Exploring In Vitro and In Vivo Pharmacology of Echinacea Purpurea (L.) Moench

Background

Echinacea purpurea has long been used for the treatment and prevention of respiratory tract infections. The medicinal plant has originally been discovered by the Native American population, who squeezed the sap from fresh plant or chewed dried roots. Today, commercially available preparations vary greatly in terms of Echinacea concentration, manufacturing methods, plant parts used, et cetera. This heterogeneity results in tremendously fluctuating bio-activities between products. Some of these products finally failed to show efficacy in large clinical studies raising principal questions about the value of the medicinal plant.

Objectives

The aim of this doctoral work was to explore in vitro and in vivo pharmacological effects, as well as clinical efficacy in prevention and acute treatment of respiratory tract infections for a single, phytochemically characterized and standardized Echinacea purpurea extract (Echinaforce®, EF).

Methodology

In vitro antiviral and anti-inflammatory (immune-modulatory) activities of EF were researched studying the most relevant respiratory pathogens including influenza, respiratory syncytial virus (RSV) or coronavirus (CoV) and using cytokine assays for interleukins IL-6 or IL-8 in airway epithelial cells. Test tube experiments were sought to be confirmed in organotypic tissues and upon peroral administration of EF ex vivo, whereas bio-availability of alkylamides in the extract was investigated to estimate systemic relevance. Two clinical studies aimed to investigate efficacy of EF for the treatment and the prevention of respiratory tract infections and subanalyses served to confirm above proposed pharmacological actions in vivo. Finally, EF’s therapeutic potential beyond its traditional use for colds and flu was researched by looking at the prevention of bacterial superinfections including bronchitis or pneumonia.

Results

EF was demonstrated to inhibit a wide range of respiratory agents, showing a primary specificity to enveloped viruses (e.g. influenza, RSV and CoV) in vitro and in a clinical prevention study. The extract modulated overexpression of inflammatory cytokines in epithelial cells and in the presence of respiratory pathogens. It is thereby expected not only to impact occurrence but also the symptomatic development of viral infections. Alkylamides were found to play a role in the systemic immune-modulation as bio-availability was demonstrated after peroral ingestion of EF.
Next, EF was administered for the treatment of clinically diagnosed influenza (flu) to find non-inferiority to the gold-standard therapy Oseltamivir in this indication. Comparable recovery rates were observed for virologically confirmed influenza infections, demonstrating clinical efficacy in the treatment of viral respiratory infections.
Another large clinical study investigated EF for the prevention of respiratory tract infections. In the placebo group a total of 188 cold episodes were identified, which lasted for 850 days in comparison to 149 episodes and 672 sick days with EF extract (p < 0.05). Enveloped viruses (influenza, RSV and CoV) were found in 24 patients with EF and in 47 with placebo (p < 0.05).
In vitro EF reduced the expression of bacteria-binding receptors (e.g. of intracellular adhesion molecule, ICAM-1) on airway epithelial cells after infection with respiratory viruses. Thereby, EF prevented the attraction of pathogenic bacteria potentially inducing bacterial superinfections of initial viral infections.

Conclusion

The evidence generated by this PhD work substantiates the medicinal value of Echinacea purpurea for the treatment and prevention of respiratory tract infections. By focussing on a single, chemically standardized extract (Echinaforce®) problems with heterogeneity between Echinacea products could be overcome to reach more consistent conclusions.
EF exhibits antiviral and anti-inflammatory effects to not only prevent occurrence but also the symptomatic development of infections. Alkylamides are bio-available and capable to systemically modulate the immune response. Bacteria-binding receptors on the epithelium are controlled with EF to finally prevent respiratory complications including bronchitis or pneumonia.