Advanced integrative molecular platform for high-throughput screening of drug-resistant tuberculosis.

A real time-polymerase chain reaction-based test in lyophilized form, was developed to simultaneously identify Mycobacterium tuberculosis complex (MTC) by targeting IS6110, rrs as dual markers, as well as mutations causing rifampicin and isoniazid resistance. The test was evaluated for pulmonary and non-pulmonary specimens from sample isolation to PCR analysis. The test demonstrated limit of detection of 25 CFU/mL for MTB, 200 CFU/mL for rpoB and inhA/katG targets with >95 % CI. The specificity for MTC was supported by a comprehensive clinical validation (n = 100). This load-and-go molecular platform, with features of high throughput, long shelf-life, room temperature storage provides simultaneous detection of MTC and its drug-resistant mutations in minimal time. The test named "PathoDetect TM MTB-RIF and INH resistance detection kit" has been approved by Central Drugs Standard Control Organisation, Indian Council of Medical Research and would have implications for tuberculosis elimination programs.

Placental neurotrophin levels in gestational diabetes mellitus.

OBJECTIVE: Neurotrophins are known to influence the development and maturation of the feto-placental unit and affect fetal growth trajectories. This study reports the levels of nerve growth factor (NGF) and brain-derived growth factor (BDNF) in the placenta of women with gestational diabetes mellitus (GDM). METHODS: A total number of 60 women with GDM and 70 women without GDM (non-GDM) were included in the study. Placental NGF and BDNF levels were measured using commercially available ELISA kits. RESULTS: Placental NGF levels were lower (p < .05) in women with GDM compared to non-GDM women. Maternal body mass index (BMI), mode of delivery, and the gender of the baby influenced the placental NGF levels. Placental BDNF levels were similar in GDM and non-GDM women. There was an influence of baby gender on the placental BDNF levels while maternal BMI and mode of delivery did not show any effect. In regression models adjusted for maternal age at delivery, gestational age, maternal BMI, mode of delivery, and baby gender, the placental NGF levels in the GDM group were lower (-0.144 pg/ml [95% CI -0.273, 22120.016] p = .028) as compared to the non-GDM group. However, there was no difference in the BDNF levels between the groups. CONCLUSION: This study for the first time demonstrates differential effects on neurotrophic factors such as BDNF and NGF in the placenta in pregnancies complicated by GDM. Alterations in the levels of placental neurotrophins in GDM deliveries may affect placental development and fetal brain growth. This has implications for increased risk for neurodevelopmental pathologies in later life.

Placental lipid metabolism in preeclampsia.

OBJECTIVES: The current study examines the placental and maternal lipid profile and expression of genes involved in placental lipid metabolism in women with preeclampsia. METHODS: The current study includes normotensive control women (n = 40) and women with preeclampsia (n = 39). Preeclampsia women were further classified into women delivering at term preeclampsia (T-PE; n = 15) and preterm preeclampsia (PT-PE; n = 24). RESULTS: There were no significant differences in maternal lipid profile between the T-PE and normotensive control groups. Maternal plasma VLDL (P < 0.05) and ratios of total cholesterol : HDL (P < 0.05), atherogenic index [log (triglycerides/HDL)] (P < 0.01) and apolipoprotein B : apolipoprotein A (P < 0.05) were higher in the PT-PE group as compared with the normotensive control group. Placental total cholesterol and HDL levels were higher (P < 0.05) in the T-PE as compared with the normotensive control group. Higher placental triglycerides (P < 0.05) were observed in PT-PE group compared with T-PE group. Placental mRNA levels of peroxisome proliferator activated receptor α, carnitine palmitoyl transferase-1, cluster of differentiation 36 and lipoprotein lipases were lower (P < 0.05) in the PT-PE than normotensive control group. A negative association of mRNA levels of peroxisome proliferator activated receptor α (r = -0.246, P = 0.032; r = -0.308, P = 0.007, respectively), carnitine palmitoyl transferase-1 (r = -0.292, P = 0.011; r = -0.366, P = 0.001), lipoprotein lipases (r = -0.296, P = 0.010; r = -0.254, P = 0.028) with SBP and DBP was observed. There was a positive association of placental triglycerides (r = 0.244, P = 0.031) with DBP. CONCLUSION: Women with preeclampsia exhibit higher lipid : lipoprotein ratios suggesting an atherogenic state particularly in women delivering preterm. Lower expression of genes involved in placental fatty acid oxidation and transport was also observed in preeclampsia.

Cross talk of vascular endothelial growth factor and neurotrophins in mammary gland development.

During the period of lactation, there is extensive growth and development of the mammary gland in order to fulfil the increased demands of milk for the growing infant. Angiogenesis plays a key role in alveolar development and facilitates optimal milk production. Vascular endothelial growth factor (VEGF) is one of the key growth factors regulating angiogenesis in mammary gland. Apart from VEGF, neurotrophins are also known to regulate angiogenesis through direct or indirect mechanisms. Few studies have demonstrated mRNA levels of neurotrophins and their receptors in mammary gland both in humans and rodents. A cross talk between VEGF and neurotrophins has been described in placental development. The enteric and central nervous system are not fully developed at birth, making it imperative to have appropriate levels of angiogenic factors and neurotrophins during postnatal period. The current review summarises studies which describe the role of neurotrophins and angiogenic factors in the mammary gland development.

