Veratramine, a lipid-soluble alkaloid, is found in a variety of plants of the lily family [1]. Veratramine can reduce blood pressure, antagonize sodium ion channels and function as an analgesic [2]. Veratramine is widely used as an anti-cancer agent to inhibit the vitality of cancer cells in various cell models[3].
In vitro, Veratramine treatment for 24 hours can significantly inhibited cell proliferation of A172 cells, HS-683 cells, and T98G cells, with IC50 values of 88.81μM, 77.82μM, and 87.12μM, respectively[4]. The 10μM Veratramine treatment of Vero-E6 cells for 2 hours significantly reduced the PEDV-nucleocapsid (N) protein after α-coronavirus porcine epidemic diarrhea virus (PEDV) infection and inhibited the PI3K/Akt activity induced by PEDV[5]. Treatment with 20μM Veratramine for 60 minutes significantly inhibited EGF-induced activator protein-1 (AP-1) transcriptional activation and EGF-induced transformation of JB6 P+ cells[6].
In vivo, Veratramine treatment via daily tail vein injection at 50μg/kg/day for 4 weeks alleviated neuropathic pain in the diabetic rat model and reduced spinal cord and sciatic nerve damage[7]. Veratramine treatment (2mg/kg; 3 times a week) via tail vein injection for 4 weeks significantly inhibited subcutaneous tumor growth of liver cancer cells in the xenograft model of mice, with a low systemic toxicity[8].
References:
[1] Seale J T, McDougal O M. Veratrum parviflorum: an underexplored source for bioactive steroidal alkaloids[J]. Molecules, 2022, 27(16): 5349.
[2] Dirks M L, Seale J T, Collins J M, et al. Veratrum californicum alkaloids[J]. Molecules, 2021, 26(19): 5934.
[3] Tang J, Li H L, Shen Y H, et al. Antitumor and antiplatelet activity of alkaloids from veratrum dahuricum[J]. Phytotherapy Research, 2010, 24(6): 821-826.
[4] Kim D, Kwon W, Park S, et al. Anticancer effects of veratramine via the phosphatidylinositol-3-kinase/serine-threonine kinase/mechanistic target of rapamycin and its downstream signaling pathways in human glioblastoma cell lines[J]. Life Sciences, 2022, 288: 120170.
[5] Chen H, Zhao P, Zhang C, et al. Veratramine inhibits porcine epidemic diarrhea virus entry through macropinocytosis by suppressing PI3K/Akt pathway[J]. Virus Research, 2024, 339: 199260.
[6] Bai F, Liu K, Li H, et al. Veratramine modulates AP-1-dependent gene transcription by directly binding to programmable DNA[J]. Nucleic acids research, 2018, 46(2): 546-557.
[7] Zhang Y, Ye G, Chen Y, et al. Veratramine ameliorates pain symptoms in rats with diabetic peripheral neuropathy by inhibiting activation of the SIGMAR1-NMDAR pathway[J]. Pharmaceutical Biology, 2022, 60(1): 2145-2154.
[8] Yin L, Xia Y, Xu P, et al. Veratramine suppresses human HepG2 liver cancer cell growth in vitro and in vivo by inducing autophagic cell death[J]. Oncology Reports, 2020, 44(2): 477-486.
Veratramine是一种脂溶性生物碱，存在于多种百合科植物中[1]。Veratramine具有降压、钠离子通道拮抗和镇痛作用[2]。Veratramine作为抗癌剂广泛应用于多种细胞模型中抑制癌细胞活力[3]。
在体外，Veratramine处理24小时可显著抑制A172、HS-683和T98G细胞增殖，IC50值分别为88.81μM、77.82μM和87.12μM[4]。10μM的Veratramine处理Vero-E6细胞2小时能显著降低α-冠状病毒猪流行性腹泻病毒（PEDV）感染后的PEDV-核衣壳（N）蛋白水平，并抑制PEDV诱导的PI3K/Akt活性[5]。20μM的Veratramine处理60分钟可显著抑制EGF诱导的激活蛋白-1（AP-1）转录激活及JB6 P+细胞转化[6]。
在体内，糖尿病大鼠模型每日尾静脉注射Veratramine（50μg/kg/day；持续4周）可缓解神经病理性疼痛并减轻脊髓和坐骨神经损伤[7]。肝细胞癌异种移植瘤小鼠每周三次尾静脉注射Veratramine（2mg/kg；持续4周）能显著抑制皮下肿瘤生长，且全身毒性较低[8]。