Botanical Substances: Echinacea (Echinacea Purpurea)

BOTANICAL SUBSTANCES

ECHINACEA (ECHINACEA PURPUREA)

Chemistry

The three most widely used species of Echinacea are Echinaceapurpurea, E pallida, and E angustifolia. The chemical constituentsinclude flavonoids, lipophilic constituents (eg, alkamides, poly-acetylenes), water-soluble polysaccharides, and water-soluble caffeoyl conjugates (eg, echinacoside, cichoric acid, caffeic acid). Within any marketed echinacea formulation, the relative amounts of these components are dependent upon the species used, the method of manufacture, and the plant parts used. E purpurea has been the most widely studied in clinical trials. Although the active constituents of echinacea are not completely known, cichoric acid from E purpurea and echinacoside from E pallida and E angustifolia, as well as alkamides and polysaccharides, are most often noted as having immune-modulating properties. Most commercial formulations, however, are not standardized for any particular constituent.

Pharmacologic Effects

A. Immune Modulation 

The effect of echinacea on the immune system is controversial. In vivo human studies using commercially marketed formulations of E purpurea have shown increased phagocytosis, total circulatingwhite blood cells, monocytes, neutrophils, and natural killer cells but not immunostimulation. In vitro, E purpurea juice increased production of interleukins-1, -6, and -10, and tumor necrosis factor-α by human macrophages. Enhanced natural killer cell activity and antibody-dependent cellular toxicity was also observed with E purpurea extract in cell lines from both healthy and immu-nocompromised patients. Studies using the isolated purified poly-saccharides from E purpurea have also shown cytokine activation. Polysaccharides by themselves, however, are unlikely to accurately reproduce the activity of the entire extract.

B. Anti-Inflammatory Effects

Certain echinacea constituents have demonstrated anti-inflammatory properties in vitro. Inhibition of cyclooxygenase, 5-lipoxygenase, and hyaluronidase may be involved. In animals, application of E purpurea prior to application of a topical irritant reducedboth paw and ear edema. Despite these laboratory findings, randomized, controlled clinical trials involving echinacea for wound healing have not been performed in humans.

C. Antibacterial, Antifungal, Antiviral, and Antioxidant Effects 

In vitro studies have reported some antibacterial, anti-fungal, antiviral, and antioxidant activity with echinacea constituents. In vitro, a standardized extract of the aerial parts of E purpurea dem-onstrated potent virucidal (MIC₁₀₀< 1 μg/mL) against influenza and herpes simplex viruses and potent bactericidal activity against Streptococcus pyogenes, Haemophilus influenzae, and Legionella pneumophila in human bronchial cells. The pro-inflammatorycytokine release caused by these viruses and bacteria were also reversed by echinacea.

Clinical Trials

Echinacea is most often used to enhance immune function in individuals who have colds and other respiratory tract infections.

Two recent reviews have assessed the efficacy of echinacea for this primary indication. A review by the Cochrane Collaboration involved 16 randomized trials with 22 comparisons. Trials were included if they involved monopreparations of echinacea for cold treatment or prevention. Prevention trials involving rhinovirus inoculation versus natural cold development were excluded. Overall, the review concluded that there was some evidence of efficacy for the aerial (above-ground) parts of E purpurea plants in the early treatment of colds but that efficacy for prevention and for other species of echinacea was not clearly shown. Among the placebo-controlled comparisons for cold treatment, echinacea was superior in nine trials, showed a positive trend in one trial, and was insignificant in six trials.

A separate meta-analysis involving 14 randomized, placebo-controlled trials of echinacea for cold treatment or prevention was published in Lancet. In this review, echinacea decreased the odds of developing clear signs and symptoms of a cold by 58% and decreased symptom duration by 1.25 days. This review, however, was confounded by the inclusion of four clinical trials involving multi-ingredient echinacea preparations, as well as three studies using rhinovirus inoculation versus natural cold development.

Echinacea has been used investigationally to enhance hemato-logic recovery following chemotherapy. It has also been used as an adjunct in the treatment of urinary tract and vaginal fungal infec-tions. These indications require further research before they can be accepted in clinical practice. E purpurea is ineffective in treating recurrent genital herpes.

Adverse Effects

Flu-like symptoms (eg, fever, shivering, headache, vomiting) have been reported following the intravenous use of echinacea extracts. Adverse effects with oral commercial formulations are minimal and most often include unpleasant taste, gastrointestinal upset, or rash. In one large clinical trial, pediatric patients using an oral echinacea product were significantly more likely to develop a rash (∼ 5%) than those taking placebo.

Drug Interactions & Precautions

Until the role of echinacea in immune modulation is better defined, this agent should be avoided in patients with immune deficiency disorders (eg, AIDS, cancer), autoimmune disorders (eg, multiple sclerosis, rheumatoid arthritis), and patients with tuberculosis. While there are no reported drug interactions for echinacea, some preparations have a high alcohol content and should not be used with medications known to cause a disulfiram-like reaction. In theory, echinacea should also be avoided in per-sons taking immunosuppressant medications (eg, organ transplant recipients).

Dosage

It is recommended to follow the dosing on the package label, as there may be slight variations in dose based on the product manufacturer. Standardized preparations made from the above-ground parts of E purpurea (Echinaforce, Echinaguard) as an alcoholic extract or fresh pressed juice have some clinical support and may be taken within the first 24 hours of cold symptoms. It should not be used as a preventative agent or for longer than 10–14 days.