Butterbur: 17th century remedy and 21st century science
The study by Schapowal1 showed that a herbal remedy, butterbur or Petasites hybridus, was as effective as second generation histamine H1-receptor antagonist, cetirizine, in improving nasal symptoms in patients with seasonal allergic rhinitis, albeit in the backdrop of major criticisms,2;3 including the use of one-sided statistical analysis in a non-placebo-controlled study based on subjective outcome measure.
In a recent randomised, double-blind, placebo-controlled study, in patients with seasonal allergic rhinitis, butterbur was shown to be effective in attenuating the response to nasal provocation testing with adenosine monophosphate,4 which acts through A2-purinoceptors on primed mast cells leading to degranulation and release of mediators such as histamine, cysteinyl leukotrienes, and prostaglandins.5 Butterbur has also been found to be equally effective compared to modern or third generation histamine H1-receptor antagonist, fexofenadine, in conferring protection against nasal adenosine monophosphate challenge as well as in improving nasal symptoms in patients with perennial allergic rhinitis.6 Furthermore, with the recognition of both the upper and lower airway as being part of a unified airway,7 butterbur has been shown to improve airway hyper-reactivity following bronchial adenosine monophosphate challenge compared to placebo in asthmatic patients maintained on inhaled corticosteroids.8 However, butterbur may not be effective in allergic skin disease as butterbur did not produce any significant effects on the histamine and allergen cutaneous response compared to placebo in atopic patients.9
Although the exact mechanism of action of butterbur has yet to be fully elucidated, petasin, the active ingredient of butterbur, has been found to inhibit the biosynthesis of histamine and cysteinyl leukotrienes in vitro, in addition to blocking the release of serum eosinophil cationic protein.10-13In vivo, butterbur has been shown to reduce levels of histamine and cysteinyl leukotrienes from nasal lavage.14
One must not forget that butterbur in its unpurified form contain toxic pyrrolizidine alkaloids which have been linked to hepatotoxicity and carcinogenicity.15 In addition, butterbur has been shown to inhibit testosterone production using an animal model.16 Therefore, even though there is potentially a therapeutic role for butterbur in allergic rhinitis and asthma, further rigorous studies relating specifically to issues surrounding the potential long-term side-effects of butterbur would need to be conducted before butterbur can be recommended for use in the treatment of allergic airway disease.
References
1. Schapowal A. Randomised controlled trial of butterbur and cetirizine for treating seasonal allergic rhinitis. BMJ 2002;324:144.
2. Shuster S. Treating seasonal allergic rhinitis. Well designed experiments should have been used. BMJ 2002;324:1277.
3. McArthur CA,.Arnott N. Treating seasonal allergic rhinitis. Trial does not show that there is no difference between butterbur and cetirizine. BMJ 2002;324:1277.
4. Lee DK, Carstairs IJ, Haggart K, Jackson CM, Currie GP, Lipworth BJ. Butterbur, a herbal remedy, attenuates adenosine monophosphate induced nasal responsiveness in seasonal allergic rhinitis. Clin Exp Allergy 2003;33:882-6.
5. Lee DK, Gray RD, Lipworth BJ. Adenosine monophosphate bronchial provocation and the actions of asthma therapy. Clin Exp Allergy 2003;33:287-94.
6. Lee DK, Gray RD, Robb FM, Fujihara S, Lipworth BJ. A placebo-controlled evaluation of butterbur and fexofenadine on objective and subjective outcomes in perennial allergic rhinitis. Clin Exp Allergy 2004;34:646-9.
7. Bousquet J, van Cauwenberge P, Khaltaev N. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol 2001;108:S147-S334.
8. Lee DK, Haggart K, Robb FM, Lipworth BJ. Butterbur, a herbal remedy, confers complementary anti-inflammatory activity in asthmatic patients receiving inhaled corticosteroids. Clin Exp Allergy 2004;34:110-4.
9. Jackson CM, Lee DK, Lipworth BJ. The effects of butterbur on the histamine and allergen cutaneous response. Ann Allergy Asthma Immunol 2004;92:250-4.
10. Thomet OA, Wiesmann UN, Blaser K, Simon HU. Differential inhibition of inflammatory effector functions by petasin, isopetasin and neopetasin in human eosinophils. Clin Exp Allergy 2001;31:1310-20.
11. Brune K, Bickel D, Peskar BA. Gastro-protective effects by extracts of Petasites hybridus: the role of inhibition of peptido-leukotriene synthesis. Planta Med 1993;59:494-6.
12. Bickel D, Roder T, Bestmann HJ, Brune K. Identification and characterization of inhibitors of peptido-leukotriene-synthesis from Petasites hybridus. Planta Med 1994;60:318-22.
13. Thomet OA, Wiesmann UN, Schapowal A, Bizer C, Simon H. Role of petasin in the potential anti-inflammatory activity of a plant extract of petasites hybridus. Biochem Pharmacol 2001;61:1041-7.
14. Thomet OA, Schapowal A, Heinisch IV, Wiesmann UN, Simon HU. Anti-inflammatory activity of an extract of Petasites hybridus in allergic rhinitis. J Immunopharmacol 2002;2:997-1006.
15. Barnes J. Safety concerns over butterbur. Pharm J 2002;268:123-30.
16. Lin H, Chien CH, Lin YL, Chen CF, Wang PS. Inhibition of testosterone secretion by S-petasin in rat testicular interstitial cells. Chin J Physiol 2000;43:99-103.
