Pharmacological evaluation of Thuja occidentalis for the attenuation of neuropathy via AGEs and TNF-α inhibition in diabetic neuropathic rats.

When diabetes neuropathy occurs, the oxidative stress caused by chronic hyperglycemia may result in chronic neuronal damage. To mitigate the effects of hyperglycemia-induced neuronal damage, it may be beneficial to address oxidative stress and inflammation in the body. The current study evaluated the neuroprotective efficacy of Thuja occidentalis in streptozotocin (STZ)-nicotinamide (NAD)-induced diabetic neuropathy in male Wistar rats. A single dose of STZ (65 mg/kg, i.p.) was used to induce diabetic neuropathy in Wistar rats. Serum insulin, glucose, hyperalgesia, oxidative stress, inflammatory markers, and histopathology of the sciatic nerve were evaluated for neuropathy. Wistar rats were treated with varying doses of hydroalcoholic extracts of Thuja occidentalis (HAETO) and gabapentin for 30 days. Thuja occidentalis considerably corrected the levels of inflammatory markers and oxidative stress caused by hyperglycemia; also, it led to the restoration of neuronal functions, indicating that it is effective in treating diabetic neuropathy. Furthermore, the molecular docking of thujone at the active pockets of various inflammatory mediators (IL-1ß, IL-6, TGF-ß1, and TNF-α) has shown good interactions with critical amino acid residues. These findings indicate that the hydroalcoholic extract of Thuja occidentalis effectively inhibits the development of diabetic neuropathy. The hypoglycemic, antioxidant, anti-hyperalgesia, and anti-inflammatory properties of Thuja occidentalis are thought to be responsible for the neuroprotective benefit.