In vitro and in vivo antidiabetic effect of extracts of Melia azedarach, Zanthoxylum alatum, and Tanacetum nubigenum.

BACKGROUND: To investigate the antidiabetic effect of Himalayan Medicinal plants from India viz. Melia azedarach (Family: Meliaceae), Zanthoxylum alatum (Family: Rutaceae), Tanacetum nubigenum (Family: Asteraceae) using in-vitro as well as in-vivo approaches. METHODS: Their effects were examined on stimulation of glucose uptake by C2C12 cultured cell line, inhibitory effect on human recombinant Protein tyrosine phosphatase-1B (PTP-1B) and followed by the hypoglycaemic activity of extracts in Streptozotocin (STZ) induced diabetic rats. RESULTS: All prepared extracts had been found to enrich with polyphenolic, flavonoids, terpenoids, anthraquinones and saponins type of compounds. n-Butanol fraction of Zanthoxylum alatum showed maximum PTP-1B inhibition (61.9%) whereas ethanol extract of Tanacetum nubigenum showed strong stimulation of glucose uptake (+61.2%) in C2Cl2 myotubes. In STZ induced Sprague-Dawley rats, significant decrease in blood glucose level was observed in ethanol extract of Melia azaderach treated group as 14.8% (p < 0.01) whereas in the ethanol extract of Tanacetum nubigenum treated group, it was observed as 15.5% (p < 0.01) compare to metformin which showed 26.8% (p < 0.01) lowering of blood glucose in the same time duration of 5 h study. CONCLUSION: This study demonstrated that these plants have a significant therapeutic value in type-2-diabetes mellitus and related complications thus supporting their traditional uses in Indian traditional system of medicine.

Nutrition for diabetic retinopathy: plummeting the inevitable threat of diabetic vision loss.

Diabetic retinopathy (DR) is among the leading causes of preventable blindness. Hyperglycemia, hypertension, hyperlipidemia and anemia majorly predispose its pathogenesis. The current treatment modalities of DR include laser photocoagulation therapy, intravitreal corticosteroids, intravitreal anti-vascular endothelial growth factor (VEGF) agents and vitreo-retinal surgery which are costly, highly invasive, unproven for prolonged use and opted in advanced stages of DR. By then retina already encounters a vast damage. Nutrients by their natural physiological, biochemical and molecular action can preserve retinal structure and functions by interfering with the various pathological steps prompting DR incidence, thereby altering the risk of developing this ocular morbidity. Nutrients can also play a central role in DR patients resistant towards the conventional medical treatments. However due to the byzantine interplay existing between nutrients and DR, the worth of nutrition in curbing this vision-threatening ocular morbidity remains silent. This review highlights how nutrients can halt DR development. A nutritional therapy, if adopted in the initial stages, can provide superior-efficacy over the current treatment modalities and can be a complementary, inexpensive, readily available, anodyne option to the clinically unmet requirement for preventing DR. Assessment of nutritional status is presently considered relevant in various clinical conditions except DR. Body Mass Index (BMI) conferred inconclusive results in DR subjects. Subjective Global Assessment (SGA) of nutritional status has recently furnished relevant association with DR status. By integrating nutritional strategies, the risk of developing DR can be reduced substantially. This review summarizes the subsisting knowledge on nutrition, potentially beneficial for preventing DR and sustaining good vision among diabetic subjects.

