Abstract
Background:
Diabetes mellitus (DM) is a chronic metabolic disorder associated with increased oxidative stress and vascular complications. This disease is managed with natural ingredients. Butternut squash is a natural ingredient with therapeutic effects due to its antioxidant content in the form of fatty acids.

Aim:
To determine the effects of butternut squash seed extract (Cucurbita moschata Duchesne) on antioxidants and kidney damage improvement in a diabetic mice model.

Methods:
The research used 30 male mice divided into 6 groups consisting of CN, C-, C+, P1 at a dose of 100 mg/kg body weight (BW), P2 at a dose of 150 mg/kg BW, and P3 at a dose of 200 mg/kg BW. Treatment was administered according to the dose in each group for 28 days. The research results were described with mean ± standard deviation, and one-way ANOVA was followed by DMRT to observe differences at a significance level of < 0.05.

Results:
Butternut squash seed extract exerted a therapeutic effect on weight gain on days 0 (p = 0.017), 7 (p = 0.000), 14 (p = 0.000), 21 (p = 0.000), and 28 (p = 0.000), decreased fasting blood glucose levels on days 0 (p = 0.000), 7 (p = 0.004), 14 (p = 0.003), 21 (p = 0.002), and 28 (p = 0.000), increased SOD levels (p = 0.007), decreased tubular cell necrosis (p = 0.000), and decreased tubular cell degeneration (p = 0.000). Additionally, the extract did not have a therapeutic effect on the increase in CAT levels (p = 0.074) and did not reduce the widening of the bowman space (p = 0.395).

Conclusion:
Butternut squash seed extract has therapeutic effects on weight gain, fasting blood glucose levels, SOD levels, tubular cell necrosis, and tubular cell degeneration, thus demonstrating that the extract is beneficial for improving oxidative stress and microvascular complications due to hyperglycemia. Further clinical trials are needed to ensure the safety and effectiveness of butternut squash seed extract as a therapy for DM.

Key words: Butternut squash seed; Catalase; Diabetic mellitus; Kidney; Superoxide dismutase.