# A Review on Flavonoids as Anti-_Helicobacter pylori_ Agents
## 3 Results
### Flavonoids Usefulness in Treating H. pylori
Additionally, apigenin has been reported to bind to Ddl, acting as a competitive and non-competitive inhibitor for its substrates ATP and D-alanine [95]. Furthermore, the administration of _Leontis nepetaefolia_ (L.) R. Br. hydroethanolic extract has been shown to disrupt the bacterial membrane. This extract contains nine flavonoid types that increase membrane permeability, leading to high potassium efflux and nucleotide leakage [124]. Another flavonoid that can influence _H. pylori_ development is myricetin. Administration of sub-MIC doses of myricetin has been shown to delay the spiral-to-cocoid transition [69]. This delay in _H. pylori_ development is significant, as it can prevent antibiotic tolerance [104]. Recently, a combined pharmacology network and structure-activity relationship analysis has given us an insight into the pharmacological activity of flavonoids. Different flavonoids preferred specific pathways or pathway groups, which is proposed to be caused by their difference in core scaffolds and side chain composition [125]. These in silico data have elucidated some general rules to predict the potential activity of flavonoids, in which they found that the parent structure, number, and positions of side chains such as hydroxyl, methoxy, and glycosylation affect their binding affinity with different receptors. This report was consistent with a previous finding regarding the effects of these factors, with an addition of planarity and degree of unsaturation of the flavonoid group [126]. Rutin has also been verified with moderate antibacterial activity against 11 strains of _H. pylori_. It was verified that the lowest MIC was 8 \(\mathrm{\SIUnitSymbolMicro g}\)/mL and the highest was 125 \(\mathrm{\SIUnitSymbolMicro g}\)/mL [106; 98]. Rutin has an inhibitory potential comparable to clarithromycin and also produces a dose-dependent anti-biofilm effect [115; 127]. Similarly, a dose of 50 \(\mathrm{\SIUnitSymbolMicro g}\)/mL of rutin also matched 10 \(\mathrm{\SIUnitSymbolMicro g}\)/mL of ampicillin in their anti-_H. pylori_ effect [127; 128]. In addition, luteolin and myricetin were found to produce an inhibition and bactericidal action towards _H. pylori_ strains, with a MIC of 125 mg/L and MBC of 1250 mg/L [71]. Furthermore, the flavonoid orientin (8-C glucoside of luteolin) exhibited a stronger bacteriostatic action against _H. pylori_, with a MIC of 15.53 \(\mathrm{\SIUnitSymbolMicro g}\)/mL, almost ten times higher than luteolin [107]. Further evidence supporting the antimicrobial potential of flavonoid-rich extracts has been observed in studies involving _Monteverdia__ilicifolia_. Among the five tested extracts, two exhibited significant antimicrobial activity against _H. pylori_, with one showing a minimum inhibitory concentration (MIC) of 64 \(\mathrm{\SIUnitSymbolMicro g}\)/mL. These two extracts, which demonstrated antimicrobial and antioxidant properties, were rich in tannins and glycosylated flavonoids. Molecular docking studies have suggested that these flavonoids, specifically kaempfer-galactosidase-rhannoside and quercetin-rhammopyranosyl-glucopyranoside-rhammoside, can interact with urease, a key enzyme associated with _H. pylori_ virulence [68]. Myricetin has demonstrated considerable antimicrobial potential against _H. pylori_, exhibiting MIC values of 160 \(\mathrm{\SIUnitSymbolMicro g}\)/mL and MBC values of 320 \(\mathrm{\SIUnitSymbolMicro g}\)/mL. This flavonoid has also been shown to reduce the spiral-to-cococoid transformation of _H. pylori_, which is associated with bacterial persistence and antibiotic resistance. Then, when combined with antibiotics, myricetin exhibited synergistic effects, reducing MIC values by 4-16 times and enhancing the activity of antibiotics such as amoxicillin, clarithromycin, tetracycline, metronidazoleazole, and levofloxacin (FICI = 0.31-0.5). Furthermore, myricetin modulates _H.