Echinacea

Chapter 3.13

Echinacea Md. M. Billah*, Md. B. Hosen*, Fazlullah Khan**,†,‡ and Kamal Niaz**,†,‡ *

Noakhali Science and Technology University, Noakhali, Bangladesh, **International Campus, Tehran University of Medical Sciences (IC-TUMS), Tehran, Iran, †Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran, ‡ Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

SOURCES AND AVAILABILITY OF ECHINACEA The high costs of prescription drugs and their increased side effects have contributed to the popularity of herbal treatments. Currently, there is a cultural attraction towards a “natural” approach to medical care. However, the discovery of medicine is not new to nature. A large number of well-known drugs, like aspirin, digitalis, and quinine originated from plants. These drugs have been assessed for their efficacy and safety over the last few decades. Echinacea is commonly known as black sampson, black sampson coneflower, Kansas snakeroot, narrow-leaf coneflower, narrow-leaved coneflower, purple coneflower, roter sonnenhut, rudbeckia, snakeroot, Kansas, and zonnehoed. Echinacea comprises a group of herbaceous flowering plants of the daisy family with nine species, commonly named purple coneflowers. They are endemic in eastern and central North America, growing in moist to dry prairies and open wooded areas (Wichtl, 2004). The generic name comes from the Greek word ἐχiν&z.omicr;ζ (ekhinos), meaning “hedgehog,” due to the plant having a spiny central disk. These flowering plants and their parts have different therapeutic uses (Table 3.13.1). Some species are grown in gardens for their showy flowers. Echinacea angustifolia, Echinacea pallida, and Echinacea purpurea, are widely used for their therapeutic effects. Earlier in 1968, E. pallida and E. angustifolia were known as the same species of different varieties. There is now an interpretation that E. purpurea (L.) Moench is used inappropriately, and therefore, a taxonomic revision of the genus has been proposed that covers two subgenera with four species: E. purpurea, E. pallida, Echinacea atrorubens, and Echinacea laevigata, with E. angustifolia and E. pallida revised as E. pallida var. angustifolia (DC.) Cronq. and E. pallida var. pallida (Nutt.) Cronq (Binns et al., 2002a,b). A wide range of dosages for Echinacea products are available, which may contain one or more crude drugs from different geographical areas, such as tinctures, tablets, capsules, and parenteral products. The phytochemical diversity of Echinacea products proves its pharmacological and clinical research findings. Echinacea has been used to treat several physical abnormalities caused by infections, such as septic wounds and syphilis. It has also been used as an “antitoxin” for snakebites and blood poisoning (Hobbs, 1994). Traditionally, Echinacea was used for bacterial and viral infections, mild septicemia, furunculosis, and some skin problems, for example, boils, carbuncles, and abscesses (Tyler, 1993). Echinacea has also been used as a supportive treatment for influenza and recurrent infections of the respiratory tract and lower urinary tract and for poor healing of superficial wounds (British Herbal Medicine Association, 1990). The rapid growth in research and information regarding Echinacea has revealed its attractiveness. The number of studies of Echinacea has increased from year to year (Wichtl, 2004; Yu, 2004). Different species of Echinacea are E. angustifolia (narrow-leaf coneflower), E. atrorubens (Topeka purple coneflower), E. laevigata (Smooth coneflower and/or smooth purple coneflower), E. pallida (pale purple coneflower), Echinacea paradoxa (yellow coneflower and/or Bush’s purple coneflower), E. purpurea (purple coneflower and/or eastern purple coneflower), Echinacea sanguinea (sanguine purple coneflower), Echinacea serotina (narrow-leaved purple coneflower), Echinacea simulata (wavy leaf purple coneflower), and Echinacea tennesseensis (Tennessee coneflower). The morphological features of Echinacea are given in Table 3.13.2.

PHYTOCHEMISTRY OF ECHINACEA There are differences in the constituents of Echinacea from species to species and between the different parts of the plant. The phytoconstituents that are responsible for showing the activity of Echinacea include alkamides, caffeic acid and its derivatives, polysaccharides, and alkenes (Matthias et al., 2004). The structure of echinacoside, which is caffeic acid glycoside, along with cichoric acid, echinaceine, and echinolone are shown in Fig. 3.13.1. Nonvitamin and Nonmineral Nutritional Supplements. https://doi.org/10.1016/B978-0-12-812491-8.00029-1 © 2019 Elsevier Inc. All rights reserved.

