Diabetes mellitus represents one of the main health challenges worldwide, characterized by hyperglycemia and long-term serious microvascular and macrovascular complications. Marine organisms are a promising reservoir of bioactive metabolites for developing effective antidiabetic therapies with fewer side effects. The sea urchin Tripneustes gratilla (T. gratilla) is widely distributed in the Red Sea, with limited reports of its pharmacological activities and chemical characterization. In this study, a nanosuspension formulation of T. gratilla extract (T. gratilla-NS) was developed to enhance the bioavailability of its bioactive constituents. This study investigated the antidiabetic potential of T. gratilla extract through an integrated approach encompassing chemical profiling of the extract, assessment of its alcoholic extract for in vitro inhibitory effects on α-amylase and α-glucosidase, and in vivo evaluation of T. gratilla-NS in an alloxan-induced diabetic rat model. We found that the alcoholic extract showed potent inhibitory action toward α-amylase with IC₅₀ 5.31 ± 0.05 µg/mL and moderate inhibitory activity toward α-glucosidase with IC₅₀ 21.36 ± 0.06 µg/mL. T. gratilla-NS significantly increased insulin levels, reduced blood glucose levels, and restored pancreatic damage. Furthermore, it enhanced the levels of superoxide dismutase and total antioxidant capacity with a concomitant decrease in malondialdehyde concentration in pancreatic tissue. The observed activities could be attributed to a wide array of diverse compounds, terpenes, mainly sesquiterpenes, diterpenes, steroids, and polyunsaturated fatty acids detected by GC-MS, compounds with a phenolic nucleus equal to 54.26 ± 1.27 mg. GAE/g of extract. This research highlights the dual role of T. gratilla-NS in combating diabetes and subsequently attenuating its associated complications.

Doxorubicin (DOX) is a commonly prescribed chemotherapeutic agent whose clinical application is limited by its toxicity to rapidly dividing organs, particularly the testes.This study explored the protective potential of ferulic acid-loaded niosomes (FA-NIO) against DOX-induced testicular dysfunction in rats and elucidated the underlying molecular mechanisms. Forty male rats were allocated into four groups: Group 1 was given saline, Group 2 was given DOX, Group 3 was given DOX + free FA, and Group 4 was given DOX + FA-NIO. Serum reproductive hormone levels, testicular oxidative stress indices, and the expression of genes and proteins relevant to NLRP3 inflammasome signaling, apoptosis (Bax and Bcl-2), and steroidogenesis (StAR, CYP11A1, and 3β-HSD) were assessed, along with histopathological changes in the testicular tissue. DOX administration significantly increased MDA (malondialdehyde) while suppressing antioxidant defences, accompanied by hormonal imbalance, severe histopathological damage, upregulation of Bax, NLRP3, and IL-1β, downregulation of Bcl-2, and inhibition of steroidogenic gene expression. On the other hand, these changes were partially mitigated in the DOX + free FA group. Notably, FA-NIO treatment reduced histopathological damage, normalised reproductive hormone levels, markedly increased steroidogenesis-related gene expression, suppressed apoptotic and inflammasome-related gene expression, and greatly restored antioxidant capacity. Compared with DOX + free FA, FA-NIO consistently demonstrated greater protective efficacy. In summary, FA-NIO targets oxidative stress-mediated apoptosis, attenuates NLRP3 inflammasome-related signaling, and restores steroidogenic function, thereby successfully attenuating DOX-induced testicular toxicity. These results suggest that FA-NIO may represent a promising nanotherapeutic strategy for attenuating chemotherapy-induced reproductive toxicity in a rat model.