Maternal fats and pregnancy complications: Implications for long-term health.

Pregnancy imposes increased nutritional requirements for the well being of the mother and fetus. Maternal lipid metabolism is critical for fetal development and long-term health of the offspring as it plays a key role in energy storage, tissue growth and cell signaling. Maternal fat composition is considered as a modifiable risk for abnormal lipid metabolism and glucose tolerance during pregnancy. Data derived from observational studies demonstrate that higher intake of saturated fats during pregnancy is associated with pregnancy complications (preeclampsia, gestational diabetes mellitus and preterm delivery) and poor birth outcomes (intra uterine growth retardation and large for gestational age babies). On the other hand, prenatal long chain polyunsaturated fatty acids status is shown to improve birth outome. In this article, we discuss the role of maternal lipids during pregnancy on fetal growth and development and its consequences on the health of the offspring.

Exploring the role of oxidative stress, fatty acids and neurotrophins in gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) constitutes an unfavorable intrauterine environment for embryonic and feto-placental development. Women with GDM are at higher risk for materno-fetal complications and placental abnormalities. The placenta acts as an interface between the maternal and fetal circulations and also plays an important role in protecting the fetus from adverse effects of maternal metabolic conditions. One of the earliest abnormalities observed in GDM pregnancies is increased oxidative stress in the placenta which affects fetal development. Imbalances in maternal nutrition particularly long-chain polyunsaturated fatty acid (LCPUFA) intake and/or metabolism lead to increased oxidative stress. Reports indicate that oxidative stress and LCPUFA such as docosahexaenoic acid affect the levels of neurotrophins. The present review aims to provide insights into a mechanistic link between oxidative stress, LCPUFA and neurotrophin in the placenta in women with GDM and its implications for neurodevelopmental outcomes in children.

Leptin as a predictive marker for metabolic syndrome.

Metabolic syndrome poses a major threat on human health affecting the quality of life. Adipose tissue is an important organ which plays a crucial role in the pathogenesis of metabolic syndrome. Adipocytokines secreted by the adipose tissue plays a critical role in storage, food intake, energy expenditure, lipid and glucose metabolism. Leptin is primarily involved in regulating food intake, body weight and energy homeostasis through neuroendocrine functions. Contemporary research suggests that leptin also influences insulin sensitivity and lipid metabolism. High leptin concentrations are directly associated with the obesity subsequent development of metabolic disease sequelae such as insulin resistance, type 2 diabetes and cardiovascular diseases. Elucidation of the mechanism of action of leptin would help to develop novel therapeutic approaches for there metabolic disorders like obesity and diabetes. This review provides an updated 'state-of-the-art' about the leptin and its role in the pathophysiology of metabolic syndrome at the molecular level.

Higher maternal plasma folate, vitamin B12 and homocysteine levels in women with preeclampsia.

Micronutrients like vitamin B12 and folate play an important role in nucleic acid metabolism, cell growth, and are important determinants of fetal growth. The present study examined the levels of maternal and cord plasma folate, vitamin B12, homocysteine, and their association with birth outcome in women with preeclampsia (PE). This study includes 450 normotensive control (NC) and 350 women with PE. PE women were further classified into women delivering at term (n = 224) and preterm (n = 126). Maternal and cord blood was collected at delivery. The levels of maternal vitamin B12 (p < 0.05), folate (p < 0.01), and homocysteine (p < 0.01) were higher in the PE group as compared to the NC group. Maternal folate levels were higher in both term and preterm groups, while vitamin B12 levels were higher only in the preterm group as compared to NC group. In contrast, homocysteine was higher only in the term PE group. Similar changes were also observed in the cord plasma. There was a positive association of maternal plasma homocysteine with systolic (r = 0.151, p = 0.000, n = 578) and diastolic blood pressure (r = 0.213, p = 0.000, n = 578) in the whole cohort. A negative association of maternal folate with systolic blood pressure (r = -0.105, p = 0.048, n = 352) while a positive association with baby weight in the NC group (r = 0.116, p = 0.029, n = 352). The present study suggests that maternal and cord micronutrient levels are altered in women with PE.

Adiponectin: A potential therapeutic target for metabolic syndrome.

Adiponectin is an important adipocytokine secreted chiefly by fat containing adipocytes, and plays a crucial role in glucose and lipid metabolism, inflammation and oxidative stress. Alterations in adiponectin levels have been shown to directly affect lipid and glucose metabolism that further increase the synthesis of lipids, free fatty acids and inflammatory cytokines. Changes in adiponectin levels also contribute to insulin resistance, obesity, cardiovascular diseases and type 2 diabetes. In the present review, we provide a comprehensive evaluation of the role of adiponectin and its molecular mechanisms in metabolic syndrome. Clinical improvement in adiponectin levels have been shown to positively modulate lipid and glucose metabolism, thus further substantiating its role in regulation of lipid and glucose metabolism. Currently adiponectin is being investigated as a potential therapeutic target for metabolic syndrome, although more research is required to understand the underlying mechanisms controlling adiponectin levels, including dietary and lifestyle interventions, that may target adiponectin as a therapeutic intervention in metabolic syndrome.

