# A Review on Flavonoids as Anti-_Helicobacter pylori_ Agents
## 3 Results
### Flavonoids Usefulness in Treating H. pylori  
Several hypotheses have been suggested to explain flavonoids' antimicrobial properties. One theory is that the hydroxyl groups present in flavonoids act as free radical  
Figure 3: The general structure and seven groups of flavonoids. Schematic representation from different groups. Created in ACD/ChemSketch Freeware version. scavengers and chelate metal ions, contributing to their antioxidant activity [89; 90]. Additionally, the hydroxyl and ketone groups in flavonoids may bind to nickel (Ni) ions or residues within the active site of the urease enzyme, thereby inhibiting its function in bacteria [91; 92]. Table 2 summarises the pharmacological activity of selected flavonoids against _H. pylori_. \begin{table}
\begin{tabular}{p{56.9 pt} p{56.9 pt} p{56.9 pt} p{56.9 pt} p{56.9 pt} p{56.9 pt} p{56.9 pt}} \hline \hline
**Flavonoid** & **Action Mechanism** & **MIC** & **In Vitro Data** & **In Vivo Data** & **Synergistic Effect** & **Scientific Reference** \\ \hline Quercetin & Urease inhibition via binding with zinc cation; binding to Ddl; lipid peroxidation of bacteria & Molecular docking; inhibits 100–200 \(\mu\)m; binding to Ddl; membrane. & Precurs & & & \\  & & & & & \\  & & & & & \\  & & & & & \\  & & & & & \\ \hline Bialelin and & Binding to urease active site & \(\geq\)1 mM (Baiclin); virulence by decreasing vacA gene expression. & Reduces virulence by lowering vacA gene expression. & Baiclein has enhanced bactericidal effects. & N/A & [100; 101; 102] \\ \hline Hesperetin & Downregulates virulence factors & Reduces expression & & & & \\  & UreA and UreB; prevents bacterial infection by gene expression & 8 mg/L development, inhibition of urease. & & Synergistic with metronidazole and clarithromycin. & [31; 75; 103] \\ \hline Chrysin & Forms a stable & & & & \\  & & & & & \\  & & & & & \\  & & & & & \\  & & & & & \\ \hline Myricein & Disrupts transcription of virulence- associated genes; delays spiral-to-occoid transformation. & Affects gene expression related monomers. & Delays morphological transformation, dimers and monomers. & Synergistic effects with antibiotics & [69; 104] \\ \hline Naringenin & Urease inhibition & N/A & Inhibits effect of urease & N/A & N/A & [75] \\ \hline Rutin & Impairs biofilm formation; moderate antibacterial activity & 8–125 \(\mu\)g/mL activity & Biofilm formation inhibition. & N/A & N/A & [105; 106] \\ \hline Apigenin & Binds to Ddl as competitive and non-competitive inhibitor; inhibits DNA-binding activity of HsrA. & 8 mg/L DNA-binding activity of HsrA. & 8 mg/L Ddl activities. & N/A & N/A & [31; 95] \\ \hline Luteolin & Inhibits _H. pylori_ strains possible action on adhesion to host cells. & & Inhibition and bactericidal action. & & \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Pharmacological Activity of Flavonoids Against _H. pylori_. Similarly, 7-O-butyl naringenin also exhibits inhibitory effects against urease [75]. Hesperetin-7-rhannoglucoside also produced a similar urease inhibitory activity via competitive inhibition [119]. Additionally, research by [PERSON] et al. found that extracts from the pedicels of persimmon, containing flavonoids and other biomolecules, synergistically inhibited \(H\). _pylori_ urease (HPU) and peptide deformylase (HPPD), as confirmed by molecular docking results [120]. Moreover, hydrophilic flavonoids have been suggested to interact with proteins located on the cell membrane or in the cytosol by forming complexes, thereby modulating various cellular functions, including those of adhesins, cell envelope transporters, transcriptional regulators, enzymes, and toxins [89; 121]. In contrast, flavonoids with higher lipophilicity can penetrate the cell membrane, affecting membrane fluidity and permeability [89; 122]. (S)-sakuranetin exhibited inhibitory activity by binding to \(\beta\)-hydroxyacyl-acyl carrier protein dehydratase (HpFabZ) through hydrophobic interactions and hydrogen bonding.