Behavioural Neurology · 3 authors, 4 centres
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This study in mice found that ethanol extract of Cucurbita maxima seeds significantly reduced anxiety and depression and improved memory at doses of 100 and 200 mg/kg. The effects were linked to elevated brain norepinephrine, dopamine, and serotonin levels. These findings support the traditional use of pumpkin seeds for neurological benefits, though clinical trials are needed.
**Background:** Neurological disorders such as anxiety, depression, and dementia are increasingly prevalent. Cucurbita maxima (pumpkin) seeds are traditionally used for nutrition and various ailments, and contain bioactive compounds like cucurbitacin, beta-sitosterol, polyphenols, and antioxidants. This study aimed to provide a pharmacological basis for the neuropharmacological benefits of C. maxima seeds, evaluating their effects on anxiety, depression, memory, and motor coordination in mice.
**Methods:** Healthy mice of either sex were divided into six groups (n=10 each): control (5% DMSO), standard drugs (diazepam 3 mg/kg, imipramine 30 mg/kg), and three test groups receiving ethanol extract of C. maxima seeds at 50, 100, and 200 mg/kg orally for 30 days. Anxiety was assessed using light/dark test, elevated plus maze (EPM), head dip test, and open field test (OFT). Depression was evaluated via forced swim test (FST) and tail suspension test (TST). Memory and learning were measured using passive avoidance test (PAT), Morris water maze, and stationary rod test (SRT). Motor coordination was assessed by rotarod. Brain biogenic amines (norepinephrine [NA], dopamine [DA], serotonin [5HT], and metabolites) were quantified using reversed-phase HPLC with electrochemical detection. Statistical analysis used one-way ANOVA followed by Dunnett's test.
**Key Results:** C. maxima at 100 and 200 mg/kg caused an 11% reduction in body weight by day 30. In anxiety models, C. maxima 100 mg/kg showed maximum anxiolytic activity in the light/dark test (58.9% and 55% time in light on days 8 and 21, respectively), comparable to diazepam (54%). In EPM, C. maxima 200 mg/kg reduced the anxiety index to 0.26 on day 8 (vs. control 0.71). In OFT, C. maxima 100 and 200 mg/kg significantly increased center entries, center time, and rearing duration on days 8 and 21. In depression models, C. maxima 200 mg/kg reduced immobility time by 49.3% in FST and 42% in TST, compared to imipramine's 54.1% and 52.5%, respectively. Memory tests showed C. maxima 100 mg/kg significantly increased latency in PAT at all time points (3h, 24h, day 8, day 21; p<0.01 vs. control). In the water maze, C. maxima 200 mg/kg reduced time to reach the platform at 24h, day 8, and day 21 (p<0.01). Motor coordination improved with C. maxima 100 and 200 mg/kg increasing fall time on rotarod at high speed on days 8 and 21 (p<0.01). Brain biogenic amine analysis revealed C. maxima 200 mg/kg significantly increased NA (697.8±35 pg/mg vs. control 56±4.4), DA (883.1±58 vs. 357±128.5), DOPAC (443.9±52 vs. 172±29.8), and 5HT (452.6±86 vs. 97±29.5) (all p<0.01).
**Clinical Implications:** This study provides preclinical evidence that chronic administration of C. maxima seed extract has anxiolytic, antidepressant, and memory-enhancing effects in mice, likely mediated by modulation of brain monoamines (NA, DA, 5HT) and possibly through cholinesterase inhibition and antioxidant properties. The weight reduction observed may offer additional metabolic benefits. These findings support the traditional use of pumpkin seeds for neurological health and suggest potential as a dietary supplement for anxiety, depression, and cognitive decline. However, adequate clinical trials in humans are necessary before widespread therapeutic use.