Umckalin

Umckalin

Identity

Chemical Name and Structure

Umckalin is a naturally occurring oxygenated coumarin. It carries the molecular formula C₁₁H₁₀O₅ and is structurally defined as 7-hydroxy-5,6-dimethoxycoumarin. It features a benzopyran backbone substituted with methoxy (−OCH₃) and hydroxy (−OH) functional groups, which grant it unique chemical properties that have made it a subject of interest in bioactivity research. The compound is also referred to by the synonymous IUPAC-style name 5,6-dimethoxycoumarin-7-ol, and its CAS registry number is 43053-62-9.

Umckalin belongs to the trioxygenated coumarin series. In the roots of Pelargonium sidoides it is accompanied by the widely occurring scopoletin, the uncommon analogue 5,6,7-trimethoxycoumarin, 7-hydroxy-5,6-dimethoxycoumarin (umckalin), and 5,6,7,8-tetramethoxycoumarin (artelin), the latter being reported from a plant source for the second time in that study.

It is important to note the naming context: the word umckalin refers strictly to this single isolated phytochemical, while Umckaloabo (sometimes written Umcka) is the commercial name for the whole-root hydroethanolic extract of P. sidoides, and EPs 7630 is the standardised proprietary preparation of that extract. Umckalin serves as the chemical marker compound used to identify and distinguish this species.

Natural Source and Botanical Context

Umckalin is predominantly found in plants of the Pelargonium genus, particularly in the root extracts of Pelargonium sidoides and Pelargonium reniforme. Umckalin has been identified as the marker compound in P. sidoides, occurring at 0.0012–0.2760% (w/w), while it occurs only in trace quantities in P. reniforme (0–0.0016% w/w). This differential distribution makes it highly useful as a botanical authenticator.

The roots of P. sidoides and P. reniforme express conspicuously distinct coumarin variations: umckalin, its 7-O-methyl ether, 7-acetoxy-5,6-dimethoxycoumarin, 6,8-dihydroxy-7-methoxycoumarin, 6,8-dihydroxy-5,7-tetramethoxycoumarin (artelin), and three unique coumarin sulfates are uncommon metabolites of P. sidoides.

Pelargonium sidoides DC. (family Geraniaceae), commonly called African geranium or South African geranium, is a perennial plant endemic to South Africa and Lesotho. It occurs throughout the Eastern Cape, Lesotho, Free State, and southern and south-western Gauteng in the Republic of South Africa. The plant grows in a rosette pattern and forms thick, very dark brown underground roots that grow up to 15 cm in length. Sparsely branched stems grow from the base, and the species is distinguished from others by its long stalks and greyish-green crinkled leaves, which are mildly aromatic, heart-shaped, and velvety.

Marker Status and Quality Control

Analytical methods developed for P. sidoides preparations use umckalin (7-hydroxy-5,6-dimethoxycoumarin) as a chemical marker. Because umckalin is present in high concentrations in the plant and has not been found in other species of the same family, such as P. reniforme, it is a good candidate as a chemical marker for products containing P. sidoides. The monograph of Pelargonium sidoides/reniforme root (Pelargonii radix) was introduced into the European Pharmacopoeia in 2008.

Common Forms and Preparations

The commercial Pelargonium product is obtained from the dried roots of Pelargonium sidoides DC. and/or Pelargonium reniforme Curt. by extraction with aqueous ethanol. The EMA herbal monograph recognises liquid extract (DER 1:8–10, extraction solvent ethanol 11% m/m), dry extract (DER 4–25:1, extraction solvent ethanol 11% m/m), and dry extract (DER 4–7:1, extraction solvent ethanol 14% v/v) as the defined herbal preparations. Outside Europe, various liquid and solid preparations are available as herbal supplements, especially in North America and Mexico. Commercial dosage forms include oral drops (tincture), film-coated tablets, and syrups. Umckalin itself is also available as an isolated reference standard for research and analytical purposes.

