title: Identification of a compound isolated from German chamomile (Matricaria chamomilla) with dermal sensitization potential.
abstract: German chamomile is one of the most popular herbal ingredients used in cosmetics and personal care products. Allergic skin reactions following topical application of German chamomile have been occasionally reported, although it is not fully understood which of the chemical constituents is responsible for this adverse effect. In the present work, three candidate sensitizers were isolated from German chamomile based on activity-guided fractionation of chamomile extracts tested using the in vitro KeratinoSens™ assay. The compounds were identified as the polyacetylene tonghaosu (1), and both trans- and cis-glucomethoxycinnamic acids (2 and 3). These three compounds were classified as non- to weakly reactive using in chemico methods; however, aged tonghaosu was found to be more reactive when compared to freshly isolated tonghaosu. The polyacetylene (1) constituent was determined to be chemically unstable, generating a small electrophilic spirolactone, 1,6-dioxaspiro[4.4]non-3-en-2-one (4), upon aging. This small lactone (4) was strongly reactive in both in chemico HTS- and NMR-DCYA methods and further confirmed as a potential skin sensitizer by Local Lymph Node Assay (LLNA).
authors.affiliation: National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, MS 38677, United States.
authors.forename: Cristina
authors.initials: C
authors.lastname: Avonto
authors.affiliation: The Center for Food Safety and Applied Nutrition, US Food and Drug Administration, College Park, MD 20740, United States.
authors.forename: Diego
authors.initials: D
authors.lastname: Rua
authors.affiliation: National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, MS 38677, United States.
authors.forename: Pradeep B
authors.initials: PB
authors.lastname: Lasonkar
authors.affiliation: National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, MS 38677, United States.
authors.forename: Amar G
authors.initials: AG
authors.lastname: Chittiboyina
authors.affiliation: National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, MS 38677, United States; Division of Pharmacognosy, Department of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, MS 38677, United States. Electronic address: ikhan@olemiss.edu.
authors.forename: Ikhlas A
authors.initials: IA
authors.lastname: Khan
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D020843:Chamomile / Q000633:toxicity; D005260:Female; D035264:Flowers; D031168:Matricaria / Q000633:toxicity*; D051379:Mice; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification* / Q000633:toxicity*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012882:Skin Tests / Q000379:methods
chemical_list: D010936:Plant Extracts
keywords: DCYA; German chamomile; LLNA; Skin sensitization; in chemico methods