# A Review on Flavonoids as Anti-_Helicobacter pylori_ Agents
## 3 Results
### Flavonoids Usefulness in Treating H. pylori
Molecular simulations revealed two potential mechanisms of action: either through a conformational change or by physically blocking the substrate from accessing the active site [123]. Quercetin administered to mouse models infected with \(H\). _pylori_ prevented the inflammation process in gastric cells. It also changed p38 MAPK, BCL-2, and BAX protein levels. These proteins are associated with apoptosis to avoid cell mutation and tumour development. Such results indicate the potential targets on cells for quercetin modulation [96]. Furthermore, quercetin inhibited urease activity through hydrogen bonding with the 3-hydroxy, 5-hydroxy, or 3\({}^{\prime}\),\({}^{\prime}\)-dihydroxy groups [93]. Some studies have reported that the MBC of quercetin against specific \(H\). _pylori_ strains ranges between 64 and 128 \(\mu\)g/mL, indicating a relatively weak bactericidal activity [31; 97; 98]. \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 \multirow{4}{*}{Catechins and Epicatechin activities} & Binding to cell membranes & & Growth inhibition at low concentrations; potential gastrorotective effects. & \(\mathrm{N/A}\) & Synergistic activity with antibiotics likely present but not fully understood. & [67; 108; 109; 110; 111; 112] \\  & Binding to cell membranes & & Growth inhibition at low concentrations; potential gastrorotective effects. & & \(\mathrm{N/A}\) & \\  & Binding to cell membranes & & Growth inhibition at low concentrations; potential gastrorotective effects. & & \(\mathrm{N/A}\) & \\  & & & & & & \\ \hline \multirow{4}{*}{Eupatilin} & Inhibits NF-kB inflammatory pathway; suppresses CagA gene. & 125-250 \(\mu\)g/mL & Anti-inflammatory effects; modulation of NF-kB and IL-6 transcription. & Clinical trial show high cure rates in groups with \(\mathrm{N/A}\) patients. & [113; 114] \\  & Bacteriactic action & 15.53 \(\mu\)g/mL & Bacteriactic effect & & \(\mathrm{N/A}\) & \(\mathrm{N/A}\) & [115] \\ \hline Isoquercetin(quercetin-in-fluibiths H. pylori 3-O-\(\beta\)-D-glucose) & Inhibits growth & 480 \(\mu\)g/mL & \(\mathrm{N/A}\) & \(\mathrm{N/A}\) & \(\mathrm{N/A}\) & [116] \\ \hline Loureirin A (from Sanguis Draconis) & bactericidal effect & 4 mg/mL & \(\mathrm{N/A}\) & \(\mathrm{N/A}\) & \(\mathrm{N/A}\) & [117] \\ \hline \multirow{4}{*}{Kaempfer} & Prevents secretion of virulence factors; prevention of transcription; forms complexes with the cell wall. & Decreases mRNA levels of T4 SS components; modifications & & & \\  & & & modulation of \(\mathrm{N/A}\) & \(\mathrm{N/A}\) & \(\mathrm{N/A}\) & [31; 98; 118] \\ \cline{1-1} \cline{2-5}  & & & & & \\ \hline \hline \end{tabular}
\end{table} 
Table 2: _Cont._To further explore the potential mechanism of action, an assay combining 1-N-phenylnaphthylamine (NPN) uptake and high-performance liquid chromatography (HPLC) demonstrated that quercetin does not affect outer membrane integrity but accumulates intracellular, suggesting it is metabolised, although the specific metabolite remains unidentified. Another study showed that quercetin can bind to Ddl (D-Alanine:D-alanine ligase) with a MIC of 100-200 \(\mathrm{\SIUnitSymbolMicro g}\)/mL, consistent with the MBC values [95]. However, a dose of 25 mg/kg body weight for in vivo quercetin administration failed to eradicate _H. pylori_ infection, resulting in only a modest reduction in colony-forming units. Another possible antimicrobial mechanism observed is forming a stable HsrA-flavonoid complex, effectively preventing HsrA from binding to transcriptional factors. This effect has been observed in flavonoids such as chrysin, apigenin, hesperetin, and kaempfer [31]. Apigenin also inhibited the DNA-binding activity of HsrA in _H. pylori_, resulting in a bactericidal effect at a concentration of 8 mg/L [31].