PHARMACOLOGICAL ACTIONS/MECHANISM OF ACTION
Antimicrobial and Antiviral Effects
The antimicrobial effects of Sinupret were evaluated in sinusitis-relevant microbes.20 Gram-positive bacteria (Staphylococcus aureus, methicillin resistant Staph. aureus [MRSA], and Streptococcus pyogenes) and gram-negative bacteria (Escherichia coli and Haemophilus influenzae) were exposed to Sinupret and the killing action was assessed. Sinupret caused relevant bacteriocidal effects on gram positive and negative bacteria.20 It was most potent against MRSA, Staph. aureus, and Strep. pyogenes. It was not effective against E. coli.
The antiviral activity of Sinupret drops were evaluated in vitro.21 Sinupret drops 0.1 mg/mL produced a 46% inhibition against human parainfluenza virus type 1; 0.01 - 0.025 mg/mL of Sinupret produced a 50% inhibition against human respiratory syncytial virus. Sinupret produced a synergistic effect against respiratory syncytial virus compared to its individual components primrose and European vervain.21
Mice were inoculated with Strep. pneumoniae to induce bacterial rhinosinusitis and then treated with Sinupret, ampicillin, dexamethasone, or sham treatment.22 All treatments (except sham) caused a reduction in bacterial growth after 4 days, which reached statistical significance after 8 days. The study was repeated in rabbits and the outcome was similar.22
The ability of Sinupret to protect against a Sendai virus (Parainfluenza viridae) respiratory tract infection was studied in mice.23 The mice were treated with Sinupret or 2 active controls (ambroxol and muramyldipeptide) several days prior to being infected with the Sendai virus. Sinupret significantly prolonged the mouse survival time compared with placebo (p < 0.05). The 2 positive controls were not as effective as Sinupret. Sinupret may be producing this effect by modulating cytokines and increasing antigen-specific CD4+ and CD8+ T-cells.23
The secretolytic activity (process of breaking down secretions and reducing the viscosity of mucus) of Sinupret was evaluated with a classical model for determining pharmacological effects on the production of tracheal secretion in rabbits.24 Sinupret, the individual herbs that are in Sinupret, and sodium chloride (control) were administered to rabbits for several days before their tracheal sections were collected. Sinupret and the individual herbs all statistically significantly increased the fluidity of respiratory tract secretions compared with baseline (p < 0.05 for all).24 Doses of Sinupret that were 50-fold and 15-fold greater than the human dose did not cause any safety problems.24
A second secretolytic study evaluated the effects of Sinupret and its individual components on secretion activity of rat respiratory epithelium.24 The method, which uses phenol red, has been used to evaluate standard secretolytics. Sinupret had a dose-dependent effect on tracheobronchial secretion.24,25 Of the individual components, European vervain and gentian root extracts (dry extracts of an ethanol-water extract) displayed the most secretolytic effects. However, secretion produced by Sinupret (also a dry extract of an ethanol-water extract) was greater than that produced by the individual components, indicating a synergistic effect.24 Saline had no secretolytic effect.
The immunological activity of Sinupret and its individual components were evaluated in vitro in human leukocytes isolated from peripheral blood.26 Phagocytotic activity of the plant extracts were evaluated in isolated human neutrophil granulocytes (a type of leukocyte). Gentian root extract and vervain extract (type of extract not reported) increased phagocytic activity of neutrophils. Sorrel inhibited phagocytosis at high concentrations.26 At low concentrations Sinupret only marginally increased phagocytosis. Sorrel extract (type of extract not reported) stimulated proliferation of lymphocytes. High concentrations of Sinupret marginally stimulated proliferation of lymphocytes in vitro. The authors concluded that human immune cells respond to the herbal extracts.26
Neutrophils are part of the first-line innate immune response.27 They can act as phagocytic cells and release reactive oxygen species (ROS) and proteases to attack bacteria and parasites. However, neutrophils can also cause inflammation—ROS is involved in the pathogenesis of some inflammatory diseases.28 Neutrophils are activated after they adhere to the endothelium. Subsequently, superoxides can be produced in a process called respiratory burst. Sinupret (water and hydroethanolic extracts) was assayed for its ability to influence the adhesion and superoxide production of ovine (sheep) neutrophils activated by phorbol 12-myristate 13-acetate (PMA).27 PMA triggers neutrophil adhesion. The hydroethanolic extract strongly blocked neutrophil adhesion and superoxide production in a dose-dependent manner. Low concentrations increased superoxide production and the high concentration inhibited superoxide production. The aqueous extract did not influence neutrophil function, indicating that the most active molecules are not water soluble. The authors hypothesized that the flavonoid content in Sinupret may be responsible for the effect on neutrophils.27 The aqueous extract stimulated cell viability, which may be related to the carotenoid content. The authors concluded that Sinupret has anti-inflammatory activity in this system.27
Respiratory infections are inflammatory processes of the respiratory epithelium, so it is not unusual to test treatments for respiratory infection in standard in vivo models of inflammation.24 Hence, Sinupret was evaluated in a rat hind paw model of inflammation. Inflammation was induced in the rat hind paw and the ability of oral Sinupret, phenylbutazone (positive control), and placebo to reduce swelling was measured.24 Sinupret reduced swelling and the highest dose tested was as effective as phenylbutazone.24 The authors attribute the anti-inflammatory effect to the polysaccharides and tannins in sorrel and the iridoids in vervain.12,15,24
Bacterial infections of the upper respiratory tract can be treated with antibiotics, which target the bacteria, or can be treated with anti-inflammatory substances, which target the host response reaction.29 This is because the initiation and persistence of rhinosinusitis involves a complex interaction between local inflammation and microbial colonization. The efficacy of Sinupret, dexamethasone (an anti-inflammatory agent), ampicillin (an antibiotic), and sham control were tested in mice inoculated intranasally with Strep. pneumoniae to induce bacterial rhinosinusitis.29,30 Sinupret significantly reduced bacterial growth (p < 0.01), the number of goblet cells (cells that secrete mucous) (p < 0.05), and the character of secretion compared with control (p < 0.01).30 The reduction in bacterial growth was similar to the positive controls. The authors stated that Sinupret is working through an anti-inflammatory mechanism.29,30