Symplocos cochinchinensis enhances insulin sensitivity via the down regulation of lipogenesis and insulin resistance in high energy diet rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: This plant has been utilized in Indian system of medicine for treatment of diabetes. This is clearly evident from the composition of Ayurvedic preparation for diabetes 'Nisakathakadi Kashayam' where this is one of the main ingredients of this preparation AIM OF THE STUDY: The study aims in elucidating the molecular mechanisms underlying the insulin sensitizing effects of Symplocos cochinchinensis ethanol extract (SCE) using a high fructose and saturated fat (HFS) fed insulin resistant rat model. MATERIALS AND METHODS: Experimental groups consisted of normal diet (ND), ND+SCE 500mg/kg bwd, HFS+vehicle, HFS+metformin 100mg/kg bwd, HFS+SCE 250/500mg/kg bwd. Initially the animals were kept under HFS diet for 8 weeks, and at the end of 8 week period, animals were found to develop insulin resistance and dyslipidemia. Post-administration of SCE, metformin or vehicle were carried out for 3 weeks. Gene and protein expressions relevant to insulin signalling pathway were analysed. RESULTS: HFS significantly altered the normal physiology of animals via proteins and genes relevant to metabolism like stearoyl-CoA desaturase (SCD1), sterol regulatory element binding protein 1 (SREBP-1c), fatty acid synthase (FAS), glucose 6 phosphatase (G6Pase), phosphoenol pyruvate carboxykinase (PEPCK), glucose transporter 2 (GLUT2), protein tyrosine phosphatse 1B (PTP1B), peroxisome proliferator activated receptor alpha (PPAR alpha), sirtuin 1 (SIRT1) and glucokinase. SCE administration attenuates the insulin resistance in HFS rat by the down regulation of SCD1 gene expression that modulates SREBP-1c dependent and independent hepatic lipid accumulation. CONCLUSION: SCE enhances insulin sensitivity via the down regulation of lipogenesis and insulin resistance in HFS rat model.

Antidiabetic property of Symplocos cochinchinensis is mediated by inhibition of alpha glucosidase and enhanced insulin sensitivity.

The study is designed to find out the biochemical basis of antidiabetic property of Symplocos cochinchinensis (SC), the main ingredient of 'Nisakathakadi' an Ayurvedic decoction for diabetes. Since diabetes is a multifactorial disease, ethanolic extract of the bark (SCE) and its fractions (hexane, dichloromethane, ethyl acetate and 90% ethanol) were evaluated by in vitro methods against multiple targets relevant to diabetes such as the alpha glucosidase inhibition, glucose uptake, adipogenic potential, oxidative stress, pancreatic beta cell proliferation, inhibition of protein glycation, protein tyrosine phosphatase-1B (PTP-1B) and dipeptidyl peptidase-IV (DPP-IV). Among the extracts, SCE exhibited comparatively better activity like alpha glucosidase inhibition (IC50 value-82.07 ± 2.10 µg/mL), insulin dependent glucose uptake (3 fold increase) in L6 myotubes, pancreatic beta cell regeneration in RIN-m5F (3.5 fold increase) and reduced triglyceride accumulation (22% decrease) in 3T3L1 cells, protection from hyperglycemia induced generation of reactive oxygen species in HepG2 cells (59.57% decrease) with moderate antiglycation and PTP-1B inhibition. Chemical characterization by HPLC revealed the superiority of SCE over other extracts due to presence and quantity of bioactives (beta-sitosterol, phloretin 2'glucoside, oleanolic acid) in addition to minerals like magnesium, calcium, potassium, sodium, zinc and manganese. So SCE has been subjected to oral sucrose tolerance test to evaluate its antihyperglycemic property in mild diabetic and diabetic animal models. SCE showed significant antihyperglycemic activity in in vivo diabetic models. We conclude that SC mediates the antidiabetic activity mainly via alpha glucosidase inhibition, improved insulin sensitivity, with moderate antiglycation and antioxidant activity.

Symplocos cochinchinensis attenuates streptozotocin-diabetes induced pathophysiological alterations of liver, kidney, pancreas and eye lens in rats.

The beneficial effects of hydroethanol extract of Symplocos cochinchinensis (SCE) has been explored against hyperglycemia associated secondary complications in streptozotocin induced diabetic rat model. The experimental groups consist of normal control (NC), diabetic control (DC), DC + metformin 100 mg kg(-1) bwd, DC + SCE 250 and DC + SCE 500. SCEs and metformin were administered daily for 21 days and sacrificed on day 22. Oral glucose tolerance test, plasma insulin, % HbA1c, urea, creatinine, aspartate aminotransferase, alanine aminotransferase, albumin, total protein etc. were analysed. Aldose reductase (AR) activity in the eye lens was also checked. On day 21, DC rats showed significantly abnormal glucose response, HOMA-IR, % HbA1c, decreased activity of antioxidant enzymes and GSH, elevated AR activity, hepatic and renal oxidative stress markers like malondialdehyde, protein carbonyls compared to NC. DC rats also exhibited increased level of plasma urea and creatinine. Treatment with SCE protected from the deleterious alterations of biochemical parameters in a dose dependent manner including histopathological alterations in pancreas. SCE 500 exhibited 46.28% of glucose lowering effect and decreased HOMA-IR (2.47), % HbA1c (6.61), lens AR activity (15.99%), and hepatic, renal oxidative stress and function markers compared to DC group. Considerable amount of liver and muscle glycogen was replenished by SCE treatment in diabetic animals. Although metformin showed better effect, the activity of SCE was very much comparable with this drug.

