| Summary: | <i>Ligusticum sinense</i> Oliv. cv. is a species of Umbelliferae (Apiaceae), a large plant family in the order Apiales. In this study, <i>L. sinense</i> 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 <i>Aedes aegypti</i>, <i>Anopheles minimus</i>, and <i>Culex quinquefasciatus</i>, 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.
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