Oregon Grape (Mahonia aquifolium / Berberis aquifolium)
1. Identity and Botanical Profile
Nomenclature and Taxonomy
Oregon grape, scientifically known as Mahonia aquifolium, is an evergreen shrub in the Berberidaceae family, native to the United States. The species carries two accepted scientific names that are used interchangeably in both botanical literature and commerce: due to genetic similarities between Mahonia and Berberis, many species are shuffled between the two genera, and Mahonia aquifolium is now synonymous with Berberis aquifolium. The species epithet "aquifolium" is derived from Latin, meaning "with leaves like holly," referring to the spiny, holly-like leaves of the plant.
Several members of the barberry family, Berberidaceae, actually go by the common name of Oregon grape, with many variations, such as Oregon hollygrape, tall Oregon grape, hollyleaved barberry, and creeping barberry. The Berberis genus also goes by Mahonia, depending on taxonomy. Medicinally related species include Mahonia nervosa (low Oregon grape or Cascade barberry) and Mahonia repens (creeping barberry). Unrelated to true grapes in the family Vitaceae, Oregon grape is an evergreen shrub, typically growing in the forest understory. In California and the Pacific Northwest, one of the most common species — and Oregon's state flower — is Berberis aquifolium (also called tall Oregon grape, or hollyleaved barberry).
Geographic Origin and Habitat
Native to western North America, Mahonia aquifolium naturally occurs from British Columbia in Canada, through Washington, Oregon, and Idaho, extending into California and parts of Montana. Oregon grape is a common name for members of the barberry family, Berberidaceae. The six native species of the plant are widely distributed through Oregon in a variety of habitats on both sides of the Cascade Mountains to the coast and in the northeastern part of the state. Some species grow in sunny or shade sites in moist, well-drained soil; others prefer dry, well-drained sites. They are shade tolerant and often are understory shrubs in coniferous forests.
Plant Description
Oregon grape (Mahonia aquifolium) is a small shrub with spiny leaves and clusters of bright yellow flowers that bloom in the spring. It produces small, blue-purple berries that resemble grapes, hence its name. Native to western North America, Berberis aquifolium is known for its yellow roots, holly-like leaves, and tart, blue berries that resemble a cluster of grapes. The yellow pigment in the stems and roots of Oregon grape is related to various antimicrobial alkaloids, most notably berberine.
Common Forms and Preparations
Oregon grape root extracts are available in both oral and topical dosage forms. The root is the primary part harvested for medicinal use. One can make a decoction (tea which is simmered for 5–20 minutes); however, this has a strongly bitter taste which makes it very much a medicinal drink, as opposed to an enjoyable tea. It is more usual to take this herb as a tincture. Oregon grape root can be extracted, added to herbal tea blends, and employed in topical care formulas. Topical preparations — including creams, ointments, and gels standardized to a defined percentage of Mahonia aquifolium bark extract — have been developed specifically for dermatological use and have been the subject of most clinical research. Demand for Oregon grape products has increased since the plant goldenseal — which also contains berberine — became endangered due to overharvesting.
2. Traditional and Historical Use
Indigenous North American Use
Oregon grape is thought to have been used for thousands of years by Native Americans, for its culinary uses, its medicinal uses, and other practical uses. Historically, knowledge of the use of Oregon grape (Mahonia aquifolium) came from First Nations peoples. Based on collected ethnographic information, Native American tribes utilized all species of Oregon grape (Moerman, 2009). The Blackfoot, Karuk, Okanagan-Colville, Samish, Sanpoil, Squaxin and Thompson tribes utilized the roots and branches for addressing a variety of ailments.
Native American tribes of the Pacific Northwest have used preparations from Oregon grape roots to treat stomach problems, hemorrhages, arthritis, and tuberculosis. Many tribes in the Pacific Northwest have used it as a blood tonic, an antimicrobial, a laxative, and to ease stomach irritability. Native American tribes used Mahonia aquifolium as a treatment for fungal infections, skin problems, and dysentery. The Blackfeet peeled the root, dried it, and made an infusion to stop rectal hemorrhage and dysentery. The Catawba used the herb for peptic ulcers.
