Bioassay-guided isolation of active compounds from Adenosma buchneroides essential oil as mosquito repellent against Aedes albopictus

Abstract

Ethnopharmacological relevanceA folk herb Adenosma buchneroides found in the previous ethnobotanical investigation plays an important role as an insect repellent among the Aini people in southwest of China, but the active compounds responsible for repellent activity of the plant have not yet been investigated. Aim of the studyThe main purpose of the study is to identify the active components of the essential oil which responsible for its repellent activity against Aedes albopictus to support the usage of the plant as mosquito repellent by Aini people. In addition, to supply a class of potential alternatives characterized carvacrol analogues to develop natural repellent products. Material and methodsThe essential oil from aerial part of Ad. buchneroides was extracted by hydrodistillation. A systematic bioassay-guided isolation of repellent compounds from the essential oil was conducted through chromatographic fractionation combined with in-cage mosquito repellent bioassay. The identification of the essential oil components was accomplished by GC-MS and GC-FID techniques. The structural elucidation of compounds was performed on the basis of IR, HR-ESI-MS and NMR. Larvicidal activity and cytotoxicity of all repellent compounds also tested by larval bioassays and MTS assays, respectively. Structure-activity relationship (SAR) of carvacrol analogues was investigated by in-cage mosquito repellent bioassay. ResultsThe essential oil of the plant showed strong mosquito repellent activity with minimum effective dosage (MED) of 0.019 ± 0.007 mg/cm2, compared to reference standard N,N-diethyl-3-methylbenzamide (DEET) (0.031 ± 0.014 mg/cm2). 26 compounds representing 97.8% of the essential oil were identified. Carvacrol, carvacrol methyl ether and a new fragrant compound, adenosmin A (1) were found to be repellent compounds by systematic bioassay-guided isolation, with MEDs in the range of 0.011–0.125 mg/cm2. An investigation on SAR of carvacrol analogues led to the discover of three analogues with further lower MEDs (0.002–0.009 mg/cm2) than that of DEET, and other three compounds with similar MEDs (0.029–0.039 mg/cm2) to that of DEET. Carvacrol (LD50 of 24.8 ppm) was the best larvicide among tested repellent compounds. The essential oil and repellent compounds against seven mammalian cell lines revealed low or no cytotoxicity. ConclusionsScientific evidences reported here validate the plant's traditional use as insect repellent and imply promising application of the essential oil and carvacrol analogues as natural mosquito repellents.