Neuroprotective and Antidepressant Effects of <i>Tenebrio molitor</i> Larvae Hydrolysate in LPS-induced Neuroinflammation Models

Environmental pollution from synthetic drugs undermines Sustainable Development Goals while exhibiting limited efficacy and adverse effects in mood disorder treatments. <i>Tenebrio molitor</i> larvae (TM) demonstrate significant health benefits including anti-inflammatory, antioxidant, and cognitive enhancing effects. Enzymatic hydrolysis enhances protein bioactivity by improving digestibility and releasing bioactive peptides. This study evaluated neuroprotective effects of TM hydrolysates (TMH) against lipopolysaccharide (LPS)-induced neuroinflammation. Cell viability was measured by WST assay and cytotoxicity was measured by LDH release assay. Inflammatory cytokine mRNA levels were quantified by qRT-PCR, and NF-κB-, MAPKs-, and apoptosis-related biomarkers protein expressions were assessed by western blot. The TMH was administered intracerebroventricularly and LPS was injected intraperitoneally into ICR mice. Behavioral assessments were performed 24 h after LPS injection for sickness-like phenotypes and 28 h after for depressive-like behavior. Mice were sacrificed immediately after the behavior test to collect hippocampal tissue for cytokine mRNA analyses. TMH prevented LPS-induced sickness-like phenotypes and depressive-like behavior increases. Hippocampal IL-1β mRNA levels decreased significantly while IL-6, TNF-α, and IL-10 expression showed downward trends. Cell viability was preserved with reduced LDH release and attenuated upregulation of IL-1β, NF-κB, JNK, ERK, and Caspase-3 in PC-12 cells. TMH demonstrated robust protection against LPS-induced neuroinflammatory and behavioral alterations, indicating therapeutic potential for mood disorder interventions through sustainable, bioactive compound utilization. TMH mitigates both neurotoxic and depressive-like effects of systemic LPS in complementary cell and animal models, supporting its potential development as an eco-friendly, non-synthetic therapeutic agent for neuroinflammatory mood disorders.