Berries were an important food source as well as medicine. Oregon grape berries are a traditional food for Northwest Native People and were often mixed with other sweeter berries like salal and made into pemmican cakes. The use of B. nervosa by Native American tribes included eating the berries for shellfish poisoning, with cautioned use based upon the perception that Oregon grape was very potent (Pojar & MacKinnon, 1994). Indigenous peoples of the Pacific Northwest used it for various purposes; the roots were used for dye, the bark for tanning leather, and the berries, although sour, were sometimes eaten or used to make jelly.
Use in 19th-Century Western Herbal Medicine
In the 19th and early 20th centuries, Oregon grape was prescribed as a detoxifier and tonic. It was an important herb in the Physiomedicalist movement, who based their therapies on a combination of orthodox and Native American practices. Oregon grape root was also once known as "Indian barberry" as it was widely used in North American tribal lineages as a gastrointestinal aid, kidney support, and general tonic for health.
The Eclectic physicians, who drew from North American indigenous herbal practice, also regarded Oregon grape root as a general tonic, but also articulated more specific indications. It was considered to be an effective remedy for liver and gallbladder ailments, gastrointestinal infections, constipation, malaria, syphilis, and uterine hemorrhage.
Use in Traditional Chinese Medicine
Plants of the Berberidaceae family have been extensively used in traditional Chinese medicine in the treatment of various conditions such as periodontitis, dysentery, tuberculosis, wounds, eczema, and icterus. In China, the herb Coptis (Coptis chinensis) is often substituted for Oregon grape. Seventeen different varieties of Berberis plants are used, all containing the constituent berberine. They are primarily used to treat intestinal infections, to stimulate the uterus, and treat congested lungs.
3. Key Constituents and Active Compounds
Primary Alkaloids
Alkaloids, including berberine, berbamine, canadine, and hydrastine, may account for the activity of Oregon grape. Alkaloids are regarded as the major constituents and perhaps responsible for most of the properties, with berberine being the most widely distributed. There are many other alkaloids in Oregon grape, including berbamine, canadine, columbamine, corydine, and more (Moore 2003). The root and wood contain isoquinoline alkaloids including jatorrhizine, palmatine, berberine, berbamine, and magnoflorine, which account for its therapeutic use.
Berberine is the most prominent and extensively studied alkaloid. Berberine is a yellowish phytochemical isoquinoline alkaloid belonging to the protoberberine group, presented in various plant families such as Berberidaceae, Papaveraceae, and Ranunculaceae. It is mainly extracted from stem, bark, rhizome, and roots of barberry (Berberis vulgaris), tree turmeric (Berberis aristata), Coptis (Coptis chinensis), goldenseal (Hydrastis canadensis), and Oregon grape (Berberis aquifolium). Berberine is a strong antimicrobial and liver stimulant that is also found in other plants including barberry, coptis, greater celandine, and goldenseal.
Other Phytochemical Classes
Additional constituents of Oregon grape include flavonoids, tannins, phytosterols, resins and lignans, and volatile oils. The bitterness of the root comes from the bitter alkaloids, which are responsible for many of the medicinal actions. The astringency comes from the tannins, which dry up excess secretions throughout the body. The combination of the tannins, bitter alkaloids, and resins leaves a dry and slightly tacky taste in the mouth.
4. Established Mechanisms of Action
Inhibition of Lipoxygenase and Anti-Inflammatory Action
The effect of Mahonia aquifolium crude extract and its two representative alkaloid fractions containing protoberberine and bisbenzylisoquinoline (BBIQ) alkaloids on the activity of 12-lipoxygenase (12-LOX) has been studied. The results indicate that although the direct radical scavenging mechanism cannot be ruled out in the lipoxygenase inhibition by Mahonia aquifolium and its constituents, other mechanisms based on specific interaction between enzyme and alkaloids could play a critical role in lipoxygenase inhibition rather than non-specific reactivity with free radicals. Lipoxygenase inhibition is of direct relevance to inflammatory skin diseases such as psoriasis, since the lipoxygenase pathway generates pro-inflammatory leukotrienes.
