curcumin and Diabetic-Neuropathies

Curcumin has anti-inflammatory, antioxidant, and anticancer effects and is used to treat diseases such as dermatological diseases, infection, stress, depression, and anxiety. J147, an analogue of curcumin, is designed and synthesized with better stability and bioavailability. Accumulating evidence demonstrates the potential role of J147 in the prevention and treatment of Alzheimer's disease, diabetic neuropathy, ischemic stroke, depression, anxiety, and fatty liver disease. In this narrative review, we summarized the background and biochemical properties of J147 and discussed the role and mechanism of J147 in different diseases. Overall, the mechanical attributes of J147 connote it as a potential target for the prevention and treatment of neurological diseases.

Topics: Anxiety; Anxiety Disorders; Curcumin; Diabetic Neuropathies; Humans

Depression in patients with diabetes is associated with poor glycemic control and linked to an increased risk for diabetes complications such as neuropathy. Curcumin has shown potential antidepressant-like activities in some studies. The present study is the first randomized controlled trial to test the efficacy of nano-curcumin supplementation on depression, anxiety, and stress in patients with diabetic polyneuropathy. Eighty patients with diabetes were enrolled in this parallel, double-blind, randomized, placebo-controlled clinical trial. The participants were allocated randomly to the intervention (n = 40) and control (n = 40) groups. They received 80 mg of nano-curcumin or placebo capsules daily for 8 weeks. At baseline and end of study, anthropometric measurements, dietary intake, physical activity, glycemic indices, and severity of neuropathy were assessed. The depression, anxiety, and stress level were measured by Depression, Anxiety, Stress Scale (DASS-21-items) questionnaire before and after the intervention. After intervention, there was a significant reduction in the mean score of depression in the nano-curcumin group (from 16.7 [3.1] to 15.3 [2.6]) compared with placebo group (17.5 [3.2] to 17.3 [3.1]; p = .02). In addition, a significant fall was found in the mean score of anxiety in the nano-curcumin group (from 22.4 [4.03] to 20.6 [3.4]) compared with the placebo group (21.9 [3.5] to 21.2 [3.5]; p = .009). Changes in stress score were not statistically significant between the two groups. These findings suggested that nano-curcumin supplementation for 8 weeks was effective in reducing depression and anxiety scores in patients with diabetic polyneuropathy.

Topics: Adult; Antidepressive Agents; Anxiety; Curcumin; Depression; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Dietary Supplements; Double-Blind Method; Female; Humans; Iran; Male; Middle Aged; Nanoparticles; Placebos; Stress, Psychological; Surveys and Questionnaires

Diabetic Sensorimotor Polyneuropathy (DSPN) is a common complication of diabetes mellitus. Curcumin is the most important ingredient found in turmeric which has a very high potential for eliminating free radicals and inhibiting oxidative stress as an antioxidant agent. The aim of this study was to determine the effect of Nano-curcumin supplementation on the severity of sensorimotor polyneuropathy in patients with Type 2 diabetes mellitus (T2DM).. This parallel, double-blind randomized, placebo-controlled clinical trial was conducted on 80 diabetic patients. Participants were allocated randomly to the intervention (n = 40) and the control group (n = 40). They received 80 mg of nano-curcumin or placebo capsules for 8 weeks. Anthropometric measurements, dietary intake, physical activity, glycemic indices and the severity of DSPN were measured before and after the intervention.. Supplementation of nano curcumin was accounted for a significant reduction in Glycated hemoglobin(HbA1c) (p < 0.001) and Fast Blood Sugar(FBS) (p = 0.004), total score of neuropathy (p < 0.001), total reflex score (p = 0.04) and temperature (p = 0.01) compared to placebo group.. Our findings indicated that curcumin supplementation for 2 months improved and reduced the severity of DSPN in patients with T2DM.

