Neuropathy In Streptozotocin-induced Diabetic Rats Research Articles

NEUROPROTECTIVE EFFECT OF POLYHERBAL FAST DISSOLVING TABLET OF CURCUMIN, QUERCETIN AND RUTIN AGAINST STREPTOZOTOCIN INDUCED DIABETIC NEUROPATHY IN RODANTS

Purpose: In the Current study we conducted the neuroprotective effect of the Polyherbal combination of curcumin, quercetin and rutin in Streptozotocin-induced Diabetic neuropathy in diabetic rat. Method: In the 12 week study, two different formulations of polyherbal fast dissolving tablets were administered to diabetic rats. Neuropathic pain was assessed in diabetic rats with numerous aching trials and these tests were carried out for the consideration of thermal, mechanical, cold and hot hyperalgesia and nerve co-ordination. At the end of this study, trial animals were sacrificed and examined for biochemical parameters. Result: Animals treated with poly herbal fast dissolving tablet to attenuate hyperglycaemia induced mechanical, thermal hyperalgesia and cold allodynia and improved the biochemical parameters in a dose-dependent manner. Conclusion From this it was conclude that polyherbal fast dissolving tablet of curcumin, quercetin and rutin significantly exhibits the antidiabetic, antioxidant and neuroprotective activities against streptozotocin-induced diabetic neuropathy in rats.

Retracted: Lidocaine Ameliorates Diabetic Peripheral Neuropathy in Streptozotocin-Induced Diabetic Rats through Modulating the c-Jun Signaling Pathway.

[This retracts the article DOI: 10.1155/2022/1888153.].

Lidocaine Ameliorates Diabetic Peripheral Neuropathy in Streptozotocin-Induced Diabetic Rats through Modulating the c-Jun Signaling Pathway.

As one of the common complications of diabetes mellitus (DM), Diabetic Peripheral Neuropathy (DPN) threatens human lives seriously. Emerging evidences have confirmed the protective effects of lidocaine on DPN. However, the possible role and underlying mechanisms of lidocaine in DPN have not been clarified. In this study, the potential role of lidocaine in DPN is explored, and the possible mechanisms are investigated. The rat DPN model is constructed through administration of streptozotocin (STZ, 60 mg/kg). All rats are randomly divided into four groups, including the control group, DPN group, lidocaine (3.78 mg/time) group, and lidocaine combined with the SP600125 (15 mg/kg) group. Mechanical threshold, thermal latency, and blood glucose of rats before and after treatment are detected, and Nerve Conduction Velocity (NCV) is assessed. Moreover, qRT-PCR and western blot assays are carried out to determine the expressions of the c-Jun signaling pathway. The experimental results demonstrate that lidocaine remarkably downregulates the mRNA and protein expressions of the c-Jun signaling pathway in serum and DRGs induced with DPN. Besides, lidocaine combined with SP600125 can obtain better effects than lidocaine alone. It is clearly evident that lidocaine has a certain therapeutic effect on DPN.

Neuroprotective and Hypoglycemic Effects of the Nanoemulsion and Nettle Aqueous Extract on Streptozotocin-Induced Diabetic Neuropathy in Rats: Molecular, Biochemical, and Histological Evidence

Neuroprotective and Hypoglycemic Effects of the Nanoemulsion and Nettle Aqueous Extract on Streptozotocin-Induced Diabetic Neuropathy in Rats: Molecular, Biochemical, and Histological Evidence

Dietary Ginger Root Extract Supplementation Mitigated Diabetic Peripheral Neuropathy in Streptozotocin-Induced Diabetic Rats by Modulating Gut Microbiota

