BackgroundAedes aegypti and Aedes albopictus and Culex pipiens pallens mosquitoes transmit dengue fever and West Nile virus diseases, respectively. This study was conducted to determine the toxicity and mechanism of action of four flavonoids and two fatty acids from Millettia pinnata (Fabaceae) seed as well as six pure fatty acids and four fatty acid esters toward third instar larvae from insecticide-susceptible C. pipiens pallens and A. aegypti as well as wild A. albopictus. Efficacy of 12 experimental liquid formulations containing M. pinnata seed methanol extract and hydrodistillate (0.5–10.0% liquids) was also assessed.MethodsThe contact toxicities of all compounds and 12 formulations were compared with those of two larvicides, temephos and fenthion and the commercial temephos 200 g/L emulsifiable concentrate (EC). The possible mode of larvicidal action of the constituents was elucidated using biochemical methods. Larval mortality and cAMP level were analyzed by the Bonferroni multiple-comparison method.ResultsPotent toxicity was produced by karanjin, oleic acid, karanjachromene, linoleic acid, linolenic acid, pongamol, pongarotene, and elaidic acid toward C. pipiens pallens larvae (24 h LC50, 14.61–28.22 mg/L) and A. aegypti larvae (16.13–37.61 mg/L). Against wild A. albopictus larvae, oleic acid (LC50, 18.79 mg/L) and karanjin (35.26 mg/L) exhibited potent toxicity. All constituents were less toxic than either temephos or fenthion. Structure–activity relationship indicates that the degree of saturation, the side chain length, and the geometric isomerism of fatty acids appear to play a role in determining the fatty acid toxicity. Acetylcholinesterase (AChE) is the main site of action of the flavonoids, oleic acid, and palmitic acid. The mechanism of larvicidal action of elaidic acid, arachidic acid, and behenic acid might be due to interference with the octopaminergic system. Linoleic acid and linolenic acid might act on both AChE and octopaminergic receptor. M. pinnata seed extract or hydrodistillate applied as 10% liquid provided 100% mortality toward the three mosquito species larvae and the efficacy of the liquids was comparable to that of temephos 200 g/L EC.ConclusionFurther studies will warrant possible applications of M. pinnata seed-derived products as potential larvicides for the control of mosquito populations.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-015-0848-8) contains supplementary material, which is available to authorized users.

We investigated the toxicity of (-)-asarinin, α-asarone, methyleugenol, pellitorine, and pentadecane identified in Asarum heterotropoides root to third instar larvae from insecticide-susceptible Culex pipiens pallens (KS-CP strain), Aedes aegypti, and Ochlerotatus togoi as well as field-collected C. p. pallens (DJ-CP colony), identified by polymerase chain reaction. Results were compared with those of two conventional mosquito larvicides: fenthion and temephos. Pellitorine (LC50, 2.08, 2.33, and 2.38 ppm) was 5.5, 10.8, and 25.6 times, 4.5, 11.6, and 24.7 times, and 6.9, 11.1, and 24.6 times more toxic than (-)-asarinin, α-asarone, and methyleugenol against susceptible C. p. pallens, A. aegypti, and O. togoi larvae, respectively. Pentadecane was least toxic. Overall, all the compounds were less toxic than either fenthion or temephos. However, these compounds did not differ in toxicity against larvae from the two Culex strains, even though the DJ-CP larvae exhibited high levels of resistance to fenthion (resistance ratio (RR), 1179), chlorpyrifos (RR, 1174), fenitrothion (RR, 428), deltamethrin (RR, 316), chlorfenapyr (RR, 225), and α-cypermethrin (RR, 94). This finding indicates that the isolated compounds and the pyrethroid, organophosphorus, and pyrrole insecticides do not share a common mode of action or elicit cross-resistance. A. heterotropoides root-derived materials, particularly (-)-asarinin and pellitorine, merit further study as potential mosquito larvicides for the control of insecticide-resistant mosquito populations in light of global efforts to reduce the level of highly toxic synthetic insecticides in the aquatic environment.

