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与 ω-3 相比,十五烷酸具有更广泛和更安全的临床相关活性:在 12 个人类原发性细胞疾病系统中评估一种新兴的必需脂肪酸。

Broader and safer clinically-relevant activities of pentadecanoic acid compared to omega-3: Evaluation of an emerging essential fatty acid across twelve primary human cell-based disease systems.

机构信息

Epitracker, Inc., San Diego, California, United States of America.

Seraphina Therapeutics, Inc., San Diego, California, United States of America.

出版信息

PLoS One. 2022 May 26;17(5):e0268778. doi: 10.1371/journal.pone.0268778. eCollection 2022.

Abstract

A growing body of evidence supports that pentadecanoic acid (C15:0), an odd-chain saturated fat found in butter, is an essential fatty acid that is necessary in the diet to support long-term metabolic and heart health. Here, dose dependent and clinically relevant cell-based activities of pure C15:0 (FA15TM) were compared to eicosapentaenoic acid (EPA), a leading omega-3 fatty acid, as well as to an additional 4,500 compounds. These studies included 148 clinically relevant biomarkers measured across 12 primary human cell systems, mimicking various disease states, that were treated with C15:0 at four different concentrations (1.9 to 50 μM) and compared to non-treated control systems. C15:0 was non-cytotoxic at all concentrations and had dose dependent, broad anti-inflammatory and antiproliferative activities involving 36 biomarkers across 10 systems. In contrast, EPA was cytotoxic to four cell systems at 50 μM. While 12 clinically relevant activities were shared between C15:0 and EPA at 17 μM, C15:0 had an additional 28 clinically relevant activities, especially anti-inflammatory, that were not present in EPA. Further, at 1.9 and 5.6 μM, C15:0 had cell-based properties similar to bupropion (Pearson's scores of 0.78), a compound commonly used to treat depression and other mood disorders. At 5.6 μM, C15:0 mimicked two antimicrobials, climabazole and clarithromycin (Pearson's scores of 0.76 and 0.75, respectively), and at 50 μM, C15:0 activities matched that of two common anti-cancer therapeutics, gemcitabine and paclitaxel (Pearson's scores of 0.77 and 0.74, respectively). In summary, C15:0 had dose-dependent and clinically relevant activities across numerous human cell-based systems that were broader and safer than EPA, and C15:0 activities paralleled common therapeutics for mood disorders, microbial infections, and cancer. These studies further support the emerging role of C15:0 as an essential fatty acid.

摘要

越来越多的证据表明,十五烷酸(C15:0)是一种存在于黄油中的奇数链饱和脂肪,是饮食中必需的脂肪酸,可支持长期的代谢和心脏健康。在这里,与二十碳五烯酸(EPA),一种领先的ω-3 脂肪酸,以及另外 4500 种化合物相比,纯 C15:0(FA15TM)的剂量依赖性和临床相关细胞活性进行了比较。这些研究包括在 12 个人类原代细胞系统中测量的 148 种临床相关生物标志物,这些系统模拟了各种疾病状态,并用 C15:0 在四个不同浓度(1.9 至 50 μM)进行处理,并与未经处理的对照系统进行比较。在所有浓度下,C15:0 均无细胞毒性,并且具有剂量依赖性的广泛抗炎和抗增殖活性,涉及 10 个系统中的 36 个生物标志物。相比之下,在 50 μM 时,EPA 对四个细胞系统具有细胞毒性。虽然在 17 μM 时 C15:0 和 EPA 之间有 12 种临床相关活性,但 C15:0 还有另外 28 种临床相关活性,尤其是抗炎活性,这些活性在 EPA 中不存在。此外,在 1.9 和 5.6 μM 时,C15:0 具有与丁胺苯丙酮(Pearson 评分 0.78)相似的细胞特性,丁胺苯丙酮是一种常用于治疗抑郁症和其他情绪障碍的化合物。在 5.6 μM 时,C15:0 模拟了两种抗微生物药物,克霉唑和克拉霉素(Pearson 评分分别为 0.76 和 0.75),在 50 μM 时,C15:0 的活性与两种常见的抗癌治疗药物,吉西他滨和紫杉醇(Pearson 评分分别为 0.77 和 0.74)相匹配。总之,C15:0 在许多人类基于细胞的系统中具有剂量依赖性和临床相关的活性,其活性范围更广,安全性更高,而且比 EPA 更安全,并且 C15:0 的活性与情绪障碍、微生物感染和癌症的常见治疗药物相似。这些研究进一步支持 C15:0 作为必需脂肪酸的新兴作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/290b/9135213/efae17259571/pone.0268778.g001.jpg

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