ObjectivesDiabetic peripheral neuropathy (DPN) is a prevalent complication of diabetes with no effective treatment currently. The relationship between gut microbiota and neurological diseases, including DNP, has received increasing attention. Previous studies have shown gingerol-enriched gingerol (GEG) has potential pain-reduction and prebiotic abilities due to its anti-inflammatory capacity. This study examined the effect of GEG on pain sensitivity and gut microbiota in DNP rats. MethodsThirty-three male rats were randomly divided into 3 groups: control group (low-fat diet), DPN group (high-fat diet plus single dose of streptozotocin at 36 mg/kg BW), and DPN + GEG at 0.75% in diet for 6 weeks. Von Frey test was used for for pain assessment. 16S rRNA gene sequencing was done from cecal samples and microbiome data analysis was performed using QIIME 2. ResultsRelative to the control group, the DNP group showed increased pain hypersensitivity, measured as decreased mechanical withdrawal thresholds. GEG supplementation mitigated pain sensitivity in DNP-treated animals. Principal component analysis showed that GEG treatment shifts the microbiome profile from control and DNP samples. Although GEG did not alter the richness of the microbiome, it significantly increased the alpha-diversity in terms of evenness in comparison to DNP (P < 0.05). Using Kruskal–Wallis test followed by the post-hoc Dunn’s test, we identified 9 specific taxa, and their abundance was significantly altered among the control, DNP, and DNP + GEG groups (P < 0.05). In comparison to the control group, the DNP group reduced the relative abundance of Eubacterium coprostanoligenes, Lachnospiraceae, Oscillospiraceae, and Peptococcceae, while DNP increased the abundance of Muribaculum intestinale. Relative to DNP group, the DNP + GEG treatment reversed DNP’s effect and reduced the abundance of Muribaculum intestinale to a level similar to the control group. GEG treatment increased the abundance of Acinetobacter, Azospirillum, Colidextribacter, and Fournierella. ConclusionsThis study demonstrated that GEG supplementation not only reduced pain but also favored the composition of gut microbiome in the DNP model, suggesting targeting gut microbiota by GEG may represent a new therapeutic strategy for the management of DNP. Funding SourcesTexas Tech University Health Sciences Center.

Jinmaitong ameliorates diabetic peripheral neuropathy in streptozotocin-induced diabetic rats by modulating gut microbiota and neuregulin 1.

Jinmaitong (JMT), a compound prescription of traditional Chinese medicine, has long been used as a therapy for diabetic peripheral neuropathy (DPN). However, the neuroprotective mechanisms of JMT and its effect on gut microbiota remained unknown. Here, we examined the effects of JMT on behavior, pathomorphology and gut microbiota in streptozotocin (STZ)-induced DPN rats. Compared to distilled water administration, JMT reversed decreases in mechanical withdraw threshold and intraepidermal nerve fiber density, improved neurological morphology of sciatic nerves, increased serum neuregulin 1 (NRG1) level and contactin-associated protein (Caspr)-positive paranodes, and decreased amyloid precursor protein (APP) accumulation in DPN rats. More importantly, JMT enriched nine species of the gut microbiota of DPN rats, helping to prevent dysbiosis. Among these species, p_Actinobacteria, p_Proteobacteria and c_Actinobacteria were negatively correlated with DPN phenotypes and positively correlated with serum NRG1 level. These results indicate that JMT may exert a neuroprotective effect by modulating phenotype-associated gut microbiota and increasing serum NRG1 level in STZ-induced DPN rats. JMT may therefore be an effective complementary and alternative anti-DPN therapy.

Neuroprotective Effect of Combined Therapy of Liraglutide with Vitamin D on Streptozotocin-Induced Diabetic Neuropathy in Rats.

