Roots Of Pelargonium Sidoides Research Articles

Multiple mechanisms enable broad-spectrum activity of the Pelargonium sidoides root extract EPs 7630 against acute respiratory tract infections.

There is clinical evidence showing that the Pelargonium sidoides root extract EPs 7630 is a safe and effective treatment for a range of acute infectious respiratory illnesses. Moreover, EPs 7630 has been shown to reduce the use of antibiotics, which is important in the context of rising antibiotic resistance levels. A wide range of mechanisms appears to contribute to the beneficial effects of EPs 7630, e.g. antibacterial, antiviral, immunomodulatory, and epithelial barrier effects. This broad spectrum of pharmacological activities seems to enable the clinical activity of EPs 7630 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. Hence, EPs 7630 is a prime example of a plant extract with evidence-based clinical efficacy, including a solid understanding of the underlying mechanisms of action. The example of EPs 7630 demonstrates that plant extracts have a potential role as evidence-based clinical treatments and that they deserve pre-clinical and clinical testing and investigation in the same way as any other drug class.

Acute and chronic rhinosinusitis age characteristics

Children's and adults' rhinosinusitis are two diseases that have both similarities and differences in anatomy, epidemiology, causes, pathogenesis, diagnosis and treatment. At the same rhinosinusitis is one of the most common in otorhinolaryngology's practice, both in children and adults. The of adults paranasal sinuses (PNS) anatomy differs from children's PNS anatomy. Although ostiomeatal complex occlusion is recognized as a major cause of poor ventilation and drainage of the adult paranasal sinuses, it does not have a strong effect on pediatric rhinosinusitis, but adenoids play a key role. Adenoids are bacteria and biofilms reservoirs that cause chronic refractory rhinosinusitis regardless of pharyngeal tonsil size. The prevalence of chronic rhinosinusitis (CRS) is lower in children than in adults. Diagnosis of children's rhinosinusitis is more difficult because nasal cavity endoscopic examination is performed rarely due to the occasional need of general anesthesia during the procedure. Moreover, it's necessary to take into account prevailing etiological role of viruses in ARS at children's age and chronic adenoiditis often accompanies pediatric CRS, which requires attention prescribing medical therapy as the basis of rhinosinusitis treatment. The DysheLORz based on Pelargonium sidoides roots is highly effective and safe for children's and adults ARS and CRS treatment, both as monotherapy and in combination with topical steroids and antibiotics. This herbal medicine immunomodulatory effect is mediated mainly by stimulating the production of TNF-α, IL-1, IL-12 and IFN-γ. It activates macrophages and improves their phagocytic activity. IL-12, together with TNF-α, enhances NK and cytotoxic CD8+ lymphocytes' activity against infected cells. IL-12 effect on Th1 lymphocytes maturation provides a link between innate and adaptive immunity. This is also increasing MCP-1, IP-10 and MIP-1β chemokines synthesis and decreasing MIP-1α, ENA-78, GROα and IL-8 production in PNS and nasal mucosa. This leads to decrease of neutrophils chemotaxis to the inflammation site, and decline of serine proteases concentration (neutrophils main enzymes), that increases mucous membrane epithelial barrier permeability, reducing bacterial infections risk. Additionally, Pelargonium sidoides increases epithelial cells beating cilia frequency and inhibits hemagglutinin and neuraminidase present on influenza virus surface. The drug increases antimicrobial peptides production as defensins, human neutrophil peptides (HNP) and bactericidal permeability-increasing protein (BPI), which is also important for rapid inflammation regression in rhinosinusitis. It causes bacterial adhesion to epithelial cells inhibition, phagocytosis stimulation, nitric oxide (NO) release and oxidative burst. The medicine had a direct effect on Streptococcus pneumoniae, Staphylococcus aureus, Neisseria, Moraxella catarrhalis and Haemophilus influenza. Based on these data, it is possible to explain the high effectiveness and safety of the drugs based on Pelargonium sidoides in ENT organs inflammation treatment, for both adults and children over 1 year old.

