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Introduction
Gastric cancer is one of the third leading causes of death related to cancer worldwide, being reported almost 1 million cases every year accounting for more than 700,000 deaths per year (Karimi et al., 2015; Plummer et al., 2015).
Among several causes of gastric diseases, the main triggers are alcohol consumption, stress, nutritional deficit, high intake of salt, ingestion of nonsteroidal anti-inflammatory drugs and the Helicobacter pylori infection (Dong and Kaunitz, 2006; Wroblewski et al., 2010).
H. pylori is a gram-negative bacteria, reaching half of the world population, with 40 % of prevalence in developed countries and above 80 % in development ones (Hooi et al., 2017; Kusters et al., 2006). The most important characteristic of H. pylori is its survival capacity in the gastric environment. This ability is due to the presence of urease, an enzyme that hydrolyzes urea to ammonia, buffering the pH around the bacteria (Montecucco and Rappuoli, 2001; Wroblewski et al., 2010).
This bacterial presence in the stomach may cause direct damage to the epithelial cells, initiating an intense inflammatory process that leads to a high production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and several reactive oxygen and nitrogen species (ROS and RNS, respectively) (O2
−, HOCl and NO) (Crabtree et al., 1995; Montecucco and Rappuoli, 2001). Additionally, H. pylori stimulates the NADH-oxidase enzyme leading to a ROS release in the extracellular environment (Allen et al., 2005). The high influx of defense cells and oxidative stress increase the tissue damage leading to the development of ulcer and gastric cancer such as adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma (Sugano et al., 2015; Wroblewski et al., 2010). This infection represents approximately 5 % of world cancer cases (Moss, 2017; Plummer et al., 2015).Since 1994, H. pylori has been classified as a class I carcinogen by the International Agency for Research on Cancer (IARC). In 2017, the World Health Organization (WHO) published a list of antibiotic-resistant priority pathogens highlighting H. pylori as a high priority to the development of new antibiotics (IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (Ed.), 1994; Tacconelli et al., 2018).
The standard protocol for anti-H. pylori treatment is comprised by the association of two antibiotics and a hydrogen pump inhibitor. However, declining patient compliance, high costs, side effects and the emerging resistance to antibiotics have contributed to the increase of research for alternative treatments (Graham and Fischbach, 2010; O’Connor et al., 2014).
Historically, natural products have been the primary source of active compounds in the treatment of several diseases. In modern drug discovery and development, natural products continue to play an important role. Newman and Cragg reported, in the period of 1981–2014, that 73 % of the approved drugs used in bacterial infections were derived from natural products. In the Clinical Trials database (http://www.clinicaltrials.gov), 15 % of drug interventions registered in the same period were related to plant species, being 60 % of these sources obtained from only 10 plant families, including the Lamiaceae family (Newman and Cragg, 2016; Sharma and Sarkar, 2013; Wang et al., 2019).
The Plectranthus barbatus Andrews (Lamiaceae) species is widespread in Africa, Asia and South America. In Brazil, it is commonly known as “falso-boldo” and its leaves used in the folk medicine for the treatment and prevention of gastric disorders (Falé et al., 2009). Previous studies with P. barbatus leaves extracts evidenced anti-inflammatory and antibacterial effects and a decrease in the gastric acid levels (Araújo et al., 2014; Fischman et al., 1991; Kapewangolo et al., 2013).
Many chemical structures have been elucidated from P. barbatus leaves and roots, comprising several diterpenes, which showed significant biological activities (Alasbahi and Melzig, 2010a; De Albuquerque et al., 2007; Falé et al., 2009; Mothana et al., 2014; Porfírio et al., 2010; Rodrigues et al., 2010; Schultz et al., 2007). In the present study, we evaluated the anti-H. pylori, immunomodulatory, antioxidant and cytotoxic activities of P. barbatus ethyl acetate fraction (EAF) and its chemical profile.
Section snippets
Chemicals
All chemicals were purchased from Sigma-Aldrich (USA) unless specified.
Plant material
The plant species were collected at the municipal Park Tabuazeiro, Vitoria/Brazil (January 2014; 20°29′31″ S latitude and 40°32′36″ W longitude) and identified at the Federal University of Espirito Santo (UFES) under the catalog number 35080, deposited at the UFES VIES Central Herbarium.
Extract and fraction
Dried and powdered leaves were macerated with EtOH:H2O (70:30, v/v) for seven days at room temperature (1:10 w/v). The hydroalcoholic
P. barbatus EAF chemical profile analysis by paper spray ionization mass spectrometry (PS-MS)
The P. barbatus EAF chemical profile analysis (Fig. 1) by PS-MS showed 63 signals ranging from m/z 255–577. The obtained signals correspond to deprotonated molecules. The PS-MS table (available in supplementary material) shows m/z measured values, error (ppm), Resolution power, DBE and m/z standard values with molecular formula of compounds detected by PS(-)-MS technique, where eight molecules were identified according to the literature described (Fig. 2) (Alasbahi and Melzig, 2010b; De
Conclusion
The results presented here suggests that P. barbatus species has the potential to inhibit H. pylori and its pathogenic mechanisms. The data obtained from antibacterial and antitumor activities were relevant for P. barbatus, suggesting that this plant species may be a source of new substances for the treatment of H. pylori infection and gastric cancer. To confirm the information obtained in the present study, subsequent assays, such as in vivo anti-H. pylori activity, as well as isolation,
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