Topics: Adult; Antioxidants; Blood Glucose; Curcuma; Curcumin; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Dietary Supplements; Double-Blind Method; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Nanoparticles; Oxidative Stress; Polyneuropathies

Increasing evidence suggested that inhibiting the apoptosis of Schwann cells (SCs) and promoting nerve growth factor (NGF) expression in sciatic nerves play key roles in preventing the onset of diabetic peripheral neuropathy (DPN). Curcumin, a primary bioactive substance in turmeric with multiple characteristics, has been shown to have many therapeutic effects in a variety of diseases. However, curcumin is poorly studied in the DPN models. We aimed to explore the therapeutic benefits and underlying mechanism of curcumin in high fat/sugar diets joint streptozotocin (STZ)-induced DPN rat models. Sprague-Dawley (SD) rats were divided into five groups (6 rats per group), control group, DPN group, Curcumin groups (50, 100, and 150 mg/kg). Curcumin was administered intragastrically once per day for 4 continuous weeks. Body weight (BW) and fasting blood glucose (FBG) were monitored in all groups. The mechanical withdraw threshold (MWT) was measured. We also assessed neuropathic change by testing nerve conductance velocity (NCV) in sciatic nerves. TEM was applied to observe the sciatic nerves ultrastructure. The SCs apoptosis in sciatic nerves was stained using TUNEL kit. NGF contents in sciatic nerves and serum were detected using western blotting and ELISA analysis. The results showed curcumin had no obvious effect on the BW and FBG change. Curcumin (100 and 150 mg/kg) attenuated the MWT, NCV, and sciatic nerves ultrastructure in DPN rats. Curcumin (50, 100 and 150 mg/kg) reduced SCs apoptosis in sciatic nerves. In addition, curcumin at 150 mg/kg had the best efficacy in increasing protein expression of NGF in sciatic nerves and serum NGF level. Our work demonstrated that curcumin has neuroprotective effects for the treatment of DPN.

Topics: Animals; Curcumin; Diabetes Mellitus; Diabetic Neuropathies; Nerve Growth Factor; Rats; Rats, Sprague-Dawley

Diabetes mellitus (DM), a multifaceted metabolic disorder if not managed properly leads to secondary complications. Diabetic peripheral neuropathy (DPN) is one such complication caused by nerve damage that cannot be reversed but can be delayed. Recently, diabetes patients are using dietary supplements, although there remains a general skepticism about this practice. Curcumin (CUR), one such supplement can help prevent underlying low-grade inflammation in diabetes, but it is plagued by poor oral bioavailability. To better understand the role of bioavailability in clinical outcomes, we have tested double-headed nanosystems containing curcumin (nCUR) on DPN. Because CUR does not influence glucose levels, we have also tested the effects of nCUR combined with long-acting subcutaneous insulin (INS). nCUR with or without INS alleviates DPN at two times lower dose than unformulated CUR, as indicated by qualitative and quantitative analysis of the hind paw, sciatic nerve, spleen, and L4-6 spinal cord. In addition, nCUR and nCUR+INS preserve hind paw nerve axons as evident by the Bielschowsky silver stain and intraepidermal nerve fibers (IENF) density measured by immunofluorescence. The mechanistic studies further corroborated the results, where nCUR or nCUR+INS showed a significant decrease in TUNEL positive cells, mRNA expression of NLRP3, IL-1β, and macrophage infiltration while preserving nestin and NF200 expression in the sciatic nerve. Together, the data confirms that CUR bioavailability is proportional to clinical outcomes and INS alone may not be one of the solutions for DM. This study highlights the potential of nCUR with or without INS in alleviating DPN and warrants further investigation.

