Antidiabetic effects of a polyherbal formulation of Nigella sativa, Origanum vulgare, and Malus asiatica in STZ-induced type 2 diabetic rats

Nigella sativa , Origanum vulgare , and Malus asiatica are traditionally used for gastrointestinal and metabolic health. A polyherbal formulation combining these herbs (NOM) has been employed as a folk remedy for diabetes, yet its efficacy and toxicity remain underexplored. This study identified bioactive compounds in NOM via UPLC-qTOF MS and assessed antidiabetic effects and cytotoxicity in vitro using STZ-treated INS-1 cells and in vivo using an STZ-induced type 2 diabetic rat model treated with NOM (200 mg/kg, orally) for 4 weeks. NOM significantly reduced blood glucose levels and mitigated cytotoxicity associated with black seed extract, both in vitro and in vivo, without evident toxicity (as assessed by body weight, organ indices, and serum biochemistry) at high doses in mice. Gene expression analysis (RT-qPCR) indicated regulation of the intrinsic apoptotic pathway as a potential mechanism. Histopathology supported these findings. Overall, NOM demonstrated effective glucose-lowering potential with reduced toxicity, highlighting the synergistic benefits of combining medicinal herbs. • A polyherbal formulation (NOM) combining Nigella sativa , Origanum vulgare , and Malus asiatica demonstrated significant antidiabetic effects in an STZ-induced type 2 diabetic rat model. • NOM extract reduced the cytotoxicity associated with Nigella sativa while preserving its glucose-lowering properties, both in vitro and in vivo. • Gene expression analysis indicated that NOM's antidiabetic mechanism may involve modulation of the intrinsic apoptotic pathway, supporting its potential as a safer natural remedy.