What Is the Active Ingredient in Echinacea Purpurea Extract?

Echinacea purpurea (L.) Moench is a perennial herb in the Asteraceae family, native to the Americas. There are about eight species in this genus, all of which are perennial herbs. Among them, Echinacea purpurea (L.) Moench, Echinacea angustifolia (DC.) Hell. and Echinacea pallida (Nutt.) Nutt. have similar compositions and have been developed and applied [1-2]. The medicinal history of echinacea goes back to the 18th century, when Native Americans used it to treat swollen gums, sore throats, skin inflammations and gastrointestinal diseases. Today, Echinacea preparations are mainly used to treat upper respiratory tract infections [3]. As early as 1989, Echinacea was listed in Germany as the 131st most commonly prescribed drug out of the top 2000. In 1982, there were already more than 300 types of single and compound preparations of Echinacea [4].

Currently, the sales volume of Echinacea in the United States has been among the top for several years in a row, and the annual sales volume of products made from Echinacea in Europe has also been among the top for several years in a row. In particular, in Germany, Echinacea has become the medicinal plant with the widest range of uses and the largest dosage [5-7]. Echinacea was successfully introduced to China in the 1970s, and it is gradually attracting the attention of domestic scholars because of its dual effects of immune regulation and anti-inflammation. This article summarizes the research on the distribution of resources, chemical composition and pharmacological activity of Echinacea purpurea, with a view to providing a basis for the further development and utilization of Echinacea purpurea in China.

1 Resource distribution

Echinacea purpurea is native to a vast area from Texas in the United States to Saskatchewan in Canada and the Rocky Mountains in the west to Minnesota [8]. It was introduced to Europe in the 19th century and has since been widely used there. Echinacea and its preparations are now commonly stocked in households in France and Germany [6, 9]. The European Medicines Agency (EMEA) report on echinacea describes that echinacea has no embryotoxic, reproductive or mutagenic toxicity, and has not shown significant toxicity in clinical applications in animals, indicating that echinacea is a relatively safe natural medicine [10]. In recent years, echinacea has also been widely used in South Korea, Japan and Australia, and is cultivated on a large scale in some provinces and regions of China [5, 11].

The chemical composition of Echinacea purpurea is greatly affected by the place of origin, the harvest season, and the medicinal part. Current research mainly uses total polyphenols and echinacoside as indicators. The total polyphenol content is divided by the time around the blooming period. Before the blooming period, the total polyphenol content of all parts generally shows a downward trend, while after the blooming period, the content of all parts shows an upward trend and gradually stabilizes. Throughout the growth cycle, the total polyphenol content of roots and leaves is higher, while that of stems is lower. The ranking of polyphenol content under different drying methods is sun-dried > shade-dried > dried (40 °C). The content of apigenin in Echinacea purpurea is highest around the time of flowering, and generally shows a downward trend in all parts after flowering, with the content in the roots > leaves > stems > flowers. The percentage content of apigenin under different drying methods is in descending order: sun-dried > shade-dried > dried (40 °C). In addition, the content of chicoric acid in two-year-old Echinacea purpurea is higher than that in one-year-old Echinacea purpurea, and the content of each part is as follows: leaves>flowers>roots>stems [5]. Therefore, you can choose the appropriate harvest time and processing method according to your needs.

2 Chemical composition

The active ingredients in Echinacea purpurea extract mainly include caffeic acids and their derivatives, alkylamide compounds, polysaccharides and glycoproteins, essential oils and other compounds [12-13].

2.1 Caffeic acid and its derivatives

Echinacea contains mainly caffeic acid and 18 caffeic acid derivatives, including chlorogenic acid, p-hydroxybenzoic acid, ferulic acid, cichoric acid, cichoric acid methyl ester, protocatechuic acid (3, 4-dihydroxybenzoic acid), siringic acid, isochlorogenic acid A, vanillic acid, p-coumaric acid, echinacoside, cynarin, ethyl caffeate, caftaric acid, di-diferuloyl tartaric acid, 2-caffeoyl-3-feruloyl tartaric acid, 2-feruloyl tartaric acid and 2-caffe oyl-3-coumaroyl tartaric acid) [7, 14].

