Neuroprotective and Antidepressant Effects of Tenebrio molitor 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. Tenebrio molitor 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.