Diabetic Neuropathy: A Repercussion of Vitamin D Deficiency.

Diabetes mellitus is a crucial health issue worldwide. The worldwide ubiquity is 8.8% among adults, which is predicted to rise to 10.4% by 2040. Diabetic neuropathy is a long-term complication associated with the diabetes mellitus condition, which primarily targets Schwann cells, peripheral axons and cell bodies (perikarya) in DRG (dorsal root ganglia). It can be accompanied by different factors such as metabolic factors such as insulin resistance, hypertension, obesity, low HDL level, and hypertriglyceridemia. The etiology of DPN is multifactorial. It is caused by hyperglycemia, micro-angiopathy, HbA1c, duration of diabetes, smoking status, high-density lipoprotein cholesterol and hypertension. Also, increased glucose conditions decrease vitamin D levels. Vitamin D, which is involved in neurotrophins such as NGF (nerve growth factor) and NCH (neuronal calcium homeostasis), plays a neuroprotective role in peripheral nerves. Depletionleads to vitamin D deficiency which further develops peripheral neuropathy in diabetic patients. Accumulation of AGEs (advanced glycation end product) plays a significant role in the pathogenesis of sensory neuronal damage. It contributes to microangiopathy and endoneurial vascular dysfunction in peripheral nerves. With vitamin D supplementation, the neuropathy pain scores were improved.

Formulation and evaluation of SGLT2 inhibitory effect of a polyherbal mixture inspired from Ayurvedic system of medicine.

Background and aim: The ingredients viz., Artemisia roxburghiana, Cissampelos pareira, Stephania glabra, Drimia indica, Roylea cinerea, Tinospora sinensis and Curcuma longa of the present formulation are used to treat diabetes in the Indian traditional medical system. Adopting the concept of multiple herbal mixtures for better therapeutic effects from the ancient Ayurvedic text Sarangdhar Samhita, the present study aimed to develop a polyherbal formulation (PHF) of seven herbs and to evaluate its sodium-glucose cotransporter protein-2 (SGLT2) inhibitory effect on type 2 diabetic rats. Experimental procedure: Streptozotocin (STZ) (60 mg/kg) and nicotinamide (NAM) (120 mg/kg) were intraperitoneally administered to induce type 2 diabetes in Wistar rats. The animals were divided into 5 groups viz. normal control, diabetic control, positive control (dapagliflozin at 0.1 mg/kg) and two test groups (PHF at 250 and 500 mg/kg). Various parameters including blood glucose, serum glutamic pyruvic transaminase (SGPT), serum glutamic-oxaloacetic transaminase (SGOT), bilirubin, triglycerides and creatinine were measured. Results and conclusion: The treatment with PHF (250 and 500 mg/kg) showed a significant (p < 0.05) decrease in blood glucose levels by 56.37% and 58.17%, respectively. The levels of SGOT, SGPT and bilirubin were significantly reduced in PHF-fed diabetic rats. Histopathological examination revealed no major changes in the treated groups as compared to the normal control. The molecular docking study showed strong binding of ß-sitosterol, insulanoline, warifteine, dehydrocorydalmine, taraxerol acetate, lupeol, corydalmine and luteolin to SGLT2 protein. The present study concludes that PHF has promising antidiabetic activity via inhibiting SGLT2 protein without showing any adverse effects.

Antidiabetic effect of aqueous-ethanol extract from the aerial parts of Artemisia roxburghiana.