ABSTRACTBackground:Liraglutide is an incretin mimetic agent that approved recently in type-2 diabetes. The use of vitamin D is associated with an improvement in diabetic neuropathy. The aim of the study: Evaluation of the effect of liraglutide and vitamin D each alone and in combination with each other on diabetic neuropathy induced by streptozotocin in rats. Materials and Methods:Five groups ofWistar rats were used in the experiment. Diabetic neuropathy was induced in groups 2, 3, 4, and 5 using a single intraperitoneal(i.p.) injection of streptozotocin(STZ) in a dose of 60 mg/kg. The third, fourth, and fifth groups were treated for 4 weeks with liraglutide (0.8 mg/kg), vitamin D3 (12 µg/kg), and combination of the 2 drugs, respectively. Then the behavioral tests were done (hot plate, tail-flick, paw withdrawal pressure, and the rotarod tests). Blood samples were used for assessment of blood glucose, tumor necrosis factor -α (TNF-α) and interleukin-Iβ(IL-Iβ). Malondialdehyde(MDA) and glutathione (GSH)were measured in the sciatic nerve homogenate. Results:Liraglutide caused significant improvement in the behavioral tests of the diabetic rats with a significant reduction in blood glucose, TNF-α, IL-1β, and malondialdehyde. Vitamin D caused mild improvement in the behavioral tests, inflammatory and oxidative stress markers. The combined use of liraglutide with vitamin D caused more improvement in diabetic neuropathy tests, inflammatory and oxidative stress markers. Conclusion: Liraglutide has a moderate neuroprotective, anti-inflammatory, and antioxidant effects in cases of streptozotocin-induced diabetic neuropathy which are enhanced by the addition of vitamin D.

Rat Bone Marrow-Derived Mononuclear Cells Outperform Folic Acid in the Treatment of Diabetic Peripheral Neuropathy in Streptozotocin-Induced Diabetic Rats

Background: Diabetes mellitus is the most common cause of peripheral neuropathy, which itself is mediated in part via oxidative stress. Recent studies have used stem-cell-based therapies to regenerate nerve tissues following diabetic neuropathy. Folic acid supplementation promotes neuronal development and protection in some neurological diseases. Aim: This study aims to compare the effects of bone marrow-mononuclear cells (BM-MNCs) and folic acid (FA) in the treatment of peripheral neuropathy in streptozotocin-induced diabetic rats. Methods: Forty adult male albino rats were randomly divided into five groups: Group I (healthy control group); Group II, diabetic group (a single intraperitoneal streptozotocin injection); Group III, diabetic rats that received BM-MNCs; Group IV, diabetic rats that were treated with FA (10 mg/kg/day intraperitoneal injection) for 4 weeks and Group V (FA): Folic Acid-treated group. Random blood sugar was measured for all groups. The animals were euthanized, and the right sciatic nerve was carefully extracted to measure sciatic nerve conduction velocity and processed for histopathological, immunohistochemical (CD68), electron microscopic and morphometric studies. Results: The diabetic group showed progressive histological changes characteristic of neuropathy in the sciatic nerve. Also increased number of CD68-immunopositive cells were detected. In BM-MNC transplantation group, the sciatic nerve sections showed improved histological changes characteristic of neuropathy with a decreased number of CD68-immunopositive cells. The diabetic group treated with FA showed less histological results relative to diabetic rats treated with BM-MNCs. Conclusion: Diabetic rats treated with BM-MNC showed better improvement in diabetic neuropathy than diabetic rats treated with folic acid.

Involvement of ciliary neurotrophic factor in early diabetic retinal neuropathy in streptozotocin-induced diabetic rats

ObjectiveCiliary neurotrophic factor (CNTF) has been evaluated as a candidate therapeutic agent for diabetes and its neural complications. However, its role in diabetic retinopathy has not been fully elucidated.MethodsThis is a randomized unblinded animal experiment. Wistar rats with streptozocin (STZ)-induced diabetes were regularly injected with CNTF or vehicle control in their vitreous bodies beginning at 2 weeks after STZ injection. A total of five injections were used. In diabetic rats, the levels of CNTF and neurotrophin-3 (NT-3) were evaluated by enzyme-linked immunosorbent assays (ELISA) and real-time PCR. The abundance of tyrosine hydroxylase (TH) and β-III tubulin was detected by western blot. Transferase-mediated dUTP nick-end labeling staining (TUNEL) was used to detect cell apoptosis in the retinal tissue. The activation of caspase-3 was also measured.ResultsThe protein and mRNA levels of CNTF in diabetic rat retinas were reduced compared to control rats. In addition, retinal ganglion cells (RGCs) and dopaminergic amacrine cells appeared to undergo degeneration in diabetic rat retinas, as revealed by transferase-mediated dUTP nick-end labeling staining (TUNEL). Tyrosine hydroxylase (TH) and β-III tubulin protein levels also decreased significantly. Intraocular administration of CNTF rescued RGCs and dopaminergic amacrine cells from neurodegeneration and counteracted the downregulation of β-III tubulin and TH expression, thus demonstrating its therapeutic potential.ConclusionOur study suggests that early diabetic retinal neuropathy involves the reduced expression of CNTF and can be ameliorated by an exogenous supply of this neurotrophin.