Topics: Animals; Curcumin; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Insulin; Insulin, Regular, Human; Rats; Rats, Sprague-Dawley

Topics: Animals; Astrocytes; Curcumin; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Disease Models, Animal; Ganglia, Spinal; JNK Mitogen-Activated Protein Kinases; Male; Rats; Rats, Sprague-Dawley

Neuropathy is a common complication of long-term diabetes. Proposed mechanisms of neuronal damage caused by diabetes that are downstream of hyperglycemia and/or loss of insulin signaling include ischemic hypoxia, inflammation and loss of neurotrophic support. The curcumin derivative J147 is a potent neurogenic and neuroprotective drug candidate initially developed for the treatment of neurodegenerative conditions associated with aging that impacts many pathways implicated in the pathogenesis of diabetic neuropathy. Here, we demonstrate efficacy of J147 in ameliorating multiple indices of neuropathy in the streptozotocin-induced mouse model of type 1 diabetes. Diabetes was determined by blood glucose, HbA1c, and insulin levels and efficacy of J147 by behavioral, physiologic, biochemical, proteomic, and transcriptomic assays. Biological efficacy of systemic J147 treatment was confirmed by its capacity to decrease TNFα pathway activation and several other markers of neuroinflammation in the CNS. Chronic oral treatment with J147 protected the sciatic nerve from progressive diabetes-induced slowing of large myelinated fiber conduction velocity while single doses of J147 rapidly and transiently reversed established touch-evoked allodynia. Conduction slowing and allodynia are clinically relevant markers of early diabetic neuropathy and neuropathic pain, respectively. RNA expression profiling suggests that one of the pathways by which J147 imparts its protection against diabetic induced neuropathy may be through activation of the AMP kinase pathway. The diverse biological and therapeutic effects of J147 suggest it as an alternative to the polypharmaceutical approaches required to treat the multiple pathogenic mechanisms that contribute to diabetic neuropathy.

Topics: AMP-Activated Protein Kinase Kinases; Animals; Anti-Inflammatory Agents, Non-Steroidal; C-Reactive Protein; Curcumin; Diabetic Neuropathies; Disease Models, Animal; Female; Gene Expression Profiling; Gene Expression Regulation; Glycated Hemoglobin; Humans; Insulin; Mice; Nerve Tissue Proteins; Neural Conduction; Pain Threshold; Physical Stimulation; Protein Kinases; Signal Transduction; Streptozocin; Tumor Necrosis Factor-alpha

To investigate the specific molecular mechanisms and effects of curcumin derivative J147 on diabetic peripheral neuropathy (DPN).. We constructed streptozotocin (STZ)-induced DPN rat models to detected mechanical withdrawal threshold (MWT) in vivo using Von Frey filaments. In vitro, we measured cell viability and apoptosis, adenosine 5'-monophosphate-activated protein kinase (AMPK) and transient receptor potential A1 (TRPA1) expression using MTT, flow cytometry, qRT-PCR and western blot. Then, TRPA1 expression level and calcium reaction level were assessed in agonist AICAR treated RSC96cells.. The results showed that J147reduced MWT in vivo, increased the mRNA and protein level of AMPK, reduced TRPA1 expression and calcium reaction level in AITCR treated RSC96 cells, and had no obvious effect on cell viability and apoptosis. Besides, AMPK negative regulated TRPA1 expression in RSC96 cells.. J147 could ameliorate DPN via negative regulation AMPK on TRPA1 in vivo and in vitro. A curcumin derivative J147might be a new therapeutic potential for the treatment of DPN.

Topics: AMP-Activated Protein Kinases; Animals; Apoptosis; Blotting, Western; Calcium; Cell Survival; Cells, Cultured; Curcumin; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Male; Microscopy, Fluorescence; Real-Time Polymerase Chain Reaction; Reproducibility of Results; Streptozocin; Time Factors; TRPA1 Cation Channel

