Finamore Claudia, Festa Carmen, Cammarota Mattia, Spinelli Lucio, Morretta Elva, Cassiano Chiara, Monti Maria Chiara, Marchianò Silvia, Massa Carmen, Moraca Federica, Lupia Antonio, Catalanotti Bruno, Fiorucci Stefano, Zampella Angela, De Marino Simona
Department of Pharmacy, University of Naples "Federico II", Via D. Montesano, 49, Naples 80131, Italy.
Department of Medicine and Surgery, University of Perugia, Piazza L. Severi, 1, Perugia 06132, Italy.
ACS Omega. 2025 May 21;10(21):22269-22284. doi: 10.1021/acsomega.5c03492. eCollection 2025 Jun 3.
Boswellia serrata, commonly known as Indian olibanum or Indian frankincense, is a medicinal plant recognized for its significant anti-inflammatory, analgesic, and anticancer activities. In our investigation, the activity of its -hexane extract was evaluated on targets never explored for , mainly involved in hepatic fibrosis and cancer development. Since this extract exhibited a significant antagonistic activity on the interaction between leukemia inhibitory factor (LIF) and its receptor (LIFR), it was subjected to an untargeted metabolomic analysis using a high-resolution mass spectrometry-based approach combined with molecular networking. An unambiguous assignment of several triterpenoid metabolites was then achieved upon isolation and NMR spectroscopic investigation to accurately identify the bioactive components responsible for the -hexane extract activity on the LIF/LIFR system. Key active metabolites, including boswellic acids and their derivatives and a small library of semisynthetic analogues, demonstrated potential inhibitory activity toward LIF/LIFR interaction. In particular, α-boswellic acid () emerged as a LIFR antagonist, able to reduce the expression of col1α1 and α-SMA in LX-2 cells. Furthermore, computational studies highlighted the role of the carboxyl group in engaging a network of electrostatic and hydrogen bond interactions within residues of human LIFR (LIFR) binding site. This finding suggests the potential use of in hepatic fibrosis and sheds light on a relatively novel target for liver fibrosis therapy.
锯叶乳香，通常被称为印度乳香或印度香脂，是一种药用植物，以其显著的抗炎、镇痛和抗癌活性而闻名。在我们的研究中，评估了其正己烷提取物对从未针对其进行过探索的靶点的活性，这些靶点主要参与肝纤维化和癌症发展。由于该提取物对白血病抑制因子（LIF）与其受体（LIFR）之间的相互作用表现出显著的拮抗活性，因此使用基于高分辨率质谱的方法结合分子网络对其进行了非靶向代谢组学分析。然后，通过分离和核磁共振光谱研究，明确鉴定了几种三萜类代谢物，以准确识别负责正己烷提取物对LIF/LIFR系统活性的生物活性成分。关键的活性代谢物，包括乳香酸及其衍生物以及一个半合成类似物的小文库，对LIF/LIFR相互作用表现出潜在的抑制活性。特别是，α-乳香酸（）成为一种LIFR拮抗剂，能够降低LX-2细胞中col1α1和α-SMA的表达。此外，计算研究突出了羧基在参与人LIFR（LIFR）结合位点残基内的静电和氢键相互作用网络中的作用。这一发现表明了其在肝纤维化治疗中的潜在应用，并为肝纤维化治疗提供了一个相对新颖的靶点。
