Objective of the present investigation was to study the effect of the flax lignan concentrate (FLC) and Omega-3-fatty acid (O-3-FA) on myocardial apoptosis, left ventricular (LV) contractile dysfunction and electrocardiographic abnormalities in pressure overload-induced cardiac hypertrophy. The rats were divided into five groups such as sham, aortic stenosis (AS), AS+FLC, AS+O-3-FA and AS+FLC+O-3-FA. Cardiac hypertrophy was produced in rats by abdominal aortic constriction. The rats were treated with FLC (400mg/kg, p.o.), O-3-FA (400mg/kg, p.o.) and FLC+O-3-FA orally per day for four weeks. The LV function, myocardial apoptosis, and oxidative stress were quantified. FLC+O-3-FA treatment significantly reduced hemodynamic changes, improved LV contractile dysfunction, reduced cardiomyocyte apoptosis and cellular oxidative stress. Moreover, it significantly up-regulated the VEGF expression and decreased TNF-alpha level in serum. The histological analysis also revealed that FLC+O-3-FA treatment markedly preserved the cardiac structure and inhibited interstitial fibrosis. In conclusion, FLC+O-3-FA treatment improved LV dysfunction, inhibited cardiomyocyte apoptosis, improved myocardial angiogenesis, conserved activities of membrane-bound phosphatase enzymes and suppressed inflammation through reduced oxidative stress in an additive manner than FLC alone and O-3-FA alone treatment in pressure overload-induced cardiac hypertrophy.

The objective of the present investigation was to evaluate the effect of L-glutamine on cardiac myopathy in streptozotocin-nicotinamide induced diabetic rats. Diabetes was induced in overnight fasted Sprague Dawely rats by using intraperitonial injection of streptozotocin (55 mg/kg). Nicotinamide (100 mg/kg, i.p.) was administered 20 min before administration of streptozotocin. Experimental rats were divided into Group I: non-diabetic control (distilled water; 10 ml/kg, p.o.), II: diabetic control (distilled water, 10 ml/kg, p.o.), III: L-glutamine (500 mg/kg, p.o.) and IV: L-glutamine (1000 mg/kg, p.o.). All groups were diabetic except group I. The plasma glucose level, body weight, electrocardiographic abnormalities, hemodynamic changes and left ventricular contractile function, biological markers of cardiotoxicity, antioxidant markers were determined after 4 months after STZ with nicotinamide injection. Histopathological changes of heart tissue were carried out by using H and E stain. L-glutamine treatment improved the electrocardiographic, hemodynamic changes; LV contractile function; biological markers; oxidative stress parameters and histological changes in STZ induced diabetic rats. Results from the present investigation demonstrated that L-glutamine has seemed a cardioprotective activity.

L-glutamine is a non-essential amino acid. It decreased blood sugar, stimulated insulin secretion in type 2 diabetic patients. The objective of the present investigation was to evaluate L-glutamine increases glucagon like peptide-1 (GLP-1) (7-36) amide secretion in streptozotocin-nicotinamide (STZ-NTM) induced diabetic Sprague Dawley rats. Molecular docking study was performed to elucidate the molecular basis for GLP-1 receptor agonistic activity. Type 2 diabetes was induced in overnight fasted Sprague Dawley rats pre-treated with nicotinamide (100 mg/kg, i.p.) followed by 20 min after administration of streptozotocin (55 mg/kg, i.p.). The rats were divided into; I - nondiabetic, II - diabetic control, III - sitagliptin (5 mg/kg, p.o.), IV - L-glutamine (250 mg/kg, p.o.), V - L-glutamine (500 mg/kg, p.o.) and VI - L-glutamine (1000 mg/kg, p.o.). The L-glutamine and sitagliptin treatment was 8 week. Plasma glucose was estimated every week. Body weight, food and water intake were recorded daily. Glycosylated haemoglobin, lipid profile, plasma and colonic active (GLP-1) (7-36) amide, mRNA expression of proglucagon GLP-1, plasma and pancreatic insulin, histology of pancreata and biomarkers of oxidative stress (superoxidase dismutase, reduced glutathione, malondialdehyde, glutathione peroxidase, glutathione S transferase) were measured after 8 week. In acute study, the rats were divided into I - glucose (2.5 g/kg, p.o.), II - sitagliptin (5 mg/kg, p.o.), III - L-glutamine (250 mg/kg, p.o.), IV - L-glutamine (500 mg/kg, p.o.) and V - L-glutamine (1000 mg/kg, p.o.). Plasma glucose, active GLP-1 (7-36) amide concentration and insulin levels were measured after glucose loading. The docking data indicated that l-glutamine bind to the GLP-1 receptor. L-glutamine decreased plasma glucose, increased plasma and pancreatic insulin, increased plasma and colonic active GLP-1 (7-36) amide secretion as well as decreased oxidative stress in streptozotocin-nicotinamide induced diabetic rats.

