Disease relevance of Usnein

• Severe hepatotoxicity associated with the use of weight loss diet supplements containing ma huang or usnic acid [1].
• Usnic acid, a lichen antibiotic, showed low-level activity in the Lewis lung carcinoma test system [2].
• This is the first report on fulminant liver failure associated with the ingestion of pure usnic acid [3].
• In this study, we examined the toxicity of usnic acid and assessed whether usnic acid may be contributing to hepatotoxicity caused by Lipokinetix [4].
• Usnic acid has been an ingredient of dietary supplements that cause liver failure [3].

High impact information on Usnein

• Usnic acid-induced necrosis of cultured mouse hepatocytes: inhibition of mitochondrial function and oxidative stress [4].
• This inhibition of mitochondria by usnic acid corresponded with a fall in ATP levels in hepatocytes [4].
• Taken together, our results suggest that usnic acid is a strong hepatotoxic agent that triggers oxidative stress and disrupts the normal metabolic processes of cells [4].
• In isolated liver mitochondria, usnic acid was observed to directly inhibit and uncouple oxidative phosphorylation [4].
• The source of reactive oxygen species after usnic acid treatment include autoxidation of usnic acid and increased hydrogen peroxide generation by mitochondria caused by usnic acid inhibition of the respiratory chain, with the latter playing a more prominent role [4].

Chemical compound and disease context of Usnein

• Regarding the effect on normal body temperature and LPS-induced hyperthermia in mice, diffractaic acid showed a significant effect only on the former and usnic acid only on the latter [5].

Biological context of Usnein

• Usnic acid treatment was associated with early inhibition and uncoupling of the electron transport chain in mitochondria of cultured hepatocytes [4].
• In primary cultured murine hepatocytes, usnic acid treatment (5 microM) resulted in 98% necrosis within 16 hr (no apoptosis was detected) [4].
• The molecular structure of usnic acid has been validated and further explored in this investigation [6].
• Mean absolute bioavailability of usnic acid following oral administration was 77.8% [7].
• This is the first attempt to compare statistically seasonal variation in usnic acid concentrations and environmental variables, and thus also the first time it is shown that the concentration in various populations of the same lichen species shows different types of correlation with seasonal climatic changes [8].

Anatomical context of Usnein

• Atranorin and fumarprotocetraric acid did not exhibit anti-proliferative effects but usnic acid was active against all test cell lines with EC50 values of 4.3-8.2 microg/ml [9].
• Treatment of infected macrophages with 40 or 80microg/ml usnic acid induced marked cytoplasm vacuolation in intracellular amastigote forms, with disorganization of parasite kinetoplast and mitochondria, but with no significant ultrastructural damage to the host cells [10].
• The slight increase in the micronucleated polychromatic erythrocytes without affecting DNA synthesis suggests an effect of usnic acid on spindle apparatus [11].
• Usnic acid (the most abundant lichen constituents), physodic, and physodalic acids isolated from Hypogymnia enteromorph (Ach.) Nyl. were tested for mutagenicity in the Ames Salmonella/microsome assay [12].
• The study was aimed to optimize the culture conditions for the production of usnic acid in the cultured cell aggregates composed of symbionts in lichen Usnea ghattensis in vitro [13].

Associations of Usnein with other chemical compounds

• Diffractaic acid and usnic acid were identified as the analgesic and antipyretic components of a lichen, Usnea diffracta [5].
• The minimal concentrations required to cause complete uncoupling of oxidative phosphorylation were as follows: (+)usnic acid (1 microM), vulpinic acid, atranorin (5 microM) and DNP (50 microM) [14].
• In water-agar medium having 4% sucrose and 4% PEG gave 3.08 g dry biomass with 1.11 microg usnic acid/g dry biomass [13].
• The usnic acid production by a mycobiont of the lichen Usnea hirta was higher in the liquid medium containing ammonium and nitrate ions than in those containing amino acids [15].
• In this study, usnic acid was measured by HPLC in Parmelia caperata and Parmelia soredians thalli treated with Paraquat, a herbicide which transfers electrons from various transport systems to oxygen, producing O2*- superoxide radicals [16].

Gene context of Usnein

• The property of usnic acid as a non-genotoxic anti-cancer agent that works in a p53-independent manner makes it a potential candidate for novel cancer therapy [17].
• In MCF7 cells treated with usnic acid, although there was an accumulation of p53 and p21 proteins, the transcriptional activity of p53 remained unaffected [17].
• Usnic acid resulted to be the best UVB filter, with an in vivo protection factor similar to Nivea sun Spray LSF 5 [18].
• (+)Usnic acid at a concentration of 0.75 microM inhibited ADP/O ratio by 50%, caused maximal stimulation of both state-4 respiration (100%) and ATPase activity (300%) [14].
• In Romania, Usnea barbata was mentioned in 1929 among the plants known by Romanian people with popular names: "Bear's beard", "Trees' dandruff", "Woman's long hair" (1). "Farmacia naturii" (2) and "Flora medicinală a Romaniei" (3) have mentioned that Usnea barbata (L) Mott contains usnic acid-substance with broad antibiotic spectrum [19].

Analytical, diagnostic and therapeutic context of Usnein

• A series of tests have been run on different biological systems such as fungi, yeasts, plant cells and neoplastic human cell cultures in order to make a general evaluation of the properties of usnic acid and to highlight any analogy between its effects on phylogenetically distant organisms [20].
• We describe a case of a 28-yr-old woman who presented with fulminant liver failure requiring orthotopic liver transplantation, after taking pure usnic acid for weight loss [3].
• Plasma samples were collected at different time intervals, and usnic acid was determined by HPLC [7].
• The method was applied to the determination of plasma levels of usnic acid after intravenous and oral administration to study its disposition in a healthy male rabbit [21].
• The lichen contains 2% usnic acid by liquid chromatography with UV quantification at 282 nm [22].

References