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Mentha villosa Hubs., M. x piperita and their bioactives against gastrointestinal nematodes of ruminants and the potential as drug enhancers
Veterinary Parasitology ( IF 2.6 ) Pub Date : 2020-11-13 , DOI: 10.1016/j.vetpar.2020.109317
Bruno Batista Bortoluzzi , Andréia Buzatti , Amanda Chaaban , Izanara Cristine Pritsch , Alan dos Anjos , Roger Raup Cipriano , Cícero Deschamps , Marcelo Beltrão Molento

Parasitic diseases caused by gastrointestinal nematodes (GIN) are responsible for a major impact on ruminant welfare. Although the available anthelmintics have a safe margin of toxicity to the animals, their indiscriminate use has increased the selection of resistant parasite populations. In this scenario, essential oils (EO) stand out as a promising ecofriendly therapeutic alternative against GIN. The objective of this work was to determine the effect of the EO of Mentha villosa Hubs (MVEO) collected in 2017 and 2018, M. x piperita (MPEO) and their main components, carvone and limonene, against the third stage larvae (L3) of Haemonchus spp. and Trichostrongylus spp. The solutions, including in nanoemulsion preparations, were tested in a range of concentrations using the larval migration inhibition test (LMIT). The EO and carvone were also tested in combination with nitroxynil (NTX) to determine their effect as drug enhancers (additive or synergy). MVEO/2017, MVEO/2018, MPEO and carvone showed 70.6 (73.4 mg/mL), 86.3 (74.9 mL/mL), 95.5 (143.6 mg/mL), and 88.2 % (38.3 mg/mL) efficacy against L3, respectively. Carvone alone had approximately a 3-fold higher efficacy when compared to its concentration in each EO: 68.8 % in MVEO/2017 and 83.9 % in MVEO/2018. Limonene did not show any significant effect on inhibiting L3 migration. The combination of MPEO and NTX, and carvone and NTX showed a statistically significantly (P < 0.05) synergic and additive effect, respectively, when compared to the isolated treatment. The nanoemulsion of MVEO/2017 at 0.367 mg/mL, inhibited L3 migration by 83.1 %, demonstrating to be highly effective (concentration ratio of 1:0.004), when compared to the MVEO/2017 (70.6 % at 73.4 mg/mL) extraction. The in vitro data from the combination of MPEO or carvone plus NTX suggest that these products can be considered for in vivo experiments against the most important GIN of ruminants as drug enhancers, possibly reducing the final concentration of NTX`. The efficacy of carvone was higher (EC50 = 1.96 mg/mL) than its expected efficacy, based on its concentrations on both EO. Therefore, this component does not need the entire EO composition to exert its L3 motility action. The remarkable efficacy demonstrated by the MVEO/2017/nanoemulsion (EC50 = 0.10 mg/mL), supports its potential to be a candidate to the next-generation therapy to alleviate clinical parasite infections and combat GIN resistant populations.



中文翻译:

薄荷麦集线器,M. X piperita和他们对反刍动物的胃肠道线虫生物活性物质和药物增强的潜力

胃肠道线虫(GIN)引起的寄生虫病是对反刍动物福利的重大影响。尽管可用的驱虫药对动物具有安全的毒性范围,但不加选择地使用驱虫药增加了抗药性寄生虫种群的选择。在这种情况下,精油(EO)可以作为对抗GIN的有前途的环保疗法脱颖而出。这项工作的目的是确定的EO的效果薄荷麦集线器(MVEO)在2017年和2018年收集,M. X piperita(MPEO)和它们的主要成分,香芹酮和柠檬烯,对第三期幼虫(L3)的Haemonchus spp。和毛圆线虫spp。使用幼虫迁移抑制试验(LMIT)对溶液(包括纳米乳液制剂)进行了一系列浓度测试。还对EO和香芹酮与硝腈(NTX)结合进行了测试,以确定它们作为药物增强剂的作用(添加剂或协同作用)。MVEO / 2017,MVEO / 2018,MPEO和香芹酮分别显示出对L3的70.6(73.4 mg / mL),86.3(74.9 mL / mL),95.5(143.6 mg / mL)和88.2%(38.3 mg / mL)的效力。与其在每个EO中的浓度相比,单独的香芹酮具有大约高三倍的功效:MVEO / 2017中为68.8%,MVEO / 2018中为83.9%。柠檬烯对抑制L3迁移没有显着影响。MPEO和NTX以及香芹酮和NTX的组合显示出统计学显着性(P <0.05)与隔离治疗相比,分别具有协同作用和累加作用。MVEO / 2017的纳米乳液0.367 mg / mL,抑制了L3迁移83.1%,与MVEO / 2017的纳米乳液(73.4 mg / mL的70.6%)相比,具有很高的有效性(浓度比为1:0.004)。 。在体外从MPEO或香芹酮加NTX的组合的数据表明,这些产品可以被认为是在体内实验对反刍动物的药物增强剂最重要GIN,可能减少NTX`的最终浓度。香芹酮的功效更高(EC 50 =等于1.96 mg / mL),基于其在两个EO上的浓度。因此,该组分不需要整个EO组合物发挥其L3运动作用。MVEO / 2017 /纳米乳剂(EC 50  = 0.10 mg / mL)表现出的显着功效证明了其成为缓解临床寄生虫感染和对抗GIN耐药人群的下一代疗法的潜力。

更新日期:2020-11-25
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