Artemisia roxburghiana is used for the management of diabetes mellitus in the Indian subcontinent. The present work aimed to validate the traditional claim of the plant in diabetes mellitus. In vitro studies were conducted using α-glucosidase and α-amylase assays whereas streptozotocin-nicotinamide-induced diabetic Wistar rats were used for in vivo study. The aqueous-ethanol extract from the aerial parts was found to exhibit α-glucosidase and α-amylase inhibitory activities with the IC50 values of 31.0 and 17.2 mg/mL, respectively when compared with acarbose (IC50 = 8.6 and 16.25 mg/mL, respectively). The extract showed a significant glucose-lowering effect in diabetic rats at the doses of 200 and 400 mg/kg in a dose-dependent manner, while acarbose (10 mg/kg) was used as a standard. The results revealed that A. roxburghiana aerial parts showed antidiabetic activity via inhibiting α-glucosidase and α-amylase enzymes. The present study also validated the ethnomedicinal claim of the plant in diabetes mellitus.

Anti-atherogenic effect of Nepitrin-7-O-glucoside: A flavonoid isolated from Nepeta hindostana via acting on PPAR - α receptor.

Atherogenic dyslipidemia is a condition and responsible for the induction of major cardiovascular diseases. Traditionally, Nepeta hindostana a medicinal plant commonly used as cardioprotective in Indo-Pak regions has gained importance because of its therapeutic active flavonoid Nepitrin-7-O-glucoside. Flavonoid-glycosides are steroids having the ability to exert specific, decisive action on the cardiac muscle. In the present research work flavonoid, Nepitrin-7-O-glucoside was isolated from methanolic extract via chromatographic techniques. The structure was elucidated and confirmed by different spectral techniques like Mass and 1H NMR spectrometry. Various preclinical atherosclerosis parameters such as lipid levels, SGOT/SGPT, body weight, histology of aorta and heart were estimated and beneficial effect of Nepitrin in high-fat diet (HFD) induced atherosclerosis for six weeks were observed. Outcomes of the preclinical results showed and proved that Nepitrin significantly improved dyslipidemia at an effective dose of 50 mg/kg as compared with HFD control and Simvastatin. Molecular docking showed significant binding affinity towards the target PPAR-α receptor (PDB: 2P54). Further the docked ligands with PDB: 2P54 were exposed to molecular dynamics studies to confirm the dynamic behaviour of PPAR-α receptor. Outcomes of the results of the in-vivo study and molecular dynamics study were in correlation with each-others. Further, it can be concluded that Nepitrin has a potent antiatherogenic agent and act by reducing the lipid levels via acting on PPAR-α receptor and regenerating the damaged cells.

Amelioration of Diabetes mellitus by modulation of GLP-1 via targeting alpha-glucosidase using Acacia tortilis polysaccharide in Streptozotocin-Nicotinamide induced diabetes in rats.

BACKGROUND: Polysaccharides decrease the glucose level by inhibiting α-glucosidase enzyme which further increases the level of GLP-1 (Glucagon-like peptide 1) to increase the insulin level as per earlier reports. OBJECTIVE: Similar hypothesis was designed in present study to investigate the α-glucosidase enzyme inhibition and involvement of GLP-1 in antidiabetic mechanism of Acacia tortilis polysaccharides (AEATP) in diabetic rats. Isolated polysaccharides were analyzed for their chemical nature by using HPLC and FTIR method. MATERIALS AND METHODS: Male albino wistar rats were divided into control, diabetic, diabetic + voglibose, diabetic + glimepiride, diabetic+250, 500, 1000 mg/kg of AEATP, diabetic + glimepiride + voglibose, diabetic + glimepiride+ 250, 500 and 1000 mg/kg AEATP, diabetic + GLP-1 antagonist+250, 500 and 1000 mg/kg AEATP. Plasma glucose, insulin and active GLP-1 levels were measured 15 min after OGTT. Fasting blood glucose, Plasma triglycerides, glycated hemoglobin (HbA1c), Fasting insulin, pancreatic insulin content, ileum and colon GLP-1 content were assessed at 5th week. Association of alpha-glucosidase was also assessed with GLP-1 and insulin. RESULTS: AEATP significantly attenuated hyperglycemia by increasing insulin level in plasma and pancreas and increased active GLP-1 as well as insulin level in diabetic rats after OGTT. GLP-1 content was significantly increased in ileum and colon by inhibiting alpha-glucosidase. Involvement of GLP-1 in antihyperglycemic effect of AEATP was confirmed by using GLP-1 antagonist. Moreover, AEATP significantly improved dyslipidemia in diabetic rats. HPLC analysis of A. tortilis polysaccharide comprised four specific monosaccharides (Rhamnose, Glucuronic acid, glucose and galactose) and FTIR spectrum shown band at 3430.6 cm-1 (O-H stretching), 2940.3 cm-1 (C-H linkage), 1630.4 cm-1 (carbonyl stretching), 1410 cm-1 (uronic acid) and 1030.5 cm-1 (glycosidic linkage). CONCLUSION: It can be concluded that antidiabetic effect of AEATP is through the modulation of GLP-1 level in plasma and intestinal tissue via alpha glucosidase inhibition.

