Echinacea



Echinacea is a genus, or group of herbaceous flowering plants in  the daisy family, Asteraceae. The nine species it contains are commonly called coneflowers. They are endemic to eastern and central North America, where they are found growing in moist to dry prairies and open wooded areas. They have large, showy heads of composite flowers, blooming from early to late summer. The generic name is derived from the Greek word ἐχῖνος (echino), meaning "sea urchin," due to the spiny central disk. Some species are used in herbal medicines and some are cultivated in gardens for their showy flowers. A few species are of conservation concern.

Description
Echinacea species are herbaceous, drought-tolerant perennial plants growing up to (140 cm or possibly 4 feet, reference needed) in height. They grow from taproots, except E. purpurea, which grows from a short caudex with fibrous roots. They have erect stems that in most species are unbranched. Both the basal and cauline leaves are arranged alternately. The leaves are normally hairy with a rough texture, having uniseriate trichomes (1-4 rings of cells) but sometimes they lack hairs. The basal leaves and the lower stem leaves have petioles, and as the leaves progress up the stem the petioles often decrease in length. The leaf blades in different species may have one, three or five nerves. Some species have linear to lanceolate shaped leaves, and others have elliptic- to ovate-shaped leaves; often the leaves decrease in size as they progress up the stems. Leaf bases gradually increase in width away from the petioles or the bases are rounded to heart shaped. Most species have leaf margins that are entire, but sometimes they are dentate or serrate. The flowers are collected together into single rounded heads that terminate long peduncles. The inflorescences have crateriform to hemispheric shaped involucres which are 12–40 mm wide. The phyllaries, or bracts below the flower head, are persistent and number 15–50. The phyllaries are produced in a 2–4 series. The receptacles are hemispheric to conic in shape. The paleae (chaffs on the receptacles of many Asteraceae) have orange to reddish purple ends, and are longer than the disc corollas. The paleae bases partially surrounding the cypselae, and are keeled with the apices abruptly constricted to awn-like tips. The ray florets number 8–21 and the corollas are dark purple to pale pink, white, or yellow. The tubes of the corolla are hairless or sparsely hairy, and the laminae are spreading, reflexed, or drooping in habit and linear to elliptic or obovate in shape. The abaxial faces of the laminae are glabrous or moderately hairy. The flower heads have typically 200-300 fertile, bisexual disc florets but some have more. The corollas are pinkish, greenish, reddish-purple or yellow and have tubes shorter than the throats. The pollen is normally yellow in most species, but usually white in E. pallida. The three or four-angled fruits (cypselae), are tan or bicolored with a dark brown band distally. The pappi is persistent and variously crown-shaped with 0 to 4 or more prominent teeth. x = 11.

Like all Asteraceae, the flowering structure is a composite inflorescence, with purple (rarely yellow or white) florets arranged in a prominent, somewhat cone-shaped head – "cone-shaped" because the petals of the outer ray florets tend to point downward (are reflexed) once the flower head opens, thus forming a cone. Plants are generally long lived, with distinctive flowers. The common name "cone flower" comes from the characteristic center “cone” at the center of the flower. The generic name Echinacea is rooted in the Greek word ἐχῖνος (echinos), meaning sea urchin, it references the spiky appearance and feel of the flower heads.

Species
The species of Echinacea are
 * Echinacea angustifolia – Narrow-leaf Coneflower
 * Echinacea atrorubens – Topeka Purple Coneflower
 * Echinacea laevigata – Smooth Coneflower, Smooth Purple Coneflower
 * Echinacea pallida – Pale Purple Coneflower
 * Echinacea paradoxa – Yellow Coneflower, Bush's Purple Coneflower
 * Echinacea purpurea – Purple Coneflower, Eastern Purple Coneflower
 * Echinacea sanguinea – Sanguine purple Coneflower
 * Echinacea simulata – Wavyleaf Purple Coneflower
 * Echinacea tennesseensis – Tennessee Coneflower

Researchers at the Agricultural Research Service are using DNA analysis to help determine the number of Echinacea species. The DNA analysis allows researchers to reveal clear distinctions among species based on chemical differences in root metabolites. The research  concluded that of the 40 genetically diverse populations of Echinacea studied, there were nine distinct species. 