Corneal nerves are mainly derived from the ophthalmic branch of the trigeminal ganglion (TG). Corneal neuropathy contributes to epithelial degenerative changes in diabetic keratopathy. Efficient drug delivery to TG may be beneficial for the treatment of diabetic keratopathy. This article described intranasal delivery of nanomicelle curcumin to correct pathophysiological conditions in TG to promote corneal epithelial/nerve wound healing in streptozotocin-induced diabetic mice. A diabetic mice model with corneal epithelium abrasion was established. Ocular topical and/or intranasal nanomicelle curcumin treatments were performed, and treatment efficacy and mechanisms of action were explored. Results showed that intranasal nanomicelle curcumin treatment promoted corneal epithelial wound healing and recovery of corneal sensation. Enhanced accumulation of reactive oxygen species, reduced free radical scavengers, increased mRNA expressions of inflammatory cytokines, and decreased mRNA expressions of neurotrophic factors in the cornea and TG neuron were observed in diabetic mice with corneal epithelium abrasions. Intranasal nanomicelle curcumin treatment effectively recovered these pathophysiological conditions, especially that of the TG neuron, and a strengthened recovery was observed with ocular topical combined with intranasal treatment. These findings indicated that intranasal curcumin treatment effectively helped promote diabetic corneal epithelial/nerve wound healing. This novel treatment might be a promising strengthened therapy for diabetic keratopathy.

Topics: Administration, Intranasal; Animals; Corneal Diseases; Curcumin; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Epithelium, Corneal; Mice; Micelles; Wound Healing

Type 2 diabetic mellitus (T2DM) has reached pandemic status and shows no signs of abatement. Diabetic neuropathic pain (DNP) is generally considered to be one of the most common complications of T2DM, which is also recognized as one of the most difficult types of pain to treat. As one kind of peripheral neuropathic pain, DNP manifests typical chronic neuralgia symptoms, including hyperalgesia, allodynia, autotomy, and so on. The injured dorsal root ganglion (DRG) is considered as the first stage of the sensory pathway impairment, whose neurons display increased frequency of action potential generation and increased spontaneous activities. These are mainly due to the changed properties of voltage-gated sodium channels (VGSCs) and the increased sodium currents, especially TTX-R sodium currents. Curcumin, one of the most important phytochemicals from turmeric, has been demonstrated to effectively prevent and/or ameliorate diabetic mellitus and its complications including DNP. The present study demonstrates that the TTX-R sodium currents of small-sized DRG neurons isolated from DNP rats are significantly increased. Such abnormality can be efficaciously ameliorated by curcumin.

Topics: Analgesics; Animals; Curcumin; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Ganglia, Spinal; Insulin Resistance; Male; Neuralgia; Neurons; Pain Threshold; Rats, Sprague-Dawley; Sodium Channels; Tetrodotoxin

Along with the development of economy and society, type 2 diabetic mellitus (T2DM) has become one of the most common diseases at the global level. As one of the complications of T2DM, diabetic neuropathic pain (DNP) stubbornly and chronically affects the health and life of human beings. In the pain field, dorsal root ganglion (DRG) is generally considered as the first stage of the sensory pathway where the hyperexcitability of injured neurons is associated with different kinds of peripheral neuropathic pains. The abnormal electrophysiology is mainly due to the changed properties of voltage-gated sodium channels (VGSCs) and the increased sodium currents (I(Na)). Curcumin is an active ingredient extracted from turmeric and has been demonstrated to ameliorate T2DM and its various complications including DNP effectively. The present study demonstrates that the I(Na) of small-sized DRG neurons are significantly increased with the abnormal electrophysiological characteristics of VGSCs in type 2 diabetic neuropathic pain rats. And these abnormalities can be ameliorated efficaciously by a period of treatment with curcumin.