Nephroprotective effect of Curculigo orchiodies in streptozotocin-nicotinamide induced diabetic nephropathy in wistar rats.

BACKGROUND: Chronic hyperglycemia induced oxidative stress and dyslipidemia in diabetic nephropathy may lead to chronic renal damage. Thus, counteracting oxidative stress might represent an interesting approach in alleviating hyperglycemia-induced renal damage. OBJECTIVE: The present experimental work was undertaken to explore nephroprotective efficacy of Curculigo orchiodies in streptozotocin-nicotinamide induced diabetic nephropathy in laboratory animals. MATERIALS AND METHODS: Single intraperitoneal introduction of freshly prepared STZ (65 mg/kg) was used for induction of diabetic nephropathy in rats, 15 min after NAD administration (230 mg/kg; i.p.). The evaluation of nephropathy was done by assessment of serum glucose level, insulin level and renal function test (albumin, urea and creatinine). In addition to this, lipid profile as well as oxidative stress (TBARS, superoxide dismutase, catalase and reduced glutathione) was evaluated. Augmented levels of blood glucose, albumin, urea and creatinine confirmed the development of nephropathic symptoms in rats. After 30 days of STZ administration, different doses (150, 300 mg/kg and 600 mg/kg; p.o.) of hydroalcoholic and ethanolic extracts of C. orchiodies were administered to rats for 45 days. CONCLUSION: Curculigo orchiodes significantly attenuated hyperglycemia induced increase in lipid profile, oxidative stress and normalized the renal functions (albumin, urea and creatinine); attributing to the efficacy of C. orchiodies in diabetic nephropathy. These findings suggest that hydroalcholic and ethanolic extract of Curculigo Orchiodes ameliorated the progression of diabetic nephropathy. The observed nephroprotective effect of C. orchiodes is attributed to its hypoglycemic, antioxidant and anti-hyperlipidemic activity.

Coriandrum sativum improve neuronal function via inhibition of oxidative/nitrosative stress and TNF-α in diabetic neuropathic rats.

ETHNOPHRAMACOLOGICAL RELEVANCE: Coriandrum sativum L. is traditionally acknowledged for its use in inflammatory disorders, altered blood lipid levels, respiratory and digestive problems. AIM OF THE STUDY: The present study investigates possible role of hydro-alcoholic extract of C. sativum (CHA) seeds in the attenuation of indices of diabetic peripheral neuropathy (DPN). MATERIALS AND METHODS: Phytochemical analysis was carried out by employing chromatographic, spectroscopic as well as spectrometric techniques. Diabetes was induced by a single i.p. injection of freshly prepared STZ (65 mg/kg). The indexed markers of DPN, i.e., thermal and mechanical hyperalgesia were found to be prominent on the 60th day of STZ administration. Administration of CHA (100, 200, and 400 mg/kg, p.o.) for 30 days was started on the substantiation of DPN onset. Molecular docking study was performed by targeting TNF-α. RESULTS: Phytochemical analysis revealed the presence of flavonoids, terpenoids, and phenolic acids. Oral administration of CHA considerably attenuated hyperglycemia and decreased pain threshold in diabetic rats as well as modulated oxidative-nitrosative stress. Docking study suggested good affinity of flavonoids when docked into the binding site of TNF-α. CONCLUSION: In conclusion, using STZ model, it was successfully predicted that CHA might be beneficial in diabetes-induced neuropathic pain by inhibiting oxidative/nitrosative stress and inflammatory cytokine.

