The efficacy of Origanum majorana nanocubosomal systems in ameliorating submandibular salivary gland alterations in streptozotocin-induced diabetic rats.

Diabetes mellitus is a challenging health problem. Salivary gland dysfunction is one of its complications. Current treatments possess numerous adverse effects. Therefore, herbal extracts have emerged as a promising approach for safe and effective treatment. However, they are required in large doses to achieve the desired effect. Accordingly, Origanum majorana extract (OE) was incorporated into nanosized systems to enhance its biological effects at lower dosages. OE was standardized against rosmarinic acid (RA) and then loaded into nano-cubosomal (NC) systems via a 2³ full-factorial design. Two optimum nano-systems at different drug loads (2.08 or 1.04mg-RA/mL) were selected and assessed in vivo to compare their effects in streptozotocin-induced diabetic rats against conventional OE (2.08 mg-RA/mL). Blood glucose was evaluated weekly. Submandibular salivary glands were processed for histopathological examination and nuclear factor-erythroid 2-related factor 2 (Nrf2), Kelch-like ECHassociated protein 1 (Keap1), and p38-MAPK gene expression analysis. NC systems were successfully prepared and optimized where the optimum systems showed nano-sized vesicles (210.4-368.3nm) and high zeta potential values. In vivo results showed a significant lower blood glucose in all treated groups, with an exceptional reduction with NC formulations. Marked histopathological improvement was observed in all OE-treated groups, with OE-NC4 (2.08 mg-RA/mL) demonstrating the best features. This was supported by RT-PCR; where the OE-NC4 group recorded the highest mean value of Nrf2 and the least mean values of Keap1 and p38-MAPK, followed by OE-NC3 and OE groups. In conclusion, OEloaded NC enhanced the anti-hyperglycemic effect of OE and ameliorated diabetic gland alterations compared to conventional OE. Thus, cubosomal nano-systems could be anticipated as potential carriers for the best outcome with OE. [ABSTRACT FROM AUTHOR]