Topics: Animals; Curcumin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Ganglia, Spinal; Neuralgia; Neurons; Rats; Sodium; Voltage-Gated Sodium Channels

Neuropathic pain is one of the most common complications of diabetes mellitus. As efficacy and tolerability of current therapy for neuropathic pain are not ideal, we need to develop the novel drug for better treatment. Curcumin as a natural flavonoid from Curcuma longa has considerable effects on nervous system such as, antidepressant, antinociceptive and neuroprotective effects. The present study was designed to investigate the effect of curcumin on diabetic peripheral neuropathic pain and possible involvement of opioid system. A single dose of 60mg/kg streptozotocin was injected intraperitoneally to induce diabetes in rats. STZ-induced diabetic rats were treated with curcumin (50mg/kg/day) acute and chronically. Thermal hyperalgesia and mechanical allodynia were measured on the days 0, 7, 14 and 21 after diabetes induction as behavioral scores of neuropathic pain. Chronic, but not acute, treatment with curcumin prevents the weight loss and attenuates mechanical allodynia in STZ-induced diabetic rats. Pretreatment with naloxone (1mg/kg) significantly reduced anti-allodynic effect of chronic curcumin in von Frey filament test. Our results suggest that curcumin can be considered as a new therapeutic potential for the treatment of diabetic neuropathic pain and the activation of opioid system may be involved in the antinociceptive effect of curcumin.

Topics: Analgesics, Opioid; Animals; Behavior, Animal; Body Weight; Curcumin; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Hyperalgesia; Male; Naloxone; Narcotic Antagonists; Neuralgia; Phytotherapy; Rats; Rats, Wistar

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are the main enzymes that produce oxidative stress, which plays an important role in painful diabetic neuropathy. Curcumin has been reported to exert an antinociceptive effect in a rat model of diabetic neuropathy by suppressing oxidative stress in the spinal cord. However, it remains unknown whether the mechanism by which curcumin ameliorates diabetic neuropathy can be attributed to spinal NADPH oxidases. This study was designed to determine the effect of curcumin on diabetic neuropathy and to investigate its precise mechanism in relation to NADPH oxidase-mediating oxidative stress in the spinal cord. Diabetic neuropathy was induced in Sprague-Dawley rats by intraperitoneal injection with 1% streptozotocin (STZ; 60 mg/kg). After the onset of diabetic neuropathy, a subset of the diabetic rats received daily intragastric administrations of curcumin (200mg/kg) or intraperitoneal injections of apocynin (2.5mg/kg) for 14 consecutive days, whereas other diabetic rats received equivalent volumes of normal saline (NS). STZ resulted in diabetic neuropathy with hyperglycemia and a lower paw withdrawal threshold (PWT), accompanied by elevations in the expression of the NADPH oxidase subunits p47(phox) and gp91(phox) and in the levels of hydrogen peroxide (H2O2) and malondialdehyde (MDA) and a reduction in superoxide dismutase (SOD) activity (P<0.05) in the spinal cord. Both curcumin and apocynin ameliorated diabetic neuropathy. In conclusion, curcumin attenuated neuropathic pain in diabetic rats, at least partly by inhibiting NADPH oxidase-mediating oxidative stress in the spinal cord.

Topics: Acetophenones; Animals; Antioxidants; Body Weight; Curcumin; Diabetic Neuropathies; Hydrogen Peroxide; Hyperalgesia; Male; Malondialdehyde; NADPH Oxidases; Oxidative Stress; Rats, Sprague-Dawley; Spinal Cord; Streptozocin; Superoxide Dismutase