Molecular Modeling Studies of Halogenated Imidazoles against 14α- Demethylase from Candida Albicans for Treating Fungal Infections.

BACKGROUND: Imidazole is one of the most explored and marketed azole utilized for the treatment of fungal infections. Lanosterol 14α-demethylase (Cytochrome P450DM) is the active target site for azole antifungals. AIM AND OBJECTIVE: This study emphasized on evaluation of a series of halogenated imidazole analogues using molecular docking studies for anti-Candidal activity. Furthermore, the model was refined by molecular dynamic simulation. METHODS: Halogenated imidazole analogues (PS1-PS30) were obtained from literature for the study. The imidazole analogues were prepared using Chem sketch and molecular docking was performed using Molergo Virtual Docker program and ADMET study was carried out by using Accelry's Accord for Excel programme. RESULTS: The docking study indicated that all the imidazole analogues (PS1-PS30) and standard drugs i.e., Ketoconazole, Miconazole and Clotrimazole possessed interaction with protein residue, heme cofactor and water molecule positioned above Heme cofactor of 14α-demethylase. Further, the ADMET study indicated that most of the halogenated imidazoles possessed good absorption, human intestinal absorption, aqueous solubility and blood brain penetration. CONCLUSION: Halogenated imidazole analogues may be used as potential lead molecules as 14α- demethylase inhibitors.

Coriandrum sativum seeds extract mitigate progression of diabetic nephropathy in experimental rats via AGEs inhibition.

Inthe present study, we have demonstrated the phytochemical composition of petroleum ether extract of C. sativum (CPE) seeds by using chromatographic, spectroscopic as well spectrometric analysis. CPE was evaluated for its possible role in mitigation of diabetic nephropathy (DN) in Streptozotocin (STZ)-nicotinamide (NAD) induced type 2 diabetes model. Administration of CPE at doses of 100, 200, and 400 mg/kg for 45 days has produced significant attenuation of elevated biochemical parameters including serum glucose, lipid and creatinine levels. CPE has also reserved albuminuria and elevated creatinine clearance in treated diabetic rats. Advanced glycation end products (AGEs) formation in kidneyswas also considerably reduced along with noteworthy increase in level of superoxide dismutase (SOD), glutathione (GSH), and decrease in lipid peroxidation in terms of thiobarbituric acid reactive species (TBARS). Molecular docking studies were also employed to reveal out the possible mechanism. In conclusion, using STZ-NAD model, we have successfully predicted that by assets of bioactive constituents CPE might inhibit the progression of DN. C. sativum may act as potential adjuvant for antidiabetic therapy and needs to be investigated further.

Ameliorative effect of Cephalandra indica homeopathic preparation in STZ induced diabetic nephropathy rats.

