Antioxidant and neuroprotective effects of Hyptis suaveolens,Hyptis pectinata and Hyptis marrubioides in Caenorhabditiselegans

The increasing trend for the use of natural products as sources of pharmacologically active molecules has changed attitudes in the population. Given the existing demand, a credible scientific analysis and validation of the effect of these natural products is necessary. The genus Hyptis Jacq. (Lamiaceae) has about 300 species with wide distribution, among which Hyptis suaveolens, Hyptis pectinata and Hyptis marrubioides (HS, HP, HM, respectively) are used in folk medicine and are commercialized in street markets for treatment of several diseases. This study aims to evaluate the neuroprotective activity, as well as to elucidate some of the cellular mechanisms involved in the pharmacological action of HS/HP/HM plant extracts using Caenorhabditis elegans, as an animal model. For this purpose, we used a C. elegans model of Machado-Joseph disease (MJD), expressing a human mutant ATXN-3 and a C. elegans model of frontotemporal dementia with parkinsonism-17 (FTDP-17), expressing a mutant form of tau protein, and tested ethanolic leaf extracts from HS, HP, and HM. Our data showed that chronic treatment with 1 mg/ mL of HS/HP/HM extracts had a beneficial impact in these diseases since it significantly ameliorated the locomotor defects exhibited by C. elegans. Moreover, with C. elegans model of MJD, the chronic treatment with the Hyptis extracts also increased the animals survival. We observed, in both models, a significant protection against jugloneinduced oxidative damage (by more than 50%), after chronic treatment with these extracts. Using C. elegans reporter strains we also observed a higher induction of gst-4, in HS/HP/HM extract-treated animals upon exposure to oxidative damage. Our findings support an antioxidant and neuroprotective activity of HS, HP e HM, suggesting the activating specific antioxidant enzymes like gst-4.This work was supported by national funds from FCT—Portuguese Foundation for Science and Technology, under the projects PTDC/AGR-ALI/105169/2008, PEst-OE/AGR/UI4033/2014, and INTERACT—ISAC project, no. NORTE-01-0145-FEDER-000017, cofinanced by the European Regional Development Fund (ERDF) through NORTE 2020 (North Regional Operational Program 2014/2020).