Medical Chronicle May 2017 | Page 52

CLINICAL RESPIRATORY CPD may be due to an activation of the immune system. This assumption was supported by Mativandlela et al (2006, 2007), who investigated various extracts and isolated compounds from Pelargonium sidoides root with regards to their antimycobacterial and especially their antitubercular activities. Strains of Moraxella catarrhalis, Aspergillus niger, Rhizopus stolonifer, Fusarium oxysporum, Haemophilus influenza, Mycobacterium tuberculosis and M. smegmatiswere exposed to acetone and ethanol root extracts, as well as four coumarins and two flavonoids isolated from Pelargonium sidoides. Significant activity could be shown for ethanol extract against Aspergillus niger and Fusarium oxysporum but limited activity against Rhizopus stolonifer and Mycobacterium tuberculosis. None of the isolated compounds showed any activity against Mycobacterium tuberculosis. Immunomodulatory properties Kayser et al (1997, 2001, 2003) investigated extracts and isolated constituents of Pelargonium sidoides for their effects on nonspecific immune functions in various bioassays. No significant activity against extracellular, promastigote Leishmania donovani, could be shown. However, all extracts and compounds significantly reduced the intracellular survival of Leishmania donovani. This implies indirect activity, possibly through activation of leishmanicidal macrophage functions. Activation was confirmed through the presence of tumour necrosis factor (TNF-alpha) and inorganic nitric oxides (iNO). Synthesis of the latter is a known mechanism of macrophages against microorganisms. Kolodziej et al (2003) and Janecki et al (2007) observed TNF inducing potencies for EPs 7630 as well as interferon-like activities in supernatants of sample-activated bone marrow- derived macrophages in several functional assays. Various subfractions of EPs 7630 were tested for their NO-, TNF- and interleukin (IL)-12-inducing capacity. EPs 7630 induced significant TNF levels in non-infected and GFP transfected-Leishmania major-infected macrophages. Production of NO and IL-12, however, were negligible, while flow cytometry indicated a decrease in parasites in cells treated with EPs 7630. This suggests that radical scavengers or low but efficient NO levels may be present in EPs 7630. Koch et al (2002) further investigated if and how EPs 7630 interferes with interferon (IFN)- beta synthesis in MG-63 human osteosarcoma cells. IFN-beta production increased in cells preincubated with Umckaloabo. Enhancement of natural killer cell mediated cytotoxicity was also found. Umckaloabo thus enhanced but did not induce IFN-beta production. Kolodziej et al (1999, 2005) investigated polyphenol-containing of HNP 1–3 and BPI. Thus EPs 7630 seem to stimulate host defence through enhancing the release of antimicrobial peptides. Effects on the mucociliary system Mickenhagen et al (2004) and Neugebauer et al (2005) presented investigations into the stimulation of ciliary beat frequency (an important defence mechanism of the mucociliary system) in ciliated cell cultures of human nasal epithelium with Eps 7630 in vitro. Three concentrations of Eps 7630 (1, 30, 100g/ml) were tested, which significantly increased ciliary beat frequency in a dose-dependent manner. Effects on symptoms of sickness behaviour Nöldner and Koch (2004) and Nöldner and Schötz (2007) studied the inhibition of sickness behaviour (anorexia, listlessness, reduced activity) by EPs 7630 in male NMRI mice induced by a cytokine-inducer (lipopolysaccaride). Oral administration of EPs 7630 antagonised the above-mentioned effects in a dose-dependent manner. CLINICAL EVIDENCE OF EFFICACY A total of 18 clinical trials have thus far been conducted, several of which were randomised, double-blind and placebo- controlled. EPs 7630 has been shown to effectively shorten the severity and duration of acute bronchitis and tonsillopharyngitis, most notably in children. Results from trials with adults and children support the use of this product as a possible alternative to antibiotics for the acute treatment of these conditions. Research also focuses on the treatment of symptoms of sickness behaviour and of acute 52 MAY 2017 | MEDICAL CHRONICLE