Biochemistry Ph.D. Program, The Graduate Center of CUNY, New York, NY 10016, USA.
Department of Chemistry, Hunter College of CUNY, New York, NY 10065, USA.
Biomolecules. 2023 May 12;13(5):828. doi: 10.3390/biom13050828.
(L.) Dunal (family ) is a medicinal plant known for, among many pharmacological properties, an immune boosting effect. Our recent study revealed that its key immunostimulatory factor is lipopolysaccharide of plant-associated bacteria. This is peculiar, because, although LPS can elicit protective immunity, it is an extremely potent pro-inflammatory toxin (endotoxin). However, is not associated with such toxicity. In fact, despite the presence of LPS, it does not trigger massive inflammatory responses in macrophages. To gain insights into the safe immunostimulatory effect of , we conducted a mechanistic study on its major phytochemical constituent, withaferin A, which is known for anti-inflammatory activity. Endotoxin-triggered immunological responses in the presence and absence of withaferin A were characterized by both in vitro macrophage-based assay and in vivo cytokine profiling in mice. Collectively, our results demonstrate that withaferin A selectively attenuates the pro-inflammatory signaling triggered by endotoxin without impairing other immunological pathways. This finding provides a new conceptual framework to understand the safe immune-boosting effect of and possibly other medicinal plants. Furthermore, the finding opens a new opportunity to facilitate the development of safe immunotherapeutic agents, such as vaccine adjuvants.
（拉丁语）Dunal（家族）是一种药用植物，具有许多药理学特性，其中包括增强免疫力的作用。我们最近的研究表明，其关键的免疫刺激因子是植物相关细菌的脂多糖。这很特别，因为尽管 LPS 可以引发保护性免疫，但它是一种极其有效的促炎毒素（内毒素）。然而， 并不具有这种毒性。事实上，尽管存在 LPS，它不会在巨噬细胞中引发大规模的炎症反应。为了深入了解 的安全免疫刺激作用，我们对其主要的植物化学成分，即具有抗炎活性的醉茄内酯 A 进行了机制研究。在存在和不存在醉茄内酯 A 的情况下，通过体外巨噬细胞测定和体内小鼠细胞因子谱分析，研究了内毒素触发的免疫反应。总的来说，我们的结果表明，醉茄内酯 A 选择性地抑制内毒素触发的促炎信号，而不损害其他免疫途径。这一发现为理解 及可能其他药用植物的安全免疫增强作用提供了一个新的概念框架。此外，这一发现为开发安全的免疫治疗药物，如疫苗佐剂，开辟了新的机会。
