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Oregon Grape Root Extract for Psoriasis
By Francis Brinker, BA, BSc, ND
A number of conventional treatment options are available and effectively reduce the symptoms of psoriasis in many patients; however, there is no cure and no one treatment works for everyone.
Like patients with other chronic conditions, the 4.5 million U.S. patients suffering from psoriasis, an immune-mediated, genetic disease characterized by patches of raised red skin covered by flaky white buildup,1 may seek out alternative therapies, including Oregon grape root, to relieve their symptoms.
Oregon grape is the state flower of Oregon. This shrub is over three feet in height and bears yellow flower clusters in the spring that develop into waxy blue berries from which it gets its name. Its compound leaves made up of spiny leaflets resembling holly leaves are responsible for the less common name, holly grape. In 1877, J.H. Bundy, an Eclectic doctor from Colusa, CA, was the first to introduce Oregon grape to the medical profession as Berberis aquifolium tincture made from the fresh bark of the root.2 Berberis aquifolium officially became recognized in the United States Pharmacopeia in 1900.
Later designated botanically as Mahonia aquifolium, this medicinal plant is known for its yellow inner bark, particularly of the root. The yellow pigment acts as a visual marker for the important alkaloid component, berberine. This alkaloid usually is considered responsible for much of Oregon grape’s therapeutic activity.
M. aquifolium originally was promoted as a remedy for syphilis. Oregon grape root also gained a reputation for controlling excessive mucus discharges. Its root bark extract was given as a bitter tonic to improve appetite and digestion, especially when there was liver involvement.3 In several cases of severe eczema, it was reported to produce great therapeutic success. At the time, it was considered the most reliable remedy for psoriasis.2 An 1896 editorial indicated that when alternated with other remedies in long-standing cases of psoriasis, addition of Oregon grape root seemed to initiate improvement.4
A cure of an extreme case of psoriasis reported in the Parke, Davis & Co. publication "New Preparations" around 1900 brought considerable attention to M. aquifolium. A Michigan man was troubled for nearly seven years by psoriasis that afflicted him from head to foot. He had used many ineffective remedies, traveling as far as England for treatment at the Royal Hospital for Skin Diseases for three months. Fowler’s Solution (potassium arsenite) finally arrested his symptoms after six months. However, it returned a year later, worse than ever. Eventually, he obtained a bottle of Oregon grape root fluid extract. Consuming a teaspoonful four times daily, he began to feel a tingling sensation in the affected skin. The skin exfoliation steadily grew less and less. After about six weeks the patches ceased to form. The red discoloration gradually disappeared, leaving only one small obstinate patch on the knee. Because this remedy was the only alteration he had made in his treatment prior to recovery, he credited the improvement to the Oregon grape extract.2
After several decades of clinical experience with this condition, it was observed that M. aquifolium worked well in conjunction with external treatment. Lesions disappeared with persistent use.3 However, with the advancement of synthetic pharmaceuticals and the closure of the last Eclectic medical college in the 1930s, Oregon grape extract went the way of many botanical products: It fell into disuse in conventional medical practice. By contrast, alternative practitioners and authors—including naturopathic doctors, herbalists, and homeopaths—continued advocating its use for psoriasis both here and abroad.
