Amphibians use their skin as an effective defense mechanism against predators and microorganisms. Specialized glands produce antimicrobial peptides (AMPs) that possess antioxidant properties, effectively reducing reactive oxygen species (ROS) levels. These peptides are promising candidates for treating diseases associated with oxidative stress (OS) and redox imbalance, including neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), as well as age-related conditions, like cardiovascular diseases and cancer. This review highlights the multifaceted roles of AMPs and antioxidant peptides (AOPs) in amphibians, emphasizing their protective capabilities against oxidative damage. They scavenge ROS, activate antioxidant enzyme systems, and inhibit cellular damage. AOPs often share structural characteristics with AMPs, suggesting a potential evolutionary connection and similar biosynthetic pathways. Peptides such as brevinin-1FL and Cath-KP demonstrate neuroprotective effects, indicating their therapeutic potential in managing oxidative stress-related diseases. The antioxidant properties of amphibian-derived peptides pave the way for novel therapeutic developments. However, a deeper understanding of the molecular mechanisms underlying these peptides and their interactions with oxidative stress is essential to addressing ROS-related diseases and advancing therapeutic strategies in clinical practice.

Background: Nosocomial infections caused by multidrug-resistant microorganisms are a significant public health concern. Antimicrobial resistance (AMR) is closely linked to the excessive and indiscriminate use of antibiotics, which creates selective pressure and promotes the emergence of resistant pathogens. Objectives: This study evaluates the synergistic potential of intragenic antimicrobial peptides (IAPs) combined with plant alkaloids against susceptible and multidrug-resistant human pathogenic bacteria, assessing antimicrobial activity, biofilm inhibition, and hemocompatibility. Methods: The tested molecules included berberine, tomatidine, sinomenine, and the IAPs Hs02 and Gr01. Minimum inhibitory concentration (MIC) and minimum microbicidal concentration (MMC) assays were performed against both ATCC (E. coli ATCC 25922 and S. aureus ATCC 25923) and clinical strains (E. coli KPC+ HRAN 1812446 and S. aureus MDR LACEN 3730529). Synergistic interactions were evaluated by checkerboard assay, followed by biofilm inhibition and hemolysis assays using human red blood cells. Results: Berberine exhibited a MIC of 1024 µM when tested individually, while tomatidine and sinomenine showed no significant activity. As expected, the IAPs showed strong antimicrobial properties at 8 µM (Hs02) and 4 µM (Gr01). When tested in synergy, alkaloids and IAPs reduced the MIC by up to 128-fold. The combination of IAPs and alkaloids reduced the biofilm biomass of S. aureus and E. coli by 50%, by the crystal violet assay (p < 0.05). Notably, sinomenine had not previously been reported to have antimicrobial activity. Conclusions: These results highlight the importance of further exploring combinations of natural and synthetic bioactive molecules as promising antimicrobial candidates. This approach may help to extend the useful life of conventional antibiotics. However, further studies are needed to assess safety, cytotoxicity, genotoxicity, inflammation, and in vivo effects.

Amphibians use their skin as an efficient defense mechanism against predators and microorganisms. Within specialized glands, they produce antimicrobial peptides endowed with antioxidant properties that have demonstrated efficacy in reducing reactive oxygen species (ROS) levels. These peptides are considered promising candidates for treating diseases related to oxidative stress (OS). Neurodegenerative disorders (NDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), along with age-related conditions like cardiovascular diseases and cancer, have been connected to redox imbalance and the associated ROS. This review explores the characteristics of antioxidant peptides (AOP) identified in amphibians, elucidates their mechanisms of action against molecular targets involved in the diseases above, and provides insights into future prospects.