Protective effects of geraniol (a monoterpene) in a diabetic neuropathy rat model: Attenuation of behavioral impairments and biochemical perturbations

Abstract

Involvement of oxidative stress, inflammatory response, and mitochondrial dysfunction in the development of diabetic neuropathy (DN) is well appreciated. The present study examines the potential of geraniol (GE), a well-known phytoconstituent commonly found in lemon, spices, rose oil, etc., to attenuate DN-associated oxidative/nitrosative stress by employing a streptozotocin (STZ) diabetic rat model. STZ-induced diabetic rats provided with oral supplements of GE (100 mg/kg bw/day, 8 weeks) exhibited significant improvement in tail-flick latency (sensory function) and the narrow beam test (motor function). Terminally, elevated levels of oxidative markers (reactive oxygen species, malondialdehyde, hydroperoxides) in cytosol of the sciatic nerve (SN) and in selected regions of the brain of diabetic rats were markedly reduced by GE supplements. Furthermore, GE significantly diminished the levels of protein carbonyls (a measure of protein oxidation) and nitrites in diabetic rats. In addition, in mitochondria, GE supplements restored the activities of enzymes, such as complexes I-III, succinate dehydrogenase, and citrate synthase, in brain regions of diabetic rats, with a concomitant reduction in the levels of oxidative markers. GE significantly lowered the enhanced cytosolic calcium levels and acetylcholinesterase activity in the SN and the brain regions of diabetic rats. Depleted dopamine levels evident in the SN and the cortex/striatum among diabetic rats were restored by GE. From our data, we hypothesize that GE may be a promising therapeutic candidate in the management of DN in humans. Further understanding of the molecular mechanisms of its neuromodulatory effects is essential in order to exploit its therapeutic efficacy.

Analysis of the Antioxidant Activity of Geraniol Employing Various in-Vitro Models: Relevance to Neurodegeneration in Diabetic Neuropathy

“…This includes their ability to reduce the levels of or the formation of ROS and RNS, concomitantly upregulating vitagenes, such as members of the heat shock protein (Hsp) family, heme oxygenase-1, and Hsp70 [8,26]. GE has been reported as an effective antioxidant and antiinflammatory agent in different experimental models from our lab and others [16][17][18][19]21,29]. Recently, the antioxidant activity of GE along with other actives has been published with respect to DPPH free radical scavenging activity and superoxide dismutase activity [30].…”

“…Recently, the antioxidant activity of GE along with other actives has been published with respect to DPPH free radical scavenging activity and superoxide dismutase activity [30]. However, this study was planned and executed bearing in mind our results in different experimental models of neurodegeneration [16,21]. These studies emphasized the modulatory potency of oral supplementation of GE against acrylamide induced neurotoxicity and DN.…”

“…It is also found in a wide range of cleansing products and cosmetics for its appealing odor [13,14]. In the recent past, several studies have recognized the pharmacological potential of GE in different models [15][16][17]. Its pharmacological property is by virtue of its antioxidant and anti-inflammatory properties [18,19].…”

“…This was followed by the investigation of the modulatory potency of GE in SHSY5Y, neuroblastoma cell line, under hyperglycemic condition simulating DN. These studies were designed based on the data pertaining to the modulatory effects of GE obtained in in vivo studies from the same lab earlier [16,21].…”

Pharmacological Properties of Geraniol – A Review

“…GE could alleviate cytosolic calcium levels and acetylcholinesterase activity. Meanwhile, GE could inhibit the protein of carbonyls and nitrites [61]. GE attenuates another diabetic induced complication, i.e., diabetes-induced cardiac functional disorder, by inhibiting oxidative stress and decreasing hyperglycemia.…”