AMPK Pathway Activation
Berberine, an alkaloid derived from various plants in the Berberidaceae family, enhances cellular defenses against oxidative stress through several mechanisms. It activates the AMP-activated protein kinase (AMPK) pathway, which reduces mitochondrial reactive oxygen species (ROS) production and improves energy metabolism. Furthermore, it boosts the activity of key antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), thus protecting cells from oxidative damage.
Berberine's primary mechanism is AMPK (AMP-activated protein kinase) activation. AMPK is often described as a cellular energy sensor — it responds to low ATP states by shifting cells toward energy production and away from energy storage. When AMPK is active, glucose uptake into cells increases, fatty acid oxidation increases, and gluconeogenesis (glucose production in the liver) decreases.
Antimicrobial Mechanisms
Extracts or alkaloids isolated from Mahonia aquifolium exhibit antimicrobial activity against Gram-positive and Gram-negative bacteria, fungi, and protozoa. The bacteriostatic and bactericidal activities of a M. aquifolium extract and two of its major alkaloids, berberine chloride and oxyacanthine sulphate, were tested in vitro against nine different oral bacteria. The main antimicrobial mechanism of berberine is suggested to be the inhibition of the activity of the cell division protein FtsZ.
A notable feature of Oregon grape is the presence of compounds that inhibit bacterial multidrug resistance (MDR) efflux pumps. The Staphylococcus aureus multidrug resistance (MDR) efflux pump NorA was reported (Stermitz et al., 2000) to be inhibited by the flavonolignan 5′-methoxyhydnocarpin-D and by the porphyrin pheophorbide a. Both compounds were isolated from leaves of Berberis aquifolium. Plants that contain berberine may participate in beneficial herb-drug interactions with antibiotics by engaging in efflux pump inhibition. Bacteria use efflux pumps to rid their internal environment of noxious chemicals (one mechanism of antibiotic resistance). Berberine inhibits this pump, enabling antibiotics to do their job more effectively (Stermitz et al. 2001).
Macrophage Stimulation
Whole Oregon grape extracts were shown in one pharmacological study to reduce inflammation (often associated with psoriasis) and stimulate the white blood cells known as macrophages. In this study, isolated alkaloids from Oregon grape did not have these actions. This finding suggests that the whole plant extract may have synergistic activity beyond that of its isolated individual constituents.
P-glycoprotein Modulation
In order to investigate whether carrier-mediated transport is involved in the transepithelial transport of berberine and berbamine, transport was evaluated as a function of time in Caco-2 cells. Because berberine has been shown to be actively effluxed by Caco-2 cells, the efflux mechanism was evaluated by measuring the permeability and the amount transported across Caco-2 and MDCKII-MDR1 cells. Results showed that the transport of berberine and berbamine was faster from the basolateral-to-apical direction. This has important implications for drug interactions (discussed below).
5. Scientific Evidence by Area of Use
5a. Dermatology: Psoriasis
Topical use of Mahonia aquifolium for plaque psoriasis is the most extensively studied clinical application for this plant. Its anti-inflammatory properties have led to its recent use in dermatologic disease. In a review, clinical trials on the use of M. aquifolium in cutaneous disorders were compiled to assess its efficacy and safety.
Key clinical trials:
- Based on pilot studies, a randomized, placebo-controlled clinical trial was set up to evaluate the efficacy and safety of Mahonia aquifolium bark extract in psoriasis patients. From autumn 1990 to spring 1992, 82 patients of all severity gradings, recruited by 22 family physicians, were treated. Patients applied two types of ointment (verum/placebo) one to the left side of their body, the other to the right. After an average treatment period of four weeks, patients as well as physicians assessed the therapy's success on a three-level ordinal rating scale. Statistically significant differences (α = 5%) could be found for patients' but not for physicians' assessments.
- Study 1 (of a three-trial monograph) was an open-label study to evaluate the safety of Mahonia aquifolium in 39 patients treated for 12 weeks. Assessments made were modified PASI, global assessment, psoriasis history questionnaire, Dermatology Life Quality Index, and Psoriasis Disability Index. The results indicate statistically significant improvement in PASI score and Dermatology Life Quality Index after 4 weeks of treatment. This response continued 1 month after the end of treatment.
