Ligusticum sinense Nanoemulsion Gel as Potential Repellent against Aedes aegypti, Anopheles minimus, and Culex quinquefasciatus (Diptera: Culicidae)

SIMPLE SUMMARY: Mosquito vectors can transmit diverse infectious pathogens and parasites that cause diseases such as dengue, Zika, Chikungunya, West Nile fever, and malaria. Botanical-derived repellents have been applied for personal protection against various species of mosquito vectors. In Thailand, numerous plant extracts have so far been investigated for mosquito repellent activity. Recently, Ligusticum sinense hexane extract (LHE) was reported as a potential candidate for the development of a new natural alternative to standard synthetic repellent. This study formulated LHE into nanoemulsion gel (LHE-NEG) and investigated its repellent activity against three mosquito vectors, including Aedes aegypti, Anopheles minimus, and Culex quinquefasciatus. The results revealed that LHE-NEG provided comparable protection times to N,N-diethyl-3-methylbenzamide nanoemulsion gel (DEET-NEG) against all mosquito species. Furthermore, LHE-NEG is safe for human health, based on the results of the skin irritation test. The repellent activity obtained from stored samples of LHE-NEG yielded satisfactory protection times of more than 2 h. Therefore, this gel formulation could be developed commercially, as an effective personal protection product against mosquito bites. ABSTRACT: Ligusticum sinense Oliv. cv. is a species of Umbelliferae (Apiaceae), a large plant family in the order Apiales. In this study, L. sinense hexane extract nanoemulsion gel (LHE-NEG) was investigated for mosquito repellency and compared to the standard chemical, N,N-diethyl-3-methylbenzamide (DEET), with the goal of developing a natural alternative to synthetic repellents in protecting against mosquito vectors. The results demonstrated that LHE-NEG afforded remarkable repellency against Aedes aegypti, Anopheles minimus, and Culex quinquefasciatus, with median protection times (MPTs) of 5.5 (4.5–6.0), 11.5 (8.5–12.5), and 11.25 (8.5–12.5) h, respectively, which was comparable to those of DEET-nanoemulsion gel (DEET-NEG: 8.5 (7.0–9.0), 12.0 (10.0–12.5), and 12.5 (10.0–13.5) h, respectively). Evaluation of skin irritation in 30 human volunteers revealed no potential irritant from LHE-NEG. The physical and biological stability of LHE-NEG were determined after being kept under heating/cooling cycle conditions. The stored samples of LHE-NEG exhibited some changes in appearance and differing degrees of repellency between those kept for 3 and 6 heating/cooling cycles, thus providing slightly shorter MPTs of 4.25 (4.0–4.5) and 3.25 (2.5–3.5) h, respectively, when compared to those of 5.0 (4.5–6.0) h in fresh preparation. These findings encourage commercially developed LHE-based products as an alternative to conventional synthetic repellents in preventing mosquito bites and helping to interrupt mosquito-borne disease transmission.