BACKGROUND: Diabetic nephropathy (DN) is the foremost cause of morbidity and has become the most recurrent cause of end-stage renal disease among diabetic patients. Thus, agents having antidiabetic effect along with safety potential in the kidneys would have a higher remedial value. OBJECTIVE: The present study aimed to investigate possible protective effect of homeopathic preparation of Cephalandra indica Mother tincture, 6C and 30 C potencies on DN in Wistar rats. MATERIALS AND METHODS: DN was induced by intraperitoneal injection of STZ (60 mg/kg) 15 min after Nicotinamide (230 mg/kg, i.p.) administration. Rats were divided into six groups (n = 6). Group 1 and 2 was kept normal control and diabetic control respectively whereas Groups 3-5 consist of diabetic nephropathy rats treated with different doses of C. indica Mother tincture, 6C and 30 C potencies for 45 days. Glimepride (10 mg/kg) was used as standard. DN was assessed by determining serum glucose, urea, uric acid, creatinine level and tissue histological examination. Tissue antioxidant enzymes (SOD, GSH, LPO) level was measured to assess the oxidative stress. Also, the level of advanced glycation end products in kidney was determined. RESULTS: Mother tincture, 6C and 30 C potencies of C. indica produced significant attenuation in the biochemical parameters used to assess diabetic nephropathy. Moreover, oxidative stress and AGE's level in kidney was also found to be significantly reduced. CONCLUSION: We conclude that Mother tincture, 6C and 30 C potencies of C. indica confers protective effect against diabetic nephropathy via inhibition of Oxidative stress and AGE's.

An allied approach for in vitro modulation of aldose reductase, sorbitol accumulation and advanced glycation end products by flavonoid rich extract of Coriandrum sativum L. seeds.

Traditional herbal medicines are attaining more popularity and are being widely practiced. Coriandrum sativum L. is one of the oldest herbal medicinal plants valued for its nutritional and medicinal properties. Present investigation was focussed on evaluation of attenuating potential of flavonoid rich extract of C. sativum (FCS) seeds against pathogenic markers of diabetic complications i.e. advanced glycation end products (AGEs), sorbitol and aldose reductase (ALR); by using in-vitro methods. Gas chromatography-mass spectrometry (GC-MS) and Infrared spectroscopy of FCS revealed the presence of different flavonoids. Results demonstrated that FCS has produced 79.80% inhibition of AGEs formation. Additionally, FCS was effective against sorbitol accumulation and ALR inhibition with IC50 values of 221 µg/ml and 6.08 µg/ml respectively. Molecular docking was conducted against three binding site for ALR, RAGEs and sorbitol dehydrogenase to explore their binding interactions with identified flavonoids. The constituents F2, F4 and F6 have shown good binding interactions with all the receptors. The visualisation of the docked complexes revealed the occurrence of hydrophobic forces and hydrogen bonding in receptor and docked constituents. The results were in support with experimental inhibitory activities of FCS against these biomarkers and provide a considerable basis for the identification and development of new inhibitors.

Dillenia indica L. attenuates diabetic nephropathy via inhibition of advanced glycation end products accumulation in STZ-nicotinamide induced diabetic rats.

The present study was aimed to evaluate advanced glycation end products (AGEs) inhibitory activity of alcohol and hydro-alcohol extract (DAE and DHE) of Dillenia indica L. (Family: Dilleniaceae) and its potential in treatment of diabetic nephropathy by targeting markers of oxidative stress. D. indica was evaluated for its in vitro inhibitory activity against formation of AGEs by using bovine serum albumin. Diabetes was induced in male Wistar rats by streptozotocin (65 mg/kg i.p.) 15 min after nicotinamide (230 mg/kg, i.p.) administration. Diabetic rats were treated with different doses of extracts (100, 200 and 400 mg/kg) to analyze their nephroprotective effect. Tissue antioxidant enzymes level was measured along with the formation of AGEs in kidney to assess the effect of D. indica in ameliorating oxidative stress. D. indica showed significant inhibition of AGEs formation in vitro. D. indica produced significant attenuation in the glycemic status, renal parameter, lipid profile and level of antioxidant enzymes proving efficacy in diabetic nephropathy. Moreover, D. indica produced significant reduction in the formation of AGEs in kidneys. The present study concludes that D. indica as a possible therapeutic agent against diabetic nephropathy.

Modulation of Advanced Glycation End Products, Sorbitol, and Aldose Reductase by Hydroalcohol Extract of Lagenaria siceraria Mol Standl in Diabetic Complications: An In Vitro Approach.