Optimizing extraction of Pelargonium sidoides roots: Impact of ethanol concentration on biological activity of extracts

Pelargonium sidoides DC. (Geraniaceae) is an important indigenous medicinal plant in South Africa, historically employed by various ethnic groups to treat respiratory and gastrointestinal ailments. The proprietary herbal tincture, Umckaloabo®, utilizes an ethanolic extract (EPs® 7630) from the roots of P. sidoides, and has demonstrated effectiveness in alleviating symptoms of respiratory infections.P. sidoides roots contain numerous highly oxygenated coumarins and phenolic metabolites, notably the marker compound umckalin. While Umckaloabo® is prepared using 11 % ethanol extraction, the South African commercial market predominantly employs 60 % ethanol extraction due to its consistent umckalin yield and antimicrobial activity. The effects of these extraction methods on chemical composition and in vitro pharmacological activity remain poorly understood.This study confirmed superior antibacterial and antifungal activity in the 60 % ethanol extracts prepared from six root samples compared to the 11 % ethanol extracts. MIC values for both Gram-negative and Gram-positive bacteria ranged from 0.078 to 2.5 mg/mL in the 60 % extracts. Remarkably, two of the root extracts exhibited excellent to very good activity against C. albicans and C. neoformans with MIC values of 0.039 and 0.078 mg/mL, respectively.A positive correlation was identified between total minimum inhibitory concentration (MIC) levels and polyphenol content, rather than umckalin levels. The influence of these extracts on the pro-inflammatory cytokine IL-6 was assessed. Both 60 % and 11 % root extracts of P. sidoides at 100 µg/mL significantly reduced IL-6 production, with the 60 % extracts demonstrating a more pronounced effect (p = 0.008).Statistical analysis revealed significant differences between 11 % and 60 % ethanol extractions in terms of average MIC overall, average Gram-negative MIC, average Gram-positive MIC, fungal MIC, and IL-6 levels. Extracts with higher polyphenol values exhibited superior antimicrobial activity and antioxidant potential, suggesting that polyphenol content may serve as a more reliable indicator of antimicrobial activity than umckalin levels. Additionally, polyphenol levels in the roots may vary with altitude and other environmental factors, warranting further research.

EPs® 7630 Stimulates Tissue Repair Mechanisms and Modifies Tight Junction Protein Expression in Human Airway Epithelial Cells

Airway epithelium repair after infection consists of wound repair, re-synthesis of the extracellular matrix (ECM), and tight junction proteins. In humans, EPs® 7630 obtained from Pelargonium sidoides roots reduces the severity and duration of acute respiratory tract infections. The effect of EPs® 7630 on tissue repair of rhinovirus-16 (RV-16) infected and control human airway epithelial cells was assessed for: (i) epithelial cell proliferation by manual cell counts, (ii) epithelial wound repair by “scratch assay”, (iii) ECM composition by Western-blotting and cell-based ELISA, and (iv) epithelial tight junction proteins by Western-blotting. EPs® 7630 stimulated cell proliferation through cAMP, CREB, and p38 MAPK. EPs® 7630 significantly improved wound repair. Pro-inflammatory collagen type-I expression was reduced by EPs® 7630, while fibronectin was increased. Virus-binding tight junction proteins desmoglein2, desmocollin2, ZO-1, claudin1, and claudin4 were downregulated by EPs® 7630. The RV16-induced shift of the ECM towards the pro-inflammatory type was prevented by EPs® 7630. Most of the effects of EPs® 7630 on tissue repair and regeneration were sensitive to inhibition of cAMP-induced signaling. The data suggest that EPs® 7630-dependent modification of epithelial cell metabolism and function might underlie the faster recovery time from viral infections, as reported by others in clinical studies.

Anti-Quorum Sensing and Anti-Biofilm Activity of Pelargonium × hortorum Root Extract against Pseudomonas aeruginosa: Combinatorial Effect of Catechin and Gallic Acid.

