No abstract

Plant molecules are continuously investigated to prevent and treat in ammatory and ulcerative disorders associated with the gastrointestinal tract, such as gastritis, colitis, mucositis, and ulcer. However, most of the work published is devoted to investigating the therapeutic properties of secondary plant metabolites. This work investigated the gastroprotective activity of a lipid transfer protein isolated from Morinda citrifolia L., named McLTP 1 , when orally administered to mice, from the perspective of its use as a novel peptide-based drug for the prevention and treatment of ulcerative gastric lesions. Pretreatment with McLTP 1 at different doses (4, 8, or 16 mg/kg) reduced ethanol-induced gastric lesions (p < 0.05) in 40%, 84%, and 88%, respectively. In ethanol-induced gastric lesions, it was demonstrated alterations in levels of GSH (↑100%; p < 0.05) and a reduction by 45% in the levels of MDA (p < 0.05) after McLTP 1 administration (8 mg/kg). McLTP 1 showed an anti-in ammatory effect through the modulation of the cytokines IL-10 (↑33%) and TNF-α (↓54%) and was able to reduce MPO levels (↓95%) in the gastric tissue. Besides, the gastroprotective of McLTP 1 also involves the production of nitric oxide. The present ndings reveal that McLTP 1 has a gastroprotective effect dependent, at least in part, on its antiin ammatory and antioxidant effects.

Plant molecules are continuously investigated to prevent and treat inflammatory and ulcerative disorders associated with the gastrointestinal tract, such as gastritis, colitis, mucositis, and ulcer. However, most of the work published is devoted to investigating the therapeutic properties of secondary plant metabolites. This work investigated the gastroprotective activity of a lipid transfer protein isolated from Morinda citrifolia L., named McLTP1, when orally administered to mice, from the perspective of its use as a novel peptide-based drug for the prevention and treatment of ulcerative gastric lesions. Pretreatment with McLTP1 at different doses (4, 8, or 16 mg/kg) reduced ethanol-induced gastric lesions (p < 0.05) in 40%, 84%, and 88%, respectively. In ethanol-induced gastric lesions, it was demonstrated alterations in levels of GSH (↑100%; p < 0.05) and a reduction by 45% in the levels of MDA (p < 0.05) after McLTP1 administration (8 mg/kg). McLTP1 showed an anti-inflammatory effect through the modulation of the cytokines IL- 10 (↑33%) and TNF-α (↓54%) and was able to reduce MPO levels (↓95%) in the gastric tissue. Besides, the gastroprotective of McLTP1 also involves the production of nitric oxide. The present findings reveal that McLTP1 has a gastroprotective effect dependent, at least in part, on its anti-inflammatory and antioxidant effects.

The emergence of antibiotic resistance poses a serious and challenging threat to healthcare systems, making it imperative to discover novel therapeutic options. This work reports the isolation and characterization of a thermostable trypsin inhibitor from chia (Salvia hispanica L.) seeds, with antibacterial activity against Staphylococcus aureus sensitive and resistant to methicillin. The trypsin inhibitor ShTI was puri ed from chia seeds through crude extract heat treatment, followed by a nity and reversed-phase chromatography. Tricine-SDS-PAGE revealed a single glycoprotein band of ~11 kDa under nonreducing conditions, con rmed by mass spectrometry analysis (11.558 kDa). ShTI was remarkably stable under high temperatures (100 °C; 120 min.) and a broad pH range (2 -10; 30 min.).Upon exposure to DTT (0.1 M; 120 min.), ShTI antitrypsin activity was partially lost (~ 38%), indicating the participation of disul de bridges in its structure. ShTI is a competitive inhibitor (Ki = 1.79 x 10-8 M; IC50 = 1.74 x 10-8 M) that forms a 1:1 stoichiometry ratio for the ShTI: trypsin complex. ShTI displayed antibacterial activity alone (MICs range from 15.83 to 19.03 µM) and in drug combination with oxacillin (FICI range from 0.20 to 0.33) against strains of S. aureus, including methicillin-resistant strains.Overproduction of reactive oxygen species and plasma membrane pore formation are involved in the antibacterial action mode of ShTI. Overall, ShTI represents a novel candidate for use as a therapeutic agent for the bacterial management of S. aureus infections.

The incidence of Candida species resistance to traditional antifungals is increasing globally. This issue significantly impacts patients' lives and raises healthcare expenses, confirming the need for developing novel therapeutic strategies. Recently, a thermostable trypsin inhibitor was isolated from Salvia hispanica L. (chia) seeds – named ShTI (MM 11.558 kDa) with an antibacterial effect against Staphylococcus aureus species. This work aimed to assess the antifungal effect of ShTI against Candida species and its synergism with fluconazole and to evaluate its mode of action. Moreover, preliminary toxicological studies using mouse fibroblast cells were performed. ShTI displayed an anticandidal effect alone against C. parapsilosis (ATCC® 22019), C. krusei (ATCC® 6258), and six clinical fluconazole-resistant strains of C. albicans (2), C. parapsilosis (2), and C. tropicalis (2) (MIC 50: 4.1 µM and MIC 100: 8.2 µM) and exhibited a synergistic effect when combined with fluconazole against C. albicans with complete alteration of the morphological structure of the yeast. The mode of action of ShTI against C. krusei (ATCC® 6258™) and C. albicans species involves cell membrane damage due to increased membrane permeabilization, overproduction of reactive oxygen species, formation of pseudohyphae, injury of cells and pore formation and consequently cell death. In addition, ShTI (8.65 and 17.3 µM) showed a noncytotoxic and nongenotoxic effect in L929 mouse fibroblast cells. These findings make it plausible to assume that ShTI is a promising antimicrobial candidate, but new assays are required to progress the application of ShTI's potential usage as a novel antifungal.