# Cytoprotective-Antioxidant Effect of _Brunfelsia grandiflora_ Extract on Neuron-like Cells
## 1 Introduction  
The imbalance in the production and deactivation of reactive oxygen species (ROS) may lead to disproportionate concentrations of ROS and generate other reactive species and free radicals that are harmful and may react indiscriminately with cellular macromolecules with potentially dramatic consequences on the cell structure and function. Some of these consequences on cells in the central nervous system may lead to neurodegeneration diseases, characterized by progressive functional deterioration and neuronal cellular aging, with severe cytological and physiological damage of neurons [1; 2; 3]. Recent evidence suggests that neuronal oxidative stress, facilitated by microglia, leads to neuroinflammation, inducing neuronal necrosis and apoptosis [1; 2; 3]. Thus, protection of neuronal tissue from oxidative stress seems to be a promising strategy to prevent the onsetand development of neurodegenerative processes; consequently, protection of neuronal and glial cells against this difficult situation is one of the objectives of recent studies on nutritional and pharmacological prevention of aging and neurodegenerative diseases. Since the culturing of primary neurons is quite difficult, the use of established cell lines is widely accepted to test the neuroregulatory effect of natural or synthetic active compounds at cellular and molecular levels. The most frequently used neuron-like cell culture is neuroblastoma SH-SYSY, an established cell line derived from the SK-N-SH cell line. This cell line, suitable for biological, biochemical, and electrophysiological investigation, has been recently validated for studies about neuronal aging [4]. In fact, regarding the use of this cell line as a model of neuronal cell culture, we recently demonstrated its chemoprotective effect against an oxidative stress-induced neurodegeneration of an aqueous extract of cocoa [5] and an extract from the South American fabaceae _Desmodium tortuosum_ rich in flavonoids [6]. The aqueous maceration of the root from the South American solanaceae _Brunfelsia glandiflora_, locally known as Chiric sanango, has been used in traditional Peruvian medicine as a drink protecting against autoimmune diseases, infections, somatic pain, and fatigue, and as an antipyretic [7]. The infusion of the leaves is used against arthritis and rheumatism and a decoction of the bark is applied to burns and areas of the body affected by leishmaniasis and as a healing agent [7,8]. The remarkable number of polyphenic compounds may be responsible for most of these effects [9], but in particular the presence of scopoletin (coumarin with anti-inflammatory activity) would strengthen the effect of _B. grandiflora_ against rheumatism, arthritis, body pain, headache, and joint and muscle pain [10]. More interestingly for the present study, extracts from the plant also show hallucinogenic and narcotic properties that might be associated with the presence of brunfelsamidine, cuscohydgin, scopolamine, scopoletin, and esculetin [11,12]. A recently published chemical characterization and description of the antioxidant capacity of _B. grandiflora_[9], shown in the Supplementary Materials (Table S1), revealed a substantial content of hydroxcinnamic acids/hydroxycinnamates that is sufficient to award an outstanding antioxidant capacity. Indeed, we have previously reported on the antioxidative potential of these phenolic compounds in cell culture models [13,14] as well as in experimental animals [15]. In addition to hydroxcinnamic derivatives, extracts from _B. grandiflora_ also show relevant amounts of gallic acid, caffe acid, catechin, and eridictylosol as well as dihydroxybenzoic, dihydroxyphenylacetic, and dihydroxy-75 phenylpropionic acids and their derivatives; all of them enhance the effect of this medicinal plant against oxidative stress. Several studies have reported on the phytotherapeutic effect against chronic neurodegenerative conditions. Phytochemicals have been found to have anti-inflammatory, antioxidant, and anticholinesterase activities.