In-vitro studies of Pelargonium have demonstrated antimicrobial and immune-modulating effects.

Antiviral properties

The licensed clinical indication for Pelargonium in the UK is for the relief of symptoms of upper respiratory tract (URT) infections. Most URT infections are viral in origin, an estimated over 90% (Gonzales and Sande, 2000).

 

Influenza virus

Michaelis (2011) reported that Pelargonium extract interfered with the replication of the enveloped viruses influenza A (H1N1 & H3N2), respiratory syncytial virus (RSV), parainfluenza virus 3, human coronavirus (HCo-229E) and the non-enveloped virus coxsackie A9. Pelargonium was not active against the avian flu virus H5N1 which was unexplained. Pelargonium was also reported to be effective against the enveloped herpes viruses HSV-1 and HSV-2 by preventing entry of the virus into the host cells in contrast to the antiviral agent aciclovir which inhibits viral replication within the host cell (Schnitzler 2008).

Theisen and Muller (2012) examined the effects of Pelargonium extract and various isolated prodelphinidins against a range of viruses. The extracted prodelphinidins ranged from simple monomers (e.g. gallocatechin) and dimers to more complex oligomers and polymers. The authors demonstrated that Pelargonium extract showed a dose-dependent activity against influenza H1N1 and H3N1 but no activity against adenovirus or measles virus despite Michaelis (2011) showing activity against another paramyxoviruses (RSV, parainfluenza). The authors demonstrated a reversible effect of the extract on hemagglutination and neuraminidase inhibition suggesting that the mode of action is inhibition of these surface proteins. There were no viricidal effects observed. Furthermore, the longer chained oligo- and polymer prodelphinidins showed more antiviral activity than the monomers and dimers. This dose dependent anti-influenza effect of Pelargonium inhibiting virus binding was also reported by Walther et al (2020) who examined the effects of a range of plant extracts.

Roth et al. (2021) reported that Pelargonium led to upregulation of vitamin D receptor and improved the response to vitamin D which reduces adherence of rhinoviruses to the host cell adhesion molecules. Linked to the upregulation of vitamin D receptor was the increased expression of the intercellular epithelial adhesion molecule, e-cadherin, which the authors suggest might reduce bronchial epithelial thickening in the presence of acute infection and/or inflammation.

A solitary published study of the effects of Pelargonium on HIV was published by Helfer et al (2014). These authors demonstrated that Pelargonium extract prevented HIV-1 entering the host cells (mononuclear cells) by interfering with the attachment of the virus to the cells.

Pelargonium has demonstrated activity against the following viruses
Influenza H1N1 & H3N2

Respiratory Syncytial Virus (RSV)

Human coronavirus (HC0-229E)

Parainfluenza virus 3

Coxsackie A9 virus

Encephalomyocarditis virus (EMCV)

Herpes Simplex Viruses HSV-1 & HSV-2

Antibacterial properties

Although licensed to treat predominantly viral infections Pelargonium has a long standing use in its native South Africa for treating a range of bacterial infections including dysentery, diarrhoea and tuberculosis. Indeed, it was for the treatment of tuberculosis that it was first commercialised in the UK by Stevens in the early 20th Century.

Pelargonium extract and isolated constituents have demonstrable activity against a range of Gram positive and negative bacteria including Staphylococcus aureus (including MRSA), Staphylocococcus epidermidis, Streptococcus pyrogenes, Escherichia coli, Helicobacter pylori and Klebsiella pneumoniae (Kayser and Kolodziej, 1997; Kolodziej et al., 2003; Lewu et al., 2006; Wittschier et al., 2007).

Since the minimum inhibitory concentrations (MIC) of Pelargonium extract recorded are modest it has been suggested that it does not act directly on the bacteria but enhances host cell phagocytosis and inhibiting interactions of the bacteria with the host epithelial cells (Conrad and Frank, 2008; Conrad et al., 2007).

Being an intracellular pathogen (phagocytes), Mycobacterial species are more difficult to treat by conventional medicine often requiring prolonged periods of antibiotics. High MICs have been reported for Pelargonium against Mycobacteria (Mativandlela et al., 2007; Taylor 2003). Stimulation of macrophage killing of Mycobacteria appears to be the effective mechanism, gallic acid and methyl gallate being the Pelargonium components responsible for this action (Kim et al., 2009).

