Shahmohammadi Niayesh, Haraji Shiva, Khan Falguni, Sørskår Åshild Moi, Danielsen Parastoo Ebrahimi, Vik Anders, Kim Yonggyun
Department of Plant Medicals, Andong National Universityong, Republic of Korea.
Department of Pharmacy, Section for Pharmaceutical Chemistry, University of Oslo, Oslo, Norway.
PLoS One. 2025 May 7;20(5):e0320488. doi: 10.1371/journal.pone.0320488. eCollection 2025.
During an infection, prostaglandin E2 (PGE2) mediates immune responses in insects and later epoxyoctadecamonoenoic acids (EpOMEs) are produced from linoleic acid to suppress excessive and unnecessary immune responses. Intracellular signaling pathway by which these oxylipins suppress the immune responses was previously unclear. This study demonstrated that EpOMEs antagonize the secondary messengers induced by PGE2 in a lepidopteran species, Maruca vitrata. PGE2 injections significantly increased hemocyte-spreading behavior, along with raised calcium ion and cAMP levels in hemocytes, and also up-regulated phenoloxidase activity and expressions of antimicrobial peptides. These cellular and humoral immune responses induced by PGE2 were dose-dependently inhibited by EpOMEs, with 12,13-EpOME being more effective than 9,10-EpOME in immunosuppression. PGE2 treatment also elevated the total number of circulating hemocytes, with the majority (88.4%) of these increased hemocytes being granulocytes. Conversely, EpOMEs suppressed the up-regulation of total hemocyte count induced by PGE2 and directly reduced the total hemocyte count by inducing apoptosis in granulocytes, as visualized by the TUNEL assay. These immunosuppressive and cytotoxic effects suggest the potential of EpOME as a lead compound for developing a novel type of insecticides. To chemically stabilize EpOMEs, the epoxide group was replaced with a propoxide group, and the carboxylic terminal was methylated. The 12-propoxyl regioisomer was selected based on immunosuppressive bioassays. Further investigation of the two possible enantiomers of 12-propoxyl regioisomer showed that the 12R-enantiomer was more effective than the 12S-enantiomer in immunosuppression. The resulting 12R-propoxy octadecamonoenoic methyl ester displayed insecticidal activities at low nanogram levels per insect by hemocoelic injection and at < 50 ppm by the leaf-dipping method against three lepidopteran insects.
在感染过程中，前列腺素E2（PGE2）介导昆虫的免疫反应，随后亚油酸产生环氧十八碳单烯酸（EpOMEs）以抑制过度和不必要的免疫反应。此前尚不清楚这些氧化脂质抑制免疫反应的细胞内信号通路。本研究表明，在鳞翅目昆虫豆野螟中，EpOMEs拮抗PGE2诱导的第二信使。注射PGE2显著增加血细胞铺展行为，同时血细胞中钙离子和cAMP水平升高，还上调酚氧化酶活性和抗菌肽表达。EpOMEs剂量依赖性地抑制PGE2诱导的这些细胞和体液免疫反应，其中12,13-EpOME在免疫抑制方面比9,10-EpOME更有效。PGE2处理还增加了循环血细胞总数，其中大部分增加的血细胞（88.4%）是粒细胞。相反，EpOMEs抑制PGE2诱导的血细胞总数上调，并通过TUNEL检测显示的粒细胞凋亡直接减少血细胞总数。这些免疫抑制和细胞毒性作用表明EpOME作为开发新型杀虫剂先导化合物的潜力。为了化学稳定EpOMEs，将环氧基团替换为丙氧基基团，并将羧基末端甲基化。基于免疫抑制生物测定选择了12-丙氧基区域异构体。对12-丙氧基区域异构体的两种可能对映体的进一步研究表明，12R-对映体在免疫抑制方面比12S-对映体更有效。所得的12R-丙氧基十八碳单烯酸甲酯通过血腔注射对三种鳞翅目昆虫在每只昆虫低纳克水平下以及通过浸叶法在<50 ppm时显示出杀虫活性。
