Diabetes mellitus (DM) is a metabolic disorder of multiple etiology, the main characteristic is that occurs with chronic hyperglycemia, due to insulin deficiency or resistance, or a combination of both. One of the organs most affected by the complications of DM is the brain because DM is closely related to an increase in the production of reactive oxygen species (ROS), an imbalance of the cellular antioxidant defense system and mitochondrial dysfunction. It has been reported that the brain is highly susceptible to oxidative stress. With the course of the disease, there are various complications at the brain level, such as the development of Alzheimer's, cognitive decline, alterations in neurotransmission, neuroinflammation, apoptosis, and necrosis, among others. On the other hand, traditional medicine has emerged as an alternative in the treatment of various diseases, including DM; one of the plants used in traditional medicine to treat diabetes is Eryngium carlinae, which has already been experimentally shown to have hypoglycemic, antioxidant and hypolipidemic properties, and can be used as an antidiabetic treatment. Moreover, new strategies have been sought to ensure a rapid and effective administration of drugs in recent years. One of these strategies is using green synthetic nanoparticles, which combine the use of plant extracts with metallic nanoparticles that ensure a more significant biological effect. The objective of this work was to compare the effect of the extract and its combination with silver nanoparticles (AgNP) on glucose levels and mitochondrial function. AgNP was obtained from the aqueous extract of E. carlinae characterized by UV‐Vis and SEM. 36 male Wistar rats without or with experimental DM (STZ 45 mg/Kg of weight) were divided into 6 groups with n = 6 and were treated or not with a dose of 30 mg/Kg of weight of the aqueous extract of E. carlinae or with a dose of 30 mg/Kg of weight of the extract‐AgNP combination for 45 days. The diabetic group showed a significant increase in glucose and triglycerides in the blood, as well as the production of ROS and lipoperoxidation in mitochondria. Also, a decrease in SODmt, GPx and complexes I, II and III activities compared to the control group. Administration with the treatments in diabetic rats showed decreased ROS production and lipoperoxidation, they also restored the activities of SODmt, GPx and CTE complexes compared to the diabetic group, and only the group treated with the extract‐AgNP combination decreased significantly the blood glucose and triglyceride levels, compared to the diabetic group. Our results suggest that the treatment with both E. carlinae aqueous extract and the extract‐AgNP combination can reverse the imbalance of the antioxidant defense system and ROS production, as well as mitochondrial dysfunction in the brain, and only with the combination (extract‐AgNP) lowers glucose and triglyceride levels in rats with DM.
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