HPLC-UV was used to compare the major constituents of two Pelargonium × hortorum cultivars and Pelargonium sidoides root extract. It revealed the presence of catechin and gallic acid in high concentrations and the absence of umckalin in P. × hortorum root extracts. The antibacterial activity of these extracts was screened against 19 Pseudomonas aeruginosa clinical isolates. P. × hortorum root extracts showed the lowest MIC values (512-1024 µg/mL). This activity was concluded to be attributable to the high concentrations of catechin and gallic acid. The anti-biofilm activity of catechin, gallic acid, and their combination was examined by a crystal violet assay. The combination reduced the percentage of strong and moderate biofilm-forming isolates from 52.63% to 5.26%. The impact on lasI and lasR genes expression using qRT-PCR and simultaneous docking against LasR protein was explored. The combination downregulated lasI and lasR gene expression in eight and six P. aeruginosa isolates, respectively, and showed the greatest docking score. Additionally, the in vivo protection capability of this combination in infected mice showed enhancement in the survival rate. Our study revealed the potential biofilm and quorum-sensing-inhibitory activity of the catechin and gallic acid combination as a novel alternative to inhibit bacterial pathogenicity.

Pelargonium sidoides Root Extract: Simultaneous HPLC Separation, Determination, and Validation of Selected Biomolecules and Evaluation of SARS-CoV-2 Inhibitory Activity.

This study aimed to establish a validated HPLC-UV analytical method for the determination of gallic acid, catechin, scopoletin, and umckalin in phytoformulations containing P. sidoides. Also, to assess the anti-SARS-CoV-2 effect of P. sidoides and these biomolecules in vitro. An HPLC-UV method was developed and verified by testing the commercial forms, Kalobin® and Umca®. It revealed low detectable scopoletin and high umckalin levels. 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). An in-silico prediction of the drugability indicated that the studied biomolecules are under the acceptable norms of Lipinski’s rule, water-soluble, and showed high GIT absorption and bioavailability. Docking study towards the essential molecular targets for viral replication and entry of SARS-CoV-2 indicated good binding affinity of scopoletin (−6.4 Kcal/mol) towards the interface region between the SARS-CoV-2 spike protein RBD and the ACE2 surface receptor indicating the probability of interference with the viral entry to the human cells and showed H-bonding with His-41 in the active site of the main protease which may explain its high antiviral activity.

Pelargonium sidoides root extract, for the treatment of acute bronchitis in adults: feasibility RCT

Pelargonium sidoides root extract, for the treatment of acute bronchitis in adults: feasibility RCT

Chemical characterisation of Pelargonium sidoides root based on LC-QToF-MS non-target screening strategies.

Pelargonium sidoides is a member of the Geraniaceae family and it originates from the coastal regions of South Africa. In the last decades, Pelargonium sidoides root has been subjected to several surveys due to the assertion of its health benefits, such as the relief of symptoms of acute bronchitis, common cold and acute rhinosinusitis. Many studies have been conducted to reveal its naturally occurring bioactive chemicals, yet no wide-scope chemical characterisation strategies have been done using mass spectrometry. This research aimed to comprehensively characterise the chemical profile of Pelargonium sidoides root via high-resolution mass spectrometry. The Pelargonium sidoides root was extracted by a mixture of methanol: water in the proportion of 80:20. The extraction procedure included vortexing, shaking as well as the use of an ultrasound sonication bath under 40°C. After centrifugation, the supernatant was evaporated to dryness. The dry residue was reconstituted with a mixture of methanol/water (50:50, v/v), filtered and injected into an ultra-high-pressure liquid chromatography-quadruple time-of-flight mass spectrometer. Overall, 33 compounds were identified in the root using suspect and non-target screening. These compounds were originated from different classes of compounds such as amino acids, phenolic acids, α-hydroxy-acids, vitamins, polyphenols, flavonoids, coumarins, coumarins glucosides, coumarin sulphates and nucleotides. Quantitative results were provided for the identified compounds, where their reference standards were available. Some important compounds were elucidated, belonging to different classes of compounds such as antioxidants (coumarins and phenolic compounds), amino acids, nucleotides and vitamins revealing the importance of the bioactive content of this root.