Herbal medicines have become a core interest, and they are used widely. Lagenaria siceraria is known for its antihyperglycemic, antidyslipidemic, antioxidant potential, and the present study was designed to explore the possible role of L. siceraria in attenuation of diabetic complications via in vitro modulation of advanced glycation end products (AGEs), sorbitol, and aldose reductase (ALR)-three major biomarkers of diabetic complications. To the best of our knowledge, no study has yet been carried out to explore L. siceraria to inhibit these biomarkers. Hydroalcohol extract of L. siceraria (LHA) was evaluated for its ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydrogen peroxide, nitric oxide, and superoxide radicals, total antioxidant capacity, and reducing-power assay. Antiglycation activity was carried out by bovine serum albumin (BSA) fluorescence method. Sorbitol accumulation was evaluated in red blood cells (RBCs) and ALR1 was obtained from kidney of rat to carry out the study. Quercetin was also quantified by high-performance liquid chromatography (HPLC) analysis with 14.3 mg per 100 g of LHA. LHA exhibited 854 mg/g gallic acid equivalent of phenol content and 104 mg/g quercetin equivalent of flavonoids and was found to be significantly active against the antioxidant assays evaluated. LHA has shown 80.12% inhibition of AGE formation. LHA was found to be effective against sorbitol accumulation and ALR1 inhibition with IC50 198.25 µg/ml and 6.24 µg/ml, respectively. These results reveal that LHA may exert beneficial effects against diabetic complications by its antioxidant and antiglycation potential.

Effect of Kaempferol isolated from seeds of Eruca sativa on changes of pain sensitivity in Streptozotocin-induced diabetic neuropathy.

Generation of excessive reactive oxygen species (ROS) and advanced glycation end products (AGEs), and cellular apoptosis are implicated in the pathogenesis of diabetic neuropathy. Present study was aimed to explore the effect of Eruca sativa and Kaempferol (KP) on hyperalgesia (thermal and mechanical); tactile allodynia, motor nerve conduction velocity (MNCV) and oxidative-nitrosative stress in streptozotocin (STZ) induced experimental diabetes. Neuropathy developed in diabetic rats was evident from a marked hyperalgesia and allodynia; reduced MNCV associated with excess formation of AGEs and ROS. Chronic treatment with E. sativa hydroalcoholic extract (EHA; 100, 200 and 400 mg/kg) and KP (5 and 10 mg/kg) for 30 days starting from the 60th day of STZ administration significantly ameliorated behavioral and biochemical changes linked to diabetic neuropathy. Present study suggested that EHA and KP corrected hyperglycemia and reversed the pain response partially in diabetic rats along via modulating oxidative and nitrosative stress along with reduction of AGEs formation in diabetic rats. Thus E. sativa might be beneficial in chronic diabetes, ameliorate the progression of diabetic neuropathy and may also find application in diabetic neuropathic pain.

Evaluation of effect of alcoholic extract of heartwood of Pterocarpus marsupium on in vitro antioxidant, anti-glycation, sorbitol accumulation and inhibition of aldose reductase activity.

Rising popularity of phytomedicines in various diseased conditions have strengthened the significance of plant-research and evaluation of phytoextracts in clinical manifestations. Pterocarpus marsupium Roxb., a medicinal plant, known for its anti-oxidant and anti-diabetic activity is a rich source of phytochemicals with antihyperglycemic and antihyperlipidemic activities. However, its possible role in diabetic complications is not evaluated yet. The present study explores the possible role of alcoholic extract of heartwood of P. marsupium in the treatment of long-term diabetic complications. The alcoholic extract of P. marsupium was evaluated for advanced glycation-end-products formation, erythrocyte sorbitol accumulation and rat kidney aldose reductase enzyme inhibition at the concentration of 25-400 µg/ml using in-vitro bioassays. Also the phytoextract at the concentration of 10-320 µg/ml was evaluated for its antioxidant potential by in-vitro antioxidant assays which includes, determination of total phenol content; reducing power assay; nitric oxide scavenging activity; superoxide radical scavenging activity; total antioxidant capacity; total flavonoid content; DPPH scavenging activity; and hydrogen peroxide scavenging activity. The alcoholic extract of P. marsupium across varying concentrations showed inhibitory effect as evident by IC50 on advanced glycation-end-products formation (55.39 µg/ml), sorbitol accumulation (151.00 µg/ml) and rat kidney aldose reductase (195.88 µg/ml). The phytoextract also exhibited high phenolic and flavonoid contents with promising antioxidant potential against the antioxidant assays evaluated. The present investigation suggests that the phytoextract showed prominent antioxidant, antiglycation property and, inhibited accumulation of sorbitol and ALR enzyme, thus promising a beneficial role in reducing/delaying diabetic complications.