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TABLE 3.13.1  Some Traditional Uses of Echinacea Species Species

Traditional use

E. atrorubens

Not frequently used

E. laevigata E. paradoxa E. sanguinea E. simulata E. tennesseensis E. purpurea

Respiratory tract infections: colds, flu, bronchitis, strep throat, and toothache Urinary tract infections: herpes sores and gonorrhea Skin disorders: Staphylococcal infections, cold sores, ulcers, wounds, burns, insect bites, eczema, and allergies Others: rheumatoid arthritis

E. angustifolia E. pallida

TABLE 3.13.2  Morphological Characteristics of Echinacea Feature

Description

Nature

Perennial herb, herbaceous

Height

Ranging from 10 to 60 cm

Adaptation

Echinacea plants are resilient and drought resistant but in such conditions their growth is slowed. They grow in moist to dry prairies and open wooded areas

Root

In contrast to Echinacea species the taproot of Parthenium integrifolium is short, only 3–8 cm long and 4 cm in diameter, bulbform, thickened, and black. The branches arise from the bottom part of the taproot. The lateral roots are partially shiny

Stem

The stem ascends either from a vertical taproot (E. angustifolia) or branched, fibrous roots (E. purpurea). Echinacea may have either simple or branched stems

Leaf

The leaf shape varies from lanceolate to ovate

Flower

Each “flower” or daisy-like head unit is actually a conglomeration of many tiny florets

Floral character

The inner (disk) florets end in spines, and are surrounded by droopy outer (ray) florets with teeth at their ends. The Echinacea genus is characterized by spiny flowering heads, with an elevated receptacle which forms the “cone”

Propagation

To grow Echinacea from seed, cut a stalk supporting a spent flower, enclose the flower in a paper bag, and hang the plant upside down. The plant will release the seeds into the bag when they are ready. Separate the seeds from the chaff, dry them for a few weeks, and then store them in a cool, dry place

About 20 alkamides including isobutylamides of long-chain fatty acids with olefinic bonds are present in Echinacea (Bauer et al., 1989; Lienert et al., 1998). Caffeic acid glycosides such as echinacoside (Table 3.13.3), verbascoside, and caffeoyl echinacoside, as well as caffeic acid esters of quinic acid (e.g., chlorogenic acid-5-caffeoylquinic acid, isochlorogenic acid-3,4- and 3,5-dicaffeoylquinic acid, cynarin-1,3-dicaffeoylquinic acid) and tartaric acid (e.g., caftaric acid2-caffeoyltartaric acid, cichoric acid-2,3-dicaffeoyltartaricacid) have medical importance having different physiological activities (Pietta et al., 1998). Two polysaccharides and a xyloglucan (molecular weight 79 kDa) were extracted from E. purpurea, the polysac­charides included PS1 (a methylglucuronoarabinoxylan, molecular weight 35 kD) and PS2 (an acidic rhamnoarabino­galactan, molecular weight 450 kDa) (Bauer, 1997). E. pallida root (0.2%–2.0%) has important constituents such as polyenes, polyalkenynes,

Echinacea Chapter | 3.13  207



CH3OH HO

O

HO HO

O OH

HO

CH

CH

COO

H3C HO

OH

CH3 O

O

CH2

CH3

OH

OH

O OH

O

OH

Echinacoside

OH H N

O OH HOOC

O

O

O

COOH

Echinaceine

HO O HO O

Cichoric acid

Echinolone

OH

FIG. 3.13.1  Major phytoconstituents of Echinacea species.

