Accelerated regeneration of epithelial cells after rhinovirus infection

A further laboratory study on human epithelial cells underpins the antiviral potential of a Pelargonium special extract. Fang et al. were able to show that in human airway epithelial cells damaged by rhinovirus infection, regeneration was stimulated in a dose-dependent manner and viral defense was improved.

The Pelargonium special extract EPs® 7630 is obtained from the roots of Pelargonium sidoides and can reduce the severity and duration of acute respiratory tract infections in humans [1,2]. Various in vitro studies have shown antiviral effects of EPs® 7630 on coronaviruses (including SARS-CoV-2), influenza A virus, respiratory syncytial virus (RSV) and also on rhinovirus-16 [3–7]. Rhinovirus (RV) infection is the most common cause of colds and pulmonary exacerbations in children, the elderly and patients with chronic inflammatory lung disease [8–11]. Considering that the homeostasis of airway epithelial cells is highly relevant not only for the defense against viral pathogens but also for the healing of respiratory infections, Fang et al. the effect of EPs® 7630 in human epithelial cells infected with RV-16 and in non-infected control samples.

The researchers assessed the following outcomes [1]:

Epithelial cell proliferation based on manual cell counting,
epithelial wound healing using the “scratch assay”,
Composition of the extracellular matrix using Western blot and cell-based ELISA,
epithelial tight junction proteins by western blot.

The most important results at a glance

A rhinovirus infection significantly reduces the number of healthy epithelial cells over a period of 48 hours [1]. Pre-incubation with EPs® 7630 counteracted this effect by stimulating cell proliferation in a concentration-dependent manner (0.1-10 µg/mL) [1]. In addition, the extract modified the extracellular matrix of epithelial cells in such a way that the expression of pro-inflammatory collagen type I was reduced and fibronectin, which is important for maintaining the barrier function of epithelial cells, was increased. This may help to prevent bacterial (super)infection of epithelial cells.

In addition to an increased expression of E-cadherin – a finding that was already evident in earlier data from this working group – EPs® 7630 also downregulated one of the most important receptors for rhinoviruses (ICAM-1), which makes it more difficult for the viruses to dock [1]. On the other hand, the significantly upregulated expression of β-defensin-1 by EPs® 7630 improves host defense [1]. Furthermore, experimentally wounded epithelial cells recovered faster under EPs® 7630, both the control epithelial cells and the epithelial cells infected by RV16.

In summary, it can be stated that the shortened duration of symptoms in viral respiratory tract infections with EPs® 7630 may be explained by the effects observed in this study. Since the regeneration of epithelial cells takes place at a later stage of an acute respiratory infection, it can be concluded that the extract is effective not only at the beginning but throughout the course of the viral respiratory infection.

Literature:

Fang L. et al: EPs® 7630 Stimulates Tissue Repair Mechanisms and Modifies Tight Junction Protein Expression in Human Airway Epithelial Cells. Int J Mol Sci 2023; 24: 11230.
https://doi.org/10.3390/ijms241311230.
Swissmedic: Medicinal product information, www.swissmedicinfo.ch,(last accessed 29.05.2024)
Roth M, et al: Pelargonium sidoides radix extract EPs 7630 reduces rhinovirus infection through modulation of viral binding proteins on human bronchial epithelial cells. PLoS ONE 2019; 14:e0210702. doi: 10.1371/journal.pone.0210702.
Roth M, Sun Q, Tamm M: Up-Regulated Vitamin D Receptor by Pelargonium sidoides Extract EPs® 7630 Contributes to Rhinovirus Defense in Bronchial Epithelial Cells. Pharmaceuticals 2021; 14: 172. doi: 10.3390/ph14020172.
Michaelis M, Doerr HW, Cinatl J, Jr: Investigation of the influence of EPs® 7630, a herbal drug preparation from Pelargonium sidoides, on replication of a broad panel of respiratory viruses. Phytomedicine 2011; 18: 384-386.
Theisen LL, Muller CP: EPs® 7630 (Umckaloabo®), an extract from Pelargonium sidoides roots, exerts anti-influenza virus activity in vitro and in vivo. Antiviral Res 2012; 94: 147-156.
Papies J, et al: Antiviral and Immunomodulatory Effects of Pelargonium sidoides DC. Root Extract EPs®7630 in SARS-CoV-2-Infected Human Lung Cells. Front. Pharmacol. 2021; 12: 757666.
doi: 10.3389/fphar.2021.757666.
Mehta AK, et al: Tumor necrosis factor family member LIGHT acts with IL-1β and TGF-β to promote airway remodeling during rhinovirus infection. Allergy 2018; 73: 1415-1424.
Oldenburger A, et al: A-kinase anchoring proteins contribute to loss of E-cadherin and bronchial epithelial barrier by cigarette smoke. Am J Physiol Cell Physiol 2014; 306: C585-C597.
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