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.
Lobetyolin是一个由Lobetyol与葡萄糖吡喃糖基取代衍生而成的化合物[1]。Lobetyolin是党参（Codonopsis Radix）中的一种重要多炔类成分，因其独特的化学结构及潜在生理功能而受到广泛关注。大量研究表明，Lobetyolin具有抗氧化、抗炎和免疫调节等多种活性，尤其具有抗肿瘤活性，这可能与多炔类化合物对蛋白质天然受体位点（Michael加成反应位点）有较强亲和力有关。Lobetyolin显著抑制了PC-3前列腺癌细胞的增殖，其IC50为5.73μM[2]。
体外实验中，源自人胚胎肾的上皮细胞经不同浓度梯度的Lobetyolin(5, 10, 15, 20, 25, 30μM)处理24小时后，再用20µM的顺铂处理。实验结果表明，Lobetyolin对顺铂诱导的HEK293细胞毒性具有剂量依赖性的细胞保护作用，确立了其作为一种有效的细胞保护剂的地位[3]。在NCI-H292细胞中，用1、10和100µM的Lobetyolin预处理30分钟，随后用10ng/mL的佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA）刺激24小时，可显著抑制由PMA诱导的MUC5AC基因表达[4]。
体内实验中，对小鼠进行10mM Lobetyolin的腹腔注射处理后，观察到血清中IL-6、TNF-α和IL-1β的产生显著减少，同时肺和肝组织损伤得到缓解，表现为炎症细胞浸润减少[5]。Lobetyolin以10、20和40mg/kg的剂量腹腔注射给药，持续两周，显著减少了肿瘤体积，并大幅降低了小鼠体内丙氨酸、丝氨酸、半胱氨酸优先转运蛋白2（ASCT2）mRNA的表达。这些结果表明，Lobetyolin在裸鼠中展现出抗癌效果，可能通过抑制谷氨酰胺代谢实现[6]。