Nebivolol, a β-blocker abrogates streptozotocin-induced behavioral, biochemical, and neurophysiological deficit by attenuating oxidative-nitrosative stress: a possible target for the prevention of diabetic neuropathy.

Metabolic abnormalities including hyperglycemia, hyperlipidemia, and oxidative-nitrosative stress are involved in the progression of diabetic neuropathy. In the present study, we targeted oxidative-nitrosative stress using nebivolol, a β1-receptor antagonist with vasodilator and antioxidant property, to evaluate its neuroprotective effect in streptozotocin-induced diabetic neuropathy in rats. Diabetic neuropathy develops within 4-6weeks after administration of streptozotocin (55mg/kg, i.p.). Therefore, after confirmation of diabetes, subtherapeutic doses of nebivolol (1 and 2mg/kg, p.o./day) were given to diabetic rats for 8weeks. Nebivolol treatment significantly improved thermal hyperalgesia, grip strength, and motor coordination. Nebivolol also reduced levels of malondialdehyde, tumor necrosis factor-α, and nitrite in diabetes. Moreover, nebivolol increased the levels of superoxide dismutase and catalase in sciatic nerve homogenate of diabetic rats. Further, nebivolol exerted positive effects on lipid profile, sciatic nerve's morphological changes and nerve conduction velocity in diabetic rats. Results of the present study suggest the neuroprotective effect of nebivolol through its antioxidant, nitric oxide-potentiating, and antihyperlipidemic activity.

Effects of moderate exercise training and detraining on diabetic peripheral neuropathy in streptozotocin-induced diabetic rats

Context Exercise training programs have been shown to have prophylactic effects on diabetes-associated complications in murine models. Objective The present study aimed to elucidate the effect of moderate exercise training for 4 weeks and detraining for 2 weeks on diabetic peripheral neuropathy in type 1 diabetic rat model. Materials and methods Type 1 diabetes was induced by a single intraperitoneal injection of streptzotocin (45 mg/kg). Exercise training lasted for 4 weeks in trained group, whereas the detrained group stopped training for 2 weeks after training for 4 weeks. After 4 weeks, tail flick test latency, body weight, serum glucose, inflammatory markers, and nerve growth factor levels were measured, and the same was done in detrained diabetic rats after 2 weeks of detraining. Results Moderate exercise training for 4 weeks increased significantly tail flick latency and nerve growth factor levels, whereas the inflammatory markers were significantly improved compared with diabetic sedentary rats. Interestingly, the prophylactic effects of exercise training were maintained in the detrained rats after 2 weeks of detraining. Conclusion Our results explore the prophylactic mechanisms underlying the exercise training in diabetic peripheral neuropathy rat model and give further insights into the maintained prophylactic effects that lasted after 2 weeks of detraining.

Maltol, a food flavor enhancer, attenuates diabetic peripheral neuropathy in streptozotocin-induced diabetic rats.

