Antibiofilm and Antimicrobial-Enhancing Activity of Chelidonium majus and Corydalis cheilanthifolia Extracts against Multidrug-Resistant Helicobacter pylori

Abstract

Helicobacter pylori is a Gram-negative bacterium that colonizes the stomach of about 60% of people worldwide. The search for new drugs with activity against H. pylori is now a hotspot in the effective and safe control of this bacterium. Therefore, the aim of this research was to determine the antibacterial activity of extracts from selected plants of the Papaveraceae family against planktonic and biofilm forms of the multidrug-resistant clinical strain of H. pylori using a broad spectrum of analytical in vitro methods. It was revealed that among the tested extracts, those obtained from Corydalis cheilanthifolia and Chelidonium majus were the most active, with minimal inhibitory concentrations (MICs) of 64 µg/mL and 128 µg/mL, respectively. High concentrations of both extracts showed cytotoxicity against cell lines of human hepatic origin. Therefore, we attempted to lower their MICs through the use of a synergistic combination with synthetic antimicrobials as well as by applying cellulose as a drug carrier. Using checkerboard assays, we determined that both extracts presented synergistic interactions with amoxicillin (AMX) and 3-bromopyruvate (3-BP) (FICI = 0.5) and additive relationships with sertraline (SER) (FICI = 0.75). The antibiofilm activity of extracts and their combinations with AMX, 3-BP, or SER, was analyzed by two methods, i.e., the microcapillary overgrowth under flow conditions (the Bioflux system) and assessment of the viability of lawn biofilms after exposure to drugs released from bacterial cellulose (BC) carriers. Using both methods, we observed a several-fold decrease in the level of H. pylori biofilm, indicating the ability of the tested compounds to eradicate the microbial biofilm. The obtained results indicate that application of plant-derived extracts from the Papaveraceae family combined with synthetic antimicrobials, absorbed into organic BC carrier, may be considered a promising way of fighting biofilm-forming H. pylori.

Dose-Dependent Changes in the Levels of Oxidative Stress Biomarkers in the Muscle Tissue of Rainbow Trout (Oncorhynchus mykiss Walbaum) after In Vitro Treatment by Extracts Derived from Stalks and Roots of Great Celadine (Chelidonium majus L.)

“…Chelidonium majus L. (CM, Papaveraceae), or greater celandine, is an important plant in western phytotherapy and in traditional Chinese medicine (Zielińska et al, 2018). Crude extracts of CM, as well as purified compounds derived from it, exhibit a broad spectrum of biological activities (antiinflammatory, antimicrobial, antitumoral, analgesic, hepatoprotective and antioxidant) that support some of the traditional uses of CM plants (Colombo and Bosisio, 1996;Nawrot, 2017;Zielińska et al, 2018;Huang et al, 2019;Popovic et al, 2021;Krzyżek et al, 2021). However, herbal medicine also claims that this plant has several important properties which have not yet been scientifically studied (Colombo and Bosisio, 1996;Gilca et al, 2010;Zielińska et al, 2018).…”

Phillygenin Inhibits Helicobacter pylori by Preventing Biofilm Formation and Inducing ATP Leakage

“…The formation of biofilms is an important cause for the drug resistance of H. pylori (Krzyzek et al, 2021 ). Phillygenin was shown to inhibit biofilms of H. pylori at 100–150 μg/ml (about 6–8 times MIC) through a detection employing the Alamar blue assay ( Figure 6A ).…”

In Silico Screening and In Vitro Assessment of Natural Products with Anti-Virulence Activity against Helicobacter pylori

“…For this purpose, we used an automatic system, namely Bioflux 1000, generating the flow of culture medium and enabling observation of microbes in real time [ 53 ]. Although this equipment has previously been used to determine the antibacterial and/or anti-biofilm activity of antibiotics and newly tested compounds against different bacterial genera [ 54 , 55 , 56 ], our team is the first to apply it to H. pylori (previously [ 57 ] and hereby). Analysis of time-lapse microscopy recordings of bacteria exposed to dioscin allowed us to confirm the concentration-dependent anti-biofilm effect of this compound ( Figure 4 , Figure 5 and Figure S2 ).…”

“…Confirmation of the anti-biofilm activity of dioscin against H. pylori J99 was performed under flow conditions created by the Bioflux 1000 system (Fluxion, San Francisco, CA, USA) [ 57 ]. To generate these conditions, 48-well low-shear plates composed of inlet and outlet wells connected by a capillary (Fluxion, San Francisco, CA, USA) were used.…”