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Traditional and Historical Use

Indigenous African Traditions

The plant species indigenous to areas of South Africa are widely used by traditional healers of the Zulu, Basuto, Xhosa, and Mfengi tribes to treat dysentery, diarrhea, hepatic complaints, wounds, colds, fatigue, fevers, generalized weakness, and infections of the respiratory tract including tuberculosis. Along with the closely related P. reniforme Curt., the root has been used for centuries by the Zulu to treat coughs, upper respiratory tract irritations, tuberculosis, and gastrointestinal complaints.

The use of Pelargonium stems or tubers for a variety of ailments, including the complications of dysentery, is an important but hitherto under-estimated part of traditional medicine in southern Africa. The roots of the plant have been used locally for many years as a traditional remedy for the treatment of a diverse group of conditions including diarrhoea, gastritis, tuberculosis, cough, menstrual complaints, and gonorrhoea.

The name umckaloabo itself carries ethnobotanical significance. The name is derived from two independent Zulu words: umkhuhlane, meaning fever and cough-related diseases, and uhlabo, meaning chest pain. The plant has several common names in various languages: rabas is commonly used by the Khoi-Khoi, khoara-enyenyane in Southern Sotho, ikhubalo in isiXhosa, kalwerbossie in Afrikaans, uvendle in isiZulu, and African geranium in English.

Preparations in traditional contexts were primarily aqueous or decoction-based. Infusions of the tuber were used to treat dysentery and diarrhoea. Decoctions of the roots were the predominant vehicle for respiratory and systemic complaints, with the roots boiled in water and the resulting liquid consumed as a tea.

Introduction to European Medicine

Western use of P. sidoides and P. reniforme species to treat tuberculosis is traced back to the Englishman Major Charles Stevens in 1897 when he was treated by a tribal healer with an extract from the roots of Pelargonium species. The medicinal potential of Pelargonium sidoides was brought to Europe in the early 1900s after a young British explorer, Charles Henry Stevens, was treated in South Africa for his pulmonary tuberculosis by a local healer. A bitter tea made of Pelargonium sidoides root drove his illness into remission.

Stevens tried to introduce the remedy in England and it was published in Secret Remedies. A decades-long medical and legal dispute followed. In 1930, Dr. Adrien Sechehaye published a study on 800 patients for the treatment of tuberculosis. In the late nineteenth century, a product made from the root gained some popularity in England as a cure for tuberculosis. The product was later known as Stevens' Cure but fell out of favour after the development of synthetic antibiotics, before being revisited by modern phytomedicine researchers.

Key elements in the successful development of Pelargonium sidoides from a profound traditional remedy to a highly successful phytomedicine include the choice of species, a favourable cost-benefit ratio, innovative marketing over many years, good scientific evidence of the botanical and chemical identity of the product, and convincing proof of concept.

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Key Constituents and Active Compounds in the Source Plant

Umckalin is one compound among a chemically rich matrix in P. sidoides roots. Understanding umckalin's activity requires considering both its isolated properties and its role within the full extract.

Coumarins

Characteristic active constituents of P. sidoides are oxygenated coumarins, including 5,6,7-trimethoxycoumarin, 6,8-dihydroxy-7-methoxycoumarin (fraxetin), 6,8-dihydroxy-5,7-dimethoxycoumarin (artelin), umckalin-7-β-glucoside, and 5,6-dimethoxycoumarin-7-sulfate. Umckalin's sulfate conjugate is also a notable metabolite: umckalin sulfate (6-hydroxy-5,7-dimethylcoumarin-8-sulfate) is a major compound in P. sidoides.

Both P. sidoides and P. reniforme contain scopoletin (7-hydroxy-6-methoxycoumarin), which is also present in the roots of many other plants. However, P. sidoides contains the trioxygenated coumarin umckalin (7-hydroxy-5,6-dimethoxycoumarin), which is not present in P. reniforme. The immunomodulatory activity of Pelargonium is attributed substantially to the coumarins.