Maltol (3-hydroxy-2-methy-4-pyrone), a potent antioxidative agent, typically is used to enhance flavor and preserve food. This study evaluated its effects on preventing diabetic peripheral neuropathy (DPN) in streptozotocin (STZ)-induced diabetic rats and explored its mechanisms. We intraperitoneally injected Sprague-Dawley (SD) rats with STZ (65 mg kg-1, ip) and treated the rats with different doses of maltol after 4 weeks of injection. During treatment, we evaluated motor nerve conduction velocity (MNCV) and thermal and mechanical hyperalgesia and assayed the oxidative stress, Na+-K+-ATPase activity, and apoptosis. Repeated treatment with maltol for 12 weeks significantly improved thermal and mechanical hyperalgesia, increased the MNCV, elevated the Na+-K+-ATPase activity, and ameliorated oxidative stress and apoptosis in STZ-induced diabetic rats. We coincubated RSC96 cells, a Schwann cell line, with maltol and hydrogen peroxide (H2O2, 0.6 mM). Evidently, maltol increased cell viability and inhibited apoptosis after injury by H2O2. Maltol was demonstrated to prevent DPN development and may provide a new alternative for the treatment of DPN.

Effects of Exercise on Neuropathy in Streptozotocin-Induced Diabetic Rats.

ObjectiveTo evaluate the effects of early regular exercise and to assess the electrophysiological and histopathological findings of the rat tail nerve in relation to the timing of exercise training for swimming exercise in rats with diabetic neuropathy.MethodsWe used 70 Sprague-Dawley male rats, and the experimental group comprised 60 rats, and the control group comprised 10 rats. Diabetes was induced by intraperitoneal injection of streptozotocin. Blood glucose concentrations were measured in tail vein blood samples. The experimental group was divided into 6 subgroups according to insulin treatment and swimming exercise: group 1, diabetic control; group 2, insulin treated; group 3, insulin untreated with early swimming exercise; group 4, insulin treated and early swimming exercise; group 5, insulin treated and late swimming exercise; and group 6, insulin untreated with late swimming exercise. Sensory and motor nerve conduction studies were performed weekly up to the 13th week using rat tail nerves. The effect on structural diabetic neuropathy was assessed by morphometry and ultrastructural examination of the rat tail nerve fiber at the 14th week.ResultsAn exercise effect was observed in the insulin treated groups, but it was not observed in the insulin untreated groups. The sensory nerve conduction study in the rat tail revealed significantly prolonged latency and decreased amplitude in groups 1 and 6, and a further delay was observed in group 5 when compared to group 4. Decreased thickness of myelin was found in groups 1 and 6 through morphometry.ConclusionEarly regular exercise programs in addition to conventional insulin treatment may retard the progression of diabetic peripheral neuropathy.

Preventive Effects of the Chinese Herbal Medicine Prescription Tangkuei Decoction for Frigid Extremities on Sciatic Neuropathy in Streptozotocin-Induced Diabetic Rats.

Ischemia and hypoxia are important physiological changes in diabetic peripheral neuropathy (DPN). Chinese herbal medicine prescription Tangkuei Decoction for Frigid Extremities (TDFE) is useful for increasing blood flow. To help determine whether TDFE could protect the peripheral nerves of diabetic patients from the degeneration caused by high blood glucose, TDFE was administered to streptozotocin-induced diabetic rats for 6 or 12 weeks. Plantar thermal stimulation reaction time thresholds, sciatic nerve conduction velocities, and the levels of HIF-1α mRNA, HIF-1α protein, VEGF protein, and the endothelial marker vWF in sciatic nerves were measured at the end of the sixth and twelfth weeks. The thermal thresholds and sciatic nerve conduction velocities of the rats differed after 12 weeks, and the sciatic nerves of the diabetic rats that were given TDFE displayed higher levels of HIF-1α protein, VEGF protein, and HIF-1α mRNA than those of the diabetic model rats. The results at 6 weeks differed from those at 12 weeks. These results suggest that the early preventive application of TDFE effectively delayed the development of DPN and that TDFE increased HIF-1α mRNA levels in the sciatic nerves of diabetic rats through 12 weeks of treatment.

Neuroprotective effects of Gymnema sylvestre on streptozotocin-induced diabetic neuropathy in rats.