TABLE 3.13.3  Major Constituents of Echinacea Species That Are Used Medicinally Species

Plant part

Compound

E. pallida

Roots

Esters of caffeic acid (e.g., echinacoside), polysaccharides, and polyacetylenes

E. angustifolia

Roots and aerial parts

Esters of caffeic acid (e.g., echinacoside), polysaccharides, polyacetylenes, and alkamides

E. purpurea

Aerial parts

Alkamides, esters of caffeic acid (e.g., cichoric acid), polysaccharides, and polyacetylenes

along with carbonyl compounds (ketones), which include ketoalkenes, ketopolyacetylenes, and pentadeca-8Z-ene-2-one, pentadeca-8Z, 13Z-diene-11-yne-2-one, tetradeca-8Z-ene-11,13-diyne-2-one, among others (Bauer et al., 1988). E. angustifolia and E. purpurea a have a wide range of constituents (alkaloids and flavonoids) including saturated pyrrolizidine-type alkaloids, tussilagine and isotussilagine (Röder et al., 1984), and flavonoids like quercetin, isorhamnetin, and kaempferol, along with their glycosides extracted from E. purpurea (0.48%) (Wichtl, 2004). Patuletin-3-rutinoside is extracted from the aerial parts of E. angustifolia (Bauer, 1998; Lin et al., 2002). A wide range of phenolic compounds have also been isolated from the aerial parts of E. angustifolia and E. purpurea, which include phenolic acids like protocatechuic acids, p-coumaric, and p-hydroxybenzoic (Glowniak et al., 1996).

HEALTH BENEFITS OF ECHINACEA A vast amount of scientific literature on Echinacea species is available about its health benefits with special focus often on immunological effects based on in  vitro and in  vivo (animal) studies. Echinacea and its preparations exert immune stimulant activity through three mechanisms: activation of phagocytosis, stimulation of fibroblasts, and the enhancement

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of respiratory activity that results in augmentation of leukocyte mobility. The production of cytokines (interleukin-1 (IL-1), IL-10) and tumor necrosis factor-α (TNF-α) is stimulated by E. purpurea (Burger et al., 1997). Several in vitro studies have proved the antiviral activity of various different preparations of Echinacea (Bodinet and Beuscher, 1991). N-hexane extract from E. purpurea roots showed antifungal properties against several yeast strains such as Saccharomyces cerevisiae and Candida albicans (Binns et al., 2000). Again, the pure polyacetylenic compound (tridec1-ene-3,5,7,9,11-pentayne) extracted from E. purpurea root has been found to provide inhibitory action against S. cerevisiae (Binns et al., 2000). The anticandida activity of E. purpurea extract has also been studied (Barrett, 2003). Some antibacterial activity of E. purpurea root extract has been found against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Proteus mirabilis (Westendorf, 1982). The antiinflammatory activity (in vivo) of E. angustifolia roots was observed through the carrageenan-induced rat paw edema test and in the croton oil-induced mouse ear test the polysaccharide fraction of E. angustifolia was found to be responsible for such antiinflammatory activity (Tubaro et al., 1987). Again in the croton oil-induced test aqueous extract of E. angustifolia roots was observed to be more effective than benzydamine (Tragni et al., 1985). Long-chain alkenes extracted from E. angustifolia possess in vivo antitumor activity. In rats, alkenes act by inhibiting the growth of Walker tumors and in mice alkenes act by inhibiting lymphocytic leukaemia (P388) (Voaden and Jacobson, 1972). A number of alkamides (e.g., a mixture of dodeca-2E,4E,8Z,10E-tetraenoic acid isobutyl amide and dodeca2E,4Z,8Z,10Z-tetraenoic acid isobutyl amide) isolated from dried E. purpurea roots exerted mosquitocidal activity (Clifford et al., 2002) as shown in Table 3.13.3. The alcoholic compounds extracted from E. purpurea, E. angustifolia, and E. pallida have been observed to provide free radical removing activity (in vitro study) (Sloley et al., 2001). The anxiolytic activity of Echinacea was found to be positive in experimental animals with lower doses than those used in traditional indications. Alkamides of Echinacea have cannabinomimetic properties on both cannabinoid CB1 and CB2 receptors, having structural similarity to the endogenous cannabinoid receptor ligand anandamide (Haller et al., 2010).