Effect of high-dose zinc supplementation with oral hypoglycemic agents on glycemic control and inflammation in type-2 diabetic nephropathy patients.

OBJECTIVE: The study aims to evaluate the effect of zinc sulfate on markers of glycemic control, lipid profile and inflammation in type-2 diabetes with microalbuminuria patients. MATERIALS AND METHODS: Type-2 diabetes with microalbuminuria patients on oral hypoglycemic agents (OHA) and angiotensin converting enzyme (ACE) inhibitors were selected and divided into 2 groups: One group (n = 27) continued with OHA alone, second group (n = 27) was on OHA and in addition 50 mg elemental zinc as zinc sulphate supplementation for 12 weeks. Fasting, post-prandial blood glucose, glycosylated hemoglobin, lipid profiles, inflammatory marker hs-CRP and urine microalbumin were measured. RESULTS: There were no significant differences in biochemical status among groups at baseline. After receiving zinc, the mean fasting blood glucose (FBS), post-prandial blood glucose (PPBS) and glycosylated hemoglobin (HbA1c) were decreased significantly (P = 0.0001). Significant decrease was observed in TG (P = 0.002) and VLDL-cholesterol (P = 0.002), whereas there was no significant decrease in TC and LDL-cholesterol. The high-density lipoprotein (HDL) cholesterol was significantly (P = 0.0001) increased from baseline. Zinc supplementation had significant effects in decreasing serum hs-CRP from 10.51 ± 1.68 mg/L to 7.75 ± 1.56 mg/L (P = 0.0001) and microalbumin level from 146.87 ± 30.83 mg/day to 80.70 ± 33.99 mg/day (P = 0.0001). There were no significant changes in the levels of all these parameters in OHA group. CONCLUSION: Our results conclude that supplementation of zinc improved the effectiveness of OHA and may be beneficial in decreasing blood glucose, TG, urinary albumin excretion and inflammation in diabetic nephropathy patients and thus reducing the risk of complications.

Oxidative stress profile in graves' ophthalmopathy in Indian patients.

PURPOSE: To report the oxidative stress profile in patient of Graves' ophthalmopathy and to study the effect of hormone level normalization on oxidative stress profile. METHODS: All first time reporting patients with Graves' ophthalmopathy to Department of ophthalmology CSM Medical University (erstwhile King George's Medical University) Lucknow during the period January 2006 to December 2008 formed the cohort. Before initiating treatment a proforma directed detailed history, complete ophthalmological examination and investigations were done. Blood sample for pro/antioxidant enzyme were withdrawn for study after taking an informed consent. Patients were treated with antithyroid drugs alone to achieve a stable euthyroid status for at least 6 months following which a blood sample was again withdrawn to study the pro/anti oxidant enzyme status following treatment. RESULTS: On normalization of thyroid status the values of reactive oxygen species decreased significantly (p<0.05) and levels of antioxidants also got corrected significantly (p<0.05). However both these values remained significantly (p<0.05) altered as compared to normal persons. CONCLUSION: We demonstrated that even after normalization of thyroid hormone level, the oxidative stress levels remain elevated. Moreover, activity of Superoxide Dismutase (SOD), Catalase (CAT), Glutathione reductase (GSHR), Glutathione peroxidise (GPx) showed decrease which could be attributed to altered metabolism and already prevalent deficiency of essential micronutrients like zinc, copper, mercury, and selenium in the Indian population. Hence, this gives way to the thought that the supplementation of these nutrients may have a role as an adjuvant to hormonal therapy in patients with Graves' ophthalmopathy.