# A Review on Flavonoids as Anti-_Helicobacter pylori_ Agents
###### Abstract  
_Helicobacter pylori_ is a Gram-negative bacterium from the Epsilonproteobacteria class, associated with various gastric diseases, including gastric cancer. It affects both adults and children, with a high prevalence in developing countries due to poor health conditions. The International Agency for Research on Cancer has classified _H. pylori_ as a class I carcinogen, linked not only to gastric cancer but also to neurological disorders. Current treatment involves proton pump inhibitors combined with antibiotics for 10 to 14 days, but patient non-compliance can lead to increased antibiotic resistance. This review examines studies from the past decade that explore flavonoids as potential future treatments for _H. pylori_. Flavonoids like kaempfer, rutin, quercetin, myricetin, catechchin, epicatechin, eupatilin, chrysin, apigenin, and hesperetin have been shown to regulate the expression of key _H. pylori_ genes, alter cell membrane permeability, and affect proton efflux. These biomolecules, found in various plants, have demonstrated the potential to inhibit _H. pylori_, even in resistant strains. Gene expression and molecular docking studies reveal how these flavonoids interact with the membrane, bacterial genes, and proteins, affecting host cell transcription, translation, and bacterial adherence. While promising, clinical trials are needed to better understand their mechanisms and efficacy. Helicobacter pylori; medicinal plants; extracts; flavonoids; antimicrobials; urease +
Footnote †: journal: Applied sciences  
0000-0001-5000-0000-0000-0000-0000-0000-0000-0000-0000-0000-0000-0000-0000-0000-0000-0000-0000-00000-00000-00000-00000-00000-00000-00000-00000-000  
cytotoxin-associated gene A (_CagA_) and the more virulent vacuolating cytotoxin gene A (_VacA_) in specific strains of _H. pylori_ can be associated with an increased risk for the development of severe gastritis, MALT lymphoma, and adenocarcinoma of the stomach [8; 9; 10; 11; 12; 13]. Thus, the International Agency for Research on Cancer has classified _H. pylori_ as a Class I carcinogen. In Africa, for example, _H. pylori_ infection has been associated with a high frequency of colorectal cancer [2; 14]. This suggests that this bacterium likely has a mutagenic effect on host DNA. Furthermore, in countries where _H. pylori_ infection has been reduced or eradicated, the incidence of gastric and colorectal cancers has also decreased, demonstrating the correlation between this pathogen and these cancer types [1; 2; 3; 4; 5; 6; 7; 9; 14]. In addition, _H. pylori_ may be linked to other diseases, such as those in dermatology (rosacea, urticaria), haematology, and neurology [15; 16; 17]. [PERSON] et al. observed that the _H. pylori_ infection may also be associated with Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis, and Guillain-Barre syndrome [18]. Furthermore, data from the meta-analysis showed that infection worsens PD clinic symptoms [16]. However, more research must be conducted to understand how this happens [2]. The current treatment for _H. pylori_ infection is not infallible. The current regime fails for more than 20% of patients due to a combination of antimicrobial resistance and patient non-compliance, which is exacerbated by the lengthy treatment time of 10-14 days, depending on the treatment. In 2017, _H. pylori_ was considered by the World Health Organization as one of 12 priority pathogens due to its antibiotic resistance, limited treatment options, problems with patient adherence to the treatment, and the disease severity [19]. All these points mentioned above help the bacteria develop resistance to antibiotics. In that sense, developing novel prevention and treatment options is crucial so plants and natural products can play a vital role [1; 19; 20]. In recent years, governmental agencies have recognised the importance of using medicinal plants as pharmacological aid. According to WHO [21] 109 countries created a regulatory framework for traditional medicines to be used on a large scale by the population.