Could the inhibition of systemic NLRP3 inflammasome mediate central redox effects of yerba mate? An in silico and pre-clinical translational approach

Abstract

Ethnopharmacological relevance

Empirically, Ilex paraguariensis A. St. Hil, or yerba-mate, has been used by natives of South America as a stimulant. Nowadays, this plant has gained popularity due to its neuroprotective effects. However, there are few studies on the biochemical-molecular mechanisms of action involved in its effect. Aim of the study: Chemically characterize an aqueous extract of yerba mate (YME) and evaluate if it could suppress the aberrant inflammatory response related to neurodegeneration. Materials and methods: Macrophages and microglia cells were exposed to lipopolysaccharide (LPS; 100 ng/mL) plus nigericin (100 μM) or quinolinic acid (QA; 5 mM). Cellular viability, oxidative, and inflammatory markers were evaluated. Chemical matrix (HPLC - DAD), antioxidant activity, safety profile in vitro and in vivo, and an in silico docking of main targets were also assessed.

Results

Pre-treatment with YME (15 μg/mL) prevented impairments in redox metabolism and inflammatory markers in BV-2 cells. In macrophages, YME showed similar results to MCC950, an inflammasome inhibitor. YME presented 282.88 mg EAG/g total phenolic content and a redox capacity of 32.94 ± 1.30 μg/mL (IC₅₀), and its major compounds were chlorogenic acid > rutin > ferulic acid > catechin > sinapic acid. Chlorogenic acid and rutin presented a high affinity to the MCC950 region. Additionally, YME did not cause genotoxicity and was safe in vivo.

Conclusion

YME has significantly affected macrophages and microglia by regulating the NLRP3 inflammatory pathway.