The leaves of Carica papaya (CP) are rich in natural antioxidants. Carica papaya has traditionally been used to treat various ailments, including skin diseases. This study aims to decipher the antioxidant effects and phytochemical content of different CP leaf extracts (CPEs) obtained using supercritical carbon dioxide (scCO₂) and conventional extraction methods. The antioxidant activities of CPEs were evaluated by cell-free (1,1-diphenyl-2-picryl-hydrazyl (DPPH) and ferric-reduced antioxidative power (FRAP)) and cell-based (H₂O₂) assay. Both C. papaya leaf scCO₂ extract with 5% ethanol (CPSCE) and C. papaya leaf scCO₂ extract (CPSC) exhibited stronger DPPH radical scavenging activity than conventional extracts. In the FRAP assay, two hydrophilic extracts (C. papaya leaf ethanol extract (CPEE) and C. papaya freeze-dried leaf juice (CPFD)) showed relatively stronger reducing power compared to lipophilic extracts. Cell-based assays showed that CPFD significantly protected skin fibroblasts from H₂O₂-induced oxidative stress in both pre-and post-treatment. CPEE protected skin fibroblasts from oxidative stress in a dose-dependent manner while CPSCE significantly triggered the fibroblast recovery after treatment with H₂O₂. GC-MS analysis indicated that CPSCE had the highest α-tocopherol and squalene contents. By contrast, both CP hydrophilic extracts (CPEE and CPFD) had a higher total phenolic content (TPC) and rutin content than the lipophilic extracts. Overall, CPEs extracted using green and conventional extraction methods showed antioxidative potential in both cell-based and cell-free assays due to their lipophilic and hydrophilic antioxidants, respectively.

Endophytic fungi are a promising source of bioactive metabolites with a wide range of pharmacological activities. In the present study, MS-based metabolomics was conducted to study the metabolomes variations of endophytic Diaporthe fraxini ED2 grown in different culture media. Total phenolic content (TPC), total flavonoid content (TFC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and ferric reducing antioxidant power (FRAP) assays were conducted to assess the antioxidant potential of the fungal extracts. Multivariate data analysis (MVDA) was employed in data analysis and interpretation to elucidate the complex metabolite profile. The supplemented culture medium of D. fraxini fungal extract stimulated the production of metabolites not occurring in the normal culture medium. Antioxidant activity studies revealed the potential of supplemented cultured fungal extract of D. fraxini as a source of antioxidants. The present findings highlight that fungal culture medium supplementation is an effective approach to unravelling the hidden metabolome in plant-associated fungal diversity.