THE APPROVAL OF COMPLEX TREATMENT EFFECTIVENESS OF GENERALIZED PERIODONTITIS FOR THE PATIENTS AFTER TRANSMITTED CORONAVIRUS DISEASE AND REMAIN ON REHABILITATION

THE APPROVAL OF COMPLEX TREATMENT EFFECTIVENESS OF GENERALIZED PERIODONTITIS FOR THE PATIENTS AFTER TRANSMITTED CORONAVIRUS DISEASE AND REMAIN ON REHABILITATION

Root extract and proanthocyanidins on oral bacteria viability - Nijole Savickiene

Elevated proportions of some subgingival microbial species have been associated with destructive periodontal disease activity. Biologically active compounds of Pelargonium sidoides root extract (PSRE) or Proanthocyanidins (PACNs) from this extract modulate bacterial virulence and stimulate host immune responses. There is no local delivery system of sustained release formulations with PSRE or PACNs available, however, bioactive capacities of these substances suggest them as promising prolonged local periodontitis treatment candidates.

Pelargonium sidoides root extract for the treatment of acute cough due to lower respiratory tract infection in adults: a feasibility double-blind, placebo-controlled randomised trial

BackgroundPelargonium sidoides DC (Geraniaceae) root extract, EPs®7630 or “Kaloba®”, is a widely used herbal remedy for respiratory infections, with some evidence of effectiveness for acute bronchitis. However, it is not yet widely recommended by medical professionals in the UK. There is a need to undertake appropriately designed randomised trials to test its use as an alternative to antibiotics. The aim was to assess the feasibility of conducting a double-blind randomised controlled trial of Pelargonium sidoides root extract for treatment of acute bronchitis in UK primary care, investigating intervention compliance, patient preference for dosage form and acceptability of patient diaries.Study designFeasibility double-blind randomised placebo-controlled clinical trial.MethodsWe aimed to recruit 160 patients with cough (≤ 21 days) caused by acute bronchitis from UK general practices. Practices were cluster-randomised to liquid or tablet preparations and patients were individually randomised to Kaloba® or placebo. We followed participants up for 28 days through self-reported patient diaries with telephone support and reviewed medical records at one month. Outcomes included recruitment, withdrawal, safety, reconsultation and symptom diary completion rates. We also assessed treatment adherence, antibiotic prescribing and consumption, mean symptom severity (at days 2–4 after randomisation) and time to symptom resolution. We interviewed 29 patients and 11 health professionals to identify barriers and facilitators to running such a randomised trial.ResultsOf 543 patients screened, 261 were eligible, of whom 134 (51%) were recruited and 103 (77%) returned a completed diary. Overall, 41% (41/100) of patients took antibiotics (Kaloba® liquid group: 48% [15/31]; placebo liquid group: 23% [6/26]; Kaloba® tablet group: 48% [9/21]; placebo tablet group: 50% [11/22]). Most patients adhered to the study medication (median 19 out of 21 doses taken in week 1, IQR 18–21 - all arms combined). There were no serious adverse events relating to treatment. Most patients interviewed found study recruitment to be straightforward, but some found the diary too complex.ConclusionsIt was feasible and acceptable to recruit patients from UK primary care to a double-blind placebo-controlled trial of herbal medicine (Kaloba®) for the treatment of acute bronchitis, with good retention and low data attrition.Trial registrationHATRIC was registered on the ISRCTN registry (ISRCTN17672884) on 16 August 2018, retrospectively registered. The record can be found at http://www.isrctn.com/ISRCTN17672884.

Herbal medicine for acute sinusitis - current trends

Was to summarize data on the role and place of herbal remedies, in particular, the extract from the roots of Pelargonium sidoides (EPs 7630) in the treatment of acute sinusitis. Materials of scientific publications included in the Cochrane Library, information bases of the RSCI, MEDLINE, PubMed were used as a data source. The choice of material was carried out according to the keywords: epidemiology of acute sinusitis, modern treatment of acute sinusitis, colds, herbal remedies, Pelargonium sidoides. Analysis of published clinical trial data demonstrates evidence that EPs 7630 is significantly superior to placebo in reducing the duration and severity of symptoms of acute respiratory infection and indicates the advisability of including an extract from Pelargonium sidoides (EPs 7630) roots in OS treatment protocols. The high safety profile and clinically significant efficacy of this drug make EPs 7630 an important component of drug therapy for acute sinusitis.

Effects of Pelargonium sidoides extract vs roxithromycin on chemokine levels in nasal secretions of patients with uncomplicated acute rhinosinusitis.

