Zaluzanin D (ZD) is a sesquiterpene lactone isolated from the leaves of Vernonia arborea. Earlier studies have highlighted the Sesquiterpene lactones (SLs) as molecules of medicinal value. The current study investigates the anti-inflammatory potential of ZD and its biotransformed derivatives in PMA differentiated human monocytic THP-1 cells. ZD and its fungal biotransformed derivatives Zaluzanin C (ZC) and 11,13- dihydrozaluzanin C (DZC) were screened for anti-inflammatory activity using their IC₅₀ concentration. ZD showed significant ability to reduce PMA mediated THP-1 activation, while both ZC and DZC did not show any anti-inflammatory activity. Further studies revealed that ZD had ability to attenuate intracellular reactive oxygen species production in THP-1 cells as confirmed with FACS and fluorescence microscope experiments. Similarly, Oil red O (ORO) assay showed ability of ZD to inhibit lipid accumulation in monocytes. ZD also significantly reduced the expression of pro-inflammatory markers, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, MMP (Matrix metalloproteinases)-9 and MMP-2 as observed with RT-PCR and ELISA. Interestingly the molecule ZD also partially reversed DNA methylation levels in the PMA activated THP-1 cells. This indicated the ability of ZD to influence the epigenetic machinery of the cell. Overall the current study indicates that ZD has ability to attenuate inflammation in differentiated human THP-1 cells by regulating genes involved in the atherosclerosis inflammatory pathway. Thus ZD could potentially be used to modulate inflammation in atherosclerosis like disorders wherein monocytes play a key role.

Zaluzanin D（ZD）是一种从倍叶草Vernonia的叶中分离出的倍半萜内酯。早期的研究强调了倍半萜内酯（SLs）具有药用价值。目前的研究调查了ZD及其生物转化衍生物在PMA分化的人单核THP-1细胞中的抗炎潜力。使用其IC ₅₀对ZD及其真菌生物转化的衍生物Zaluzanin C（ZC）和11,13-二氢Zaluzanin C（DZC）进行了抗炎活性筛选浓度。ZD显示出降低PMA介导的THP-1激活的显着能力，而ZC和DZC均未显示任何抗炎活性。进一步的研究表明，如FACS和荧光显微镜实验所证实的，ZD具有减弱THP-1细胞中细胞内活性氧产生的能力。同样，油红O（ORO）分析显示ZD抑制单核细胞中脂质蓄积的能力。与RT-PCR和ELISA相比，ZD还显着降低了促炎标记，肿瘤坏死因子-α（TNF-α），白介素（IL）-1β，MMP（基质金属蛋白酶）-9和MMP-2的表达。有趣的是，分子ZD还可以部分逆转PMA激活的THP-1细胞中的DNA甲基化水平。这表明ZD影响细胞表观遗传机制的能力。总的来说，当前的研究表明，ZD具有通过调节参与动脉粥样硬化炎症途径的基因来减轻分化的人类THP-1细胞炎症的能力。因此，ZD可能潜在地用于调节动脉粥样硬化样疾病（其中单核细胞起关键作用）的炎症。