###### Abstract  
We investigated the antioxidant activity and neuroprotective effects of an enzymatic hydrolyzate from silkworms fed the leaves of _Cudrania tricuspidata_ (ESLC) produced by enzymatic treatment. The proteins in silkworms fed the leaves of _Cudrania tricuspidata_ (SLC) were effectively hydrolyzed using enzymatic treatment. The total polyphenols of ESLC were significantly higher, and the superoxide dismutase-like activity and 2,2\({}^{\prime}\)-azino-bis (3-hylbenzothazoline-6-sulfonicacid) diammonium salt radical scavenging capacity of ESLC were significantly increased compared to the SLC group. We evaluated the properties of ESLC to protect SH-SY5Y cells from H\({}_{2}\)O\({}_{2}\)-induced oxidative stress. The viability rate of SH-SY5Y neuroblastoma cells was significantly restored when treated with ESLC at a concentration of 100 \(\upmu\)g/mL or 250 \(\upmu\)g/mL. Furthermore, the mitogen-activated protein kinase (MAPK) pathway was investigated, and ESLC significantly inhibited the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38. Therefore, ESLC can potentially be used as an antioxidant. The polyphenol content increases owing to hydrolysis through enzymatic treatment, which increases the antioxidant effect and inhibits the phosphorylation of JNK, ERK, and p38 by activating the MAPK pathway, which inhibits cell death from oxidative stress and exerts cytoprotective effects. silkworm; leaves of _Cudrania tricuspidata_; antioxidant effects; polyphenol; mitogen-activated protein kinase +
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larvae, _Protaeta brevitarsis_ seuensis larvae, _Tenebrio molitor_ [PERSON] larva, and _Locusta migratoria migratoria_ [PERSON] [7]. These insects have excellent nutritional value, and their safety has been confirmed by analyzing harmful substances, such as pesticide residues, heavy metals, microbes, and mycotoxins [8]. Furthermore, their safety has been scientifically proven by showing no toxicity in repeated doses, single doses, and genotoxicity tests [9; 10]. Animal studies that measured immunoglobulin E and histamine levels to analyze safety confirmed safety against allergies [11]. Among edible insects, the silkworm is a larva belonging to the family Bombycidae and has excellent nutritional value because of its very high protein content [12]. The silkworm has been used as a functional material in the food industry because it has been reported to have various functions such as hepatoprotective effects [13], blood sugar improvement effects [14], gut microbiota composition modulation [15], and antioxidant activity [16]. Mulberry leaves are rich in nutrients and contain high levels of various bioactive substances such as polyphenols and flavonoids [17; 18]. The nutritional and functional components of mulberry leaves significantly affect silkworm growth and quality [19]. _Cudrania tricuspidata_ belongs to the family Moraceae, and compared to ordinary mulberry leaves, the leaves are rich in functional components and bioactive substances such as gamma-aminobutyric acid, rutin, dihydroquercetin, and 1-deoxynojiramycin [20; 21]. Particularly, it has been reported to have excellent antioxidant activity and neuroprotective effects owing to its high bioactive substance content, such as polyphenols and flavonoids [22; 23]. Enzymes can hydrolyze proteins in a material into smaller molecules, such as peptides, which have various functionalities [24]. These components can be used as bioactive substances, and it has been reported that the antioxidant effects of hydrolyzes produced by enzymatic treatment increase with an increase in the degree of protein hydrolysis [25]. Hydrolysis by enzymatic treatment can increase the polyphenol and flavonoid contents in the material, thereby increasing its antioxidant activity [26]. In addition, [PERSON] et al.