2.2 Alkyl amides

The alkyl amides in Echinacea purpurea are unsaturated fatty amides. The compounds obtained after isolation and identification are shown in Table 1.

2.3 Polysaccharides and glycoproteins

Echinacea polysaccharides contain the highest level of inulin [9]. Egert et al. [19] isolated three glycoproteins from Echinacea with relative molecular masses (Mr) of 17,000, 21,000 and 30,000, respectively. The glycosylated portion mainly contains arabinose, glucosamine, and galactose, while the protein portion mainly contains aspartic acid, glutamic acid, glycine, and alanine. Proksch et al. [20] extracted and isolated the aerial parts of Echinacea purpurea, obtaining 4-methoxy-glucuronoarabi-noxylan (PS I, 4-O-methyl-glucuronoarabi-noxylan) with a Mr of 35,000 and acidic arabinorhamnogly-lactan (PS II, arabinorhamnogly-lactan). Zhang et al. [21] obtained three polysaccharides from Echinacea purpurea cell culture that were different from those in the aboveground parts, including two neutral galactose xylose polysaccharides (Mr 10,000 and 25,000, respectively) and one acidic arabinogalactan (Mr 75,000).

2.4 Volatile oil compounds

Zeng Dong et al. [22] used traditional reflux extraction and solid-phase microextraction (SPME) to isolate several aliphatic hydrocarbons from the dried roots of Echinacea purpurea, including 1, 11-dodecadiene, n-hexadecanoic acid and geranyl-trans-cinnamal, 1-pentadecen-1-ol, etc. They also obtained aromatic hydrocarbons, including phenyl isocyanate, aniline, butylated hydroxyanisole, butylated hydroxytoluene, methyl 9, 12-octadecadienoate, methyl 14-methylpentadecanoate, 2, 3-dihydro-3, 5-dihydro-6-methyl-4-hydro-pyran-2-one, cyclotetradecane, 3-ethyl-cyclooctene, ethyl hexadecanoate, n-hexadecanoic acid. Xue Yafeng[7] used a combination of water vapor distillation and GC-MS to extract and analyze the buds of Echinacea purpurea, and identified the compounds caryophyllene, (1S-cis)-1,2, 3, 5, 6, 8α-hexahydro-4, 7-dimethyl-1-(1-methylethylidene)-naphthalene, [S-(E, E)]-1-methyl-5-methylene-8-(1-methylethyl)-1, 6-aromatic decadiene and n-palmitic acid and other compounds. SPME-GC/MS analysis identified 1R-α-pinene, α-phellandrene, α-terpinene, α-pinene, acetic acid, 1-methyl-3-(1-methylethyl)-benzene and other compounds.

In addition, Echinacea purpurea also contains flavonoids, alkaloids, steroidal compounds and various inorganic elements [23].

3 Pharmacological effects

Modern pharmacological studies have shown that Echinacea purpurea has various biological activities, such as immunomodulation, anti-inflammatory, antibacterial and antiviral, antioxidant, and free radical scavenging [24-25].

3.1 Immune regulation

Echinacea ethanol extract can enhance the body's immunity by enhancing the functions of macrophages, neutrophils, and natural killer (NK) cells, and can also promote the secretion of cytokines [26]. E.g., Ijarnin et al. [27] found that after mice were given cyclophosphamide intraperitoneally to cause immunosuppression, the content of serum cytokines interleukin 2 (IL-2), IL-6, and tumor necrosis factor alpha (TNF-α) in the mice's bodies increased significantly. This indicates that echinacea extract can promote the secretion of IL-2, IL-6, and TNF-α in mice and improve their immunity. The polysaccharides in Echinacea purpurea also have a significant immune-enhancing effect [23]. Zhang Yanying et al. [28] used lipopolysaccharide (LPS) to stimulate rat intestinal epithelial cells (IEC-6), which resulted in increased secretion of the cytokine IL-6 mRNA. After being given Echinacea purpurea polysaccharides at different concentrations, it was found that they could inhibit the expression of IL-6 mRNA secreted by LPS-stimulated cells, and the effect was concentration-dependent. In addition, Goel et al. [29] conducted an in vitro experiment on rat alveolar macrophages and showed that the alkylamide compounds contained in Echinacea purpurea can increase the phagocytic activity and phagocytic index of macrophages.

