Department of Comparative Biomedical Sciences, Royal Veterinary College, London NW1 0TU, UK.
Department of Biological and Medical Sciences, Oxford Brookes University, Oxford OX3 0BP, UK.
Int J Mol Sci. 2024 Jun 4;25(11):6177. doi: 10.3390/ijms25116177.
sp. (mulberry) has a long tradition of use as a medicinal treatment, including for cardiovascular disease and type 2 diabetes, being shown to have antioxidant properties and to promote wound healing. Extracellular vesicles (EVs) are sub-micron, membrane-enclosed particles that were first identified in mammalian bodily fluids. EV-like particles have been described in plants (PDVs) and shown to have similar characteristics to mammalian EVs. We hypothesised that some of the health benefits previously attributed to the fruit of sp. could be due to the release of PDVs. We isolated PDVs from and via ultracentrifugation and incubated THP-1 monocytes, differentiated THP-1 macrophages, or HMEC-1 endothelial cells with pro-oxidant compounds DMNQ (THP-1) and glucose oxidase (HMEC-1) or lipopolysaccharide (LPS) in the presence of different fractions of mulberry EVs. Mulberry EVs augmented ROS production with DMNQ in THP-1 and caused the downregulation of ROS in HMEC-1. Mulberry EVs increased LPS-induced IL-1β secretion but reduced CCL2 and TGF-β secretion in THP-1 macrophages. In scratch wound assays, mulberry EVs inhibited HMEC-1 migration but increased proliferation in both low and high serum conditions, suggesting that they have opposing effects in these two important aspects of wound healing. One of the limitations of plant-derived therapeutics has been overcoming the low bioavailability of isolated compounds. We propose that PDVs could provide the link between physiological dose and therapeutic benefit by protecting plant active compounds in the GIT as well as potentially delivering genetic material or proteins that contribute to previously observed health benefits.
桑属植物（mulberry）作为一种药用治疗方法有着悠久的历史，包括治疗心血管疾病和 2 型糖尿病，其具有抗氧化特性，并能促进伤口愈合。细胞外囊泡（EVs）是亚微米大小的、膜包裹的颗粒，最初在哺乳动物体液中被发现。已经在植物中描述了类似 EV 的颗粒（PDVs），并显示出与哺乳动物 EV 相似的特征。我们假设，以前归因于桑属植物果实的一些健康益处可能是由于 PDVs 的释放。我们通过超速离心从桑属植物中分离出 PDVs，并在存在不同比例的桑属植物 EV 的情况下，用促氧化剂 DMNQ（THP-1）和葡萄糖氧化酶（HMEC-1）或脂多糖（LPS）孵育 THP-1 单核细胞、分化的 THP-1 巨噬细胞或 HMEC-1 内皮细胞。桑属植物 EV 与 DMNQ 一起增强了 THP-1 中的 ROS 产生，并导致 HMEC-1 中 ROS 的下调。桑属植物 EV 增加了 LPS 诱导的 THP-1 中 IL-1β 的分泌，但减少了 CCL2 和 TGF-β 的分泌。在划痕伤口测定中，桑属植物 EV 抑制了 HMEC-1 的迁移，但在低血清和高血清条件下均促进了增殖，表明它们在伤口愈合的这两个重要方面具有相反的作用。植物来源的治疗药物的一个局限性是克服分离化合物的低生物利用度。我们提出，PDVs 可以通过保护胃肠道中的植物活性化合物，并可能传递有助于先前观察到的健康益处的遗传物质或蛋白质，在生理剂量和治疗益处之间提供联系。