Polyphenols and Tannins

Beyond coumarins, the extract contains catechins, gallic acid derivatives, and condensed tannins (proanthocyanidins). Other isolated components of P. sidoides include proanthocyanidins, gallic acid, methyl-gallate, quercetin-3-O-β-d-glucoside, myricetin, scopoletin, catechin, epigallocatechin, 6,8-dihydroxy-5,7-dimethoxy-2H-benzopyran-2-one, and 6,8-dihydroxy-7-methoxy-2H-benzopyran-2-one. Compounds containing gallic acid subunits, such as methyl gallate, have been tested for immunomodulatory activity, where they were found to activate cells of the immune system, such as T cells or macrophages.

The EPs 7630 tannin fractions with constituent (epi)gallocatechin/(epi)catechin units were found to inhibit bacterial neuraminidases.

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Established Mechanisms of Action

Anti-Inflammatory Mechanisms (Umckalin-Specific)

A 2025 in vitro study published in Future Pharmacology (MDPI) using LPS-stimulated RAW 264.7 murine macrophages specifically investigated umckalin's anti-inflammatory mechanisms. Umckalin suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), leading to decreased nitric oxide (NO) and prostaglandin E₂ (PGE₂) production. The compound is a key bioactive agent known for its antimicrobial, antiviral, antitubercular, and immunomodulatory properties.

Umckalin effectively regulated inflammatory responses by reducing the phosphorylation of MAPK signaling pathways, including JNK, p38 MAPK, and ERK. These findings indicate that umckalin inhibits the production of TNF-α, IL-6, IL-1β, and NO, while regulating MAPK signaling pathways, thereby suppressing the expression of iNOS and COX-2. These results are preliminary (in vitro only) and have not been confirmed in human studies for umckalin as an isolated compound.

Immunomodulatory Effects (Whole Extract)

Studies examining EPs 7630 as a whole extract have documented immunomodulatory effects through several pathways. EPs 7630 induced a rapid and dose-dependent production of TNF-α, IL-6, and IL-10 by human blood immune cells, and this cytokine profile was more pro-inflammatory in comparison with the profile induced by viral or bacterial infection-mimicking agents. In contrast to lymphocytes, monocytes showed clear intracellular TNF-α staining after EPs 7630 treatment, identifying monocytes as primary target cells for this immunostimulatory effect.

Several in vitro studies conducted with EPs 7630 showed an inhibitory effect against several bacterial strains (including Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, and Staphylococcus aureus, especially multi-resistant strains). This effect is brought about by an immune modulation mechanism mediated by the activation of macrophages (with the involvement of cytokine interferon-gamma) and the consequent increase in the production of nitric oxide. The activated macrophages produce, in turn, different cytokines, such as interleukin (IL)-1, IL-2, and tumor necrosis factor-alpha.

Antiviral Mechanisms

In vitro, EPs 7630 shows efficacy against cellular infections with influenza virus, HSV, EMCV, RSV, coronavirus, parainfluenza virus, and coxsackie virus, and this appears to be mainly mediated indirectly by inhibition of virus attachment and spreading.

A wide range of mechanisms contributes to the beneficial effects of EPs 7630, including antibacterial, antiviral, immunomodulatory, and epithelial barrier effects. This broad spectrum of pharmacological activities enables clinical activity against multiple respiratory infections. In particular, the combination of antiviral and immunomodulatory effects may enable EPs 7630 to tackle acute viral respiratory infections both in early stages of the disease process, which are driven by virus replication, as well as in later stages, which are caused by an overshooting immune response.

Antibacterial Mechanisms

The antibacterial activity of extracts and isolated constituents including scopoletin, umckalin, 5,6,7-trimethoxycoumarin, 6,8-dihydroxy-5,7-dimethoxycoumarin, (+)-catechin, gallic acid and its methyl ester of Pelargonium sidoides and Pelargonium reniforme was evaluated against eight microorganisms, including three Gram-positive (Staphylococcus aureus, Streptococcus pneumoniae, and beta-hemolytic Streptococcus 1451) and five Gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Haemophilus influenzae). Minimum inhibitory concentrations (MICs) varied with the preparation and organisms tested, from about 0.6 mg/ml for aqueous phases to over 10 mg/ml for crude extracts.