Mechanism of Action
Modern research helps explain the reason for M. aquifolium root’s effectiveness in psoriasis. This condition is characterized by chronic hyperproliferation of the epidermis. Pathological changes in psoriasis also involve inflammation mediated by lipoxygenase-derived products of arachidonic acid. M. aquifolium bark extract containing 1.12% alkaloids (including berberine, oxyacanthine, and berbamine) inhibited the in vitro growth of a rapidly multiplying human keratinocyte cell line, HaCaT. The same degree of activity was obtained from its alkaloid components oxyacanthine and berbamine, while equivalent activity using berberine occurred at a slightly higher concentration. By comparison, the drugs triamcinolone, hydrocortisone, and fluorouracil were inactive at similar concentrations. Only the antipsoriatic agent anthralin (dithranol) proved to be more potent.5
This same M. aquifolium extract was tested in vitro for its antioxidant properties. The inhibitory concentration for 50% reduction (IC50) of lipid peroxidation in bovine brain phospholipid liposomes was 5 mM. The IC50 in this liposome model was 46 mM for berbamine and 40 mM for oxyacanthine, while anthralin and berberine required concentrations of 79 mM and 118 mM, respectively, for the same activity. When tested for their radical scavenging activity, the potency of these agents from greatest to least was berbamine > oxyacanthine > M. aquifolium extract > anthralin > berberine. These tests indicate that although anthralin is superior as an antiproliferant and equivalent to M. aquifolium extract as a lipoxygenase inhibitor, the extract and its alkaloids are superior as antioxidants.5,6
Lipid peroxidation also was inhibited by minor alkaloids derived from the roots of M. aquifolium. The greatest inhibition was about 50% and occurred using 100 mM oxyberberine and 300 mM jatrorrhizine. Other minor alkaloids that were less potent included columbamine and magnoflorine, while the major alkaloid berberine inhibited even less at similar concentrations. The order of potency was oxyberberine > crude extract > columbamine > jatrorrhizine > magnoflorine > berberine. Correlation of the antioxidant activity and lipoxygenase inhibition of these alkaloids is evident, and their presence likely contributes to the effect of the extract.7
A recent randomized, placebo-controlled clinical trial evaluated the safety and efficacy of M. aquifolium bark extract on 82 psoriasis patients as a local application.8 The study included 43 men and 39 women. Patients selected for the study had lesions that were bilaterally symmetrical. A placebo ointment was applied to one side of the body, while M. aquifolium extract ointment was applied to the other. The M. aquifolium ointment was made with a 10% content of the bark extract prepared according to the German Homeopathic Pharmacopeia. The ointments were massaged into the psoriatic patches 2-3 times daily and applied on bandages at night for about eight weeks.
The psoriasis was categorized as light in 9.5%, moderate in 36.5%, and severe in 54.1%. Although other systemic and local treatments were forbidden, 13 patients admitted during the follow-up that they violated this protocol by using other types of medications at times as well. The severity or concurrent use of other medications did not make a significant difference in the comparative outcomes. According to assessments by the patients themselves, a total of 38.8% responded favorably to the M. aquifolium ointment, while 23.8% improved on the side receiving the placebo. Assessment by physicians indicated that lesions in 36.3% improved or disappeared using M. aquifolium, and 22.5% showed these positive results on the placebo side. Systemic efficacy on the control side due to percutaneous resorption on the treated side was not ruled out.
Another study compared M. aquifolium ointment used topically three times each day in a randomized, half-side study with anthralin applied in rising concentrations once daily in 49 patients.9 Biopsies of the skin lesions in these test areas were conducted before therapy and after four weeks. Following therapy, the monoclonal antibodies ICAM-1, CD3, HLA-DR, and keratin 6 and 16 were markedly reduced by the M. aquifolium ointment. However, anthralin produced significantly greater reductions in ICAM-1, CD3, and HLA-DR. Both agents were effective in reducing hyperproliferation of keratinocytes and cellular cutaneous immune mechanisms.
Documented adverse effects are lacking for Oregon grape with internal use in appropriate doses. Its alkaloid berberine is considered a moderate toxin with a human LD50 of 27.5 mg/kg. Berberine may cause hypotension, dyspnea, and cardiac damage in overdoses. Berberine is considered safe and well tolerated in doses up to 500 mg, or about 8 g of the root bark yielding a content of 6%. It should not be used during pregnancy due to the potential uterine-contracting activity of berberine.10
When used only topically in a clinical trial, four of 82 patients (5%) experienced local adverse effects from M. aquifolium, ranging from allergic sensitivity in one to burning or itching of the skin in the others; withdrawals were not noted.8
A recent review of randomized and/or double-blind English-language studies from 1966 to 2002 on conventional topical treatments for psoriasis found adverse effects ranged widely for monotherapy agents: corticosteroids (3.2-23%), vitamin D analogues (4.8-35%), tazarotene (13-50%), and anthralin [dithranol] (40.5-72%).11 Maximum percentage withdrawals from the studies due to adverse effects varied as follows: tazarotene (18%), anthralin (5.4%), vitamin D analogues (4.6%), and corticosteroids (2.5%).
