Apamin Enhances Neurite Outgrowth and Regeneration after Laceration Injury in Cortical Neurons

Abstract

Apamin is a minor component of bee venom and is a polypeptide with 18 amino acid residues. Although apamin is considered a neurotoxic compound that blocks the potassium channel, its neuroprotective effects on neurons have been recently reported. However, there is little information about the underlying mechanism and very little is known regarding the toxicological characterization of other compounds in bee venom. Here, cultured mature cortical neurons were treated with bee venom components, including apamin, phospholipase A2, and the main component, melittin. Melittin and phospholipase A2 from bee venom caused a neurotoxic effect in dose-dependent manner, but apamin did not induce neurotoxicity in mature cortical neurons in doses of up to 10 µg/mL. Next, 1 and 10 µg/mL of apamin were applied to cultivate mature cortical neurons. Apamin accelerated neurite outgrowth and axon regeneration after laceration injury. Furthermore, apamin induced the upregulation of brain-derived neurotrophic factor and neurotrophin nerve growth factor, as well as regeneration-associated gene expression in mature cortical neurons. Due to its neurotherapeutic effects, apamin may be a promising candidate for the treatment of a wide range of neurological diseases.

Beneficial Effect of Bee Venom and Its Major Components on Facial Nerve Injury Induced in Mice

“…This study builds on previous work in which BV and its major components (bvPLA2, melittin, and apamin) demonstrated a neuroprotective effect on neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, and multiple sclerosis, as well as on neurite outgrowth and regeneration after cortical neuron injury [ 28 , 38 , 39 ].…”

“…These two major components of BV showed a minor effect on re-innervation in contrast to the whole bee venom. This can be explained by the involvement of other BV molecules in the regeneration process such as apamin that accelerate neurite outgrowth and axon regeneration after a laceration injury in vitro [ 28 ]. It was found that the whole BV and melittin are efficient in the treatment of chemotherapy-induced neuropathy [ 52 ].…”

“…Conversely, other BV compounds may have other activities, such as apamin, which can improve neuronal excitability and synaptic plasticity by blocking calcium-activated K+ channels in Alzheimer’s disease [ 27 ]. Recently, its neuroprotective effects on cortical neurons have been reported with limited information on the underlying mechanism [ 28 ].…”

Novel Nanoconjugate of Apamin and Ceftriaxone for Management of Diabetic Wounds

“…Further, it gains indirect support by the notion that mellitin, another related bee venom, enhances wound healing [ 34 , 37 ]. In addition, apamin has been shown to enhance the regeneration of injured cortical neurons in vitro [ 38 ].…”

Pharmacological effects and mechanisms of bee venom and its main components: Recent progress and perspective

“…The above results showed that MEL could be a candidate agent for neurodegenerative disorders ( Cong Duc and Lee, 2021 ). Apamin enhanced neurite outgrowth and axon regeneration after laceration injury, and increased the expression of BDNF, nerve growth factor (NGF) and regeneration-related genes in mature cortical neurons ( Kim H. et al, 2021 ). Apamin inhibited LPS-induced neuroinflammatory responses in BV2 and rat primary microglial cells.…”