Chromane isolated from leaves of Dillenia indica improves the neuronal dysfunction in STZ-induced diabetic neuropathy.

ETHNOPHARMACOLOGICAL RELEVANCE: According to the Indian traditional medicine, Dillenia indica L. has shown therapeutic efficacy in various diseases. Fruits and leaves of the plant possess anti-oxidant and anti-inflammatory properties. Reactive oxygen species, formation of advanced glycation end products (AGEs) and apoptosis are implicated in the pathogenesis of diabetic neuropathy. AIM OF THE STUDY: The aim of the present study was to explore the effect of D. indica and its isolate, chromane (CR), on thermal and mechanical hyperalgesia, allodynia, MNCV and oxidative-nitrosative stress in streptozotocin-induced experimental diabetes. MATERIAL AND METHODS: Diabetes was induced by intraperitoneal administration of Streptozotocin (STZ; 65mg/kg) for the development of diabetic neuropathy. Chronic treatment with DAE (100, 200 and 400mg/kg, p.o.) and CR (5 and 10mg/kg, p.o.) for 30 days was started from the 60th day of STZ administration. Development of neuropathy was evident from a marked hyperalgesia and allodynia; reduced MNCV associated with increased formation of AGEs and reactive oxygen species. RESULTS: significantly attenuated behavioral and biochemical changes associated with diabetic neuropathy. Present study suggested that DAE and CR ameliorated hyperglycemia and diabetic neuropathic pain via modulation of oxidative-nitrosative stress and reduction in AGEs formation in the diabetic rats. CONCLUSION: Thus D. indica might be beneficial in chronic diabetics, ameliorate the progression of diabetic neuropathy and may also find application in diabetic neuropathic pain.

Renoprotective effect of Bacopa monnieri via inhibition of advanced glycation end products and oxidative stress in STZ-nicotinamide-induced diabetic nephropathy.

Hyperglycemia and oxidative stress are involved in the development of diabetic nephropathy (DN). This study was designed to evaluate the effect of alcohol and hydroalcohol extract of Bacopa monnieri and stigmasterol isolated from B. monnieri in the treatment of DN. Diabetes was induced in male wistar rats by streptozotocin (65 mg/kg i.p.) 15 min after nicotinamide (230 mg/kg, i.p.) administration. After 30 days, the rats were treated with different doses of extracts (100, 200, and 400 mg/kg) and stigmasterol (5 and 10 mg/kg) for 45 days to analyze their nephroprotective effect and produced significant attenuation in the serum glucose level, uric acid, creatinine, and lipid levels. Moreover, there is improvement in the level of superoxide dismutase (SOD), glutathione (GSH), and decrease in lipid peroxidation in terms of TBARS. The formation of AGEs in kidneys was also significantly reduced. These findings suggest that B. monnieri and its isolate (stigmasterol) might inhibit the progression of DN.

Attenuating Diabetes: What Really Works?