To evaluate the protective effect of phyllanthin and hypophyllanthin of standardized aqueous extract of Phyllanthus amarus in acetic acid induced colitis model of inflammatory bowel disease in Wistar rats. Rats were rendered colitic by a colonic instillation of 2 ml (4%) acetic acid solution. Rats were pretreated orally for 7 days before induction of colitis with P. amarus (50, 100 and 200 mg/kg) or vehicle (1 ml of distilled water). Colonic inflammation was evaluated by disease activity index, gross morphologic damage, histological injury and different biochemical markers of colonic inflammation such as superoxide dismutase (SOD), reduced glutathione (GSH), malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide (NO) and tumor necrosis factor-α (TNF-α) were performed in colonic contents from colitic rats. DNA damage, a marker of apoptosis was also assessed in colonic contents. The results show that P. amarus (100 and 200 mg/kg) exerted a preventive anti-inflammatory, antioxidant and anti-apoptotic effect in this model of rat colitis, as evidenced by a significant increase in SOD and GSH content as well as reduction of MPO activity, by a decrease of MDA and reduction in NO as well as TNF-α production which is unregulated as a consequence of the inflammatory status. It also significantly decreased the extent of DNA fragmentation. In conclusion, it is strongly suggested that the potent anti-inflammatory and anti-apoptotic effects of P. amarus in rats with acetic acid induced colitis are mediated via the neutrophil infiltration inhibition, inhibition of pro-inflammatory mediator production and reducing DNA damage due to the presence of phyllanthin and hypophyllanthin phytoconstituents which offers a promising means for the treatment of diseases characterized by inflammation of the gastrointestinal tract.

Beneficial effects of dietary flaxseed oil or fish oil on streptozotocin–nicotinamide induced diabetic rats were investigated. Rats were divided into three diabetic and three non-diabetic groups and received control, flaxseed oil or fish oil diets (10%w/w). Both diets reduced blood glucose, TBARS and hepatic NO. The extent of glycation measured in terms of glycated albumin and hemoglobin was reduced significantly with both diets. Flaxseed oil diet up-regulated hepatic catalase (CAT) (activity and expression), superoxide dismutase (SOD) (activity and expression) and glutathione peroxidase (GPx) expression. Fish oil diet up-regulated hepatic CAT (activity and expression), paraoxonase-1 (PON-1) expression and down-regulated heme oxygenase-1 (HO-1) expression. Furthermore, both diets down-regulated the expression of hepatic inflammatory genes TNF-α, IL-6, MCP-1, INF-γ and NF-κB. These results were supported by histopathological observations which showed better tissue preservation in both the diets. Thus, both the diets proved to be beneficial in preventing tissue injury and alleviating diabetic insults in the livers of STZ–NIC diabetic rats.

Dietary omega-3 fatty acids have been demonstrated to have positive physiological effects on lipid metabolism, cardiovascular system and insulin resistance. Type-2 diabetes (T2DM) is known for perturbations in fatty acid metabolism leading to dyslipidemia. Our objective was to investigate beneficial effects of dietary flaxseed oil and fish oil in streptozotocin–nicotinamide induced diabetic rats. Thirty-six adult, male, Wistar rats were divided into six groups: three diabetic and three non-diabetic. Diabetes was induced by an injection of nicotinamide (110 mg/kg) and STZ (65 mg/kg). The animals received either control, flaxseed oil or fish oil (10 % w/w) enriched diets for 35 days. Both diets lowered serum triglycerides and very low-density lipoprotein cholesterol levels and elevated serum high-density lipoprotein cholesterol levels in diabetic rats, while serum total cholesterol and LDL-C levels remained unaffected. Both the diets increased omega-3 levels in plasma and RBCs of diabetic rats. Flaxseed oil diet significantly up-regulated the key transcription factor peroxisome proliferator-activated receptor-α (PPAR-α ) and down-regulated sterol regulatory element-binding protein-1 (SREBP-1) in diabetic rats, which would have increased β-oxidation of fatty acids and concomitantly reduced lipogenesis respectively, thereby reducing TG levels. Fish oil diet, on the contrary lowered serum TG levels without altering PPAR-α while it showed a non-significant reduction in SREBP-1 expression in diabetic rats. Another key finding of the study is the activation of D5 and D6 desaturases in diabetic rats by flaxseed oil diet or fish oil diets, which may have resulted in an improved omega-3 status and comparable effects shown by both diets. The reduced expression of Liver–fatty acid binding protein in diabetic rats was restored by fish oil alone, while both diets showed equal effects on adipocyte fatty acid–binding protein expression. We also observed down-regulation of atherogenic cytokines tumor necrosis factor-α and interleukin-6 by both the diets. In conclusion, dietary flaxseed oil and fish oil have therapeutic potential in preventing lipid abnormalities in T2DM.

