Apamin

Apamin is a polypeptide neurotoxin derived from bee (Apis mellifera) venom ^[1-2]. Apamin is a highly selective small-conductance calcium-activated potassium channel (SK channel, especially the SK2 subtype; IC₅₀=0.06–0.4nM) blocker. Apamin enhances neuronal excitability and synaptic plasticity by preventing the hyperpolarization phase following neuronal action potentials, thereby influencing physiological functions such as learning and memory^[3-4].

In vitro, Apamin (0.1μM) treatment of differentiated N1E 115 neuroblastoma cells for 2 minutes selectively blocks Ca²⁺-dependent K⁺ channels, increasing neuronal excitability^[5]. In SH-SY5Y human neuroblastoma cells pretreated with Apamin (0.5μg/mL) for 1 hour, followed by stimulation with 1-methyl-4-phenyl pyridinium (MPP⁺; 3mM) for 12–24 hours, Apamin significantly inhibits the downregulation of tyrosine hydroxylase (TH) expression and abnormal aggregation of α-synuclein (αSYN), while reducing mitochondrial membrane potential disruption and apoptosis by blocking SK2 channel-mediated calcium overload^[6].

In vivo, in a cholestatic liver fibrosis model induced by 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine (DDC) diet, intraperitoneal injection of Apamin (0.1mg/kg) twice weekly for 4 weeks in 8-week-old C57BL/6 male mice significantly alleviates DDC-induced liver tissue damage and collagen deposition^[7]. In a lipopolysaccharide (LPS; 10mg/kg)-induced acute kidney injury model, a single intraperitoneal injection of Apamin (0.1mg/kg) in 8-week-old C57BL/6N male mice significantly improves LPS-induced renal dysfunction and kidney tissue damage^[8].

References:
[1] Gu H, Han SM, Park KK. Therapeutic Effects of Apamin as a Bee Venom Component for Non-Neoplastic Disease. Toxins (Basel). 2020 Mar 19;12(3):195.
[2] Laurindo LF, de Lima EP, Laurindo LF, et al. The therapeutic potential of bee venom-derived Apamin and Melittin conjugates in cancer treatment: A systematic review. Pharmacol Res. 2024 Nov;209:107430.
[3] Strong PN, Stocker M, Jenkinson DH. Apamin binding proteins and oligosaccharyltransferases. Toxicon. 1996 May;34(5):507-9.
[4] Lazdunski M, Fosset M, Hughes M, et al. The apamin-sensitive Ca2+-dependent K+ channel molecular properties, differentiation and endogenous ligands in mammalian brain. Biochem Soc Symp. 1985;50:31-42.
[5] Hugues M, Romey G, Duval D, et al. Apamin as a selective blocker of the calcium-dependent potassium channel in neuroblastoma cells: voltage-clamp and biochemical characterization of the toxin receptor. Proc Natl Acad Sci U S A. 1982 Feb;79(4):1308-12.
[6] Park J, Jang KM, Park KK. Effects of Apamin on MPP+-Induced Calcium Overload and Neurotoxicity by Targeting CaMKII/ERK/p65/STAT3 Signaling Pathways in Dopaminergic Neuronal Cells. Int J Mol Sci. 2022 Dec 3;23(23):15255.
[7] Kim JY, An HJ, Kim WH, et al. Apamin suppresses biliary fibrosis and activation of hepatic stellate cells. Int J Mol Med. 2017 May;39(5):1188-1194.
[8] Kim JY, Leem J, Park KK. Antioxidative, Antiapoptotic, and Anti-Inflammatory Effects of Apamin in a Murine Model of Lipopolysaccharide-Induced Acute Kidney Injury. Molecules. 2020 Dec 3;25(23):5717.