- Study 2 was a clinical trial of 32 patients with mild to moderate bilateral psoriasis treated up to 6 months. One side of the body received Mahonia and the other standard psoriatic treatment (e.g., Dovonex cream). The primary outcomes were patient ratings of the Mahonia-treated side alone and the comparison between treatments received on each side of their body. Eighty-four percent of patients rated the Mahonia-treated psoriasis as good to excellent response. When compared with standard treatment, 63% of patients rated Mahonia aquifolium equal to or better than the standard psoriatic treatment.
- A double-blind, placebo-controlled study using Reliéva (a proprietary form of M. aquifolium) indicated statistically significant improvements in PASI and QLI in the Mahonia-treated group, compared with the control group, indicating that Reliéva is effective and well tolerated in patients with mild to moderate psoriasis.
Systematic review conclusions: The 12 included studies in one systematic review investigated extracts of Mahonia aquifolium (n = 5), Aloe vera (n = 3), indigo naturalis (n = 2), kukui nut oil (n = 1) and Camptotheca acuminata nut (n = 1). Methodological quality was variable. Six studies provided data suitable for meta-analysis of clinical efficacy, and five were vs. placebo (relative risk 3.37, 95% confidence interval 1.36–8.33). The clinical trial evidence provides limited support for preparations containing extracts of M. aquifolium, indigo naturalis, and Aloe vera for the topical management of plaque psoriasis based on multiple studies. No serious adverse events were reported. Because of the small size of most studies and methodological weaknesses, strong conclusions cannot be made. The magnitudes of any effects cannot be measured with accuracy, so it is difficult to assess the clinical relevance of these preparations.
Several studies have shown that Mahonia aquifolium leads to a statistically significant improvement of symptoms in psoriasis and atopic dermatitis with minimal side effects. Overall, evidence is promising but limited: the body of research is larger than for most herbal dermatological treatments, but most studies are small, open-label, or methodologically heterogeneous, and large rigorous RCTs are still lacking.
5b. Dermatology: Atopic Dermatitis (Eczema)
One clinical study was conducted to determine the efficacy and safety of Reliéva cream in adult patients with atopic dermatitis (eczema). This was an open-label trial in 42 patients with atopic dermatitis treated for 12 weeks with Reliéva cream (a homeopathic product containing Psorberine, a proprietary Mahonia aquifolium extract). Efficacy and safety was assessed using Eczema Area and Severity Index scores and a Subject Reported Evaluation of Treatment. The results showed significant (P < 0.05) improvements with respect to Eczema Area and Severity Index scores compared to subjects' baseline scores. Subjects responding to a post-treatment evaluation questionnaire indicated a substantial benefit when rating effectiveness, itching, and appearance. Reliéva cream appears to be a safe and effective treatment for adult patients with atopic dermatitis (eczema).
Evidence for atopic dermatitis is preliminary: available data come primarily from open-label or uncontrolled designs, and the evidence base is smaller than for psoriasis. Studies of the effectiveness of the herb as a treatment for fungal infections, acne, and eczema are very preliminary and inconclusive. Oregon grape shows promise as a treatment for autoimmune diseases of the skin, but there are currently no conclusive clinical results.
5c. Antimicrobial Activity
The antimicrobial activity of the protoberberine alkaloid berberine, isolated from Mahonia aquifolium, was evaluated against 17 microorganisms including two Gram-negative bacteria — Pseudomonas aeruginosa and Escherichia coli (both resistant and sensitive), two Gram-positive bacteria — Bacillus subtilis and Staphylococcus aureus, Zoogloea ramigera, six filamentous fungi, including Penicillium chrysogenum, Aspergillus niger, Aureobasidium pullulans, Trichoderma viride, Fusarium nivale, Mycrosporum gypseum, and two yeasts — Candida albicans and Saccharomyces cerevisiae. Due to its isoquinoline alkaloids like berberine, Oregon grape has demonstrated antimicrobial activity against numerous bacteria, such as E. coli and MRSA. It also possesses antimycotic activity against pathogenic fungal species like Candida and Aspergillus (Mills and Bone 2013).
Research data showed berberine was effective against MRSA at MIC values varying from 256 to 64 mg/L for different MLST types. Berberine alone, and when combined with clindamycin and rifampicin separately, displayed excellent antibacterial activity which reduced bacterial counts by 2 lgCFU/mL within 24 hours and significantly weakened biofilm formation compared with control strain. Additionally, bacterial cytological profiling indicated that berberine destroyed the structure of the cell walls, membrane integrity, and further changed cell morphology with increased concentration.
