Maad Rayan Publishing Company Biomedicine Advances 3080-0382 3 4 2026 10 01 Protective Effects of Combining Atorvastatin and Crocin on Hippocampal Neurodegeneration in Streptozotocin-Induced Alzheimer’s Rats 155 160 10.34172/bma.92 EN Sayyed Jafar Hasani https://orcid.org/0009-0002-0381-271X Mohammad Sodouri https://orcid.org/0009-0004-9754-1520 Zahra Niknam https://orcid.org/0000-0002-1681-2594 Leila Chodari https://orcid.org/0000-0002-9263-8583 Journal Article 10.34172/bma.92 2026 07 29 2026 09 06 Introduction: The global prevalence of Alzheimer’s disease (AD) continues to increase, posing a major public health challenge. Although currently available treatments provide limited symptomatic relief, no effective therapy has been shown to reverse disease progression. Consequently, exploring novel therapeutic approaches, particularly combination therapies with complementary neuroprotective mechanisms, has become increasingly important. Therefore, this study aimed to investigate the combined neuroprotective effects of Atorvastatin (Ator) and Crocin (Cro) on the hippocampus of rats with streptozotocin (STZ)-induced AD. Methods: Thirty male Wistar rats were randomly assigned to five groups (n=6 per group): Sham, STZ, Cro (30 mg/kg), Ator (5 mg/kg), and Cro + Ator. AD was induced by intracerebroventricular injection of STZ (3 mg/kg). Following STZ administration, the treatment groups received their respective interventions orally by gavage once daily for 21 consecutive days. Therapeutic efficacy was subsequently evaluated by assessing neuronal density in both CA1 and CA2 regions of the hippocampus using Nissl body staining. Results: STZ administration caused severe neuronal loss in the hippocampus (19.21% survival in CA1 and 44.39% in CA2). Monotherapy with Cro or Ator significantly improved both parameters, but the combined Cro+Ator treatment showed the most potent effect, restoring neuronal survival to 87.63%. The combination was significantly superior to either monotherapy. Conclusion: The additive neuroprotective effects of the Cro–Ator combination are likely mediated by their complementary mechanisms of action, which preserve hippocampal integrity. By simultaneously targeting multiple pathological processes, this dual-agent therapy represents a promising therapeutic strategy for the management of AD.