The toxicity of several compounds isolated from Asarum heterotropoides root steam distillate to third-instar larvae of Culex pipiens pallens Coquillett, Aedes aegypti (L.), and Ochlerotatus togoi Theobald was examined using a direct contact mortality bioassay. Safrole was the most toxic constituent to Cx. p. pallens and Ae. aegypti larvae, whereas terpinolene was most toxic to Oc. togoi. However, LC50 values of these three mosquito larvae to both essential oils as well as the remainder of the 26 compounds identified in A. heterotropoides were considerably greater than for fenthion or temephos. However, we suggest that constituents of A. heterotropoides root steam distillate merit further study as potential mosquito larvicides due to global efforts to reduce the level of highly toxic synthetic pesticides in the aquatic environment.

Background Gold nanoparticles (AuNPs) have potential applications in the treatment and diagnosis process, which are attributed to their biocompatibility and high efficiency of drug delivery. In the current study, we utilized an extract of Euphrasia officinalis , a traditional folk medicine, to synthesize gold nanoparticles (EO-AuNPs), and investigated their anti-inflammatory effects on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Materials and methods The AuNPs were synthesized from an ethanol extract of E. officinalis leaves and characterized using several analytical techniques. Anti-inflammatory activities of EO-AuNPs were detected by a model of LPS-induced upregulation of inflammatory mediators and cytokines including nitric oxide (NO), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), IL-1β, and IL-6 in RAW 264.7 cells. The activation of nuclear factor (NF)-κB and Janus kinase/signal transducer and activators of transcription (JAK/STAT) signaling pathways was investigated by Western blot. Results The results confirmed the successful synthesis of AuNPs by E. officinalis. Transmission electron microscopy images showed obvious uptake of EO-AuNPs and internalization into intracellular membrane–bound compartments, resembling endosomes and lysosomes by RAW 264.7 cells. Cell viability assays showed that EO-AuNPs exhibited little cytotoxicity in RAW 264.7 cells at 100 µg/mL concentration after 24 hours. EO-AuNPs significantly suppressed the LPS-induced release of NO, TNF-α, IL-1β, and IL-6 as well as the expression of the iNOS gene and protein in RAW 264.7 cells. Further experiments demonstrated that pretreatment with EO-AuNPs significantly reduced the phosphorylation and degradation of inhibitor kappa B-alpha and inhibited the nuclear translocation of NF-κB p65. In addition, EO-AuNPs suppressed LPS-stimulated inflammation by blocking the activation of JAK/STAT pathway. Conclusion The synthesized EO-AuNPs showed anti-inflammatory activity in LPS-induced RAW 264.7 cells, suggesting they may be potential candidates for treating inflammatory-mediated diseases.

Probiotic Gluconacetobacter strains are intestinal microbes with beneficial effects on human health. Recently, researchers have used these strains to biosynthesize metal and non-metal nanoparticles for treating various chronic diseases. Despite their importance in nanotechnology, gold nanoparticles (AuNPs) biosynthesized by Gluconacetobacter species have not been clearly identified for treating inflammation and inflammation-associated diseases. While ginsenoside CK has strong pharmaceutical activity, it also has strong cytotoxicity and hydrophobicity which is hurdle to make formulation. Peptide-nanoparticle hybrids are gaining increasing attention for their potential biomedical applications, including human inflammatory diseases. Herein, we developed peptide CopA3 surface conjugated and ginsenoside compound K (CK) loaded gold nanoparticles (GNP-CK-CopA3), which intracellularly synthesised by the probiotic Gluconacetobacter liquefaciens kh-1, to target lipopolysaccharide (LPS)-activated RAW264.7 macrophages. The synthetic GNP-CK-CopA3 was characterised by various instrumental techniques. The results of our cellular uptake and MTT assays exhibited obvious drug intracellular delivery without significant cytotoxicity. In addition, pre-treatment with GNP-CK-CopA3 significantly ameliorated LPS-induced nitric oxide (NO) and reactive oxygen species (ROS) production and suppressed the mRNA and protein expression of pro-inflammatory cytokines in macrophages. Furthermore, GNP-CK-CopA3 efficiently inhibited the activation of the nuclear factor-jB (NF-jB) and mitogen-activating protein kinase (MAPK) signalling pathways. Taken together, our findings highlight the potential of using peptide-nanoparticle hybrids in the development of anti-inflammatory approaches and providing the experimental foundation for further application.