The application of traditional medicine for diabetes and associated complications, such as diabetic neuropathy (DN), has received increasing attention. The aim of the present study was to investigate the potential ameliorative effect of Gymnema sylvestre (Gs) in a rat model of DN. Diabetes was induced via a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg). Treatment with Gs extract (50 or 100 mg/kg/day) began two weeks following the administration of STZ and was continued for five weeks. Pain threshold behavior tests were performed subsequent to the five-week Gs treatment period. In addition, the serum levels of glucose, insulin and proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, were determined. Furthermore, the sciatic tissue levels of nitric oxide, thiobarbituric acid reactive substances and reduced glutathione were determined, as well as the activity levels of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. Levels of insulin-like growth factor (IGF), nerve growth factor (NGF), TNF-α, IL-1β and IL-6 were also assessed in the sciatic tissue. In addition, the sciatic nerve tissue samples were analyzed for histopathological alterations. The diabetic rats exhibited apparent reductions in the paw-withdrawal (31%; P<0.01) and tail-flick latencies (38%; P<0.05). Furthermore, the diabetic rats demonstrated an evident elevation in serum and sciatic levels of proinflammatory cytokines. Measured oxidative stress biomarkers were significantly altered in the sciatic nerve tissue of the diabetic rats. Treatment with Gs attenuated diabetes-induced modifications with regard to the levels of serum glucose, insulin and proinflammatory cytokines. In the sciatic nerve tissue, the diabetes-induced alterations in IL levels and oxidative stress biomarkers were significantly improved in the Gs-treated rats. Furthermore, the reduction in the sciatic tissue expression levels of IGF and NGF was also ameliorated by Gs treatment. Histological analysis indicated that Gs corrected the sciatic tissue in the diabetic rats. Therefore, the results demonstrated that the neuroprotective effect of Gs may be associated with the inhibitory effect on the excessive activation of inflammatory molecules and oxidative stress mediators.

Effects of Icariside II on corpus cavernosum and major pelvic ganglion neuropathy in streptozotocin-induced diabetic rats.

Diabetic erectile dysfunction is associated with penile dorsal nerve bundle neuropathy in the corpus cavernosum and the mechanism is not well understood. We investigated the neuropathy changes in the corpus cavernosum of rats with streptozotocin-induced diabetes and the effects of Icariside II (ICA II) on improving neuropathy. Thirty-six 8-week-old Sprague-Dawley rats were randomly distributed into normal control group, diabetic group and ICA-II treated group. Diabetes was induced by a one-time intraperitoneal injection of streptozotocin (60 mg/kg). Three days later, the diabetic rats were randomly divided into 2 groups including a saline treated placebo group and an ICA II-treated group (5 mg/kg/day, by intragastric administration daily). Twelve weeks later, erectile function was measured by cavernous nerve electrostimulation with real time intracorporal pressure assessment. The penis was harvested for the histological examination (immunofluorescence and immunohistochemical staining) and transmission electron microscopy detecting. Diabetic animals exhibited a decreased density of dorsal nerve bundle in penis. The neurofilament of the dorsal nerve bundle was fragmented in the diabetic rats. There was a decreased expression of nNOS and NGF in the diabetic group. The ICA II group had higher density of dorsal nerve bundle, higher expression of NGF and nNOS in the penis. The pathological change of major pelvic nerve ganglion (including the microstructure by transmission electron microscope and the neurite outgrowth length of major pelvic nerve ganglion tissue cultured in vitro) was greatly attenuated in the ICA II-treated group (p < 0.01). ICA II treatment attenuates the diabetes-related impairment of corpus cavernosum and major pelvic ganglion neuropathy in rats with Streptozotocin-Induced Diabetes.