The aim of the present investigation was to evaluate the effect of C oenzyme Q 10 and its combination with vitamin E in alcohol‐induced chronic neuropathic pain. Male W istar rats were orally treated with alcohol (10 g/kg, 35% v/v, b.i.d.) for 10 weeks. Coenzyme Q 10 (25, 50, and 100 mg/kg) and vitamin E (100 mg/kg) were coadministered orally for 1 h after ethanol administration for 10 weeks. Various nerve functions, biochemical, and molecular parameters were assessed. Chronic administration of ethanol for 10 weeks resulted significant development of neuropathic pain. Treatment with C oenzyme Q 10 (50 and 100 mg/kg) for 10 weeks showed significant and dose dependently increased in level of nociceptive threshold, endogenous antioxidant, and N a, K ‐ ATP ase enzyme. Coenzyme Q 10 (50 and 100 mg/kg) significantly restored the levels of motor nerve conduction velocity and sensory nerve conduction velocity. It also showed significant decrease in levels of endogenous calcium, oxidative–nitrosative stress, TNF ‐α, IL ‐1β, and IL ‐4 level. Alteration in protein expression of polymerase gamma (pol γ) was significantly restored the C oenzyme Q 10 treatment. The important finding of the study is that, C oenzyme Q 10 (100 mg/kg) and α‐tocopherol (100 mg/kg) combination‐treated rats showed more significant prevention of behavioral, biochemical, and molecular neurotoxic effect of alcohol administration than C oenzyme Q 10 or α‐tocopherol alone treated group. It is evident from the finding of present investigation that plethora of mechanism including inhibition of oxido‐nitrosative stress, release of pro‐inflammatory cytokine, modulation of endogenous biomarker, and protection of pol γ protein expression simultaneously orchestrate to exhibits neuroprotective effect of C oenzyme Q 10, vitamin E and their combination.

The objective of the present study was to investigate antiarrhythmic effect of flax lignan concentrate (FLC) and omega 3 fatty acid (omega) in digoxin induced ventricular arrhythmia and lethality in rats. Male wistar rats (250–300g) were divided into four groups: control (received saline 1mL/kg/day p.o. for 28days); omega (received omega 1mL/kg for 28days); FLC (Animals received FLC 400mg/kg/day p.o. for 28days); FLC+omega (received concomitant treatment of FLC and omega for 28days). On last day, digoxin was infused by jugular vein until the cardiac arrest. Concomitant treatment of FLC and omega significantly increased the concentration of digoxin required to produce ectopic beats (P<0.05), ventricular fibrillation (P<0.05) and cardiac arrest (P<0.01), reduced the serum levels of CKMB (P<0.05), LDH (P<0.01) and restored the activities of endogenous antioxidant enzymes. FLC+Omega treatment showed antiapoptotic effect as evidenced by reduction in myocardial apoptosis. Transmission electron microscopy and histology of heart confirmed cardioprotective effect of concomitant treatment. The mechanism of this protective effect appears to be mediated through conservation of endogenous myocardial antioxidant enzymes and inhibition of apoptotic death of myocardial cells.

