Inulicin (1-O-Acetylbritannilactone) is a natural active sesquiterpene lactone that inhibits angiogenesis. Inulicin inhibits VEGF-mediated Src and FAK activation. Inulicin inhibits LPS-induced PGE2 and COX-2 expression, inhibits NF-κB/AP-1 inflammatory signaling. Inulicin can be used for research on lung cancer, vascular inflammation/neointimal hyperplasia, and inflammatory diseases[1-4].
In vitro, treatment of LPS-induced RAW264.7 cells with Inulicin for 24 hours inhibited nitric oxide and prostaglandin E2 production and inhibited inducible nitric oxide synthase and cyclooxygenase-2 protein expression[5]. Treatment of A549 cells with 10µM Inulicin for 72 hours inhibited cell growth, induced apoptosis, downregulated NF-κB p65 and Bcl-2 expression, and upregulated inhibitor of nuclear factor kappa B kinase inhibitor IκBα and Bax expression[6]. Pretreatment of vascular smooth muscle cells with 5-20µM Inulicin for 1 hour followed by LPS stimulation inhibited LPS-induced PGE2 production and COX-2 expression, inhibited IKB-α phosphorylation and degradation thereby reducing NF-κB p65 nuclear translocation, and inhibited activated NF-κB DNA binding[7].
In vivo, intraperitoneal injection of 12mg/kg/day Inulicin into A549 xenograft nude mice for 20 days. Inulicin inhibited tumor growth, reduced tumor weight, and decreased p-Src and CD31 intensity in tumor tissues[8]. Oral administration of 5-10mg/kg Inulicin to high-fat diet-fed C57BL/6J mice every two days for 8 weeks. Inulicin reduced liver weight/tibia length ratio, alleviated liver pathological changes and steatosis, decreased serum AST, ALT, TG, TCH, and LDL-C, reduced hepatic lipid accumulation and fibrosis, lowered serum and liver IL-1β, and inhibited NLRP3 and NEK7 interaction in liver tissues[9]. A single intraperitoneal injection of 40-60mg/kg Inulicin into ICR mice followed 30 minutes later by intravenous injection of 1mg/kg LPS. Inulicin reduced serum and peritoneal lavage fluid levels of CCL2, TNF-α, and IL-6[10].
References:[1] Du GX, He LQ, Qin MX, et al. Synthesis and antihepatoma activity of dimeric 1-O-acetylbritannilactone derivatives. Med Chem Res. 2026 May;35(5):986-1001.
[2] Zhi XY, Zhang Y, Li YF, et al. Discovery of Natural Sesquiterpene Lactone 1-O-Acetylbritannilactone Analogues Bearing Oxadiazole, Triazole, or Imidazole Scaffolds for the Development of New Fungicidal Candidates. J Agric Food Chem. 2023 Aug 2;71(30):11680-11691.
[3] Dong S, Tang JJ, Zhang CC, et al. Semisynthesis and in vitro cytotoxic evaluation of new analogues of 1-O-acetylbritannilactone, a sesquiterpene from Inula britannica. Eur J Med Chem. 2014 Jun 10;80:71-82.
[4] Xie LY, Yang Z, Wang Y, et al. 1-O-Actylbritannilactone Ameliorates Alcohol-Induced Hepatotoxicity through Regulation of ROS/Akt/NF-κB-Mediated Apoptosis and Inflammation. ACS Omega. 2022 May 16;7(21):18122-18130
[5] Lee I.S, Lee Y.-R, Sim J.H, et al. The Effects of 1-O-Acetylbritannilactone Isolated from Inula britannica Flowers on Human Neutrophil Elastase and Inflammation of RAW 264.7 Cells and Zebrafish Larvae. Molecules. 2023;28(11):4320.
[6] Wang F, Li H, Qiao J, et al. 1-O-acetylbritannilactone combined with gemcitabine elicits growth inhibition and apoptosis in A549 human non-small cell lung cancer cells. Mol Med Rep. 2015;12(4):5568-5572.
[7] Liu Y-P, Wen J-K, Zheng B, et al. Acetylbritannilactone suppresses lipopolysaccharide-induced vascular smooth muscle cell inflammatory response. Eur J Pharmacol. 2007;577(1-3):28-34.
[8] Zhengfu H, Hu Z, Huiwen M, et al. 1-o-acetylbritannilactone(ABL) inhibits angiogenesis and lung cancer cell growth through regulating VEGF-Src-FAK signaling. Biochem Biophys Res Commun. 2015;464(3):422-427.
[9] Jin T, Zhao Y, Xu T, et al. 1-O-acetylbritannilactone alleviates high-fat diet-induced fatty liver by covalently targeting NLRP3. Int Immunopharmacol. 2026;174:116351.
[10] Yan J, Cai M, Zang C, et al. The natural sesquiterpene lactone inulicin suppresses the production of pro-inflammatory mediators via inhibiting NF-κB and AP-1 pathways in LPS-activated macrophages. Immunopharmacology and Immunotoxicology. 2024;46(5):583-593.