Ascaridole

Chemical composition, antioxidant and cytotoxic activity of Artemisia gmelinii essential oil growing wild in Kashmir valley.[Pubmed:30618281]

Nat Prod Res. 2019 Jan 8:1-6.

The present study was carried to observe the phytochemical profile of aromatic constituents of Artemisia gmelinni essential oil using GC-FID, GC-MS and (13)C NMR and to evalute anticancer and antioxidant activities. Twenty chemical constituents were detected from EO accounting 92.05% of total oil composition. Oxygenated monoterpenes (73.64%) were dominant class of compounds. The major constituents are isoascaridol (29.70%), alpha-terpinolene (25.37%), phellandrene (9.26%) and Ascaridole (4.17%). Ascaridole and isoAscaridole are first time identified to be the constituents of this essential oil. The essential oil effectively inhibit the growth of cancer cells and showed maximum anti-proliferative activity at 125microg/mL concentration, but highest inhibition in cell growth was found in A-549 cell line. Our study revealed that EO was effective in restricting the migration of A-549 cells up to 15% than control at 125 microg/mL concentration. The essential oil also showed moderate antioxidant activity.

What Happens after Activation of Ascaridole? Reactive Compounds and Their Implications for Skin Sensitization.[Pubmed:27513446]

Chem Res Toxicol. 2016 Sep 19;29(9):1488-92.

To replace animal testing and improve the prediction of skin sensitization, significant attention has been directed to the use of alternative methods. The direct peptide reactivity assay (DPRA), the regulatory agencies' approved alternative in chemico method, has been applied for understanding the sensitization capacity of activated Ascaridole. Ascaridole, the oxidative metabolite of alpha-terpinene, is considered to be one of the components responsible for the contact allergy associated with essential oils derived from Chenopodium and Melaleuca species. The recently developed high-throughput screening based on the dansyl cysteamine (HTS-DCYA) method was applied to understand the reported enhanced reactivity of activated Ascaridole and possibly to identify the resulting elusive radical or other reactive species. For the first time, a substituted cyclohexenone was identified as a potential electrophilic intermediate resulting in higher depletion of nucleophilic DCYA, along with several nonreactive byproducts of Ascaridole via a radical degradation mechanism. Formation of electrophilic species via radical degradation is one of the possible pathways should be considered for the peptide reactivity of in aged tea tree oil or oils rich in terpinenes along with commonly believed reactants, allylic-epoxides and allylic-peroxides.

Activation of the Endoperoxide Ascaridole Modulates Its Sensitizing Capacity.[Pubmed:26185204]

Toxicol Sci. 2015 Oct;147(2):515-23.

The monoterpene Ascaridole, a fairly stable endoperoxide found in essential oils such as tea tree oil can provoke allergic contact dermatitis which has been evidenced under patch test conditions. However, concomitantly we observed irritative skin reactions that demand further data underlining the sensitization potential of Ascaridole. Here, we studied the effects of Ascaridole on dendritic cell (DC) activation and protein reactivity, 2 key steps of chemical-induced skin sensitization. Treatment of human monocyte-derived DC with Ascaridole found support for full DC maturation, a capability of sensitizers but not irritants. It induced significant upregulation of the expression of the costimulatory molecules CD86, CD80, CD40, and the adhesion molecule CD54 in a time-dependent manner. Maturation was accompanied by release of proinflammatory cytokines interleukin (IL)-1ss, tumor necrosis factor-alpha, IL-6, and IL-8. Similar to other chemical skin sensitizers including hydroperoxides, we observed a certain reactivity of Ascaridole toward cysteine- but not lysine-containing peptides. During recent years, evidence accumulated for a radical mechanism as trigger for protein reactivity of peroxides. Treatment of the fairly stable endoperoxide Ascaridole with iron as radical inducer ("activated Ascaridole") resulted in cysteine peptide reactivity exceeding by far that of Ascaridole itself. Furthermore, activated Ascaridole showed increased potential for induction of the Nrf2 target gene heme oxygenase 1 and upregulation of CD86 and CD54 on THP-1 cells, an established DC surrogate. These results indicate that radical formation could be involved in the steps leading to skin sensitization induced by the endoperoxide Ascaridole.