Diosgenin Attenuates Cognitive Impairment in Streptozotocin-Induced Diabetic Rats: Underlying Mechanisms.

OBJECTIVE: Prolonged diabetes mellitus causes impairments of cognition and attentional dysfunctions. Diosgenin belongs to a group of steroidal saponins with reported anti-diabetic and numerous protective properties. This research aimed to assess the effect of diosgenin on beneficially ameliorating learning and memory decline in a rat model of type 1 diabetes caused by streptozotocin (STZ) and to explore its modes of action including involvement in oxidative stress and inflammation. METHODS: Rats were assigned to one of four experimental groups, comprising control, control under treatment with diosgenin, diabetic, and diabetic under treatment with diosgenin. Diosgenin was given daily p.o. (40 mg/kg) for 5 weeks. RESULTS: The administration of diosgenin to the diabetic group reduced the deficits of functional performance in behavioral tests, consisting of Y-maze, passive avoidance, radial arm maze, and novel object discrimination tasks (recognitive). Furthermore, diosgenin treatment attenuated hippocampal acetylcholinesterase activity and malon-dialdehyde, along with improvement of antioxidants such as superoxide dismutase and glutathione. Meanwhile, the hippocampal levels of inflammatory indicators, namely interleukin 6, nuclear factor-κB, toll-like receptor 4, tumor necrosis factor α, and astrocyte-specific biomarker glial fibrillary acidic protein, were lower and, on the other hand, tissue levels of nuclear factor (erythroid-derived 2)-related factor 2 were elevated upon diosgenin administration. Besides, the mushroom-like spines of the pyramidal neurons of the hippocampal CA1 area decreased in the diabetic group, and this was alleviated following diosgenin medication. CONCLUSIONS: Taken together, diosgenin is capable of ameliorating cognitive deficits in STZ-diabetic animals, partly due to its amelioration of oxidative stress, inflammation, astrogliosis, and possibly improvement of cholinergic function in addition to its neuroprotective potential.

Diosgenin ameliorates development of neuropathic pain in diabetic rats: Involvement of oxidative stress and inflammation.

Neuropathic pain is one of the prevalent complications of diabetes mellitus (DM). Oxidative stress and inflammation are the principal determinants for its development. Pharmacological interventions targeted at alleviating or suppressing these pathways are clinically promising. Diosgenin is a natural steroidal saponin with anti-diabetic and multiple protective properties. This study was designed to study the efficacy of chronic diosgenin administration on alleviation of hyperalgesia in streptozotocin (STZ)-diabetic rats. Rats were allocated to control, diosgenin-treated control, diabetic, and diosgenin-treated-diabetic groups. Diosgenin was daily administered at a dose of 40mg/kg for 5 weeks. Nociceptive behavior was assessed using paw pressure, hot tail immersion, and formalin tests. In addition, some oxidative stress and inflammation markers were measured. Diosgenin treatment of diabetic group increased mechanical and thermal nociceptive thresholds and lowered pain score at late phase of the formalin test, but not at its early phase. Biochemical analysis of serum samples and sciatic nerve and dorsal root ganglion (DRG) lysates showed restoration or improvement of nuclear factor-B (NF-κB), malondialdehyde (MDA) level, activity of superoxide dismutase (SOD), catalase, tumor necrosis factor α (TNFα), and interleukin 1ß (IL-1ß) upon diosgenin treatment of diabetic rats. The obtained results exhibited antinociceptive potential of diosgenin in diabetic rats through lowering oxidative stress and inflammation and improving antioxidant defense system. This suggests possible therapeutic potential of diosgenin for alleviation and management of diabetic neuropathic pain.