Echinacea – so many new interesting medicinal applications!

Echinacea was highly regarded as a medicine by the indigenous north Americans, who used the roots of both Echinacea purpurea (purple coneflower) and Echinacea angustifolia (narrow-leaved purple coneflower) to treat animal bites and a wide range of infectious and inflammatory conditions(1-3). Early European settlers adopted echinacea as a treatment for wounds, sepsis and glandular inflammation, and it was a preferred treatment for infections by many clinicians until discovery of penicillin in 1928(1-6)

Any plant with such a reputation should be of interest to infectious disease scientists in the world today. With growing worries about antibiotic resistance and highly pathogenic viruses such as SARS-CoV-2 (Covid-19), echinacea is one of a number of medicinal herbs currently receiving more attention from researchers (7, 8).

Ive previously suggested that echinacea’s immunomodulatory and anti-inflammatory actions may offer considerable hope in the ongoing management of this virus (9, 10). Since then a trial involving 100 suspected Covid-19 outpatients, found those who took a combined echinacea and ginger product for 7 days in addition to standard hydroxychloroquine treatment, reported significant improvements in coughing, dyspnoea and muscle pain. A reduced rate of hospitalisation (2%) also occurred in the echinacea and ginger treated group, versus 6% for the drug-only group(11i). While this difference in the need to be hospitalised failed to reach statistical significance, larger well-designed trials are warranted, and are likely underway. Most recently, constituents which exhibit promise as potential inhibitors of the main protease enzyme involved in replication of the SARS-CoV-2 (Covid-19) coronavirus have been identified in Echinacea angustifolia(12).

Apart from research into applications for infectious disease management, there’s also other largely forgotten or new potential applications that some of this research is revealing for Echinacea, a summary of which is below.

Effects on endocannabinoid receptors

Echinacea alkylamides (the main bioavailable active constituents) were first reported in 2004 to bind strongly with endogenous cannabinoid 2 (CB2) receptors(13), which are mainly found on immune cells and unlike CB1 receptors, do not seem to be involved much in the psychoactive effects of cannabinoids. Potential therapeutic uses of cannabinoid receptor agonists include pain management, anxiety, cancer-related symptoms, inflammatory disorders, and epilepsy.

Activation of these endocannabinoid receptors has been associated with various modulatory effects on cytokines by alkylamide-rich Echinacea preparations, such as upregulation of tumour necrosis factor (TNF)-alpha mRNA, and activation of the signalling pathway NF-κB, in human white blood cells(13). The pronounced anti-inflammatory properties of Echinacea and its alkylamides, have also been related at least in part to activation of these CB2 receptors(14, 15)

Anxiolytic

Work by Hungarian researchers in animals and human volunteers, observed anxiolytic (anti-anxiety) effects for high but not low doses of Echinacea angustifolia given for 1 week to healthy volunteers scoring high on a validated anxiety measurement scale(16). A subsequent double blind, placebo controlled trial in 64 participants found the Echinacea angustifolia root preparation performed better than placebo in patients with high baseline anxiety(17).  However, a recent trial in Australia failed to find greater improvements in anxiety in adults with mild-to-moderately severe anxiety compared to the placebo. Some improvements were detected in emotional wellbeing, suggesting potential antidepressant activity, as a secondary outcome. This suggests further trials with greater participant numbers, are warranted(18).

Eczema and hayfever

Contrary to what is sometimes popularly believed, various studies are now suggesting potential applications for alkylamide-rich preparations of Echinacea, in the management of allergic conditions.

European workers have recently reported promising outcomes suggesting echinacea could be an efficacious topical treatment for eczema. Anti-inflammatory effects were shown on human keratinocytes in vitro, and favourable results recorded from Human Repeat Insult Patch testing. These and a clinical study concluded echinacea and various isolated alkylamides showed good potential in alleviating skin symptoms of atopic eczema. Anti-inflammatory actions and restoration of the epidermal lipid barrier, were identified as likely mechanisms of action in echinacea’s benefits in this common chronic inflammatory skin condition(19).

This comes after an earlier study finding that an ethanolic extract of Echinacea purpurea root and one of its isolated alkylamides displays anti-histamine like properties and inhibits the release of histamine and other inflammatory cytokines from mast cells(20, 21). Applications for allergic rhinitis (hayfever) stem from this.

Analgesic

A dose dependent analgesic activity has been reported for both echinacea species in a rodent model of chronic inflammatory pain(22). Again, alkylamides were shown to be key, and modulation of the endogenous endocannabinoid systems a likely mechanism of action. This supports potential applications for peripheral inflammatory pain such as arthritis and burns, which are other traditional uses for echinacea by indigenous North Americans.

A small clinical trial involving a combined ginger and Echinacea angustifolia product taken for 30 days by patients with osteoarthritis of the knee, reported a reduction in pain as well as knee circumference and inflammation(23). These anti-inflammatory and analgesic effects may also be mediated through endocannabinoid receptor modulation, as well as inhibition of the inflammatory enzymes cyclooxygenase -2 (COX-2) and prostaglandin E2 (PGE(2)), by alkylamides(24, 25). These are also mechanisms of action of some anti-inflammatory drugs prescribed for chronic arthritis.

Male fertility?

Possible applications for male reproductive functions have been revealed for Echinacea purpurea through recent research in diabetic rats(26). Echinacea administration for 4 weeks not only improved hyperglycemia and insulin resistance, but also increased sperm motility, protected sperm morphology and had other benefits on related testosterone synthesis pathways.  Levels of superoxide dismutase, catalase, and glutathione antioxidants in sperm were increased, whereas proinflammatory cytokines such as NO, IL-1β, and TNF-α, were decreased by Echinacea treatment. This suggests similar possible outcomes not only in men with diabetes-related fertility issues, but also in non-diabetic men wanting to optimise their fertility. Studies in humans, will hopefully soon be undertaken.

