The above study justifies diosgenin as a promising candidate in diabetes associated complication through its antioxidant and anti-inflammatory activity.

Epilepsy is a brain disorder characterized by sudden recurrent seizures. Considering the fact that epileptogenesis is a process that affects the quality of life, our goal is to delay the process of epileptogenesis and to increase the latency of epileptic attacks, offering better quality of life to patients. Traditional system of medicines has a promise in some of the medicines, which have been used for the treatment of epilepsy. One such medicinal plant is Eclipta alba (EA). According to Ayurvedic philosophy, the juice of leaves of EA is pounded with garlic and pepper for the treatment of epilepsy. Taking clue from the Ayurvedic system of medicines, we formulated coumarin fraction of EA, namely, coumarin nasal formulation (CNF) for its nasal delivery. CNF was analyzed by using high performance liquid chromatography (HPLC) and ultraviolet absorption spectroscopy for its drug content determination. In vitro drug release studies were performed in simulated nasal electrolyte solution (SNES) maintaining constant pH of 5.5 at 37°C. Irritation by CNF was evaluated using hen’s egg test chorioallantoic membrane (HET-CAM) assay. Formulation was found to be non-irritant in HET-CAM assay. CNF was further assessed in vivo by measuring the progress and attainment of pentylenetetrazole (PTZ) kindling in mice. Neuronal changes were assessed by hematoxylin and eosin (H&E) and Nissl staining technique. Glial fibrillary acidic protein (GFAP) a neuroinflammatory marker and tumor necrosis factor alpha (TNF-α) an inflammatory marker were also measured. CNF (10 mg/kg, nasal route) when given as a pretreatment lowered seizure score and delayed the progression of seizure similar to diazepam. CNF decreased the PTZ induced oxidative damage, TNF-α as well as GFAP levels in the midbrain tissue particularly in hippocampus region. The results suggest that CNF may be a promising therapeutic approach to offer protection from sudden recurrent seizures alone or in combination with current drugs in management of epilepsy.

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Diabetic nephropathy affects approximately 20%-40% of diabetes patients worldwide and is the leading cause of end-stage renal failure. Oxidative stress has been identified as a major causative factor in the development and progression of diabetic nephropathy; Nuclear factor erythroid 2-related factor 2 (Nrf2) activation protects the body against oxidative stress by induction of antioxidant enzymes. The renoprotective effect of ethyl ferulate was investigated in diabetes-induced renal injury. Ethyl ferulate was administered orally at three doses (50 mg/kg, 75 mg/kg, and 100 mg/ kg). Metformin (500 mg/kg, p.o.) was used as a standard. Ethyl ferulate treatment decreased serum advanced glycation end products, glycosylated hemoglobin (HbA1c) levels, renal oxidative stress, tumor necrosis factorα (TNFα) level, and kidney hypertrophy index. It restored serum lipid profile, biomarkers of renal function, and mitigated histopathological signs of renal damage. Immunohistochemistry demonstrated higher Nrf2 protein levels in kidney sections of ethyl ferulate-treated rats. These findings suggest that ethyl ferulate ameliorated hyperglycemia-induced oxidative stress by increasing renal Nrf2 levels, thereby preventing diabetes-induced kidney injury. In conclusion, the present study endorses the usefulness of Nrf2 activators, such as ethyl ferulate, as adjuvant therapy for preventing the diabetic nephropathy.How to cite this article: Kaikini AA, Muke S, Peshattiwar V, Bagle S, Dighe V, Sathaye S. Ethyl ferulate, a lipophilic phenylpropanoid, prevents diabetes-associated renal injury in rats by amelioration of hyperglycemia-induced oxidative stress via activation of nuclear factor erythroid 2-related factor 2. J