EPs 7630 inhibits the adherence of bacteria such as Streptococcus pyogenes and Helicobacter pylori to epithelial cells in vitro. Furthermore, ciliated cells isolated from the nasal epithelium enhance their ciliary beat frequency in the presence of EPs 7630, which should allow better removal of excess mucus and bacteria.

Antitubercular Activity

Research testing Pelargonium sidoides root extract against Mycobacterium smegmatis identified scopoletin, umckalin, catechin, and epigallocatechin as active ingredients. Notably, the root extract was effective at lower concentrations than the investigated compounds, suggesting that its antimycobacterial activity is the consequence of the combination of different extract constituents.

Catechin and umckalin exhibited MIC values of 31.25 and 62.5 µg/mL respectively against M. smegmatis. Scopoletin, umckalin, catechin, and epigallocatechin did not affect Mycobacterium tuberculosis growth at concentrations up to 200 µg/mL; in contrast, EPs 7630 at 12.5 µg/mL reduced the growth of M. tuberculosis strain H37Rv ATCC 27294 by 96%. This indicates that the whole extract's anti-tubercular activity is greater than that of any single isolated constituent, including umckalin.

If Umckaloabo does possess clinically relevant antituberculosis efficacy, it is probable that, in addition to conventional bacteriostatic or bactericidal activity, the concoction contains components with immunomodulatory properties that help in the eradication of mycobacterial pathogens by phagocytic cells. It is likely that a combination of both its antibacterial and immunomodulatory properties modulates the intracellular parasitic state.

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Scientific Evidence by Area of Use

A critical note on the evidence base: the overwhelming majority of published clinical trials assess the standardised whole-root extract EPs 7630 (Umckaloabo), not isolated umckalin. Evidence specifically attributable to umckalin as an isolated compound is, at the time of writing, restricted to in vitro (cell and test-tube) studies. The clinical evidence summarised below therefore pertains to the source plant's extract, within which umckalin is the primary chemical marker.

1. Acute Bronchitis

A systematic review and meta-analysis (Agbabiaka et al., published in Phytomedicine, 2008) identified six RCTs that met inclusion criteria for Pelargonium sidoides in acute bronchitis, of which four were suitable for statistical pooling. The methodological quality of most trials was good. One study compared EPs 7630 against conventional non-antibiotic treatment (acetylcysteine); the other five tested EPs 7630 against placebo. All RCTs reported findings suggesting the effectiveness of P. sidoides in treating acute bronchitis. Meta-analysis of the four placebo-controlled RCTs suggested that EPs 7630 significantly reduced bronchitis symptom scores in patients with acute bronchitis by day 7.

A pivotal RCT (Matthys et al., Phytomedicine, 2003) enrolled 468 adults with acute bronchitis present ≤48 hours, a Bronchitis Severity Score (BSS) ≥5 points. Intervention was EPs 7630 or placebo (30 drops three times daily) for 7 days. The decrease of BSS from baseline to day 7 was 5.9 ± 2.9 points under EPs 7630 (n=233), and 3.2 ± 4.1 points under placebo (n=235).

A large observational multicentre study (Matthys et al., Phytomedicine, 2007) was also conducted: a multi-centre, prospective, open observational study at 440 study sites in Germany enrolled 2,099 patients aged 0–93 years with productive cough for less than six days without indication for antibiotic treatment, who were given EPs 7630 solution in an age-dependent dosage for 14 days. During treatment, the mean BSS of all patients decreased from 7.1 ± 2.9 points at baseline to 1.0 ± 1.9 points at the patients' individual last visit. Adverse events occurred in 26/2,099 (1.2%) patients; serious adverse events were not reported.

