Page 1148 - Basic _ Clinical Pharmacology ( PDFDrive )

1134 SECTION X Special Topics

■ BOTANICAL SUBSTANCES activity and neuraminidase activity in vitro) involved in early
virus replication and cellular entry. It was less effective against
ECHINACEA (ECHINACEA PURPUREA) intracellular virus. Newer in vitro research in human skin fibro-
blasts also suggests bactericidal activity and inhibition of secre-
Chemistry tion of inflammatory cytokines produced by Propionibacterium
acnes with Echinaforce.
The three most widely used species of Echinacea are Echinacea
purpurea, E pallida, and E angustifolia. The chemical constitu- Clinical Trials
ents include flavonoids, lipophilic constituents (eg, alkamides,
polyacetylenes), water-soluble polysaccharides, and water-soluble Echinacea is most often used to enhance immune function in
caffeoyl conjugates (eg, echinacoside, cichoric acid, caffeic acid). individuals who have colds and other respiratory tract infec-
Within any marketed echinacea formulation, the relative amounts tions. Two reviews have assessed the efficacy of echinacea for this
of these components are dependent upon the species used, the primary indication. A review by the Cochrane Collaboration
method of manufacture, and the plant parts used. E purpurea, involved 24 randomized, double-blind trials with 33 comparisons
the purple coneflower, has been the most widely studied in of echinacea mono-preparations, which are single-ingredient
clinical trials. Although the active constituents of echinacea are echinacea preparations, and placebo. Trials were included if they
not completely known, cichoric acid from E purpurea and echi- involved echinacea for cold treatment or prevention, where the
nacoside from E pallida and E angustifolia, as well as alkamides primary efficacy outcome was cold incidence in prevention trials
and polysaccharides, are most often noted as having immune- and duration of symptoms in treatment trials. Overall, the review
modulating properties. Most commercial formulations, however, did not find significant evidence of benefit for echinacea (among
are not standardized for any particular constituent. all species) in treating colds. Preparations made from the aerial
parts of E purpurea plants and prepared as alcoholic extracts or
Pharmacologic Effects pressed juices were discussed as possibly being preferred to other
formulations for cold treatment in adults, but still having a weak
1. Immune modulation—The effect of echinacea on the
immune system is controversial. In vivo human studies using overall treatment effect. In prevention trials, pooling results sug-
commercially marketed formulations of E purpurea have shown gested a small relative risk reduction of 10–20%, but no statisti-
increased phagocytosis, total circulating monocytes, neutrophils, cally significant benefit within individual trials.
and natural killer cells, indicative of general immune modula- A separate meta-analysis involving 14 randomized, placebo-
tion. In vitro, a standardized ethanol extract of the aerial (above- controlled trials of echinacea for cold treatment or prevention
ground) parts of E purpurea, known as Echinaforce, inhibited the was published in Lancet. In this review, echinacea decreased the
rise in pro-inflammatory cytokines and interleukins-6 and -8, and risk of developing clear signs and symptoms of a cold by 58%
also inhibited mucin secretion caused by exposure to rhinovirus and decreased symptom duration by 1.25 days. This review,
type 1A in a 3D tissue model of human airway epithelium. This however, was confounded by the inclusion of four clinical trials
type of model is intended to mimic what would be seen in vivo. involving multi-ingredient echinacea preparations, as well as
The extract had no effect on cytokine actions. three studies using rhinovirus inoculation versus natural cold
development.
2. Anti-inflammatory effects—Certain echinacea constituents Echinacea has been used investigationally to enhance hemato-
have demonstrated anti-inflammatory properties in vitro. Inhibi- logic recovery following chemotherapy. It has also been used as an
tion of cyclooxygenase, 5-lipoxygenase, and hyaluronidase may be adjunct in the treatment of urinary tract and vaginal fungal infec-
involved. In animals, application of E purpurea prior to applica- tions. These indications require further research before they can be
tion of a topical irritant reduced both paw and ear edema. Despite accepted in clinical practice. E purpurea is ineffective in treating
these preclinical findings, randomized, controlled clinical trials recurrent genital herpes.
involving echinacea for wound healing have not been performed
in humans. Adverse Effects

3. Antibacterial, antifungal, antiviral, and antioxidant Adverse effects with oral commercial formulations are minimal
effects—In vitro studies have reported some antibacterial, anti- and most often include unpleasant taste, gastrointestinal upset,
fungal, antiviral, and antioxidant activity with echinacea constit- or allergic reactions (eg, rash). In one large clinical trial, pediatric
uents. For example, Echinaforce demonstrated virucidal activity patients using an oral echinacea product were significantly more
(MIC < 1 mcg/mL) against influenza and herpes simplex likely to develop a rash than those taking placebo. In a small Nor-
100
viruses and bactericidal activity against Streptococcus pyogenes, wegian mother and child cohort study, 0.5% of women reported
Haemophilus influenzae, and Legionella pneumophila in human taking any formulation of echinacea during early-stage (concep-
bronchial cells. In vitro, Echinaforce inactivated both avian tion up to pregnancy week 17) or late-stage pregnancy and had no
influenza virus (H5N1, H7N7) and swine-origin influenza virus adverse pregnancy outcomes compared to pregnant women who
(H1N1) at doses consistent with recommended oral consump- did not use echinacea. Herbal supplements, and particularly those
tion. The extract blocked key steps (ie, viral hemagglutination made from alcoholic extracts, should only be used in pregnancy