Modulation of Neuropsychiatric Symptoms by a Volatile Phytocomplex from Tetraclinis articulata in an Aβ1–42 Rat Model of Alzheimer’s Disease

Tetraclinis articulata volatile phytocomplexes contain numerous bioactive terpenoids with neuroprotective potential; however, their efficacy in Alzheimer’s disease (AD)-related neuropsychiatric symptoms remain insufficiently explored. This study investigated the therapeutic effects of a Tetraclinis articulata-derived volatile phytocomplex (TLO) administered via inhalation at 1% and 3% concentrations for 21 consecutive days in a rat model of AD induced by intracerebroventricular injection of amyloid-beta 1–42 peptide (Aβ1–42). Behavioral assessment revealed that both 1% and 3% TLO significantly ameliorated anxiety- and depression-like behaviors, with effects comparable to diazepam (3 mg/kg, i.p.) and imipramine (20 mg/kg, i.p.), respectively. These behavioral improvements coincided with a partial restoration of brain-derived neurotrophic factor (BDNF) expression in the amygdala, whereas activity-regulated cytoskeleton-associated protein (ARC) levels remained unaffected. TLO also attenuated oxidative stress by reducing malondialdehyde (MDA) accumulation and enhancing superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities, thereby contributing to the recovery of redox homeostasis. Furthermore, TLO provided significant protection against Aβ1–42-induced apoptotic DNA fragmentation, although it produced only minimal reductions in IL-1β expression, indicating limited anti-inflammatory effects. Collectively, these findings demonstrate that inhaled TLO, particularly at 1% and 3%, alleviates Aβ1–42-induced neuropsychiatric disturbances through antioxidant, anti-apoptotic, and BDNF-associated mechanisms, supporting its potential as an adjuvant phytotherapeutic strategy for managing behavioral symptoms in AD.