자폐증 및 유방암 세포 모델에서 곤충 추출물의 생리활성 효과에 관한 연구 = Bioactive Effects of Insect Extracts in Autism Spectrum Disorder and Breast Cancer Cell Models

다국어 초록 (Multilingual Abstract)

Global environmental changes and the growing instability of food resources have intensified the need to identify sustainable biological materials with therapeutic potential. Edible insects have attracted significant attention not only as alternative protein sources but also as reservoirs of bioactive compounds with diverse pharmacological activities. Among these, lipid-soluble and water-soluble insect extracts have been reported to exhibit antioxidant, neuroprotective, and anti-cancer properties; however, their mechanistic contributions to complex human diseases remain incompletely understood. This dissertation aims to elucidate the therapeutic roles and underlying mechanisms of insect-derived extracts in two distinct pathological conditions—autism spectrum disorder (ASD) and breast cancer—using a combination of animal models, cellular systems, and biochemical analyses. The first part of this research examined whether lipid-soluble extracts from Gryllus bimaculatus (Gb; crickets) and Oxya chinensis sinuosa (Ocs; grasshoppers) could ameliorate ASD-like phenotypes in a valproic acid (VPA)–induced mouse model. Behavioral assessments demonstrated significant recovery of social interaction, anxiety-like symptoms, and repetitive behaviors following extract administration. Metagenomic analyses further revealed that these bioactive insect lipids restored VPA-disrupted gut microbial composition, particularly the Bacteroidetes/Firmicutes ratio, along with improvements in metabolic pathway activities. These findings suggest that Gb and Ocs extracts modulate the gut–brain axis to restore physiological homeostasis associated with ASD pathology. The second part of the dissertation explored neuroglial mechanisms underlying ASD using lipid-soluble Gb extract as a biological probe. In neural progenitor cells, primary cortical neurons, and astrocytes derived from VPA-exposed mice, Gb extract reversed deficits in synaptic development, restored expression of key synaptic proteins (neuroligins, neurexin, synaptophysin), and reestablished the excitation/inhibition (E/I) balance. Notably, Gb extract normalized transporter expression in astrocytes (EAAT1/2, vGluT1, VGAT), indicating that astrocytic dysfunction plays a central role in ASD-related synaptic abnormalities. Co-culture experiments confirmed that Gb extract effectively corrected astrocyte-mediated disruptions in neuronal signaling, highlighting its potential as a modulator of neurodevelopmental stability. The final part of this dissertation investigated the anti-cancer potential of lipid-soluble extracts from four edible insects—Gb, Tenebrio molitor (Tm; mealworms), Protaetia brevitarsis seulensis (Pbs), and Ocs—in breast cancer models representing both triple-negative (MDA-MB-231) and hormone receptor–positive (MCF-7) subtypes. Combined treatment with paclitaxel and insect extracts produced synergistic cytotoxic effects, enhanced apoptotic cell death, and markedly inhibited clonogenic survival and migration. Mechanistic studies demonstrated significant suppression of the PI3K/Akt/mTOR signaling pathway as well as downregulation of angiogenic and chemokine-associated molecules, including VEGF, TM4SF3, and CXCL12/CXCR4. Among the tested species, lipid-soluble extracts from Gb and Pbs exhibited the strongest chemosensitizing activities. Collectively, the findings of this dissertation demonstrate that insect-derived lipid-soluble extracts exert multi-targeted biological effects across both neurodevelopmental and oncogenic disease contexts. By regulating cellular signaling, inflammatory responses, synaptic function, and microbial metabolic homeostasis, these extracts highlight the therapeutic versatility of edible insects as sources of novel bioactive molecules. This research provides a foundation for developing insect-based interventions for neurological disorders and cancer, and contributes to expanding the biomedical applications of sustainable bioresources.

목차 (Table of Contents)

• GENERAL ABSTRACT 15
• Chapter I 18
• ABSTRACT 18
• I-1. Introduction 20
• I-2. Materials and Methods 22
• I-3. Results 27
• I-4. Discussion 33
• I-5. Conclusion 37
• Chapter II 55
• ABSTRACT 55
• II-1. Introduction 57
• II-2. Materials and methods 60
• II-3. Results 66
• II-4. Discussion 72
• II-5. Conclusion 76
• Chapter III 98
• ABSTRACT 98
• III-1. Introduction 100
• III-2. Materials and methods 103
• III-3. Results 109
• III-4. Discussion 115
• III-5. Conclusion 120
• References 153
• 국문 초록 174
• 감사의 글 177
• Publication 179