RESUMEN
Inflammation plays a crucial role in COVID-19, and when it becomes dysregulated, it can lead to severe outcomes, including death. Naphthoquinones, a class of cyclic organic compounds widely distributed in nature, have attracted significant interest due to their potential biological benefits. One such naphthoquinone is 3,5,8-trihydroxy-6-methoxy-2-(5-oxohexa-1,3-dienyl)-naphthanthene-1,4-dione (3,5,8-TMON), a compound produced by fungi. Despite its structural similarity to shikonin, limited research has been conducted to investigate its biological properties. Therefore, the objective of this study was to evaluate the effects of 3,5,8-TMON and its synthetic derivatives in the context of inflammation induced by lipopolysaccharide (LPS) and SARS-CoV-2 infection in vitro using cell cultures. 3,5,8-TMON was obtained by acid treatment of crude extracts of fermentation medium from Cordyceps sp., and two derivatives were accessed by reaction with phenylhydrazine under different conditions. The results revealed that the crude extract of the fungi (C. Ex) inhibited the activity of transcription factor NF-kB, as well as the production of nitric oxide (NO) and interleukin-6 (IL-6) when LPS induced it in RAW 264.7 cells. This inhibitory effect was observed at effective concentrations of 12.5 and 3.12 µg mL-1. In parallel, 3,5,8-TMON and the new derivatives 3 and 4 demonstrated the ability to decrease IL-6 production while increasing TNF, with a specific effect depending on the concentration. These concentration-dependent agonist and antagonist effects were observed in THP-1 cells. Furthermore, 3,5,8-TMON inhibited IL-6 production at concentrations of 12.5 and 3.12 µg mL-1 in Calu-3 cells during SARS-CoV-2 viral infection. These findings present promising opportunities for further research into the therapeutic potential of this class of naphthoquinone in the management of inflammation and viral infections.
RESUMEN
The aim of the present study was to investigate the photochemical behavior of DHHB and its photostabilizing effect on avobenzone (AVO) in different sunscreen formulations. The formulations were subjected to photostability studies by HPLC and spectrophotometry. In vitro phototoxicity was assessed using 3T3 fibroblast cultures. The mechanism of interaction between DHHB and AVO was investigated by steady state and time-resolved fluorescence spectroscopy. All formulations provided ultra-protection against UVA radiation. HPLC results demonstrated that DHHB did not present a photostabilizing effect on AVO. Fluorescence spectroscopy showed that AVO and DHHB interact by a static quenching mechanism and DHHB did not affect the AVO excited state lifetime. In addition, the energy transfer by Förster mechanism (FRET), which is the most often mechanism responsible for singlet-singlet quenching, is unlikely in this work. These results suggest why DHHB did not work as a photostabilizer on AVO singlet excited state. Phototoxicity results demonstrated that combinations containing DHHB (C2) did not show a phototoxic potential. Finally, although DHHB was considered to be photostable for all formulations studied (F2 and F3) it did not increase the photostability of AVO (F3). Thus, we suggested that formulations containing DHHB (F2) should be considered more advantageous than formulations containing AVO and AVO/DHHB (F1 and F3 respectively).