Extracts from the roots of Ononis spinosa L. (restharrow roots) are traditionally used for the treatment of patients with urinary tract infections due to its mild diuretic activity, caused by the inhibition of renal human hyaluronidase-1 by isoflavonoids. Preliminary studies also indicated anti-inflammatory effects. The following study aimed at investigating potential anti-inflammatory effects of restharrow extracts, prepared with solvents of different polarity. A dichloromethane extract (OS1), mainly composed of isoflavonoids and triterpenes as characterized by LC-MS, showed a concentration-dependent (25-100 mg/ml) inhibition of IL-8 and TNF-a release from LPS-stimulated human neutrophils. Significant inhibition was also found for the triterpene a-onocerin and the norneolignan clitorienolactone B, isolated from OS1. Further, OS1 and both compounds significantly decreased the expression of the adhesion molecules CD11b/CD18 and conversely increased the expression of CD62L in LPS-stimulated human neutrophils. This finding corresponds to a reduced inflammatory response by the inhibition of adhesion and migration of immune cells. As all of the observed effects are potentially mediated via Tolllike receptor 4 (TLR4) signaling, TLR4 transfected HEK293 cells were incubated with OS1. LPS-induced IL-8 secretion was significantly inhibited in a concentration-dependent manner, confirming TLR4 antagonism. This inhibition, however, was in part caused by an interaction of OS1 with LPS. In addition, also an aqueous extract containing high amounts of isoflavonoid glycosides and saponins from the roots of O. spinosa showed anti-inflammatory effects by interacting with the TLR4 signaling pathway. This study rationalizes the traditional use of extracts from O. spinosa for therapy of urinary tract infections, due to its potential anti-inflammatory effects that are mediated via TLR4 receptor antagonism.
A hybrid of six (6) 4-hydroxyindole azo compounds was synthesised by the diazotization and coupling strategy via electrophilic aromatic substitution reaction. Characterisation by Infrared and UV-Vis spectroscopic studies was carried out and the antimicrobial activity and structure-activity relationship were explored. Amongst the compounds, 4d was the most active against Pseudomonas aeruginosa than the other organisms from the high-throughput spot culture growth inhibition (HTSPOTi) antimicrobial assay. According to the resistant modulation study, the compounds did not show significant activity against the panel of pathogens used. Furthermore, compounds 4a and 4f inhibited biofilm formation in Pseudomonas aeruginosa and Staphylococcus aureus at 70% (31.25 µg/mL) and 57% (125 (µg/mL) respectively. Additionally, 4c and 4e have biofilm inhibition potential against Pseudomonas aeruginosa and Staphylococcus aureus which are implicated in antimicrobial resistance. Hence, the compounds are promising leads with potential to be developed into new antibacterial agents to combat the menace of antimicrobial resistance.
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