The anthocyanin-rich extract of Hibiscus sabdariffa enhances nuclear area, stratum thickness, and dendritic spines of hippocampal pyramidal cells in ovariectomized Wistar rats.

Ovarian hypofunction is associated with morphological alterations in the hippocampus, including a reduced nuclear area of pyramidal cells and changes in dendritic length and branching, which are linked to cognitive decline. Synthetic estrogens can partially mitigate these effects; however, their use is associated with adverse outcomes, such as increased cancer risk and cardiovascular complications. Therefore, natural alternatives such as phytoestrogens, particularly anthocyanins, have gained attention as potential neuroprotective agents against ovarian hypofunction and menopause-related neurodegenerative and cognitive impairments. We previously reported that the anthocyanin-rich extract from the calyces of Hibiscus sabdariffa (HSE) increases estrogen receptor alpha (ERα) levels, restores brain-derived neurotrophic factor (BDNF) expression, and improves spatial memory in ovariectomized Wistar rats. The present study evaluated the effect of HSE on the nuclear area, thickness of the stratum Oriens and stratum Radiatum, and spine number of hippocampal pyramidal neurons in ovariectomized Wistar rats. Adult female Wistar rats were ovariectomized, except for sham-operated and intact control groups, and treated with HSE in drinking water for six weeks (50 or 100 mg/kg body weight). Morphological parameters were analyzed and quantified using hematoxylin-eosin staining, while dendritic spine number was assessed by Golgi silver impregnation. HSE administration increased the pyramidal neuron nuclear area, thickness of the Oriens and Radiatum strata, and dendritic spine number in CA1 and CA3 regions of the hippocampus, counteracting the deleterious effect of ovariectomy-induced ovarian hypofunction. These findings support the therapeutic potential of H. sabdariffa as a natural strategy to prevent morphological alterations in hippocampal pyramidal neurons associated with ovarian hypofunction and menopause.