A Comparative Study of Nanoconjugates of a Synthetic and a Natural Drug Against T2DM-Induced Cognitive Dysfunction

Type II Diabetes Mellitus (T2DM) is one of the risk factors for the development of dementia leading to cognitive dysfunctions. The present study evaluates the efficacy of a synthetic drug (Vildagliptin, VLD) and a natural glycosidic compound (Hesperidin, HSP) against T2DM-induced cognitive dysfunction in rats. The drugs were conjugated with metal nanoparticles like gold (Au) and selenium (Se) to enhance their efficacy. The synthesis of the monometallic and bimetallic nanoparticles of VLD and HSP was established via the turkevich method and characterised by different spectroscopical techniques like UV (Ultraviolet)-visible, FTIR (Fourier Transform Infrared Spectroscopy), zeta potential, particle size, HR-TEM (High Resolution Transmission Electron Microscopy), SAED (Selected Area Electron Diffraction) and SEM-EDX (Scanning Electron Microscopy with Energy Dispersive X-ray Analysis). Both Streptozotocin (STZ) of 65 mg/kg (Group I-X) and Alloxan (ALX) of 150 mg/kg (Group I-X) were injected into 120 Wistar rats to induce cognitive dysfunction. After the induction, the BGL levels were evaluated and rats with BGL > 250 mg/dl were used in the study. Then the test drug and nanoformulations were administered for 21 days. Neurobehavioral assessment, antioxidant studies, and estimation of AChE (acetylcholinesterase) and nitrite levels were done. The VLD and HSP with its nanoconjugates significantly attenuated the effect of STZ and ALX by improving the memory and learning function in Y-maze, radial arm maze (RAM), and elevated plus maze (EPM), increased antioxidant levels of SOD (superoxide dismutase), CAT (catalase), and GSH (glutathione); decreased lipid peroxidation and reduced the AChE and nitrite levels in the rat brain. The bimetallic nanoconjugates of both VLD and HSP were more effective than the monometallic forms of VLD and HSP. However, VLD and its nanoconjugates exhibited better neuroprotective activity than HSP and its nanoconjugates in STZ and ALX animal models. VLD and its nanoformulations were more effective against long-term memory than HSP and its nanoconjugates. Both VLD and HSP may be a potential lead for cognitive and neurodegenerative diseases.