Sesquiterpene lactones (SL) are natural bioactive molecules indicated as potential scaffolds for anti-inflammatory and analgesic drug design. However, their anti-inflammatory applicability remains underestimated since the impact of SL on inflammatory nociception and tissue repair are overlooked. Thus, we used an integrated in silico, in vitro and in vivo framework to investigate the impact of tagitinin F (TAG-F) on lipopolysaccharide (LPS)-challenged macrophages, excisional skin wounds, and carrageenan-induced paw edema and mechanical hyperalgesia in mice. RAW 264.7 macrophages in culture were challenged with LPS and treated with TAG-F (5, 10, 50 and 100 µM). The paw of BALB/c mice was injected with carrageenan and treated with 0.5% and 1% TAG-F. Excisional wounds were also produced in BALB/c mice and treated with 0.5% and 1% TAG-F. Our results indicated a consistent concentration-dependent downregulation in 5-lipoxygenase, cyclooxygenase 1 and 2 (COX-1 and COX-2), matrix metalloproteinase 1 and 2 (MMP-1 and MMP-2) activities; as well as attenuation in prostaglandin E2 (PGE2), leukotriene B4 (LTB4) and tumor necrosis factor-α (TNF-α) production in both in vitro and in vivo models. In vivo, TAG-F also attenuated carrageenan-induced paw edema and mechanical hyperalgesia in mice. From the excisional skin wound, TAG-F was still effective in reducing neutrophils and macrophages infiltration and stimulating collagen deposition in the scar tissue, accelerating tissue maturation. Together, our findings indicate that the anti-inflammatory effect of TAG-F is more comprehensive than previously suggested, exerting a significant impact on the control of edema, inflammatory pain and modulating central metabolic processes linked to skin wound healing.

倍半萜内酯 (SL) 是天然的生物活性分子，被认为是抗炎和镇痛药物设计的潜在支架。然而，由于 SL 对炎症伤害感受和组织修复的影响被忽视，因此它们的抗炎适用性仍然被低估。因此，我们使用一个集成在硅片，在体外和体内框架来研究 tagitinin F (TAG-F) 对脂多糖 (LPS) 攻击的巨噬细胞、切除性皮肤伤口和角叉菜胶诱导的小鼠爪水肿和机械痛觉过敏的影响。培养中的 RAW 264.7 巨噬细胞受到 LPS 攻击并用 TAG-F（5、10、50 和 100 µM）处理。BALB/c 小鼠的爪子注射角叉菜胶，并用 0.5% 和 1% TAG-F 处理。在 BALB/c 小鼠中也产生了切除伤口，并用 0.5% 和 1% TAG-F 处理。我们的结果表明 5-脂加氧酶、环氧合酶 1 和 2（COX-1 和 COX-2）、基质金属蛋白酶 1 和 2（MMP-1 和 MMP-2）活性的一致浓度依赖性下调；以及在体外抑制前列腺素 E2 (PGE2)、白三烯 B4 (LTB4) 和肿瘤坏死因子-α (TNF-α) 的产生和体内模型。在体内，TAG-F 还减轻了角叉菜胶诱导的小鼠爪水肿和机械痛觉过敏。从切除的皮肤伤口来看，TAG-F 仍然有效减少中性粒细胞和巨噬细胞的浸润，并刺激疤痕组织中的胶原蛋白沉积，加速组织成熟。总之，我们的研究结果表明，TAG-F 的抗炎作用比之前提出的更全面，对控制水肿、炎性疼痛和调节与皮肤伤口愈合相关的中枢代谢过程产生显着影响。