Medicinal effects
Marketed and studied medicinal products contain different species (E. purpurea, E. angustifolia, E. pallida), different organs (roots and herbs) and different preparations (extracts and expressed juice). Their chemical compositions are very different.

Multiple scientific reviews and meta-analyses have evaluated the published peer reviewed literature on the immunological effects of Echinacea. Reviews of the medicinal effects of Echinacea are often complicated by the inclusion of these different products. Evaluation of the literature within the field suffers generally from a lack of well-controlled trials, with many studies of low quality.

A 2007 study by the University of Connecticut combined findings from 14 previously reported trials examining Echinacea and concluded that Echinacea can cut the chances of catching a cold by more than half, and shorten the duration of a cold by an average of 1.4 days. However, Dr. Wallace Sampson, an editor of Scientific Review of Alternative Medicine and a Stanford University emeritus clinical professor of medicine, says that the referenced trials lack the similarities necessary to provide definitive results when combined into one report. "If you have studies that measure different things, there is no way to correct for that. These researchers tried, but you just can’t do it."

A 2003 controlled double-blind study from the University of Virginia School of Medicine and documented in the New England Journal of Medicine stated that echinacea extracts had "no clinically significant effects" on rates of infection or duration or intensity of symptoms. The effects held when the herb was taken immediately following infectious viral exposure and when taken as a prophylaxis starting a week prior to exposure. In a press release, Dr. Michael Murray, the Director of Education for Factors Group of Nutritional Companies, a manufacturer of Echinacea-related products, calls the study "faulty and inaccurate." According to Dr. Murray, none of the three extracts used on the 399 study participants contained all three of the components of Echinacea responsible for its immune-enhancing effects: polysaccharides, alkylamides and cichoric acid. In addition, Dr. Murray said "the standard dosage for dried Echinacea angustifolia root is normally three grams per day or more and this study used less than one gram."

An earlier University of Maryland review based on 13 European studies concluded that echinacea, when taken at first sign of a cold, reduced cold symptoms or shortened their duration. The review also found that three of four published studies concluded that taking echinacea to prevent a cold was ineffective.

The European Medicines Agency (EMEA) assessed the body of evidence and approved the use of expressed juice and dried expressed juice from fresh flowering aerial parts of Echinacea purpurea for the short-term prevention and treatment of the common cold. According to their recommendations:"It should not be used for more than 10 days. The use in children below 1 year of age is contraindicated, because of theoretically possible undesirable effect on immature immune system. The use in children between 1 and 12 years of age is not recommended, because efficacy has not been sufficiently documented although specific risks are not documented. In the absence of sufficient data, the use in pregnancy and lactation is not recommended."

Cancer Research UK has provided some commentary on the use of Echinacea by people with cancer. They state:"There is no scientific evidence to show that echinacea can help treat, prevent or cure cancer in any way. Some therapists have claimed that echinacea can help relieve side effects from cancer treatments such as chemotherapy and radiotherapy. But this hasn’t been proved either."

Popular belief and traditional use
Echinacea is popularly believed to be an immunostimulator, stimulating the body's non-specific immune system and warding off infections and also being used as a laxative. A study commonly used to support that belief is a 2007 meta-analysis in The Lancet Infectious Diseases. The studies pooled in the meta-analysis used various types of echinacea, various parts of the plant, and various dosages. This review cannot inform recommendations on the efficacy of any particular type of echinacea, dosage, or treatment regimen. The safety of echinacea under long-term use is also unknown.

History
Echinacea angustifolia was widely used by the North American Plains Indians for its general medicinal qualities. Echinacea was one of the basic antimicrobial herbs of eclectic medicine from the mid 19th century through the early 20th century, and its use was documented for snakebite, anthrax, and for relief of pain. In the 1930s echinacea became popular in both Europe and America as an herbal medicine. According to Wallace Sampson, MD, its modern day use as a treatment for the common cold began when a Swiss herbal supplement maker was "erroneously told" that echinacea was used for cold prevention by Native American tribes who lived in the area of South Dakota. Although Native American tribes didn't use echinacea to prevent the common cold, some Plains tribes did use echinacea to treat some of the symptoms that could be caused by the common cold: The Kiowa used it for coughs and sore throats, the Cheyenne for sore throats, the Pawnee for headaches, and many tribes including the Lakotah used it as an analgesic.

