Satureja khuzestanica attenuates apoptosis in hyperglycemic PC12 cells and spinal cord of diabetic rats.

Several studies have indicated the involvement of oxidative stress and high glucose-induced cell death in the development of diabetic neuropathy. Satureja khuzestanica has been recommended in the literature as a remedy for the treatment of diabetes, and also contains antioxidant agents. Here, we investigated the possible neuroprotective effects of Satureja khuzestanica extract (SKE) on in vitro and in vivo models of diabetic neuropathy pain. High-glucose-induced damage to pheochromocytoma (PC12) cells and in streptozotocin-induced diabetic rats was studied. Tail-flick and rotarod treadmill tests were used to access nociceptive threshold and motor coordination, respectively. Cell viability was determined by MTT assay. Activated caspase 3 and Bax/Bcl-2 ratio-biochemical markers of apoptosis-were evaluated using immunoblotting. We found that elevating the glucose in the medium (to 4× normal) increased cell toxicity and caspase-3 activation in PC12 cells. Incubation with SKE (200 and 250 μg/ml) decreased cell damage. Furthermore, the diabetic rats developed neuropathy, which was evident from thermal hyperalgesia and motor deficit. Administering SKE at a daily dose of between 50 and 200 mg/kg to the diabetic animals for 3 weeks ameliorated hyperglycemia, weight loss, hyperalgesia, and motor deficit, inhibited caspase 3 activation, and decreased the Bax/Bcl-2 ratio. The results suggest that SKE exerts neuroprotective effects against hyperglycemia-induced cellular damage. The mechanisms of these effects may be related to (at least in part) the prevention of neural apoptosis, and the results suggest that Satureja has the therapeutic potential to attenuate side effects of diabetes, such as neuropathy.