In numerous RCTs and systematic reviews such as those published by the Cochrane Collaboration, Pelargonium sidoides extract EPs 7630 was shown to be effective in acute respiratory tract infections in all investigated age groups.

2. Acute Respiratory Tract Infections in Children

Eight RCTs investigating the application of EPs 7630 in acute bronchitis, acute tonsillopharyngitis, and aRTI in the context of chronic preconditions were identified in a 2018 review. Results showed a statistically significant improvement of aRTI symptom severity for EPs 7630 compared to controls.

Eight randomised, double-blind, placebo-controlled trials involving 1,253 children and adolescents demonstrated the safety and efficacy of EPs 7630 for the treatment of ARTIs. A meta-analysis conducted with five RCTs comprising a total of 990 patients revealed further evidence for efficacy and safety in the treatment of respiratory tract infections in children and adolescents.

In children/adolescents with acute bronchitis, 79.6% of participants treated with EPs 7630 and 41% treated with placebo showed a reduction in the intensity of cough by at least 50% of baseline values at day 7.

Investigation of EPs 7630 in asthmatic children and adolescents with acute RTI demonstrated a significant symptom-alleviating effect and a possibly associated reduction of asthma attacks. This finding is preliminary and based on a single study.

3. Acute Tonsillopharyngitis

A RCT (Bereznoy et al., J Compr Ped) enrolled 143 children aged 6–10 years with non-GABHS tonsillopharyngitis present ≤48 hours. Intervention was EPs 7630 or placebo (20 drops three times daily) for 6 days. EPs 7630 was superior compared to placebo for the treatment of acute non-GABHS tonsillopharyngitis in children; treatment reduced the severity of symptoms and shortened the duration of illness by at least 2 days.

4. Common Cold

EPs 7630 had previously been shown to be effective and safe in the treatment of acute respiratory tract infections such as acute bronchitis, acute rhinosinusitis, and acute tonsillopharyngitis. A multicenter, randomised, double-blind phase 3 clinical trial enrolled 105 adults with common cold symptoms, randomised to thrice-daily administration of either one film-coated tablet containing 40 mg EPs 7630 or matched placebo for 10 days. On day 5, the mean (±SD) sum of the symptom intensity differences (SSID) was significantly higher in the EPs 7630 group (12.5 ± 4.4 points) versus the placebo group (8.8 ± 6.8 points).

Across multiple systematic reviews and meta-analyses of double-blind randomised controlled trials, authors consistently observed significant advantages of EPs 7630 for efficacy outcomes assessed including primary outcomes measured by disease-specific symptom scores, and secondary outcomes including time to substantial improvement or complete remission, disease-associated quality of life, concomitant use of paracetamol, and days missed at work or school.

5. Anti-Inflammatory Activity (Isolated Umckalin, In Vitro Only)

A 2025 study aimed to evaluate the potential of umckalin as a therapeutic agent for chronic inflammatory diseases and to elucidate its underlying mechanisms of action. Using LPS-stimulated RAW 264.7 macrophages as an experimental model, investigators measured levels of NO, PGE₂, TNF-α, IL-6, and IL-1β, and assessed the expression of iNOS and COX-2. Results demonstrated significant inhibitory effects across these markers. This study was entirely in vitro; no human or animal studies on umckalin as an isolated anti-inflammatory agent have been published.

6. Antiviral Activity Against SARS-CoV-2 (Preliminary)

In a 2022 PMC study, Pelargonium sidoides exhibited a significant reduction of SARS-CoV-2-induced cytopathic effect in Vero E6 cells (IC₅₀ 13.79 µg/mL and selectivity index, SI 6.3), whereas scopoletin showed a remarkable anti-SARS-CoV-2 activity with better selectivity (IC₅₀ 17.79 µg/mL and SI 14.22). Recent findings have also suggested that umckalin exhibits mild antiviral activity against SARS-CoV-2, expanding its potential beyond traditional uses to include modern therapeutic applications. These findings are in vitro only.