BackgroundPrevious investigations suggest the use of extract from the roots of Pelargonium sidoides (EPs 7630) for the therapy of uncomplicated rhinosinusitis. The aim of this prospective study was to compare the effects of herbal drug EPs 7630 and antibiotic roxithromycin on chemokine production in nasal mucosa and clinical parameters in patients with uncomplicated acute bacterial rhinosinusitis (ABRS).MethodsSeventy‐eight ABRS patients were divided into 26 patients receiving EPs 7630 tablets, 3 × 20 mg/day per os (group 1), 26 patients receiving roxithromycin tablets, 2 × 150 mg/day per os (group 2), both for 10 days, and 26 patients who received no therapy (Control group). We measured chemokine levels in nasal secretions by flow cytometry and assessed clinical parameters on day 0 and day 10 of investigation.ResultsEPs 7630 increased concentrations of MCP‐1 (P = .001) and IP‐10 (P = .049) and decreased levels of MIP‐1α (P < .001), ENA‐78 (P < .001), and IL‐8 (P < .001). Roxithromycin increased levels of IP‐10 (P = .049) and decreased levels of MCP‐1 (P < .001), MIP‐1α (P < .016), ENA‐78 (P < .001), and IL‐8 (P < .001). Comparison of the non‐treated patients' group with groups 1 and 2 revealed significant improvement of all clinical parameters in treated patients (P < .001), but therapy with roxithromycin resulted in better improvement in nasal symptoms and endoscopic findings than therapy with EPs 7630.ConclusionOur results suggest the presence of similar modulatory effects of both therapies on production of chemokines that regulate the function of neutrophils and monocytes in nasal mucosa. Roxithromycin shows better clinical efficacy than EPs 7630 in patients with uncomplicated ABRS.Level of Evidence1b.

The herbal extract EPs\xae 7630 increases the antimicrobial airway defense through monocyte-dependent induction of IL-22 in T cells

The phytotherapeutic compound EPs® 7630, an extract manufactured from Pelargonium sidoides roots, is frequently used for the treatment of airway infections. Nevertheless, the knowledge of the mode of action of EPs® 7630 is still sparse. Our study aimed at further elucidating the underlying pharmacological mechanisms by focusing on antimicrobial defense mechanisms of EPs® 7630. While investigating the influence of EPs® 7630 on lymphokine production by PBMCs, we found that EPs® 7630 is a novel inducer of IL-22 and IL-17. This cytokine-inducing effect was most pronounced for IL-22 and clearly dose-dependent starting from 1 μg/ml of the extract. Furthermore, EPs® 7630 pretreatment selectively enhanced the IL-22 and IL-17 production capacity of CD3/28-activated PBMCs while strongly limiting the IFN-γ production capacity of innate lymphoid cells. The relevance of EPs® 7630–induced IL-22 production was proven in vitro and in vivo, where IL-22 provoked a strong increase of the antimicrobial protein S100A9 in lung epithelial cells and pulmonary tissue, respectively. A detailed analysis of IL-22 induction modi revealed no direct influence of EPs® 7630 on the basal or anti-CD3/CD28 antibody-induced IL-22 production by CD4+ memory T cells. In fact, EPs® 7630–induced IL-22 production by CD4+ memory T cells was found to be essentially dependent on soluble mediators (IL-1/IL-23) as well as on direct cellular contact with monocytes. In summary, our study reveals a new immune-modulating function of EPs® 7630 that might confer IL-22 and IL-17-induced protection from bacterial airway infection.Key messagesEPs® 7630 selectively strengthens IL-22 and IL-17 production of memory T cells.EPs® 7630 limits the IFN-y production capacity of innate lymphoid cells.EPs® 7630–caused IL-22 production by T cells is essentially dependent on monocytes.IL-22 increase antimicrobial proteins (AMPs) in airway epithelium.EPs® 7630 might protect against airway infection by induction of AMP-inducers.

Does Pelargonium sidoides root extract shorten duration and lessen severity of the common cold?

