# A Review on Flavonoids as Anti-_Helicobacter pylori_ Agents
## 3 Results
### Review on H. pylori Infection and Treatment
#### 3.1.2 Diagnosis and Treatment  
The diagnostic accuracy for _H. pylori_ will depend on the protocol used for each patient. There are non-invasive and invasive protocols, but the false negative frequency is important to consider, according to the protocol [2; 20]. Although the endoscopic examination is an invasive protocol, it is a common method used as it allows for the detection  
Figure 1: Flow diagram for the systematic review of the anti-_H. pylori_ action of flavonoids. The diagram describes the screening process undertaken for all articles retrieved from databases, which underwent title and abstract screening, full-text analysis, and inclusion of relevant references not originally included in the search criteria. of many abnormalities and allows the collection of a gastric biopsy to confirm _H. pylori_ infection [2; 27]. The options for treatment nowadays encompass the traditional use of proton pump inhibitors (PPIs) and two antibiotics. PPIs can be omeprazole, lansoprazole, pantoprazole, rabeprazole, and esomeprazole, while antibiotics commonly used are amoxicillin, clarithromycin, levofloxacin, and metronidazolezole. The treatment period usually is around 10-14 days. However, sometimes, the patient may have difficulties following all these days, which is a problem that may lead to increased antibiotic resistance [10; 20]. The other protocol used is the bismuth quadruple therapy, which uses PPI plus bismuth and two antibiotics (e.g., metronidazolezole and tetracycline). Bismuth acts as a mucosal protective agent and inhibits some enzymes, such as urease, fumarase, alcohol dehydrogenase, and phospholipase, necessary for colonisation and infection [28]. This protocol is administered over 10 days and has an effective rate of 95% infection eradication in children. One problem that has been observed is the _H. pylori_ resistance to clarithromycin and levofloxacin. Then, new drugs were searched to improve the eradication of bacteria. In the USA, there is a new treatment in clinical trial phase 3 for a drug approved by the FDA called RHB-105 (protocol ERADICATE Hp; NCT03198507 and ERADICATE Hp2; NCT01980095). [PERSON] et al. evaluated the patients treated with RHB-105 in combination with PPIs, rifabutin, and amoxicillin versus placebo or dual therapy [5]. They verified an effectiveness of 63% in the treatment of 14 days. [PERSON] et al. raised some points related to the ideal treatment needed to eradicate _H. pylori_ without affecting the gut microbiota of patients [29]. Considering these aspects, they proposed a dual therapy using vanoprazan-amoxicillin with PPIs that may facilitate the therapy for patients and have fewer adverse effects with a rate of 90% of _H. pylori_ elimination. That is considered very good, as it depends on the bacteria's genotypes and polymorphism in the patient. Considering all these problems, there are also adjuvant therapies to be used, such as probiotics (_Lactobacillus_ and _Limosillactobacillus reuter_) that may secrete antimicrobial compounds to improve the mucosal barrier and compete with binding sites, consequently helping the eradication [30]. Therefore, the use of probiotics is a new protocol, and the results obtained are not clear enough. Then, more laboratory research and clinical trials are necessary when using these protocol combinations to improve these results [2]. In addition, there is some research about the use of inhibitors of biofilm formation, as well as the use of medicinal plants and plant extracts based on Traditional Chinese medicine (TCM) (e.g., _Impatiens balsamina_ L., _Chenopodium ambrosioides_ L., _Adina pillifera, Bryophyllum pinntatum_) in addition to the use of pure natural products such as flavonoids (chrysin, apigenin, hesperidin, kaempfer) and other bioactive molecules and antimicrobial peptides (AMPs) [1; 2; 31]. It has been verified that the AMPs may be an efficient protocol to replace antibiotics in the treatment [1; 32; 33]. These peptides are produced by host cells as part of innate immunity, and they protect against different pathogens.