In hamster models, EPs 7630 reduced viral load early in the course of infection and displayed significant immunomodulatory properties positively modulating disease progression. In addition, EPs 7630 differentially inhibits SARS-CoV-2 variants in nasal and bronchial human airway epithelial cells. No formal conclusions about the efficacy of EPs 7630 in COVID-19 can be drawn from pharmacovigilance case reports, though a beneficial effect would be explainable by the pharmacological profile of the extract. No randomised controlled trials have been completed on EPs 7630 or umckalin specifically for COVID-19.

7. Antimicrobial Breadth (In Vitro)

Research showed that EPs 7630 inhibits Mycobacterium tuberculosis glycerol kinase and shikimate kinase, and the neuraminidase of Vibrio cholerae and Clostridium perfringens. Proanthocyanidins isolated from Pelargonium sidoides root extracts displayed activity against Porphyromonas gingivalis, a periodontal and peri-implant pathogen, but not against the beneficial oral commensal Streptococcus salivarius. These antimicrobial findings are from in vitro systems and their clinical relevance is not established.

Summary of Evidence Strength

• Acute bronchitis (adults and children): Multiple RCTs and Cochrane-reviewed meta-analyses; evidence is robust for the whole extract EPs 7630.
• Acute tonsillopharyngitis and common cold: Supported by RCTs; evidence moderate to good.
• Umckalin as isolated anti-inflammatory agent: Preliminary in vitro only (2025 cell study); no human data.
• Antiviral activity (SARS-CoV-2): In vitro and animal data only; no clinical trial evidence for COVID-19.
• Antitubercular activity: Historical traditional use and in vitro activity of whole extract; umckalin alone does not inhibit M. tuberculosis at tested concentrations.

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Body Systems and Health Areas

Respiratory System

The primary documented area of application. There is clinical evidence demonstrating that EPs 7630 is a safe and effective treatment for a range of acute infectious respiratory illnesses, and that it can also improve conditions like COPD and asthma. Results from a number of clinical studies including several randomised, double-blind, and placebo-controlled trials support the use of Umckaloabo in respiratory tract infections such as bronchitis, sinusitis, and tonsillitis.

Immune System

EPs 7630 induces a rapid and dose-dependent production of TNF-α, IL-6, and IL-10 by human blood immune cells. EPs 7630 also has the potential to reduce the use of antibiotics, which is highly desirable given the threat posed by increasing levels of antibiotic resistance.

Gastrointestinal System

The use of Pelargonium tubers for a variety of ailments including the complications of dysentery is an important part of traditional medicine in southern Africa. This is predominantly a traditional-use association; clinical evidence for gastrointestinal indications in contemporary medicine is limited.

Potential Anti-Inflammatory Applications

In vitro studies highlight the potent anti-inflammatory effects of umckalin and suggest its potential as a promising candidate for the treatment of chronic inflammatory diseases. This potential is as yet unvalidated in human subjects.

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Dosage Forms and Dosages Reported in Studies

The following dosages are those reported in clinical studies and regulatory documents; they refer to preparations of P. sidoides extract, not isolated umckalin.

• Adults and adolescents over 12 years (liquid drops): 30 drops three times daily.
• Children between 6 and 12 years (liquid drops): 20 drops three times daily.
• Tablets (adults, common cold study): One film-coated tablet containing 40 mg EPs 7630 three times daily for 10 days.
• Children (tonsillopharyngitis RCT): EPs 7630 or placebo at 20 drops three times daily for 6 days.
• Acute bronchitis adult RCT: EPs 7630 or placebo at 30 drops three times daily for 7 days.
• Young children (syrup/solution safety study): EPs 7630 syrup (2.5 ml by measuring cup) or solution (10 drops) three times daily.

According to the EMA monograph, the use of P. sidoides in children under 6 years of age has not been established due to lack of adequate data.

For isolated umckalin studied in vitro, cells were treated with umckalin at concentrations of 75, 150, and 300 µM alongside LPS (1 µg/mL) in the 2025 mechanistic study. These are research concentrations with no established human equivalents.