Competing interests:
None declared
Competing interests:
No competing interests
11 April 2004
Daniel K C Lee
Respiratory Physician
Department of Respiratory Medicine, Ipswich Hospital, Heath Road, Ipswich IP4 5PD, Suffolk, England
Rapid Response:
Butterbur: 17th century remedy and 21st century science
The study by Schapowal1 showed that a herbal remedy, butterbur or Petasites hybridus, was as effective as second generation histamine H1-receptor antagonist, cetirizine, in improving nasal symptoms in patients with seasonal allergic rhinitis, albeit in the backdrop of major criticisms,2;3 including the use of one-sided statistical analysis in a non-placebo-controlled study based on subjective outcome measure.
In a recent randomised, double-blind, placebo-controlled study, in patients with seasonal allergic rhinitis, butterbur was shown to be effective in attenuating the response to nasal provocation testing with adenosine monophosphate,4 which acts through A2-purinoceptors on primed mast cells leading to degranulation and release of mediators such as histamine, cysteinyl leukotrienes, and prostaglandins.5 Butterbur has also been found to be equally effective compared to modern or third generation histamine H1-receptor antagonist, fexofenadine, in conferring protection against nasal adenosine monophosphate challenge as well as in improving nasal symptoms in patients with perennial allergic rhinitis.6 Furthermore, with the recognition of both the upper and lower airway as being part of a unified airway,7 butterbur has been shown to improve airway hyper-reactivity following bronchial adenosine monophosphate challenge compared to placebo in asthmatic patients maintained on inhaled corticosteroids.8 However, butterbur may not be effective in allergic skin disease as butterbur did not produce any significant effects on the histamine and allergen cutaneous response compared to placebo in atopic patients.9
Although the exact mechanism of action of butterbur has yet to be fully elucidated, petasin, the active ingredient of butterbur, has been found to inhibit the biosynthesis of histamine and cysteinyl leukotrienes in vitro, in addition to blocking the release of serum eosinophil cationic protein.10-13In vivo, butterbur has been shown to reduce levels of histamine and cysteinyl leukotrienes from nasal lavage.14
One must not forget that butterbur in its unpurified form contain toxic pyrrolizidine alkaloids which have been linked to hepatotoxicity and carcinogenicity.15 In addition, butterbur has been shown to inhibit testosterone production using an animal model.16 Therefore, even though there is potentially a therapeutic role for butterbur in allergic rhinitis and asthma, further rigorous studies relating specifically to issues surrounding the potential long-term side-effects of butterbur would need to be conducted before butterbur can be recommended for use in the treatment of allergic airway disease.
References
1. Schapowal A. Randomised controlled trial of butterbur and cetirizine for treating seasonal allergic rhinitis. BMJ 2002;324:144.
2. Shuster S. Treating seasonal allergic rhinitis. Well designed experiments should have been used. BMJ 2002;324:1277.
3. McArthur CA,.Arnott N. Treating seasonal allergic rhinitis. Trial does not show that there is no difference between butterbur and cetirizine. BMJ 2002;324:1277.
4. Lee DK, Carstairs IJ, Haggart K, Jackson CM, Currie GP, Lipworth BJ. Butterbur, a herbal remedy, attenuates adenosine monophosphate induced nasal responsiveness in seasonal allergic rhinitis. Clin Exp Allergy 2003;33:882-6.
5. Lee DK, Gray RD, Lipworth BJ. Adenosine monophosphate bronchial provocation and the actions of asthma therapy. Clin Exp Allergy 2003;33:287-94.
6. Lee DK, Gray RD, Robb FM, Fujihara S, Lipworth BJ. A placebo-controlled evaluation of butterbur and fexofenadine on objective and subjective outcomes in perennial allergic rhinitis. Clin Exp Allergy 2004;34:646-9.
7. Bousquet J, van Cauwenberge P, Khaltaev N. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol 2001;108:S147-S334.
8. Lee DK, Haggart K, Robb FM, Lipworth BJ. Butterbur, a herbal remedy, confers complementary anti-inflammatory activity in asthmatic patients receiving inhaled corticosteroids. Clin Exp Allergy 2004;34:110-4.
9. Jackson CM, Lee DK, Lipworth BJ. The effects of butterbur on the histamine and allergen cutaneous response. Ann Allergy Asthma Immunol 2004;92:250-4.
10. Thomet OA, Wiesmann UN, Blaser K, Simon HU. Differential inhibition of inflammatory effector functions by petasin, isopetasin and neopetasin in human eosinophils. Clin Exp Allergy 2001;31:1310-20.
11. Brune K, Bickel D, Peskar BA. Gastro-protective effects by extracts of Petasites hybridus: the role of inhibition of peptido-leukotriene synthesis. Planta Med 1993;59:494-6.
12. Bickel D, Roder T, Bestmann HJ, Brune K. Identification and characterization of inhibitors of peptido-leukotriene-synthesis from Petasites hybridus. Planta Med 1994;60:318-22.
13. Thomet OA, Wiesmann UN, Schapowal A, Bizer C, Simon H. Role of petasin in the potential anti-inflammatory activity of a plant extract of petasites hybridus. Biochem Pharmacol 2001;61:1041-7.
14. Thomet OA, Schapowal A, Heinisch IV, Wiesmann UN, Simon HU. Anti-inflammatory activity of an extract of Petasites hybridus in allergic rhinitis. J Immunopharmacol 2002;2:997-1006.
15. Barnes J. Safety concerns over butterbur. Pharm J 2002;268:123-30.
16. Lin H, Chien CH, Lin YL, Chen CF, Wang PS. Inhibition of testosterone secretion by S-petasin in rat testicular interstitial cells. Chin J Physiol 2000;43:99-103.
Competing interests:
None declared
Competing interests: No competing interests