 

Pelargonium has demonstrated activity against the following bacteria
Staphylococcus aureus (including MRSA)

Staphylococcus epidermidis

Streptococcus pyrogenes

Streptococcus pneumoniiae

Escherichia coli

Klebsiella pneumoniae

Pseudomonas aeruginosa

Haemophilus influenza

Mycobacterium tuberculosis

Mycobacterium fortuitum

Immunomodulatory properties

In addition to the direct antimicrobial effects of Pelargonium, a number of immune modulating effects have been reported, especially non-specific (innate) immunity .

Pelargonium extract or its components have been reported to activate macrophages evidenced by nitric oxides (NO) production and tumour necrosis factor (TNF-α, cachexin) (Kolodziej et al., 2003; Kayser et al., 2001; Thale et al., 2008). Additionally, Thäle et al (2008) reported increased production of interleukins IL-1 and IL-12. IL-1 works with TNF-α  are important in the innate immune response and induce IL-12 which in turn induces interferon (IFN-γ). IFN-γ is secreted by T-helper cells, cytotoxic T-cells, macrophages and natural killer cells and serves as an important bridge between non-specific and specific immunity. It stimulates macrophages, natural killer cells and neutrophils (innate) and the production of immunoglobulins and expression of antigen processing genes (specific immunity).

Witte et al (2020) reported a novel observation that Pelargonium extract induced IL-22 and IL-17. IL-22 provoked a strong increase in the antimicrobial protein S100A9 in lung epithelial cells and suggested that this immune modulating function might confer protection from bacterial airway infection.

Other cellular effects

A novel observation that Pelargonium extract increased the ciliary beat frequency by up to 133% of cultured nasal epithelial cells was reported by Neugebauer (2005).

Pereira et al (2016) observed that Pelargonium extract increased the number of cells arresting at the Go/G1 phase of the cell cycle compared to the control in Jurkat (T-cell leukaemia) cell lines. The proportion of apoptotic and necrotic cells was also increased. These authors suggested that gallic acid, proanthocyanidins or dihydroxycoumarins were responsible for the observed effect. The same authors also used in silico target identification coupled with network pharmacology and reported that the major protein targets of the P. sidoides compounds were protein kinases involved in signal transduction (Pereira et al., 2017).

Given that clinically Pelargonium reduces symptoms and duration of many respiratory infections, Fang et al (2023) examined the effect of Pelargonium extract on tissue repair  rhinovirus infected and control human airway cells. They reported that Pelargonium extract produced down regulation of type-I collagen (proinflammatory) and upregulated fibronectin. Three epithelial tight junction proteins (claudin4, desmocollin2 and desmoglein2) were upregulated by Pelargonium which the authors speculated could contribute to viral defence. Downregulation of the rhinovirus receptor ICAM-1 by Pelargonium was also reported.

Immune modulating references

Fang L, Zhou L, Kulic Z, et al. (2023) EPs((R)) 7630 Stimulates Tissue Repair Mechanisms and Modifies Tight Junction Protein Expression in Human Airway Epithelial Cells. Int J Mol Sci 24.

Kayser O, Kolodziej H and Kiderlen AF. (2001) Immunomodulatory principles of Pelargonium sidoides. Phytother Res 15: 122-126.

Kolodziej H, Kayser O, Radtke OA, et al. (2003) Pharmacological profile of extracts of Pelargonium sidoides and their constituents. Phytomedicine 10 Suppl 4: 18-24.

Neugebauer P, Mickenhagen A, Siefer O, et al. (2005) A new approach to pharmacological effects on ciliary beat frequency in cell cultures--exemplary measurements under Pelargonium sidoides extract (EPs 7630). Phytomedicine 12: 46-51.

Pereira A, Bester M, Soundy P, et al. (2016) Anti-proliferative properties of commercial Pelargonium sidoides tincture, with cell-cycle G0/G1 arrest and apoptosis in Jurkat leukaemia cells. Pharm Biol 54: 1831-1840.

Pereira ASP, Bester MJ and Apostolides Z. (2017) Exploring the anti-proliferative activity of Pelargonium sidoides DC with in silico target identification and network pharmacology. Mol Divers 21: 809-820.

Thale C, Kiderlen A and Kolodziej H. (2008) Anti-infective mode of action of EPs 7630 at the molecular level. Planta Med 74: 675-681.

Witte K, Koch E, Volk HD, et al. (2020) The herbal extract EPs(R) 7630 increases the antimicrobial airway defense through monocyte-dependent induction of IL-22 in T cells. J Mol Med (Berl) 98: 1493-1503.