Oxidative stress and apoptotic cell death in kidney have been suggested as contributing factors in the development and complication of diabetes especially in diabetic nephropathy (DN). This study investigated the effects of trigonelline (TG) on the renal functional, morphological changes and renal apoptosis in neonatal diabetic rats, a model of non-insulin-dependent diabetes mellitus. Diabetes mellitus was induced in one day old neonatal Wistar rat pups by an intraperitoneal (i.p.) injection of streptozotocin (STZ) (50 mg/kg) and monitored for 16 weeks thereafter. The diabetic rats were divided as follows: the nSTZ diabetic group, the TG (50 mg/kg) treated diabetic group, and the TG (100 mg/kg) treated diabetic group. The age matched nondiabetic group received an injection of citrate buffer (0.1 M, pH 4.5). At the end kidney samples were taken for light microscopic examinations. The levels of serum creatinine and BUN were significantly low in TG (100 mg/kg) treated diabetic rats. Glomerular filtration rate was improved in TG treated rats. The activities of antioxidant enzyme and membrane bound enzyme were decreased and the levels of tumor necrotic factor (TNF-α) and hydroxyproline content were increased in renal tissues of the diabetic group. TG (100 mg/kg/day) treatment for a period of 4 weeks showed significant ameliorative effects on all the biochemical parameters studied. Biochemical findings were supported by histological studies. The degenerative changes in kidney tissue and fibrosis were alleviated in the TG treated groups. These results suggested that TG might have a significant role in alleviating kidney damage in nSTZ-diabetic rats.

Painful peripheral neuropathy induced by chronic ethanol consumption is a major medico-socioeconomical problem. The objective of present investigation was to study the effect of curcumin (20, 40 and 80mg/kg; p.o.) in alcohol-induced neuropathy in rats. Ethanol (35% v/v, 10g/kg; p.o.) was administered for 10 weeks which showed a significant decrease in thermal hyperalgesia, mechanical hyperalgesia, mechanical allodynia and nerve conduction velocity. It caused enhanced malondialdehyde, oxidative-nitrosative stress, total calcium levels, inflammatory mediators (TNF-α and IL-1β levels) along with DNA damage. Co-administration of curcumin and α-tocopherol for 10 weeks significantly and dose-dependently improved nerve functions, biochemical as well as molecular parameters and DNA damage in sciatic nerve of ethanol treated rats. Hence, it was concluded that curcumin is of potent therapeutic value in the amelioration of alcoholic neuropathy in rats and acts by inhibition of pro-inflammatory mediators like TNF-α and IL-1β.

The objective of the present investigation was to study the neuroprotective effect of the quercetin in alcohol induced neuropathy in rats.

Objective:To elucidate the ameliorative effect of liydrualcuholic extract of leaves of Hibiscus rosa sinensis(HRS) in acetic acid induced experimental colitis in male wistar rats.Methods: The animals were administered with 2 mL acetic acid(4%) via intra rectal.The animals were divided into various treatment groups(n=6).Prednisolone was used as standard drug and HRS was administered at a dose of 50,100 and 200 mg/kg p.o.The control group of animals received 1 mL of vehicle(distilled water).Ulcer area,ulcer index,spleen weight,colon weight to length ratio, macroscopic score,haemalological parameters,colonic superoxide dismutase(SOD),glutathione(GSH),myeloperoxidase(MPO),malondialdchyde(MDA),tumor necrosis factor-α(TNK- α), nitric oxide(NO) and histological changes were recorded after the treatment regimen of 11 days. Results:Intrarectal instillation of acetic acid caused enhanced ulcer area,ulcer index,spleen weight,colon weight to length ratio,colonic MPO,MDA,NO and TNF-α It caused significant decreased level of SOD and GSH.Pretreatment with HRS for 7 days exhibited significant effect in lowering of oxidative stress,colonic NO,TNF- α and elevation of SOD and GSH at a dose of 100 and 200 mg/kg in acetic acid induced colilis.Conclusions:The present investigation demonstrates HRS is of potent therapeutic value in the amelioration of expcrimenlal colilis in laboralory animals by inhibiting the proinflammatory mediator like NO and TNK-α.

Pongamia pinnata (L.) Pierre popularly known as ‘Karanj’ or ‘Karanja’ in Hindi, Indian beech in English is a medium-sized glabrous tree. The objective of the present investigation was to evaluate analgesic and anti-inflammatory activity of PPSBAE in laboratory animals. Analgesic activity was carried out by acetic acid-induced abdominal writhing and hot plate test in mice at the dose level of 100, 300 and 1000mg/kg. Anti-inflammatory activity was carried out by carrageenan (acute) and cotton pellet granuloma (chronic) tests in rats. Serum TNF-α and IL-1β were measured by ELISA. The observed results suggested the PPSBAE showed significant analgesic and anti-inflammatory activity. PPSBAE decreased serum TNF-α and IL-1β in acute as well as chronic anti-inflammatory studies.

