chelidonium majus. Rev Med Chir Soc Med Nat Lasi 1980;84:559–61 [in Romanian].
14. Vavreckova C, Gawlik I, Muller K. Benzophenanthridine alkaloids of Chelidonium majus; I. Inhibition of 5- and 12-lipoxygenase by a non-redox mechanism. Planta Med 1996;62:397–401.
15. Sokoloff B, Saelhof CC, Takeuchi Y, Powella R. The antitumor factors present in Chelidonium majus L. I. Chelidonine and protopine. Growth 1964;28:225–31.
16. Molochko VA, Lastochkina TM, Krylov IA, Brangulis KA. The antistaphylococcal properties of plant extracts in relation to their prospective use as therapeutic and prophylactic formulations for the skin. Vestn Dermatol Venerol 1990;(8):54–6 [in Russian].
17. Mitra S, Gole K, Samajdar K, et al. Antihepatotoxic activity of Chelidonium majus. Int J Pharmacognosy 1992;30:125–8.
18. Mitra S, Sur RK, Roy A, Mukherjee AS. Effect of Chelidonium majus L on experimental hepatic tissue injury. Phytother Res 1996;10:354–6.
19. Ritter R, Schatton WFH. Clinical trial on standardized celandine extract in patients with functional epigastric complaints: Results of placebo-controlled double-blind trial. Comp Ther Med 1993;1:189–93.
20. Kniebel R, Urlacher W. Z Allgemeinmed 1993;69:680–4.
21. Bone K (ed). Chelidonium--A medicinal poppy. MediHerb Professional Newsletter 1996;49:1–3.
22. Susak YM, Zemskov VS, Yaremchuk OY, et al. Comparison of chemotherapy and x-ray therapy with Ukrain monotherapy for colorectal cancer. Drugs Exptl Clin Res 1996;22:115–22.
23. Weiss RF. Herbal Medicine. Gothenburg, Sweden: Ab Arcanum and Beaconsfield, UK: Beaconsfield Publishers Ltd, 1985, 84–8.
24. Bone K (ed). Chelidonium--A medicinal poppy. MediHerb Professional Newsletter 1996;49:1–3.
25. Ritter R, Schatton WFH. Clinical trial on standardized celandine extract in patients with functional epigastric complaints: Results of placebo-controlled double-blind trial. Comp Ther Med 1993;1:189–93.
26. Weiss RF. Herbal Medicine. Gothenburg, Sweden: Ab Arcanum and Beaconsfield, UK: Beaconsfield Publishers Ltd, 1985, 84–8.
27. McGuffin M, Hobbs C, Upton R, Goldberg A (eds). American Herbal Products Association’s Botanical Safety Handbook. Boca Raton, FL: CRC Press, 1997.
28. Etxenagusia MA, Anda M, Gonzalez-Mahave I, et al. Contact dermatitis from Chelidonium majus (greater celandine). Contact Derm 2000;43:47.
29. McGuffin M, Hobbs C, Upton R, Goldberg A (eds). American Herbal Products Association’s Botanical Safety Handbook. Boca Raton, FL: CRC Press, 1997.
30. Benninger J, Schneider HT, Schuppan D, et al. Acute hepatitis induced by greater celandine (Chelidonium majus). Gastroenterol 1999;117:1234–7.

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