Evidence in this area is largely in vitro. Direct clinical trials of oral Oregon grape for human infections are absent from the published literature, and efficacy in vivo has not been established in controlled human trials. The efflux pump inhibition data are particularly intriguing but remain at the preclinical stage.
5d. Metabolic and Cardiovascular Effects (Berberine Data)
Much of the metabolic research relates to berberine as an isolated compound rather than Oregon grape extracts specifically. Multiple meta-analyses show berberine significantly reduces LDL cholesterol (by approximately 0.65 mmol/L on average) and triglycerides while modestly raising HDL. The mechanism involves upregulation of LDL receptors in the liver via a pathway distinct from statins, which theoretically means additive effects when combined with statins. Several RCTs show modest but significant reductions in body weight (1 to 3 kg over 12 weeks) with berberine supplementation, likely through combined effects on insulin sensitivity, gut microbiome, and adipogenesis.
NCCIH notes that some small studies link berberine to modest weight or waist-circumference reductions in people with obesity or metabolic conditions, but the evidence is limited and short term. Unlike prescription GLP-1 agonists such as semaglutide, berberine has not been shown in large, long-term trials to reduce cardiovascular events or complications of obesity.
Evidence for metabolic benefits should be interpreted with caution when applied to Oregon grape specifically: these data primarily derive from studies on isolated berberine or other berberine-containing plants, and Oregon grape root preparations standardized for metabolic endpoints have not been studied in clinical trials of their own.
5e. Digestive and Hepatobiliary Support
Oregon grape root has synergistic antibacterial, anti-inflammatory, and bile-stimulating properties and is used for chronic eruptions, rashes associated with pustules, and rashes associated with eating fatty foods. Isolated berberine has been shown to effectively treat diarrhea in patients infected with E. coli. The cholagogue (bile-stimulating) action of Oregon grape, attributed primarily to its bitter alkaloids, has a long traditional basis, though controlled human trials specifically evaluating Oregon grape extract for liver or gallbladder disease are lacking.
6. Body Systems and Health Areas Associated with Oregon Grape
- Integumentary system (skin): Roots and stem-bark of Mahonia aquifolium (Oregon grape) (Berberidaceae) are effectively used in the treatment of skin inflammatory conditions. Psoriasis and atopic dermatitis are the best-documented applications.
- Gastrointestinal system: Oregon grape root was widely used in North American tribal lineages as a gastrointestinal aid. Berberine's documented anti-diarrheal effects support traditional use for dysentery and bowel infections.
- Hepatobiliary system: Isoquinoline alkaloids (berberine and berbamine) are cholagogue and hepatoprotective.
- Immune system: Berberine and berbamine are also immuno-stimulant.
- Antimicrobial/infectious disease: Extracts or alkaloids isolated from Mahonia aquifolium exhibit antimicrobial activity against Gram-positive and Gram-negative bacteria, fungi, and protozoa.
- Metabolic system: Berberine, the key alkaloid, has demonstrated effects on glucose regulation and lipid metabolism in clinical trials, primarily studied as an isolated compound.
- Oral health: The bacteriostatic and bactericidal activities of a M. aquifolium extract and two of its major alkaloids were tested in vitro against nine different oral bacteria. Minimum inhibitory concentrations were in the range from ≤0.0031% to 0.1993% for the M. aquifolium extract.
7. Dosage Forms and Reported Dosages
Oregon grape root extracts are available in both oral and topical dosage forms. Dosages reported in published clinical research are as follows:
- Topical cream (psoriasis studies): A 10% topical cream formulation of Mahonia aquifolium has been the subject of three clinical trials and is part of the worldwide clinical experience with the plant for the treatment of plaque psoriasis. The treatment period in studies ranged from 4 weeks to 6 months.
- Topical cream (atopic dermatitis): A proprietary Mahonia aquifolium extract (Psorberine) in cream form was used in a 12-week open-label trial in 42 patients.
