Veratramine

Veratramine (NSC17821; NSC23880) is an orally active inhibitor of the PI3K/Akt/mTOR signaling pathway and a SIGMAR1 modulator. Veratramine induces autophagic apoptosis of tumor cells, arrests the cell cycle at the G0/G1 phase, and inhibits epithelial-mesenchymal transition (EMT)-related proteins to reduce tumor migration. Veratramine reduces spinal cord and sciatic nerve pathological damage in a neuropathy model by inhibiting SIGMAR1 binding to NMDAR and phosphorylation of NMDAR Ser896. Veratramine has anti-tumor proliferation, apoptosis induction, anti-inflammatory and neuroprotective activities, and can be used in the study of cancers such as liver cancer and osteosarcoma, as well as diabetic peripheral neuropathy^[1][2][3][4]. In Vitro:Veratramine (2.5-80 μM; 24-72 h) inhibits cell proliferation, migration and invasion, induces G0/G1 arrest and autophagic apoptosis, and downregulates proteins related to the PI3K/Akt/mTOR signaling pathway in human hepatoma HepG2 cell experiments^[1].
Veratramine (30-50 μM; 24-48 h) inhibits cell viability, migration and invasion, induces apoptosis, and downregulates p-PI3K, p-Akt, and EMT-related proteins N-cadherin and vimentin in human osteosarcoma 143B and HOS cell experiments^[2].
In Vivo:Veratramine (2 mg/kg; tail vein injection; 3 times a week; 4 weeks) inhibits tumor growth and reduces tumor weight in the subcutaneous transplant model of liver cancer in BALB/c nude mice, without obvious systemic toxicity^[1].
Veratramine (20-40 mg/kg; oral gavage; once every 2 days; 21 days) reduces the tumor fluorescence signal intensity and inhibits tumor growth in the orthotopic model of osteosarcoma in BALB/c nude mice, without significant effect on mouse body weight^[2].
Veratramine (50 μg/kg; tail vein injection; once a day; 4 weeks) increases the mechanical pain threshold in the diabetic peripheral neuropathy model of Sprague-Dawley rats, prolongs the tolerance time to cold and hot stimuli, and reduces the pathological damage of the spinal cord and sciatic nerve^[3].