Fermented Crescentia cujete (SFC) shows oral safety, boosts GM-CSF and antioxidants, and suppresses COX-2 in rats.

Ischemic stroke remains a leading cause of disability and mortality, often involving complex inflammatory and oxidative stress pathways. Current therapeutic strategies primarily focus on reperfusion, but there's a significant need for adjunctive therapies that can mitigate secondary injury. Fermented Crescentia cujete (SFC) has emerged as a potential natural alternative, traditionally used for its medicinal properties. However, its systemic safety profile, particularly its effects on various organs, the immune system, and antioxidant status, has not been thoroughly characterized, leaving a critical gap in understanding its therapeutic potential and safety for broader application.

Researchers conducted a 14-day repeated-dose oral toxicity study using 20 male Sprague Dawley rats, divided into four groups (n=5 per group). Rats received daily oral gavage of 0, 50, 500, or 2,000 mg/kg BW of fermented Crescentia cujete (SFC). On day 15, animals were euthanized, and samples were collected from various organs and serum. Primary endpoints included histopathological examination of tissues, ELISA for serum GM-CSF and COX-2 levels, and biochemical assays to measure antioxidant enzyme activities (catalase, glutathione peroxidase, superoxide dismutase), total glutathione, total antioxidants, and MDA levels.

The 14-day oral administration of SFC demonstrated a favorable safety profile, with no significant histopathological changes observed across most organs (p ≥ 0.05). However, specific localized effects included an increase in bronchial associated lymphoid tissue activity in lung tissue and congestion in the stomach mucosa (p ≤ 0.05), suggesting mild, localized immune and vascular responses. Serum protein levels remained unaffected (p ≥ 0.05). Crucially, SFC significantly modulated immune and oxidative stress markers: > SFC increased serum GM-CSF levels and decreased COX-2 levels in both serum and various organs (p ≤ 0.05), indicating a systemic anti-inflammatory effect. Furthermore, the highest dose of 2,000 mg/kg BW SFC significantly boosted antioxidant defenses, increasing the activity of catalase, glutathione peroxidase, superoxide dismutase, and total glutathione, alongside elevating total antioxidant capacity (p ≤ 0.05). Concurrently, this dose led to a significant reduction in MDA levels (p ≤ 0.05), a key marker of lipid peroxidation and oxidative damage. These findings suggest a dose-dependent protective effect against oxidative stress.