Evidence-Based Practice: June 2021 - Volume 24 - Issue 6 - p 25-26 doi: 10.1097/EBP.0000000000000909

ПЕРЕВАГА МЕТОДУ ЕКСТРАКЦІЇ З ПОСТІЙНИМ РУХОМ ЕКСТРАГЕНТА НА ПРИКЛАДІ ОДЕРЖАННЯ ЕКСТРАКТУ КОРЕНЯ ПЕЛАРГОНІЇ ОЧИТКОВОЇ (PELARGONIUM SIDOIDES)

The article shows the relevance of the manufacture of medicines containing the extract of Pelargoniumsidoides root pelargonium for the prevention and treatment of respiratory diseases. The results of thestudy of the process of extraction of Pelargonium sidoides root extraction (Pelargonium sidoides) arepresented in two ways: the traditional method of extraction - maceration

Reduced antibiotic use after initial treatment of acute respiratory infections with phytopharmaceuticals- a retrospective cohort study

ABSTRACT Objectives: We examined the relationship between the initial treatment of acute lower and upper tract respiratory infections with phytopharmaceuticals and the duration of the disease as well as between the initial treatment and the use of antibiotics in the further course of the disease. Method: Outpatients from the IMS® Disease Analyzer database with diagnoses of acute respiratory infections between January 2015 and March 2019 were observed for 30 days. Patients who had been prescribed phytopharmaceuticals on the day of their diagnosis were matched with controls who had not received such prescriptions by treating practice, diagnosis, age, sex, insurance status, index year, and Charlson comorbidity score. Patients antibiotic precriptions on the day of diagnosis were excluded. Logistic regression was used to investigate the relationship between phytopharmaceutical prescription, antibiotic prescription in the further course of the disease, and duration of sick leave. Results: A total of 117,182 patients who had been prescribed phytopharmaceuticals and an equal number of controls were available for analysis. Phytotherapeutics were associated with fewer antibiotic prescriptions. Extract of Pelargonium sidoides root (odds ratio (OR) 0.49 [0.43–0.57]) and thyme extract (OR 0.62 [0.49–0.76]) exhibited the strongest effect among patients treated by general practitioners, while Pelargonium sidoides root extract (OR 0.57 [0.38–0.84]), thyme and ivy extract (OR 0.66 [0.60–0.73]), and thyme and primrose root extract (OR 0.67 [0.47–0.96]) proved most effective in pediatric patients. Patients receiving phytopharmaceuticals had a significantly lower risk of prolonged periods of sick leave. The risk of sick leave durations of >7 days was most markedly reduced in patients taking cineole (OR 0.74 [0.63–0.86]) and Pelargonium root extract (OR 0.79 [0.54–0.96]). Conclusion: The use of selected phytopharmaceuticals for acute respiratory infections is associated with a significantly reduced need for antibiotic prescriptions in the further course of the disease, as well as significantly shorter sick leaves.

Effects of Pelargonium sidoides extract on chemokine levels in nasal secretions of patients with non-purulent acute rhinosinusitis

Objective Previous investigations suggest the use of extract from the roots of Pelargonium sidoides (EPs 7630) for improvement of the symptoms of uncomplicated upper airway inflammations, due to its antimicrobial and immunomodulatory actions. The aim of this investigation was to evaluate the effects of EPs 7630 on chemokine production in nasal mucosa and clinical parameters of patients with acute postviral rhinosinusitis (APRS). Methods Twenty-six (n = 26) APRS patients and 25 (n = 25) control subjects were included in this prospective study. We measured the concentrations of thirteen chemokines in nasal secretions of APRS patients and controls by flow cytometry. The patients with APRS were treated by EPs 7630 20 mg oral tablets, three times daily for 10 days. We compared the chemokine levels in nasal secretions, nasal symptoms and endoscopic findings in patients, before and after therapy. Results We found higher Total Symptom Score (TSS) and higher concentrations of MCP-1, MIP-1α, MIP-1β, MIP-3α, ENA-78 and IL-8 in nasal secretions of APRS patients than in controls. After therapy by EPs 7630, we found significant improvement in all symptoms and endoscopic findings of APRS. The concentrations of MCP-1, IP-10 and MIP-1β were significantly increased and levels of MIP-1α, ENA-78, GROα and IL-8 significantly decreased in nasal fluid samples after therapy. No adverse effects were reported during the treatment. Conclusion Our results suggest the presence of modulatory effects of EPs 7630 on production of chemokines regulating the function of neutrophils and monocytes in the site of inflammation of the nasal mucosa in patients with APRS.