- Oral decoction (traditional): A decoction can be made by simmering the root for 5–20 minutes. No specific oral dosage has been established in controlled clinical trials for Oregon grape preparations specifically.
- Tincture: Tincture is described as the more usual form to take this herb. Specific tincture dosages in clinical trials are not established in the peer-reviewed literature; those reported in herbal practice references are outside the scope of the clinical trial literature reviewed here.
It should be noted that clinically studied preparations — particularly those used in psoriasis trials — employ proprietary standardized extracts (e.g., "Reliéva" containing "Psorberine"). The alkaloid content of commercial Oregon grape root preparations varies, and the exact berberine content of Oregon grape root is not uniformly standardized. The exact berberine content of Oregon grape root is unknown. Mills and Bone (2013) cite the alkaloid content of barberry to be 13%, and goldenseal to contain 2.5–6% alkaloids. It is reasonable to assume that Oregon grape root has alkaloid content in this range.
8. Safety Considerations and Drug Interactions
Pregnancy and Lactation
Oregon grape is likely unsafe when taken by mouth during pregnancy. Oregon grape contains a chemical called berberine, which might cause harm to the fetus. It crosses the placenta and can displace bilirubin from albumin in fetal blood, potentially causing kernicterus (a type of brain injury in newborns from bilirubin buildup). Oregon grape is likely unsafe when taken by mouth while breast-feeding, as berberine can be transferred to the infant through breast milk.
Infants and Children
Oregon grape is likely unsafe when given to infants by mouth. The berberine in Oregon grape can cause brain damage in newborns, particularly premature newborns who have jaundice. There is not enough reliable information to know if Oregon grape is safe when used by older children.
Drug Interactions via CYP Enzyme Inhibition
Berberine can interact with many medicines because it affects liver enzymes (such as CYP2D6, CYP3A4, and CYP2C9) and drug transporters that help clear drugs from the body. By slowing these pathways, berberine may raise the blood levels of certain drugs and increase side-effect risks.
Research shows berberine inhibits CYP2D6 (9-fold), CYP2C9 (2-fold), and CYP3A4 — enzymes that metabolize roughly 75% of all prescription medications. Specific interactions of clinical concern include:
- Cyclosporine: Berberine inhibits CYP3A4 and P-glycoprotein, which are the primary metabolism pathways for cyclosporine. Co-administration can increase cyclosporine blood levels substantially, risking toxicity. This combination is contraindicated without close medical supervision.
- Warfarin: Berberine may potentiate anticoagulant effects; INR should be monitored.
- Metformin: The combination is synergistic but increases hypoglycemia risk.
- By slowing CYP3A4 and P-glycoprotein, berberine can cause certain medications to build up to higher levels in the blood than intended. Affected drugs include statin cholesterol drugs (atorvastatin, simvastatin) — where the interaction raises the risk of muscle damage and heart-related toxicity — calcium channel blockers like verapamil, digoxin (which has a narrow margin between a therapeutic dose and a toxic one), and immunosuppressants like cyclosporine.
P-glycoprotein (P-gp) Transport Modulation
Some medications are moved in and out of cells by pumps. Oregon grape might change how these pumps work and change how much medication stays in the body. In some cases, this might change the effects and side effects of a medication. In vitro studies in Caco-2 and MDCKII-MDR1 cell lines have confirmed that Oregon grape root extracts modulate P-glycoprotein-mediated transport, with potential implications for co-administered P-gp substrate drugs such as digoxin and cyclosporine.
Local Adverse Effects
Adverse drug reactions such as itching and burning sensations and "allergic reactions" occurred in four patients across a clinical psoriasis trial. These reactions were reported with topical application. In the clinical psoriasis and atopic dermatitis literature, no serious adverse events were reported.
Population-Level Risk Groups
NCCIH and other experts highlight specific high-risk groups: infants and newborns, pregnant or breastfeeding people, and those with severe liver or kidney disease, heart rhythm problems, or very low blood pressure. In these groups, berberine should generally be avoided unless a specialist specifically recommends and monitors its use.
Sustainability Consideration
Oregon grape root is at risk from overharvesting and habitat loss. This concern parallels the situation with goldenseal (Hydrastis canadensis), which Oregon grape has increasingly been used to substitute due to goldenseal's endangered status.
References
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