Diabetes mellitus is a chronic hyperglycemic condition with deleterious effects on microcirculation, resulting in diabetic complications. Chronic hyperglycemia induces the generation of reactive oxygen species (ROS), which are the key pathological triggers in the development of diabetic complications. ROS are responsible for the activation of various pathways involved in the genesis of diabetic complications, mitochondrial dysfunction, as well as insulin resistance. The review describes normal mitochondrial physiology and abnormal alterations, which occur in response to hyperglycemia. Mitochondrial biogenesis is a highly regulated process mediated by several transcription factors, wherein mitochondrial fusion and fission occur in harmony in a normal healthy cell. However, this harmony is disrupted in hyperglycemic condition indicated by alteration in functions of essential transcription factors. Hyperglycemia-induced mitochondrial dysfunction plays a key role in diabetic complications, pancreatic β-cell dysfunction, as well as skeletal muscle insulin resistance as demonstrated by various in vitro, preclinical, and clinical studies. The review focuses on the various factors involved in mitochondrial biogenesis and maintenance of healthy mitochondrial function. Several phytoconstituents act through these pathways, either directly by stimulating biogenesis or indirectly by inhibiting or preventing dysfunction, and produce a beneficial effect on overall mitochondrial function. These phytoconstituents have enormous potential in amelioration of diabetic complications by restoring normal mitochondrial physiology and need detailed evaluation by preclinical and clinical studies. Such phytoconstituents can be included as nutraceuticals or adjuvant therapy to the mainstream treatment of diabetes.

Background Diabetic retinopathy is a slow progressing complication of diabetes mellitus with multifactorial aetiology affecting approximately 80% of diabetics worldwide. Chronic hyperglycemic milieu of Diabetes induces biochemical changes which contribute to the pathogenesis of Diabetic retinopathy. Objective The present study examined the protective effect of Vasant Kusumakar Ras , an Ayurvedic herbo-mineral formulation, in diabetic retinopathy. Materials and Methods Diabetes was induced in rats by intraperitoneal injection of streptozotocin (45 mg/kg). Rats were kept without any treatment for period of three weeks for induction of Diabetic retinopathy followed by treatment with Vasant Kusumakar Ras (11.25 mg/kg, p.o) for further 5 weeks. Fasting blood glucose levels, lipid profile and HbA1c were determined. Eye tissue homogenates were subjected to biochemical analysis to determine the levels of oxidative stress parameters (superoxide dismutase, catalase, reduced glutathione, lipid peroxidation), vascular endothelial growth factor and aldose reductase activity. Histopathological analysis of retinal tissue was conducted using Hematoxylin and Eosin staining. Results Vasant Kusumakar Ras treatment restored serum lipid profile which was altered in diabetic rats. Treatment with Vasant Kusumakar Ras significantly ameliorated the oxidative stress in eye tissue resulting in decreased lipid peroxidation and increase in endogenous antioxidant levels. Levels of aldose reductase and vascular endothelial growth factor in eye tissue were significantly decreased in Vasant Kusumakar Ras treated rats. Hematoxylin and Eosin staining indicated that the Vasant Kusumakar Ras treatment significantly restored the normal architecture of the retinal tissue. Conclusion Vasant Kusumakar Ras exhibits protective effect and prevents the development of Diabetic retinopathy through its effects on multiple biochemical pathways implicated in pathogenesis of Diabetic retinopathy.

Background:Overactivation of aldose reductase (AR) enzyme has been implicated in the development of various diabetic complications. In the present study, the inhibitory effect of thymol was investigated on AR enzyme and its anti-cataract activity was also examined on isolated goat lens.Materials and Methods:Various concentrations of thymol were incubated with AR enzyme prepared from isolated goat lens. Molecular docking studies were carried out using Schrodinger software to verify the binding of thymol with AR as well as to understand their binding pattern. Further, thymol was evaluated for its anti-cataract activity in high-glucose-induced cataract in isolated goat lens in vitro. Quercetin was maintained as standard (positive control) throughout the study.Results:Thymol showed potent inhibitory activity against goat lens AR enzyme with an IC50 value of 0.65 μg/ml. Docking studies revealed that thymol binds with AR in similar binding pattern as that of quercetin. The high–glucose-induced cataract in isolated goat lens was also improved by thymol treatment. Thymol was also able to significantly (P < 0.001) reduce the oxidative stress associated with cataract.Conclusion:The results suggest that thymol may be a potential therapeutic approach in the prevention of diabetic complications through its AR inhibitory and antioxidant activities.

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