## 1 Introduction  
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by motor neuron death in the motor cortex, brainstem, and spinal cord (SC) [1]. Clinically, ALS is characterized by muscle dysfunction, which progresses to muscle paralysis and respiratory failure, leading to death. The pathological mechanism of ALS involves excitotoxicity, oxidative damage, protein aggregate formation, autophagy dysfunction, and mitochondrial dysfunction [2]. Despite extensive drug development studies using animal models, only edaravone and riluzole have been approved by the Food and Drug Administration for ALS treatment. However, these drugs exert adverse effects, including gastrointestinal (GI) disturbances, nausea, headache, diarrhea, hepatotoxicity, and asthenia [3]. Moreover, these drugs do not cure the disease; they only preserve motor function and delay disease progression [4]. Therefore, effective treatments without adverse effects are urgently needed for patients with ALS. Neuroinflammation is a critical pathological feature of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and ALS. Neuroinflammation, which is caused by reactive astrocytes (astrogliosis) and activated microglial cells (microgliosis), induces the release of inflammatory cytokines, leading to neuron death [5]. In addition, hSOD1-mutant mice exhibit neuroinflammatory events and regulation of inflammatory responses involved in disease progression [6]. Antibiotics that reduce inflammation, such as minocycline, increase the survival rate of patients with ALS [7]. However, the inhibition of TNF-\(\alpha\) activity blocked the proliferation of microglia, but did not improve the survival rate of mutant hSOD1 mice [8], suggesting that drugs inhibiting microglia proliferation do not sufficiently increase the survival rate or improve motor activity in patients with ALS. Oxidative stress is also a principal factor that induces neuroinflammation, which in turn, contributes to the pathogenesis of ALS. Oxidative stress, including processes such as lipid peroxidation, oxidation, and DNA damage, is related to inflammation and mitochondrial dysfunction [9]. In addition, neuroinflammation induced by an increase in the number of reactive microglia is related to the induction of oxidative-stress-inducing radical generation, including reactive oxygen species (ROS) and reactive nitrogen species (RNS) [10]. Oxidative stress caused by an increase in the levels of free radicals induces neuroinflammation in neurodegenerative diseases [11]. The levels of 3-nitrotyrosine, a marker of peroxynitrite-mediated damage, and 8-hydroxy-2\({}^{\prime}\)-deoxyguanosine, a marker of oxidized DNA, are increased in the motor neurons of the SC of patients with ALS [12; 13]. Furthermore, oxidative stress involves other pathological mechanisms such as glutamate excitotoxicity, cytoskeletal dysfunction, and activation of glial cells in ALS animal models and patients with ALS [14]. ROS-induced motor neuron damage causes glutamate transmission in astrocytes, leading to glutamate excitotoxicity [15]. Therefore, anti-oxidants, including selegiline, N-acetylcysteine, and coenzyme 10, have been used for ALS treatment, but an effective outcome has not been achieved in patients with ALS [16]. This finding suggests that treatment of ALS should involve multi-targeting drugs and not a single targeted therapy. Herbal medicine has been used for treating various diseases, including gastrointestinal tract disorders; cancer; and neuronal disorders, such as AD, PD, and ALS, in East Asian (including Korea, China, and Japan), European, and Western countries [17]. In particular, herbal medicine has been used for incurable and chronic diseases, such as ALS [18] and cancer [19], owing to its minimal adverse effects, such as fever, nausea, vomiting, dizziness, and fatigue [20]. _Gastrodia elata_ has been used for alleviating hand and foot problems, numbness of the limbs, and rheumatic arthalgia [21].