In previous study, we have reported cycloart-23-ene-3β, 25-diol is an active antidiabetic constituent isolated from stem bark of Pongamia pinnata (Linn.) Pierre. The objective of the present investigation was to evaluate cycloart-23-ene-3β, 25-diol stimulates glucagon like peptide-1 (GLP-1) (7-36) amide secretion in streptozotocin-nicotinamide induced diabetic Sprague Dawley rats. Molecular docking studies were performed to elucidate the molecular basis for GLP-1 receptor agonistic activity. Type 2 diabetes was induced in overnight fasted Sprague Dawley rats pre-treated with nicotinamide (100mg/kg, i.p.) followed by administration of streptozotocin (55 mg/kg, i.p.) 20 min after. The rats were divided into following groups; I- non-diabetic, II- diabetic control, III- sitagliptin (5mg/kg, p.o.), IV- cycloart-23-ene-3β, 25-diol (1mg/kg, p.o.). The cycloart-23-ene-3β, 25-diol and sitagliptin treatment was 8 week. Plasma glucose was estimated every week (week 0 to week 8). Body weight, food and water intake were recorded daily. Glycosylated haemoglobin, lipid profile, plasma and colonic active (GLP-1) (7-36) amide, mRNA expression of proglucagnon GLP-1, plasma and pancreatic insulin, histology of pancreata as well as biomarkers of oxidative stress (superoxidase dismutase, reduced glutathione, malondialdehyde, glutathione peroxidase, glutathione S transferase) were measured after 8th week treatment. In acute study, active GLP-1 (7-36) amide release, plasma glucose and insulin were measured during oral glucose tolerance test. The docking data clearly indicated cycloart-23-ene-3β, 25-diol bind to the GLP-1 receptor. It decreased plasma glucose level, increased plasma and pancreatic insulin level as well as increased plasma and colonic active GLP-1 (7-36) amide secretion in streptozotocin-nicotinamide induced diabetic Sprague Dawley rats.

Diabetes mellitus is a serious debilitating epidemic affecting all social strata in developing as well as developed countries. Diabetic neuropathy is most common of secondary complications associated with diabetes mellitus and is characterized by slowing of nerve conduction velocity, elevated pain, sensory loss and nerve fiber degeneration. The aim of the present investigation was to evaluate the neuroprotective effect of naringin against streptozotocin (STZ) induced diabetic neuropathic pain in laboratory rats. Four weeks after intraperitoneal injection of STZ resulted in significant decrease in mechano-tactile allodynia, mechanical hyperalgesia, thermal hyperalgesia and motor nerve conduction velocity. Activity of endogenous antioxidant like superoxide dismutase as well as membrane bound inorganic phosphate enzyme was also found to be significantly decreased. It not only caused neural cell apoptosis but also enhanced lipid peroxide, nitrite, and inflammatory mediators' (TNF-α) level. Chronic treatment with naringin (40 and 80mg/kg) for 4weeks significantly and dose dependently attenuated the decrease in level of nociceptive threshold, endogenous antioxidant and membrane bound inorganic phosphate enzyme. It also decreased the elevated levels of oxidative–nitrosative stress, inflammatory mediators as well as apoptosis in neural cells significantly and dose dependently. The important finding of the study is that, the naringin–insulin combination not only attenuated the diabetic condition but also reversed the neuropathic pain, whereas insulin or naringin alone only improved hyperglycemia but partially reversed the pain response in diabetic rats. Thus, naringin is a potential flavonone bearing antioxidant, antiapoptotic and disease modifying property acting via modulation of endogenous biomarker to inhibit diabetes induced neuropathic pain.

In developing as well as developed countries, diabetes mellitus is one of the major problems. Oxidative stress plays a vital role in generation and maintenance of the diabetic neuropathy. The aim of present investigation was to study the effect of quercetin (10, 20 and 40mg/kg; p.o.) in n-STZ-induced diabetic neuropathy in rats. Streptozotocin (90mg/kg i.p.) was administered to rat pups of age 2days (10–12g), resultedin significant decrease in mechanical and thermal hyperalgesia, mechanical allodynia, motor and sensory nerve conduction velocity as well as superoxide dismutase, glutathione peroxidase along with membrane bound inorganic phosphate which was confirmed after 6weeks of induction of diabetes. It caused enhanced hyperlipidemia, blood glucose level, glycated hemoglobin, oxidative-nitrosative stress, total calcium levels, inflammatory mediators (TNF-α and IL-1β levels) along with DNA damage. The 8-week treatment of quercetin (10, 20 and 40mg/kg; p.o.) started 6weeks after diabetes induction significantly improved nerve functions, biochemical as well as molecular parameters and DNA damage in sciatic nerve evidence in histological findings that were associated with n-STZ-induced diabetic neuropathic pain. Results of the present investigation suggest the neuroprotective effect of quercetin may be mediated through the inhibition of hyperglycemia and modulation of oxidative-nitrosative stress, pro-inflammatory cytokine (TNF-α and IL-1β) as well as DNA damage.