The EMA HMPC monograph indicates traditional use for the common cold (approved), with acute bronchitis supported by clinical studies, and sinusitis under discussion. The ESCOP monograph covers respiratory tract infections, common colds, sore throat, and cough.

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Safety Considerations and Interactions

General Tolerability

Potential adverse reactions related to EPs 7630 use include mild gastrointestinal side effects (diarrhoea, epigastric discomfort, nausea or vomiting, dysphagia), mild nasal and gingival bleeding, and allergic reactions. The most frequent suspected adverse reactions observed in pharmacovigilance data were gastrointestinal complaints and hypersensitivity reactions, both of which may occur as known adverse effects of EPs 7630.

Hepatotoxicity Controversy

Although previous reports raised suspicion about this herbal medicine and possible hepatotoxicity, subsequent articles were published stating that hepatotoxicity was not related to P. sidoides. Investigators concluded that there is currently no evidence of hepatotoxicity related to the use of Pelargonium. Specifically, studies in rats and dogs involving oral administration of up to 3,000 mg/kg EPs 7630 provided no evidence of liver damaging effects.

Blood Coagulation and Warfarin Interaction

Due to the coumarin content of the roots of P. sidoides, an enhancement of the anticoagulant action of coumarin-derivative preparations by co-administration of Pelargonium root extract is theoretically possible. However, Koch and Biber (2007) investigated whether a change in blood coagulation parameters occurred after administration of EPs 7630 to rats. No effect on (partial) thromboplastin time or thrombin time was observed after oral administration of EPs 7630 at doses of 10, 75, and 500 mg/kg for 2 weeks, while treatment with warfarin (0.05 mg/kg) for the same period resulted in significant changes in blood coagulation parameters.

The extract did not interfere with the pharmacokinetics of warfarin even with 2 weeks of concomitant administration. This can be justified by the fact that EPs 7630 does not influence the metabolisation of markers by human recombinant CYP450 isoenzymes and does not influence their expression in human hepatocytes.

Antibiotic Interaction

A placebo-controlled, randomised, double-blind clinical trial in healthy volunteers demonstrated a lack of pharmacological interaction between EPs 7630 and penicillin.

Comprehensive Toxicology (Preclinical)

Published toxicological studies of EPs 7630 covered cytotoxicity, acute and 4-week toxicology in rats, 2-week dose verification and 13-week toxicology in dogs, Ames test, chromosome-aberration test, micronucleus test in mouse cells, tumour promotion, local tolerability, immunotoxicity, and reproduction toxicology. All tests showed no negative effects.

Age-Related Restrictions

Use in children under 6 years of age is not recommended. This is the position stated in the EMA/HMPC assessment, reflecting insufficient clinical data for that age group rather than evidence of specific harm.

Bioavailability (Preclinical)

In silico prediction of the drug-ability of key constituents including umckalin indicated that the studied biomolecules are under the acceptable norms of Lipinski's rule, are water-soluble, and showed high GIT absorption and bioavailability. These are computational predictions, not measured human pharmacokinetic data.

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Regulatory and Monograph Status

The monograph of Pelargonium sidoides/reniforme root (Pelargonii radix) was introduced into the European Pharmacopoeia in 2008. Pelargonium is licensed in the United Kingdom under the Traditional Herbal Registration scheme to treat upper respiratory tract infections. Umckaloabo was approved in Germany as a drug for treating acute bronchitis. Standard scientific monograph compilations of the German Commission E, ESCOP, and WHO monographs do not include dedicated sections on Pelargonium sidoides. However, the EMA HMPC monograph covers traditional use for the common cold and includes acute bronchitis as an indication supported by clinical studies.

The EPs 7630 extract has been the subject of 20 clinical studies involving more than 9,000 patients, including 3,900 children. It has been shown to safely and effectively treat acute upper respiratory tract infections such as bronchitis, tonsillopharyngitis, sinusitis, and the common cold.

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References

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