Anticancer effects

In vitro anticancer effects against human lung cancer cells have been reported recently for Echinacea purpurea root extracts, in a time and dose dependent manner(27). Activation of cannabinoid CB2 receptors and enhanced apoptosis (programmed cell death to eliminate unwanted cells) was associated with this activity.  Longevity enhancing and cancer protective actions have previously been reported for Echinacea purpurea in mice(28)In vitro anticancer activity of Echinacea angustifolia, has also been reported and a synergistic in vitro effect with paclitaxel in two different breast cancer cell lines(29). These studies support clinical trials using Echinacea as an adjunct to this and potentially other chemotherapy drugs, to see if such effects can be achieved in clinical practice. Protective effects against gene and plant damage due to mercury poisoning have been revealed by Turkish workers, as a result of which further research will now take place into other possible uses against genotoxic contaminants(30).

Finally, the risk of interactions between Echinacea and other drugs being taken at the same time, is something that requires consideration in many situations and particularly with chronic illnesses where other medication is often prescribed. I’ve reviewed and written about this previously, and at that time found there to be very little evidence of clinically relevant interactions(31). Reassuringly, a recent study which examined the potential of phytochemical constituents of Echinacea purpurea to cause herb-drug interactions via ABCB1 and ABCG2 efflux transporter proteins (a common mechanism of such interactions), failed to find evidence of significant inhibition of these transporters at clinically relevant concentrations(32).

In conclusion, traditional and modern day use experience and a growing body of research, suggests potential benefits to daily prophylactic use of echinacea by those wanting to enhance their immunity, or as an alternative or adjunct to other medications for the management of an increasingly large and diverse range of common health conditions.

References:

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  18. Lopresti AL, Smith SJ. An investigation into the anxiety-relieving and mood-enhancing effects of Echinacea angustifolia (EP107™): A randomised, double-blind, placebo-controlled study. J Affect Disord. 2021 Oct 1;293:229-237. doi: 10.1016/j.jad.2021.06.054. Epub 2021 Jun 24. PMID: 34217960.
  19. Oláh A, Szabó-Papp J, Soeberdt M, Knie U, Dähnhardt-Pfeiffer S, Abels C, Bíró T. Echinacea purpurea-derived alkylamides exhibit potent anti-inflammatory effects and alleviate clinical symptoms of atopic eczema. J Dermatol Sci. 2017 Oct;88(1):67-77. doi: 10.1016/j.jdermsci.2017.05.015. Epub 2017 May 27. PMID: 28610718.
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  24. Hinz B, Woelkart K, Bauer R. Alkamides from Echinacea inhibit cyclooxygenase-2 activity in human neuroglioma cells. Biochem Biophys Res Commun. 2007 Aug 24;360(2):441-6. doi: 10.1016/j.bbrc.2007.06.073. Epub 2007 Jun 19. PMID: 17599805.
  25. Lalone CA, Huang N, Rizshsky L, Yum MY, Singh N, Hauck C, Nikolau BJ, Wurtele ES, Kohut ML, Murphy PA, Birt DF. Enrichment of Echinacea angustifolia with Bauer alkylamide 11 and Bauer ketone 23 increased anti-inflammatory potential through interference with cox-2 enzyme activity. J Agric Food Chem. 2010 Aug 11;58(15):8573-84. doi: 10.1021/jf1014268. PMID: 20681645; PMCID: PMC3738191.
  26. Mao CF, Sudirman S, Lee CC, Tsou D, Kong ZL. Echinacea purpurea Ethanol Extract Improves Male Reproductive Dysfunction With Streptozotocin-Nicotinamide-Induced Diabetic Rats. Front Vet Sci. 2021 Apr 28;8:651286. doi: 10.3389/fvets.2021.651286. PMID: 33996978; PMCID: PMC8113381.
  27. Hosami F, Manayi A, Salimi V, Khodakhah F, Nourbakhsh M, Nakstad B, Tavakoli-Yaraki M. The pro-apoptosis effects of Echinacea purpurea and Cannabis sativa extracts in human lung cancer cells through caspase-dependent pathway. BMC Complement Med Ther. 2021 Jan 14;21(1):37. doi: 10.1186/s12906-021-03204-6. PMID: 33446187; PMCID: PMC7809807.
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  29. Espinosa-Paredes DA, Cornejo-Garrido J, Moreno-Eutimio MA, Martínez-Rodríguez OP, Jaramillo-Flores ME, Ordaz-Pichardo C. Echinacea Angustifolia DC Extract Induces Apoptosis and Cell Cycle Arrest and Synergizes with Paclitaxel in the MDA-MB-231 and MCF-7 Human Breast Cancer Cell Lines. Nutr Cancer. 2020 Sep 22:1-19. doi: 10.1080/01635581.2020.1817956. Epub ahead of print. PMID: 32959676.
  30. Yalçın E, Macar O, Kalefetoğlu Macar T, Çavuşoğlu D, Çavuşoğlu K. Multi-protective role of Echinacea purpurea L. water extract in Allium cepa L. against mercury(II) chloride. Environ Sci Pollut Res Int. 2021 Jul 3:1–9. doi: 10.1007/s11356-021-15097-6. Epub ahead of print. PMID: 34218367; PMCID: PMC8254617.
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