Formulation and Dosage
The two human studies accomplished two goals by using only local applications. First, topical use concentrated the active alkaloids in the affected tissues. Secondly, it avoided compliance difficulties due to the bitter flavor of these alkaloids. However, adequate penetration through the thick scales is a potential limitation of topical application. Topical use alone would be a prudent initial intervention, but one might theorize that internal use together with local use might achieve even better results than either approach alone.
Traditionally, Oregon grape root or root bark was administered by using oral liquid extracts. For chronic skin diseases, prescriptions of 8-ounce bottles with Oregon grape fluid extract combined with equal parts of simple syrup were administered in teaspoon doses (4 mL) four times daily continuously for a few months.2 Oregon grape root fluid extract consists of a 1:1 strength liquid extract in 40% ethanol in which the dry root weight (g) is equivalent to extract volume (mL). The daily dosage of the Oregon grape portion would therefore be in the range of 8 mL (about 0.25 ounce) of fluid extract representing 8 g of the dried root.
Equivalent doses of other hydro-alcoholic extracts (i.e., tinctures) also are appropriate and may be adjusted by size and frequency to accommodate patient age, size, and compliance. If it is considered desirable to avoid consumption of the alcohol (about one teaspoon daily), a tea can be made by simmering 8 g of root powder in a covered vessel with a cup of water for 10 minutes; this tea should be consumed daily in divided doses.
In all of these forms, the taste of the extract is bitter. The flavor can be improved by adding 2 mL of yerba santa tincture and a little sweetener with each dose.
Oregon grape root extract has a history in America of being an effective internal treatment of psoriasis for more than a century. A recent clinical trial assessing only its topical application confirms its modern usefulness in this form. Aside from berberine, pharmacological studies describe mechanisms for several of its other alkaloids that appear to be primarily responsible for its beneficial influence in this condition. As with all therapeutic agents for psoriasis, Oregon grape root extract lacks universal efficacy, but for select patients it provides a reasonable alternative.
Although no treatment is successful in all cases, conventional topical treatments usually are adequate for controlling the expression of mild-to-moderate psoriasis in most patients. While short-term efficacy and safety of these agents are acceptable, long-term exposure to drugs such as corticosteroids is undesirable. For those resistant to conventional therapy or who may prefer a different approach, a trial with topical Oregon grape root extract should be considered.
Topical and internal application of M. aquifolium extract deserves further consideration and investigation for this difficult to treat chronic condition.
Dr. Brinker is an Instructor at the Program in Integrative Medicine at the University of Arizona, Tucson.
1. National Psoriasis Foundation. Available at: www.psoriasis.org. Accessed May 8, 2003.
2. Webster HT. Berberis aquifolium. Ecl Med J 1906;66:430-435.
3. Felter HW. Berberis and barberry. Ecl Med J 1922;82:45-46.
4. Editorial. Berberis aquifolium. Ecl Med J 1896;56:148-149.
5. Muller K, et al. The antipsoriatic Mahonia aquifolium and its active constituents; II. Antiproliferative activity against cell growth of human keratinocytes. Planta Med 1995;61:74-75.
6. Muller K, Ziereis K. The antipsoriatic Mahonia aquifolium and its active constituents; I. Pro- and antioxidant properties and inhibition of 5-lipoxygenase. Planta Med 1994;60:421-424.
7. Misik V, et al. Lipoxygenase inhibition and antioxidant properties of protoberberine and aporphine alkaloids isolated from Mahonia aquifolium. Planta Med 1995;61:372-373.
8. Wiesenauer M, Ludtke R. Mahonia aquifolium in patients with psoriasis vulgaris—an intraindividual study. Phytomedicine 1996;3:231-235.
9. Augustin M, et al. Effects of Mahonia aquifolium ointment on the expression of adhesion, proliferation, and activation markers in the skin of patients with psoriasis. [German] Forsch Komplementarmed 1999;6(Suppl 2):19-21.
10. McGuffin M, et al. American Herbal Products Association’s Botanical Safety Handbook. Boca Raton, FL: CRC Press; 1997.
11. Bruner CR, et al. A systematic review of adverse effects associated with topical treatments for psoriasis. Dermatol Online J 2003;9(1). Available at: www.medscape.com/viewarticle/451658.