POSSIBLE INTERACTION OF ECHINACEA WITH OTHER SUPPLEMENTS/DRUGS/FOODS A drug interaction occurs when a drug affects the action of another drug due to the concomitant administration of both drugs. This action could be synergistic (increased drug effect) or antagonistic (decreased drug effect) or could even produce a new effect that neither of the drugs produces alone. Generally, interactions exist between drugs and drugs (drug– drug interaction), drugs and foods (drug–food interactions), as well as drugs and medicinal plants or herbs (drug–plant interactions). Here we discussed the major interaction between Echinacea and some selected drugs/foods/supplements (Table 3.13.4). The antifungal activity of Echinacea has been evaluated and identified to reduce the symptoms of athlete’s foot. Echinacea and econazole have an important interaction leading to the possible inhibition of yeast infections (Binns et al., 2000). Echinacea and immunosuppressants have synergistic effects which may harm normal cellular physiology, so the use of a combination of the two should be consciously prescribed (Binns et al., 2000). Specifically, the use of immunosuppressants should not be use along with Echinacea in organ transplant situations. This combination therapy has been mostly used for cancer treatment and to produce immune-suppressing effects. One study noted that caffeine when taken along with Echinacea, sustained caffeine’s effects on the nervous system, with a special focus neurological

TABLE 3.13.4  Possible Interaction of Echinacea With Drugs/Food Drugs

Effect

References

Echinacea and econazole

Reduces yeast infection rate

Binns et al. (2000)

Echinacea and immunosuppressants

Enhances immune function. Therefore, immunosuppressant should not be used with Echinacea

Binns et al. (2000)

Echinacea and caffeine

Increases the duration of caffeine in the body

Sloley et al. (2001)

Echinacea and midazolam

Increases the effects and side effects of midazolam

Barrett (2003)



Echinacea Chapter | 3.13  209

effects (Sloley et al., 2001), as its breakdown caffeine and maintain in the blood plasma. When Echinacea interacts with midazolam it demonstrates side effects on cellular and molecular levels (Barrett, 2003), since its increases midazolam absorption. These interactions should be evaluated in this new era which has more drug–drug, drug–food, and drug– supplement interactions.

CONCLUSIONS In conclusion, Echinacea plays many roles in biological systems, extending from being a structural component to having antiviral, antifungal, antibacterial, antiinflammatory, and mosquitocidal activities. Currently, in the treatment of a number of physiological conditions, Echinacea is widely used in both traditional and modern medicines, in addition to its special focus on cancers. It contains large amounts of compounds with diversified therapeutic properties. Further studies are warranted to discover its supreme potential in the field of medicinal and pharmaceutical sciences for innovative and productive uses. More research is needed to find out the diverse and protective effects of Echinacea against critical diseases like neurodegenerative disorders and cancers.

ACKNOWLEDGMENTS This article is the outcome of an in-house financially nonsupported study. All authors have directly participated in the planning or drafting of the manuscript and have read and approved the final version. The authors declare no conflicts of interest.

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Tragni, E., Tubaro, A., Melis, S., Galli, C.L., 1985. Evidence from two classical irritation tests for an anti-inflammatory action of a natural extract, Echinacea B. Food Chem. Toxicol. 23, 317–319. Tubaro, A., Tragni, E., DelNegro, P., Galli, C.L., DellaLoggia, R., 1987. Anti-inflammatory activity of a polysaccharidic fraction of Echinacea angustifolia. J. Pharm. Pharmacol. 39, 567–569. Tyler, V.E., 1993. The Honest Herbal, third ed. Strickley, Philadelphia, PA. Voaden, D.J., Jacobson, M., 1972. Tumour inhibitors 3. Identification and synthesis of an oncolytic hydrocarbon from American coneflower roots. Med. Chem. 15, 619–623. Westendorf, J., 1982. Carito 1: in-vitro untersuchungen zum nachweiss spasmolytischer und kontraktiler einflüsse. Therapiewoche 32, 6291–6297. Wichtl, M. (Ed.), 2004. Herbal Drugs and Phytopharmaceuticals: A Handbook for Practice on a Scientific Basis. third ed. Medpharm Scientific Publishers, Stuttgart. Yu, H., 2004. Echinacea. In: Miller, S.C., Yu, H. (Eds.), The Genus Echinacea. CRC Press, Boca Raton, FL.

FURTHER READING World Health Organization, 1999. WHO Monographs on Selected Medicinal Plants. 1. World Health Organization, Geneva.