Assessment of diabetic peripheral neuropathy in streptozotocin-induced diabetic rats with magnetic resonance imaging

To determine the role of magnetic resonance (MR) imaging and quantitative T2 value measurements in the assessment of diabetic peripheral neuropathy (DPN). Sequential MR imaging, T2 measurement, and quantitative sensory testing of sciatic nerves were performed in streptozotocin-induced diabetic rats (n = 6) and normal control rats (n = 6) over a 7-week follow-up period. Histological assessment was obtained from 48 diabetic rats and 48 control rats once weekly for 7weeks (n = 6 for each group at each time point). Nerve signal abnormalities were observed, and the T2 values, mechanical withdrawal threshold (MWT), and histological changes were measured and compared between diabetic and control animals. Sciatic nerves in the diabetic rats showed a gradual increase in T2 values beginning at 2weeks after the induction (P = 0.014), while a decrease in MWT started at 3weeks after the induction (P = 0.001). Nerve T2 values had a similar time course to sensory functional deficit in diabetic rats. Histologically, sciatic nerves of diabetic rats demonstrated obvious endoneural oedema from 2 to 3weeks after the induction, followed by progressive axonal degeneration, Schwann cell proliferation, and coexistent disarranged nerve regeneration. Nerve T2 measurement is potentially useful in detecting and monitoring diabetic neuropathy. • Sciatic nerves in diabetic rats showed a gradual increase in T2 values • Nerve T2 values were negatively correlated with sensory function impairment • Longitudinal T2 values can be used to monitor the disease progress • Nerve degeneration contributed mainly to progressive prolongation of nerve T2 values.

Neuroprotective effect of a triterpenoid saponin isolated from Momordica cymbalaria Fenzl in diabetic peripheral neuropathy

Objectives:To investigate the neuroprotective potential of a saponin isolated from the roots of Momordica cymbalaria against peripheral neuropathy in streptozotocin-induced diabetic rats.Materials and Methods:A steroidal saponin (SMC) was isolated from M. cymbalaria Fenzl and purified by preparative high-performance liquid chromatography. Diabetes was induced in male Wister rats by injecting streptozotocin 45 mg/kg. Diabetic rats were divided into six groups for neuroprotective effect—three each for preventive and curative groups. Neuropathic analgesia was assessed by tail-flick and hot-plate methods. Dorsal root ganglion (DRG) neurons and sciatic nerves were isolated, and histopathological analysis was performed. Antioxidant activity (superoxide dismutase, catalase, and inhibition of lipid peroxidation) of the saponin was also carried out on the isolated DRG neurons and sciatic nerves to assess total oxidative stress.Results:In both preventive and curative protocols, rats administered with SMC showed significant decrease in tail immersion latency time and increase in pain sensitivity when compared to diabetic control group. There was improvement in the myelination and degenerative changes of the nerve fiber in both the groups, and an obvious delay in the progression of neuropathy was evident. SMC treatment showed significant decrease in superoxide dismutase, catalase activity, and lipid peroxidation in the nerves.Conclusions:The steroidal saponin of M. cymbalaria (SMC) possesses potential neuroprotective effect in diabetic peripheral neuropathy with respect to neuropathic analgesia, improvement in neuronal degenerative changes, and significant antioxidant activity.

The effect of lithium on painful diabetic neuropathy in streptozotocin-induced diabetic rats

Background: Lithium is widely used in treatment of bipolar disorder as a mood stabilizer. Recently, increasing body of evidences report the neuroprotective effects of lithium against cell injuries caused by different noxious stimuli in cultured cells and animal model of neurodegenerative diseases.

Inhibition of AGEs formation by natural products

Since advanced glycation end-products (AGEs) inhibitors such as benfotiamine, pyridoxamine and aminoguanidine significantly inhibit the development of retinopathy and neuropathy in streptozotocin-induced diabetic rats, treatment with AGEs inhibitors is believed to be a potential strategy for preventing lifestyle-related diseases such as diabetic complications and atherosclerosis. Furthermore, preventive medicine is the most important approach to preventing lifestyle-related diseases, and improving daily nutritional intake is thought to prevent the pathogenesis of such diseases. Therefore, AGEs inhibitors that can be obtained from daily meals are preferred to prescribed drugs. In this article, we describe a strategy for developing new AGEs inhibitors from natural products.