Lobetyolin is a derivative of lobetyol substituted with a glucopyranose[1]. Lobetyolin is an important polyacetylene in Codonopsis Radix, which is of great interest on account of its unique chemical structures as well as its potential physiological functions. As suggested by extensive studies, Lobetyolin shows diverse functions such as antioxidant, anti-inflammatory, and immunomodulatory activities, especially antitumor activity, which may be due to the strong affinity of polyacetylenes to bind to proteins serving as the natural receptors of Michael response. Lobetyolin greatly impaired the proliferation of PC-3 cells, with corresponding IC50 values of 5.73μM[2].
In vitro, epithelial cells derived from human embryonic kidney were treated with a gradient of different Lobetyolin concentrations (5, 10, 15, 20, 25, 30μM) for 24 hours, followed by treatment with cisplatin at a concentration of 20µM. The experimental results demonstrate that Lobetyolin exhibits a dose-dependent cytoprotective effect against cisplatin-induced toxicity in HEK293 cells, establishing it as an effective cytoprotective agent[3]. Pre-treatment with Lobetyolin (1, 10, and 100µM) for 30 minutes, followed by stimulation with phorbol 12-myristate 13-acetate (PMA, 10ng/mL) for 24 hours in NCI-H292 cells, significantly inhibited the expression of MUC5AC gene induced by PMA[4].
In vivo, 10mM Lobetyolin with intraperitoneal injections treatment in mice demonstrated a remarkable reduction in the production of IL-6, TNF-α, and IL-1β in the serum, along with mitigated lung and liver tissue damage characterized by reduced inflammatory cell infiltration[5]. Lobetyolin, when administered intraperitoneally at doses of 10, 20, and 40mg/kg for two weeks, significantly reduced tumor volume and markedly decreased the expression of Alanine, Serine, Cysteine-Preferring Transporter 2 (ASCT2) mRNA in mice. These results suggest that Lobetyolin exhibits anti-cancer effects in nude mice, possibly through the inhibition of glutamine metabolism[6].
Reference:
[1] Bailly C. Anticancer Properties of Lobetyolin, an Essential Component of Radix Codonopsis (Dangshen). Nat Prod Bioprospect. 2021;11(2):143-153.
[2] Xie Q, Wang H, Guan H, et al. The in vitro/in vivo metabolic pathways analysis of lobetyol, lobetyolin, and lobetyolinin, three polyacetylenes from Codonopsis Radix, by UHPLC-Q/TOF-MS and UHPLC-MS/MS. J Pharm Biomed Anal. 2023;223:115140.
[3] Hou YY, Qi SM, Leng J, et al. Lobetyolin, a Q-marker isolated from Radix Platycodi, exerts protective effects on cisplatin-induced cytotoxicity in HEK293 cells. J Nat Med. 2023;77(4):721-734.
[4] Yoon YP, Ryu J, Park SH, et al. Effects of Lobetyolin, Lobetyol and Methyl linoleate on Secretion, Production and Gene Expression of MUC5AC Mucin from Airway Epithelial Cells. Tuberc Respir Dis (Seoul). 2014;77(5):203-208.
[5] Chen Z, Su Y, Ding J, He J, Lai L, Song Y. Lobetyolin protects mice against LPS-induced sepsis by downregulating the production of inflammatory cytokines in macrophage. Front Pharmacol. 2024;15:1405163.
[6] He W, Tao W, Zhang F, et al. Lobetyolin induces apoptosis of colon cancer cells by inhibiting glutamine metabolism. J Cell Mol Med. 2020;24(6):3359-3369.