Native Americans learned of E. angustifolia by observing elk seeking out the plants and consuming them when sick or wounded, and identified those plants as elk root.

Active substances
Like most unrefined drugs from plant or animal origin, the constituent base for echinacea is complex, consisting of a wide variety of chemicals of variable effect and potency. Some chemicals may be directly antimicrobial, while others may work at stimulating or modulating different parts of the immune system. All species have chemical compounds called phenols, which are common to many other plants. Both the phenol compounds cichoric acid and caftaric acid are present in E. purpurea, other phenols include echinacoside, which is found in greater levels within E. angustifolia and E. pallida roots than in other species. When making herbal remedies, these phenols can serve as markers for the quantity of raw echinacea in the product. Other chemical constituents that may be important in echinacea health effects include alkylamides and polysaccharides.

The immunomodulatory effects of echinacea preparations are likely caused by fat-soluble alkylamides (alkamides), which occur mostly in E. angustifolia and E. purpurea but not in E. pallida. Alkylamides bind particularly to human CB2 and to a much lesser degree to CB1 cannabinoid receptors; as a result they are implicated in a variety of modulatory functions, including immune suppression, induction of apoptosis, cell migration and inhibition of tumor necrosis factor α TNF-alpha These Alkylamides have similar potency to that of THC at the CB2 receptor, with THC being around 1.5 times stronger (~40 nm vs ~60 nm affinities). However, potency is dramatically less than that of THC at the psychoactive CB1 receptor (~40 nm vs ~ >1500 nm affinities).

As with any herbal preparation, individual doses may vary significantly in active chemical composition. In addition to poor process control which may affect inter- and intra-batch homogeneity, species, plant part, extraction method, and contamination or adulteration with other products all lead to variability between products.

Root or whole plant
As with any plant, the chemical makeup of echinacea is not consistent throughout the organism. In particular, the root has been promoted as containing a more efficacious mixture of active chemicals. A 2003 study in the Journal of the American Medical Association (Taylor et al. 2003 ) found that when echinacea products made from the entire plant were taken after the second cold symptom appeared they provided no measurable beneficial effect for children in treating the severity or duration of symptoms caused by the common cold virus. A 2005 study in the New England Journal of Medicine (Turner, 2005 ) focused on several root extracts, but still found no statistically significant effects on duration, intensity, or prevention of symptoms.

Side effects and contraindications
When taken by mouth, Echinacea does not usually cause side effects. One of the most extensive and systematic studies to review the safety of Echinacea products concluded that overall, "adverse events are rare, mild and reversible," with the most common symptoms being "gastrointestinal and skin-related." Such side effects include nausea, abdominal pain, diarrhea, itch, and rash. Echinacea has also been linked to rare allergic reactions, including asthma, shortness of breath, and one case of anaphylaxis. Muscle and joint pain has been associated with Echinacea, but it may have been caused by cold or flu symptoms for which the Echinacea products were administered. There are isolated case reports of rare and idiosyncratic reactions including thrombocytopenic purpura, leucopenia, hepatitis, renal failure, and atrial fibrillation, although it is not clear that these were due to Echinacea itself.

There are concerns that by stimulating immune function, Echinacea could potentially exacerbate autoimmune disease and/or decrease the effectiveness of immunosuppressive drugs, but this warning is based on theoretical considerations rather than human data. There have been no case reports of any drug interactions with Echinacea and "the currently available evidence suggests that echinacea is unlikely to pose serious health threats for patients combining it with conventional drugs."

As a matter of manufacturing safety, one investigation by an independent consumer testing laboratory found that five of eleven selected retail Echinacea products failed quality testing. Four of the failing products contained levels of phenols below the potency level stated on the labels. One failing product was contaminated with lead.

Other uses
Some species of echinacea, notably E. purpurea, E. angustifolia, and E. pallida, are grown as ornamental plants in gardens. Many cultivars exist, and many of them are asexually propagated to keep them true to type.

They tolerate a wide variety of conditions, maintain attractive foliage throughout the season, and multiply rapidly. Appropriate species are used in prairie restorations. Echinacea plants also reseed in the fall. New flowers will grow where seeds have fallen from the prior year.

Ecinacea extracts inhibited growth of three species of trypanosomatids: Leishmania donovani, Leishmania major, and Trypanosoma brucei.