Abstract

Microsorum scolopendria (Burm.f.) Copel. is a traditional medicinal fern with reported antioxidant and anti-inflammatory properties. In this study, we investigated the protective effects of leaf (HH) and rhizome (RH) extracts of MS on oxidative stress and inflammation in human dermal fibroblast (HDFa) cells infected with Staphylococcus aureus and Staphylococcus epidermidis. Cytotoxicity assays revealed that both extracts were safe up to 100 µg/mL, although RH exhibited a slight reduction in viability (?20%) at 63 µg/mL. In infection assays, pretreatment with HH and RH extracts (63–100 µg/mL) for 3 h significantly reduced ROS levels by up to 45% compared with infected controls, while LDH release decreased by ~30%, indicating protection against membrane damage. Regarding anti-inflammatory activity, both extracts showed selective inhibition of COX-2 over COX-1, with RH inhibiting COX-2 by 62% and HH by 55% at 100 µg/mL, whereas COX-1 inhibition remained below 20%. These results highlight differential biological performance between leaf and rhizome extracts, with RH showing slightly higher anti-inflammatory activity but also a modest cytotoxic effect at intermediate concentrations. Overall, MS extracts demonstrated protective effects against oxidative and inflammatory damage induced by bacterial infection, supporting their potential as safe natural therapeutic agents for managing infection-associated skin stress and inflammation. © 2025 by the authors.