3.2 Anti-inflammatory effect

Jia Qinghui [30] confirmed through animal experiments that the polysaccharides in Echinacea purpurea have an anti-inflammatory effect. BALB/C mice were made to inhale LPS through the nose, causing pathological damage to their lung tissue and a significant increase in pro-inflammatory factors such as TNF-α and IL-1β. After mice were given an Echinacea polysaccharide enema, it was found that Echinacea polysaccharide could significantly inhibit the increased secretion of IL-1β, IL-6, TNF-α and IL-8, and inhibit the expression of IL-1β, IL-6, TNF-α, Toll-like receptor 4 (TLR4) and nitric oxide synthase (iNOS) mRNA in lung tissue. LPS pretreatment of mouse alveolar macrophages RAW264.7 followed by echinacea polysaccharide administration was found to significantly inhibit the secretion of pro-inflammatory factors and mRNA expression, thereby inhibiting the activation of nuclear factor κB (NF-κB) and the transduction of mitogen-activated protein kinase (MAPK) signals. Fast et al. [31] showed that Echinacea purpurea water extract can inhibit the secretion of TNF-α by human monocytes THP-1 induced by triacylglycerol peptide (Pam3csk40). Attila et al. [32] showed in vitro and clinical trials that emulsions made from the alkylamides in echinacea can treat atopic eczema (AE). The alkylamide in the Echinacea extract exerts an anti-inflammatory effect by regulating the expression of TNF-α mRNA in human macrophages and monocytes via the cannabinoid 2 (CB2) receptor, and also inhibits LPS-stimulated TNF-α expression.

3.3 Antibacterial and antiviral

Sharma et al. [33] showed that an ethanol extract of 65% of Echinacea purpurea can inactivate bacteria that cause respiratory tract infections and also reverse the inflammatory response caused by the bacteria in epithelial cells. These bacteria include Streptococcus pyogenes, Haemophilus influenzae, Legionella pneumophila, Staphylococcus aureus, Mycobacterium avium and Candida albicans, which can cause sore throats and severe lung infections.

Selvarani et al. [34] showed that influenza A (H3N2) virus increased the adhesion of Haemophilus influenzae and Staphylococcus aureus to bronchial epithelial cells by upregulating the expression of intercellular adhesion molecule-1 (ICAM-1), fibronectin and platelet-activating factor receptor (PAFr), increased the adhesion of Haemophilus influenzae and Staphylococcus aureus to bronchial epithelial cells. Echinacea purpurea 65% ethanol extract significantly reduced the expression of ICAM-1, fibronectin and PAFr, thereby reducing the adhesion of the two strains and achieving an antiviral effect.

3.4 Antioxidant and free radical scavenging

The phenolic compounds in Echinacea purpurea have the effect of scavenging free radicals. Ivana et al. [35] added Echinacea purpurea 70% extract at different concentrations to an ethanol solution containing 1, 1-diphenyl-2-trinitrobenzene hydrazone (DPPH). They found that the scavenging ability of DPPH was dose-dependent on the concentration of Echinacea purpurea, and the higher the concentration of Echinacea purpurea extract, the stronger the scavenging ability against DPPH.

4 Conclusion

Echinacea extract contains a variety of active ingredients and exhibits different pharmacological activities, which can be used to treat a variety of diseases. Echinacea, as a natural antibiotic [36], has broad development and application prospects due to its lack of toxic side effects. Abroad, echinacea extract and its preparations have been widely used in clinical treatment of various types of infections and wounds, but its specific immunomodulatory effects still need to be elucidated [37].

Echinacea has been successfully introduced in some provinces and regions in China, solving the problem of raw materials. In addition, because its component content is higher than that of the original producing area, it has laid a good foundation for the development and utilization of echinacea in China. However, because it has been introduced for a short time, it has not yet been included in the Chinese Pharmacopoeia, and there has been little research on its clinical application. Therefore, standardizing the identification and quality evaluation methods of echinacea and clarifying its specific active ingredients have become urgent problems that need to be solved.

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