Redox characterization of usnic acid and its cytotoxic effect on human neuron-like cells (SH-SY5Y)

Abstract

Usnic acid (UA) is the most common and abundant lichenic secondary metabolite with potential therapeutic application. Anti-inflammatory and antitumour properties have already been reported and UA-enriched extracts are widely used to treat several diseases in the folk medicine. First, we performed in silico evaluation of UA interactions with genes/proteins and important compounds for cellular redox balance and NO pathway. Then, we assessed UA redox properties against different reactive species (RS) generated in vitro, and evaluated its action on SH-SY5Y neuronal like cells upon hydrogen peroxide (H(2)O(2)), since no in vitro neurotoxicological data has been reported so far. Total reactive antioxidant potential index (TRAP) showed a significant antioxidant capacity of UA at the highest tested concentration; UA was also effective against hydroxyl radicals and reduced the formation of nitric oxide. In vitro, lipoperoxidation was enhanced by UA and changed the cellular viability at highest concentration of 20μg/mL for 1 and 4h, as well as 2 and 20μg/mL for 24h of treatment, according to MTT reduction assay. Moreover, UA did not display protective effects against H(2)O(2)-induced cell death in any case. Evaluation of intracellular RS production by the DCFH-based assay indicated that UA was able to induce changes in basal RS production at concentration of 20μg/mL for 1h and from 2ng/mL to 20μg/mL for 4 and 24h. In conclusion, UA could display variable redox-active properties, according to different system conditions and/or cellular environment. Moreover, our results suggest that potential neurotoxicological effects of UA should be further studied by additional approaches; for instance, in vivo and clinical studies.

Antinociceptive Activity and Redox Profile of the Monoterpenes (+)-Camphene,p-Cymene, and Geranyl Acetate in Experimental Models

“…NO scavenging activity was quantified as previously described [25]. NO was generated from spontaneous decomposition of sodium nitroprusside (SNP) in 20 mM phosphate buffer (pH 7.4).…”

Usnic acid biological activity: history, evaluation and usage

“…20 Rabelo et al, added that this effect is related to the capacity of usnic acid to increase intracellular ROS synthesis in these cells . 21 In another study performed by Kohlhardt-Floehr et al, low concentrations of UA extracted from Xanthoparmelia farinosa (Vainio) and under physiological UVB intensity, exhibit an antioxidant function. 22 …”

Anti-angiogenic and antiproliferative properties of the lichen substances (-)-usnic acid and vulpinic acid

“…Usnic acid displays in vitro antiproliferative activity against a wide variety of human and murine cancer cell lines [13,14]. The toxicity of usnic acid has been related to induction of apoptosis in L1210 (murine leukemia) and A549 (human lung carcinoma) cells [15][16][17], to mitochondrial dysfunction in A549, T-47D (breast cancer), Capan-2 (pancreatic cancer) and HepG2 (human hepatoblastoma) cell lines [17][18][19] and with increased cytochrome P450 activity and/or oxidative stress in HepG2 and SH-SY5Y (human neuroblastoma) cell lines [19,20]. In addition, Song et al [7] reported that (+)-usnic acid inhibited angiogenesis by suppressing the VEGFR2-mediated downstream AKT and ERK1/2 signaling pathways.…”