Diabetes mellitus is characterized by loss of glucose homeostasis; altered metabolism of glucose, proteins and lipids. Although a number of effective allopathic medicines are currently available for treatment and management of diabetes, but prevalence of side effects and higher cost poses a big challenge to the goal of pharmacotherapy. Herbs are mine of medicinal agents that are found to be efficacious, cost effective and safe in preventing diabetes and a number of plants have been used in management or treatment of diabetes. Modern pharmacopoeia has a healthy number of plant derived medicines and a large number of medicines from allopathic system are derived from the plant sources. This review aims to assess currently available preclinical and clinical knowledge of medicinal herbs intended for the management of diabetes and their mode of action.

Antidiabetic activity of Acacia tortilis (Forsk.) Hayne ssp. raddiana polysaccharide on streptozotocin-nicotinamide induced diabetic rats.

The present study was designed to investigate the antidiabetic activity of aqueous extract of Acacia tortilis polysaccharide (AEATP) from gum exudates and its role in comorbidities associated with diabetes in STZ-nicotinamide induced diabetic rats. Male albino Wistar rats were divided into control, diabetic control, glimepiride treated (10 mg/kg), and diabetic rats treated with 250, 500, and 1000 mg/kg dose of AEATP groups and fasting blood glucose, glycated hemoglobin, total cholesterol, triglyceride, LDL, VLDL, HDL, SGOT, and SGPT levels were measured. STZ significantly increased fasting blood glucose level, glycated hemoglobin, total cholesterol, triglyceride, LDL, VLDL, SGOT, and SGPT levels, whereas HDL level was reduced as compared to control group. After 7 days of administration, 500 and 1000 mg/kg dose of AEATP showed significant reduction (P < 0.05) in fasting blood glucose level compared to diabetic control. AEATP has also reduced total cholesterol, triglyceride, LDL, VLDL, SGOT, and SGPT levels and improved HDL level as compared to diabetic control group. Our study is the first to report the normalization of fasting blood glucose level, lipid profile, and liver enzyme in AEATP treated diabetic rats. Thus, it can be concluded that AEATP may have potentials for the treatment of T2DM and its comorbidities.

Management of diabetic complications: a chemical constituents based approach.

ETHNOPHARMACOLOGICAL RELEVANCE: Long term hyperglycemia leads to development of complications associated with diabetes. Diabetic complications are now a global health problem without effective therapeutic approach. Hyperglycemia and oxidative stress are important components for the development of diabetic complications. Over the past few decades, herbal medicines have attracted much attention as potential therapeutic agents in the prevention and treatment of diabetic complications due to their multiple targets and less toxic side effects. This review aims to assess the current available knowledge of medicinal herbs for attenuation and management of diabetic complications and their underlying mechanisms. MATERIAL AND METHODS: Bibliographic investigation was carried out by scrutinizing classical text books and peer reviewed papers, consulting worldwide accepted scientific databases (SCOPUS, PUBMED, SCIELO, NISCAIR, Google Scholar) to retrieve available published literature. The inclusion criteria for the selection of plants were based upon all medicinal herbs and their active compounds with attributed potentials in relieving diabetic complications. Moreover, plants which have potential effect in ameliorating oxidative stress in diabetic animals have been included. RESULTS: Overall, 238 articles were reviewed for plant literature and out of the reviewed literature, 127 articles were selected for the study. Various medicinal plants/plant extracts containing flavonoids, alkaloids, phenolic compounds, terpenoids, saponins and phytosterol type chemical constituents were found to be effective in the management of diabetic complications. This effect might be attributed to amelioration of persistent hyperglycemia, oxidative stress and modulation of various metabolic pathways involved in the pathogenesis of diabetic complications. CONCLUSION: Screening chemical candidate from herbal medicine might be a promising approach for new drug discovery to treat the diabetic complications. There is still a dire need to explore the mechanism of action of various plant extracts and their toxicity profile and to determine their role in therapy of diabetic complications. Moreover, a perfect rodent model which completely mimics human diabetic complications should be developed.