FORESTRY BYPRODUCTS AS NOVEL THERAPEUTICS FOR PARASITE CONTROL IN LIVESTOCK

林业副产品作为控制牲畜寄生虫的新疗法

• 批准号: BB/X017397/1
• 负责人: Spiridoula Athanasiadou
• 金额: $ 36.66万
• 依托单位: Scotland's Rural College
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX017397%2F1
• 关键词: FORESTRY; BYPRODUCTS; NOVEL; THERAPEUTICS; PARASITE

"Sustainable food production" - the process by which we feed the ever-growing world population - is at the top of every agenda. To deliver sustainable food production, it is essential that livestock live in excellent conditions and are healthy throughout their lives. Gastrointestinal parasitism is a direct challenge to this due to negative consequences on animal health and welfare and on the environment. In addition, parasitic disease directly results in a 30% increase in greenhouse gas emissions, which exacerbates climate change and so also threatens food production.Drugs are often used to treat parasitic disease, but resistance to the drugs that kill these types of parasites is now widespread throughout the world, with a prevalence of nearly 100% in many countries. This leads to worldwide costs for food soaring by billions of pounds. In other words, the continuous use of drugs in livestock over the last 60 years has been positive in that it has increased livestock productivity and profitability, but the positive effects of the current generation of drugs (known as anthelmintics) is under threat due to global challenges, including antimicrobial resistance, climate change and maintenance of biodiversity. This project therefore directly addresses the impact that parasitism has on sustainable food production. It does this by using a low-value by-product for the UK's forestry industry and by incorporating this by-product into a next generation natural dietary supplement for livestock.Natural compounds extracted from plants (often called plant secondary metabolites (PSM)), are known to disrupt the life cycle of parasitic nematodes both in the animal and in the environment. PSM can therefore act as anthelmintics, controlling the disease these parasites cause. However, using a single pure PSM is expensive. Attention has therefore turned to PSM-rich extracts that contain a complex mixture of PSM as this is cheaper. However, this approach is hampered by large variations in the PSM content. Variability in PSM-content across different extracts leads to irreproducible biological activity. Whilst studies have demonstrated the anthelminitic effects of individual PSMs and/or plant extracts, the use of PSM-rich extracts is still understudied. There are insufficient reports on the effect on biological activity of combinations of PSMs or the contributions of individual PSM. Repeatable production of extracts (and thus consistent biological activity) requires a more detailed understanding of both the chemistry contained within PSM-extracts and the biological interactions of the active compounds in PSM-extracts with the parasites.Tree bark is particularly rich in antiparasitic PSM and it is very likely that the UK forestry industry creates enough bark waste to treat the UK livestock population, so long as the PSM-extract is administered at key times of parasite susceptibility. This project therefore brings together the forestry, livestock and bioprocessing industries with academic experts in parasitology, chemical biology, analytical and statistical analysis to understand the full extent of the interaction of the parasites with the tree bark extracts. In doing so, it will identify, and isolate compounds present in the bark extracts that demonstrate anthelmintic activity. This will enable the creation of an "Activity Index" - a tool to predict the anthelmintic activity of any future bark extract. This Activity Index will subsequently guide the characterisation of future large scale bark extracts, predicting their anthelmintic potential and optimise their inclusion in parasite control strategies. To achieve this, we will identify and test compounds for their presence in bark extracts and their anthelmintic activity. We will select potentially bioactive compounds on literature reports, preliminary evidence already available to us from previous work and novel work described in this proposal.

“可持续粮食生产”（我们养活不断增长的世界人口的过程）是每个议程的首要任务。为了提供可持续的粮食生产，至关重要的是，牲畜在良好的条件下生活并且一生都健康。由于对动物健康和福利以及环境的负面影响，胃肠道寄生虫是对此的直接挑战。此外，寄生疾病直接导致温室气体排放量增加了30％，这加剧了气候变化，从而威胁着食品生产。药物通常用于治疗寄生虫病，但在许多国家 /地区，对杀死这些类型的寄生虫的药物的抵抗力在世界范围内广泛存在，在许多国家 /地区的患病率近100％。这导致全球供应数十亿英镑的食品成本。换句话说，在过去60年中，在牲畜中不断使用药物是积极的，因为它提高了牲畜的生产力和盈利能力，但是由于包括抗药性，气候变化和生物多样性的抗药性，当前一代药物的积极影响（称为Anthelmintics）受到了全球挑战，包括全球挑战。因此，该项目直接解决了寄生虫对可持续粮食生产的影响。它通过为英国林业行业使用低价值的副产品，并将该副产品纳入牲畜的下一代天然饮食补充剂中。从植物中提取的自然化合物（通常称为植物二级代谢产物（PSM）），众所周知，可以破坏寄生虫在寄生虫中的生命周期。因此，PSM可以充当驱虫药，控制这些寄生虫引起的疾病。但是，使用单个纯PSM很昂贵。因此，注意到富含PSM的提取物，这些提取物包含PSM的复杂混合物，因为这更便宜。但是，这种方法受PSM含量的巨大变化所阻碍。不同提取物的PSM含量的变异性会导致不可培养的生物学活性。尽管研究表明，单个PSM和/或植物提取物的驱虫作用，但仍在使用富含PSM的提取物。关于对PSM组合或单个PSM贡献的生物学活性影响的报道不足。 Repeatable production of extracts (and thus consistent biological activity) requires a more detailed understanding of both the chemistry contained within PSM-extracts and the biological interactions of the active compounds in PSM-extracts with the parasites.Tree bark is particularly rich in antiparasitic PSM and it is very likely that the UK forestry industry creates enough bark waste to treat the UK livestock population, so long as the PSM-extract is administered at key寄生虫敏感性的时代。因此，该项目汇集了林业，牲畜和生物处理行业与寄生虫学，化学生物学，分析和统计分析方面的学术专家，以了解寄生虫与树皮提取物的相互作用的全部程度。这样一来，它将识别和分离出表现出驱虫活性的树皮提取物中的化合物。这将使创建“活动索引” - 一种预测未来任何树皮提取物的驱虫活动的工具。该活动指数随后将指导未来的大规模树皮提取物的表征，预测其驱虫潜力，并优化其纳入寄生虫控制策略。为了实现这一目标，我们将确定和测试化合物在树皮提取物及其驱虫活动中的存在。我们将在文献报告中选择潜在的生物活性化合物，以前的工作中已经为我们提供的初步证据以及本提案中描述的新工作。