To investigate the effect ofcurcumin on microvasculature changes in STZ-induced diabetic rat' choroid ofeye.. Male rats were divided into three groups: control (C) Diabetic rats were induced by streptozotocin (STZ) (60 mg/kg BW) (DM) diabetic rats treated with curcumin (DMC) (200 mg/kg BW). After 8 weeks of experiments, microvasculature changes of rat's choroid were studied under vascular corrosion cast technique with scanning electron microscope (SEM).. There were pathology and destruction of choroid microvasculature of DM group that revealed reduced and shrunken sizes of large and small blood vessels, compared with control group; long posterior ciliary arteries (LPCAs) (C = 113.70 +/- 1.38, DM = 83.53 +/- 2.70, DMC = 109.64 +/- 3.41 microm), choroid arteries (C = 94.97 +/- 2.79, DM = 59.36 +/- 2.61, DMC = 80.31 +/- 3.73 microm), vortex veins (C = 74.11 +/- 3.24, DM = 46.71 +/- 2.56, DMC = 64.66 +/- 3.60 microm), and Choriocapillaris (choroidal capillaries) (C = 13.61 +/- 0.62, DM = 4.46 +/- 0.24, DMC = 9.96 +/- 0.70 microm), respectively. In DM group, LPCAs and Choroid arteries were tortuous and showed shrinkage. Vortex veins became narrow. Choriocapillaris showed the pathological characteristics of vascular lesions including of shrinkage, constriction, microaneurysm and blind ending. Fascinatingly, Choroid microvasculature of the eye in curcumin treated group developed into regenerate and repaired conditions with healthy and normal characteristics.. Efficiency of curcumin treatment beneficially repaired and regenerated the redevelopment of choroid's microvascular complications of eye in 8-week experiments. Potential treatment with curcumin in diabetes has demonstrated in a meaningful way the therapeutic consequences in the improvement and recovery of choroidal blood vessels in eye pathology ofdiabetic rats.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Capillaries; Choroid; Curcumin; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Male; Microscopy, Electron, Scanning; Microvessels; Rats

The mechanisms involved in diabetic neuropathic pain are complex and involve peripheral and central pathophysiological phenomena. Proinflammatory tumour necrosis factor α (TNF-α) and TNF-α receptor 1, which are markers of inflammation, contribute to neuropathic pain. The purpose of this experimental study was to evaluate the effect of curcumin on diabetic pain in rats. We tested 24 rats with diabetes induced by a single intraperitoneal injection of streptozotocin and 24 healthy control rats. Twelve rats in each group received 60 mg/kg oral curcumin daily for 28 days, and the other 12 received vehicle. On days 7, 14, 21, and 28, we tested mechanical allodynia with von Frey hairs and thermal hyperalgesia with radiant heat. Markers of inflammation in the spinal cord dorsal horn on day 28 were estimated with a commercial assay and Western blot analysis. Compared to control rats, diabetic rats exhibited increased mean plasma glucose concentration, decreased mean body weight, and significant pain hypersensitivity, as evidenced by decreased paw withdrawal threshold to von Frey hairs and decreased paw withdrawal latency to heat. Curcumin significantly attenuated the diabetes-induced allodynia and hyperalgesia and reduced the expression of both TNF-α and TNF-α receptor 1. Curcumin seems to relieve diabetic hyperalgesia, possibly through an inhibitory action on TNF-α and TNF-α receptor 1.

Topics: Animals; Blood Glucose; Curcumin; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Disease Models, Animal; Down-Regulation; Gene Expression Regulation; Humans; Hyperalgesia; Male; Neuralgia; Rats; Tumor Necrosis Factor-alpha

Curcumin has shown to be effective against various diabetes related complications. However major limitation with curcumin is its low bioavailability. In this study we formulated and characterized self nano emulsifying drug delivery system (SNEDDS) curcumin formulation to enhance its bioavailability and then evaluated its efficacy in experimental diabetic neuropathy. Bioavailability studies were performed in male Sprague Dawley rats. Further to evaluate the efficacy of formulation in diabetic neuropathy various parameters like nerve function and sensorimotor perception were assessed along with study of inflammatory proteins (NF-κB, IKK-β, COX-2, iNOS, TNF-α and IL-6). Nanotechnology based formulation resulted in prolonged plasma exposure and bioavailability. SNEDDS curcumin provided better results against functional, behavioural and biochemical deficits in experimental diabetic neuropathy, when compared with naive curcumin. Further western blot analysis confirmed the greater neuroprotective action of SNEDDS curcumin. SNEDDS curcumin formulation due to higher bioavailability was found to afford enhanced protection in diabetic neuropathy.. In this study the authors formulated and characterized a self-emulsifying drug delivery system for formulation to enhance curcumin bioavailability in experimental diabetic neuropathy. Enhanced efficacy was demonstrated in a rat model.

