Spirulina platensis Extract Stabilizes Hepatic HIF-1α and Activates Caspase-3 in Aging Wistar Rat Liver

Abstract

Background: Liver aging is accompanied by progressive hypoxia, impaired redox homeostasis, and dysregulated programmed cell death, for which safe complementary interventions are needed. Spirulina platensis (Arthrospira platensis), a marine cyanobacterium rich in the antioxidant phycobiliprotein C-phycocyanin, is widely used in Indonesian complementary medicine, yet its effect on the hepatic hypoxia–apoptosis–autophagy network across biological age is undefined.

Objective: To examine whether oral Spirulina extract modulates hepatic HIF-1α, caspase-3, and p62/SQSTM1 in young (12-week) and older (24-week) male Wistar rats.

Methods: Animals (n = 5 per group) received Spirulina extract 200 mg/kg body weight or aquabidest vehicle once daily for 29 days; livers were harvested and marker concentrations quantified by ELISA, with one-way ANOVA, Tukey HSD, η², Cohen’s d, and Pearson correlation.

Results: Spirulina increased hepatic HIF-1α by 60.0% in older rats (688.0 ± 55.0 versus 430.0 ± 40.0 pg/mg protein; p < 0.001; Cohen’s d = 5.37) but not in young rats (p = 0.539). Caspase-3 rose 21.2% in older rats (145.68 ± 12.80 versus 120.23 ± 11.00 ng/mg protein; p = 0.010; d = 2.13), whereas p62 was unchanged (ANOVA p = 0.903). HIF-1α and caspase-3 were strongly correlated (r = 0.879; 95% CI 0.714–0.951; p < 0.001). Spirulina also raised the hepatosomatic ratio and attenuated body-weight gain.

Conclusion: Spirulina engages the hepatic hypoxia–apoptosis axis in an age-dependent manner while preserving autophagy, providing mechanistic support for its use as a herbal hepatoprotective modality.