Pleiotropic Actions of Gastrodia Elata Glucosides in the Treatment of Painful Neuropathies and CNS Disorders: Focus on MitochondrialDysfunction and Modulation of Ion Channels

Glycosides contained in Gastrodia elata have consistently shown neuroprotective and antiinflammatory activity in preclinical models of neurological disorders, including peripheral neuropathies, cerebrovascular disorders, and chronic neurodegenerative disorders. In a commercial product used in Italy, gastrodin has replaced α-lipoic, the use of which is now limited by unexpected adverse effects, such as severe hypoglycemia. The clinical efficacy of gastrodin in traditional Chinese medicine has been ascribed to a plethora of mechanisms, which involve the modulation of intracellular signaling pathways and membrane ion channels. Moving from the pathophysiology of diabetic neuropathy, Alzheimer's disease, and Parkinson's disease, we now focus on what we consider a key mechanism in the action of gastrodin, i.e., the regulation of mitochondrial quality control. Gastrodin is able to enhance mitochondrial fusion and biogenesis, as shown by the induction of specific biochemical markers, such as mitofusins and mitochondrial transcription factors. This supports mitochondrial health, preventing the loss of energy production and formation of reactive oxygen species associated with disorders of the central and peripheral nervous system. In addition, gastrodin physically interacts with, and restrains the expression and activity of, voltage-sensitive ion channels and acid-sensing ion channels, which play a central role in pain transmission and nociceptive sensitization. Thus, gastrodin and other constituents of Gastrodia elata show promising potential to support first-line treatments, based on preclinical evidence in models of neurological disease.