Topics: Animals; Biological Availability; Curcumin; Diabetic Neuropathies; Drug Delivery Systems; Emulsions; Humans; Male; Nanoparticles; Neuroprotective Agents; Pain; Rats

Diabetic neuropathy is the most common chronic complication of diabetes. The aim of the present study was to evaluate the protective effects of curcumin against neuropathy in gliclazide-treated diabetic rats. Diabetes was induced by an intraperitoneal injection of streptozotocin (45 mg/kg). Diabetic animals were given gliclazide (10 mg/kg, orally) alone or combined with curcumin (100 mg/kg, orally) or gabapentin (30 mg/kg, intraperitoneally as a positive control). Behavioral responses to thermal (hot plate and tail flick) and mechanical (tail pinch) pain, and some biochemical tests (serum glucose, C-peptide, peroxynitrite, lipid peroxides, and tumor necrosis factor-α) were assessed after 5 consecutive weeks of daily treatment. Combined treatment of curcumin with gliclazide significantly increased hot-plate and tail-flick latencies in comparison with that of the diabetic control group. The threshold of mechanical hyperalgesia was also significantly elevated. Serum glucose and C-peptide levels were significantly increased in the combined treatment compared with the diabetic control group, whereas serum levels of peroxynitrite, lipid peroxide, and tumor necrosis factor-α production were significantly decreased. The data suggest that the combination of curcumin with gliclazide may protect against the development of diabetic neuropathy, with favorable effects with respect to the gliclazide/gabapentin combination.

Topics: Amines; Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Glucose; C-Peptide; Curcumin; Cyclohexanecarboxylic Acids; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Drug Therapy, Combination; Gabapentin; gamma-Aminobutyric Acid; Gliclazide; Hyperalgesia; Hypoglycemic Agents; Lipid Peroxides; Male; Pain Threshold; Peroxynitrous Acid; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

Diabetic neuropathic pain, an important microvascular complication in diabetes mellitus, is recognized as one of the most difficult types of pain to treat. The underlying mechanisms of painful symptoms may be closely associated with hyperglycaemia but a lack of the understanding of its proper aetiology, inadequate relief, development of tolerance and potential toxicity of classical antinociceptives warrant the investigation of newer agents to relieve this pain. The aim of the present study was to explore the antinociceptive effect of insulin and its combinations with resveratrol and curcumin in attenuating diabetic neuropathic pain. The study also aimed to examine the effect of these combinations on tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) levels in streptozotocin (STZ) induced diabetic mice. Four weeks after a single intraperitoneal injection of streptozotocin (200 mg/kg), mice were tested in the tail immersion and hot-plate assays. Diabetic mice exhibited significant hyperalgesia along with increased plasma glucose and decreased body weights compared with control mice. Chronic treatment with insulin (10 IU/kg/day, s.c.) and its combinations with antioxidants (resveratrol 20 mg/kg or curcumin 60 mg/kg, p.o.) for 4 weeks starting from the 4th week of STZ injection significantly attenuated thermal hyperalgesia and the hot-plate latencies. There was a significant inhibition of TNF-alpha and NO levels when these drugs were given in combination compared with their effects per se. These results indicate an antinociceptive activity of resveratrol and curcumin and point towards the beneficial effect of these combinations with insulin in attenuating diabetic neuropathic pain, possibly through the participation of NO and TNF-alpha.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Drug Therapy, Combination; Hot Temperature; Insulin; Male; Mice; Nitric Oxide; Pain; Pain Measurement; Phytotherapy; Plant Extracts; Plants, Medicinal; Resveratrol; Stilbenes; Streptozocin; Tumor Necrosis Factor-alpha