HATRIC: a study of Pelargonium sidoides root extract EPs\xae7630 (Kaloba\xae) for the treatment of acute cough due to lower respiratory tract infection in adults\u2014study protocol for a double blind, placebo-controlled randomised feasibility trial

BackgroundAcute lower respiratory tract infection is a common acute infection managed in primary care. The current dominant management strategy in the UK is antibiotics, despite widespread publicity regarding antimicrobial resistance and evidence that the small benefits of antibiotics do not outweigh the harms. There is a need to address the rising problem of antibiotic resistance by providing credible alternative strategies, which reduce symptom burden. There is sufficient evidence to recommend the use of Pelargonium sidoides root extract in order to warrant undertaking an independent clinical trial.We propose a feasibility study to demonstrate our ability to recruit and retain patients and conduct a placebo-controlled trial of Pelargonium sidoides extract EPs®7630 in lower respiratory tract infection where pneumonia is not suspected. Both the tablet and liquid formulations will be included.MethodsThe HATRIC trial is a double-blind randomised placebo-controlled feasibility study aiming to determine the potential to conduct a fully powered trial of Pelargonium sidoides root extract as an alternative to the inappropriate use of antibiotics for acute bronchitis in UK primary care.Primary care sites will be equally randomised to one of two formulation groups (tablet or liquid preparation). Additionally, within each site, patients will be evenly randomised to active or placebo treatment. Antibiotic consumption will be monitored during the trial, but the use of a delayed prescription strategy is encouraged. The target sample size for this study is 160 patients overall or 40 per arm, recruited from approximately 20 primary care sites. The analysis will be descriptive focusing on estimation with no formal comparison of groups taking place.DiscussionIf this trial demonstrates the feasibility of recruitment and delivery, we will seek funding for a fully powered placebo-controlled trial of Pelargonium sidoides root extract for the treatment of lower respiratory tract infections in primary care.Trial registrationHATRIC was registered on the ISRCTN registry (ISRCTN17672884) on 16 August 2018.

Endophytic fungi isolated from Pelargonium sidoides DC: Antimicrobial interaction and isolation of a bioactive compound

The aim of this study was to investigate the antimicrobial activity of endophytes isolated from the root of Pelargonium sidoides DC., and to explore the antimicrobial interactions between endophytic fungi and the host plant. The hypothesis explored is that medicinal plants used as an anti-infective may not only rely on the properties of the medicinal plant alone but also on the residing endophytes within the botanical matrix. The study further aimed to isolate and identify secondary metabolites from the endophyte exhibiting promising antimicrobial activity. Fungal cultures were isolated from P. sidoides root material, and extracts were prepared and tested independently and in combination with the host plant to determine the interactions. Antimicrobial studies were undertaken using the minimum inhibitory concentration (MIC) assay against Gram-positive (Staphylococcus aureus ATCC 25923 and Enterococcus faecalis ATCC 29212) and Gram-negative (Escherichia coli ATCC 8739 and Pseudomonas aeruginosa ATCC 27853) bacteria. The bioactive compound was identified using High Performance Liquid Chromatography–Mass Spectrometry–Solid Phase Trapping–Nuclear Magnetic Resonance (HPLC–MS–SPT–NMR). The identification of the bioactive endophyte was undertaken by polymerase chain reaction (PCR) amplification and deoxyribonucleic acid (DNA) sequence analysis of the internally transcribed spacer regions and intervening 5.8S nrRNA gene and partial beta-tubulin gene. The crude extract from the fungal isolate Penicillium skrjabinii exhibited antimicrobial activity against S. aureus and E. coli at 0.03 and 0.09 mg/mL, respectively. Bioassay-guided isolation was carried out and the major compound, dibutyl phthalate (which is known to be produced by micro-organisms) was isolated from the most active fraction. A number of endophytes displayed a synergistic interaction with the host plant. This is the first study reporting P. skrjabinii as an endophyte that produces dibutyl phthalate and further provides insight to endophytic interactions with the host plant (Pelargonium sidoides root).