Pentalinonsterol, a Constituent of Pentalinon andrieuxii, Possesses Potent Immunomodulatory Activity and Primes T Cell Immune Responses,Journal of Natural Products

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Pentalinonsterol, a Constituent of Pentalinon andrieuxii, Possesses Potent Immunomodulatory Activity and Primes T Cell Immune Responses
Journal of Natural Products ( IF 3.3 ) Pub Date : 2017-09-06 00:00:00 , DOI: 10.1021/acs.jnatprod.7b00445
Steve Oghumu _{1,

2} , Sanjay Varikuti _{1,

2} , Noushin Saljoughian _{1,

2} , Cesar Terrazas _{1,

2} , Andrew C Huntsman _{1,

2} , Narasimham L Parinandi _{1,

2} , James R Fuchs _{1,

2} , A Douglas Kinghorn _{1,

2} , Abhay R Satoskar _{1,

2}

Affiliation

The use of natural products as adjuvants has emerged as a promising approach for the development of effective vaccine formulations. Pentalinonsterol (PEN) is a recently isolated compound from the roots of Pentalinon andrieuxii and has been shown to possess antileishmanial activity against Leishmania spp. The objective of this study was to examine the immunomodulatory properties of PEN and evaluate its potential as an adjuvant. Macrophages and bone-marrow-derived dendritic cells (BMDCs) were stimulated with PEN and tested for gene expression, cytokine production, and their ability to activate T cells in vitro. PEN was also evaluated for its ability to generate antigen-specific Th1 and Th2 responses in vivo, following ovalbumin (OVA) immunization using PEN as an adjuvant. The results obtained demonstrate that PEN enhances the expression of NF-κB and AP1 transcription factors, promotes gene expression of Tnfα, Il6, Nos2, and Arg1, and upregulates MHCII, CD80, and CD86 in macrophages. PEN also enhanced IL-12 production in BMDCs and promoted BMDC-mediated production of IFN-γ by T cells. Further, mice immunized with OVA and PEN showed enhanced antigen-specific Th1 and Th2 cytokines in their splenocytes and lymph node cells, as well as increased levels of IgG1 and IgG2 in their sera. Taken together, this study demonstrates that PEN is a potent immunomodulatory compound and potentially can be used as an adjuvant for vaccine development against infectious diseases.

中文翻译：

Pentalinonsterol 是 Pentalinon andrieuxii 的一种成分，具有有效的免疫调节活性并引发 T 细胞免疫反应

使用天然产物作为佐剂已成为开发有效疫苗制剂的一种有前景的方法。Pentalinonsterol (PEN) 是最近从Pentalinon andrieuxii根中分离出来的化合物，已被证明具有对抗利什曼原虫属的抗利什曼原虫活性。本研究的目的是检查 PEN 的免疫调节特性并评估其作为佐剂的潜力。用 PEN 刺激巨噬细胞和骨髓源性树突状细胞 (BMDC)，并测试其基因表达、细胞因子产生及其在体外激活 T 细胞的能力。使用 PEN 作为佐剂进行卵清蛋白 (OVA) 免疫后，还评估了 PEN 在体内产生抗原特异性 Th1 和 Th2 反应的能力。获得的结果表明，PEN增强巨噬细胞中NF-κB和AP1转录因子的表达，促进Tnfα、Il6、Nos2和Arg1的基因表达，并上调MHCII、CD80和CD86。PEN 还增强 BMDC 中 IL-12 的产生，并促进 BMDC 介导的 T 细胞产生 IFN-γ。此外，用 OVA 和 PEN 免疫的小鼠的脾细胞和淋巴结细胞中抗原特异性 Th1 和 Th2 细胞因子增强，血清中 IgG1 和 IgG2 水平升高。综上所述，这项研究表明 PEN 是一种有效的免疫调节化合物，有可能用作传染病疫苗开发的佐剂。

更新日期：2017-09-06

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