To evaluate the effect of ethanolic extract of seeds of Linum usitatissimum (EELU) in hyperglycemia associated reactive oxygen species (ROS) production in peripheral blood mononuclear cells (PBMNCs) and pancreatic antioxidant enzymes in alloxan induced diabetic rat. Diabetes was induced in male Wistar rats by alloxan (120 mg/kg, i.p.). After acute and subacute treatment serum glucose was determined. Oral glucose tolerance test (OGTT) was performed in EELU pretreated animals. ROS production in PBMNCs and pancreatic antioxidant enzymes were measured in alloxan induced diabetic rat. Our results showed that, treatment of EELU (200 and 400 mg/kg) significantly reduced serum glucose level in acute and subacute study. The antihyperglycaemic effects of EELU showed onset at 4th h (P<0.001) and peak effect at 6th h (P<0.001). The effect was sustained until 24th h with 400 mg/kg. In subacute study, significant antihyperglycaemic effect was observed from 14th day (P<0.001) onwards. In EELU treated rat the body weight was significantly (P<0.001) increased as compared to diabetic group on 21st day onwards. In OGTT, increased glucose utilization was observed. Treatment of EELU 400 mg/kg showed significant reversal in pancreatic GSH (P<0.01) and SOD (P<0.05) indicating antioxidant nature of EELU. Flow cytometric estimation of total ROS production in PBMNCs in diabetic rats was significantly increased (P<0.001), whereas EELU treatment showed significant (P<0.001) decrease in PBMNCs ROS. It is concluded from the investigation that EELU showed antihyperglycaemic effect mediated through inhibition of ROS level in PBMNCs and preservation of endogenous antioxidant enzymes in pancreatic tissue in alloxan induced diabetic rat.

Hyperglycemia-caused imbalances in metabolic pathways as well as microvascular changes in neuron lead to development of diabetic neuropathy. It is the most common long-term complications of diabetes, affecting 50% of the patient worldwide and characterized by clinical symptoms like elevated levels of allodynia and hyperalgesia, reduced nerve conduction velocity, neuronal hypoxia and nerve fibre degeneration. The aim of present investigation was to determine the therapeutic potential of Coenzyme Q10 and its combination with Pyridoxine in streptozotocin (STZ) induced diabetic neuropathic pain. Intraperitoneal administration of STZ to male Sprague Dawley rats (150–200 g) resulted in significant increase in blood glucose level, cholesterol as well as triglyceride concentration, aldose reductase, glycated Hb, neural calcium level along with oxidative–nitrosative stress and it significantly reduced the level of membrane bound inorganic phosphate enzyme, i.e. Na+K+ATPase. These biochemical alterations resulted in a decrease in mechano-tactile allodynia, mechanical hyperalgesia, thermal hyperalgesia, motor nerve conduction velocity along with sensory nerve conduction velocity and thus the development of diabetic neuropathy. Chronic treatment with Coenzyme Q10 (50 and 100 mg/kg) for 4 weeks significantly and dose dependant attenuated (P < 0.05) this elevated levels of blood glucose, cholesterol as well as triglyceride, aldose reductase, glycated Hb, neural calcium along with endogenous enzymes to reduce oxido-nitrosative stress. Thus, it significantly restored (P < 0.05) the level of nociceptive threshold, motor nerve conduction velocity along with sensory nerve conduction velocity and thus improved STZ-induced diabetic neuropathic pain. Major finding of the investigation was the combination of Coenzyme Q10 (100 mg/kg) along with Pyridoxine (100 mg/kg) showed more significant attenuation of the neuropathic pain than Coenzyme Q10 (100 mg/kg) or Pyridoxine (100 mg/kg) alone treated groups. The combination of Coenzyme Q10 and Pyridoxine not only attenuated the hyperglycemia but also showed the significant decrease in neuropathic pain via inhibition of elevated levels of hyperlipidemia, glycated Hb, oxidative–nitrosative stress as well as elevation in the membrane bound inorganic phosphate enzyme that leads to diminution in the allodynia and hyperalgesia.