Attenuation of glycation-induced multiple protein modifications by Indian antidiabetic plant extracts.

CONTEXT: Protein glycation is the major contributing factor in the development of diabetic complications. The antiglycation potential of medicinal plants provides a promising opportunity as complementary interventions for complications. OBJECTIVE: To investigate the antiglycation potential of 19 medicinal plants extracts using albumin by estimating different indicators: (1) glycation (early and late), (2) albumin oxidation, and (3) amyloid aggregation. MATERIALS AND METHODS: The effect of aqueous plant extracts (1% w/v) on protein glycation was assessed by incubating albumin (10 mg/mL) with fructose (250 mM) for 4 days. Degree of protein glycation in the absence and presence of plant extracts was assessed by estimating fructosamine, advanced glycation end products (AGEs), carbonyls, free thiol group and ß-amyloid aggregation. RESULTS: Petroselinum crispum, Boerhavia diffusa, Terminalia chebula, Swertia chirayita and Glycyrrhiza glabra showed significant antiglycating activity. P. crispum and A. barbadensis inhibited the carbonyl stress and protected the thiol group from oxidative damage. There was significant correlation between protein thiols and amyloid inhibition (R = -.69, p < .001). CONCLUSION: P. crispum, B. diffusa and T. chebula had the most potent antiglycation activity. These plant exerted noticeable antiglycation activity at different glycation modifications of albumin. These findings are important for identifying plants with potential to combat diabetic complications.

Vitamin B12 Deficiency Across Three Generations Adversely Influences Long-chain Polyunsaturated Fatty Acid Status and Cardiometabolic Markers in Rats.

BACKGROUND AND AIMS: Vitamin B12 and omega-3 fatty acid deficiency is prevalent in the vegetarian population and is associated with adverse pregnancy outcomes and cardiometabolic risk. The present study investigates the long-term effects of vitamin B12 deficiency/supplementation in the presence of omega-3 fatty acids on cardiometabolic profile and long-chain polyunsaturated fatty acid levels (LCPUFA) in the F3 generation offspring. METHODS: Three generations of rats were fed the following diets: control; vitamin B12 deficient; vitamin B12 supplemented; vitamin B12 deficient + omega-3 fatty acid supplemented; vitamin B12 + omega-3 fatty acid supplemented. Animals were sacrificed at 3 months of age. RESULTS: Vitamin B12 deficiency lowered (p <0.01 for both) plasma eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), liver DHA (p <0.05), plasma/liver omega-3 fatty acids (p <0.05 for both), increased triglycerides (p <0.05) and systolic BP (p <0.01) and lowered cholesterol levels (p <0.05) as compared to control. Vitamin B12 deficiency in the presence of omega-3 fatty acids improved plasma/liver EPA, DHA and omega-3 fatty acid profile and maintained cholesterol, triglyceride and BP levels. Vitamin B12 supplementation lowered liver DHA (p <0.05) and cholesterol (p <0.01), whereas BP was similar to control. Combined supplementation of vitamin B12 and omega-3 fatty acids improved omega-3 fatty acid profile, lowered cholesterol/triglyceride levels and maintained the BP similar to that of control. CONCLUSION: Vitamin B12 deficiency across three generations adversely affects LCPUFA and cardiometabolic profile in the adult offspring. This study provides clues for a combined supplementation of vitamin B12 and omega-3 fatty acids to reduce the risk for noncommunicable diseases.

A combined supplementation of vitamin B12 and n-3 polyunsaturated fatty acids across two generations improves nerve growth factor and vascular endothelial growth factor levels in the rat hippocampus.

Vitamin B12 and n-3 polyunsaturated fatty acid (n-3 PUFA) are known to influence cognition. This study aims to examine if these nutrients affect the protein levels and gene expression of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) in the cortex and hippocampus in the second-generation offspring at 3 mo of age. Wistar rats were fed the following diets for two generations: Control (CON), vitamin B12 deficient (VBD), vitamin B12 deficient supplemented with n-3 PUFA (VBDO), vitamin B12 supplemented (VBS), vitamin B12 supplemented with n-3 PUFA (VBSO). The VEGF and NGF gene expression and protein levels in the hippocampus were lower (P⩽0.01) in the VBD group as compared to the CON group while the VBDO group restored the VEGF and NGF gene expression (P⩽0.01). The VBS group showed similar levels of NGF and VEGF to that of the CON group. However, the VBSO group demonstrated higher (P⩽0.05) NGF gene expression and protein levels in the hippocampus and higher cortex NGF protein levels as compared to the CON group. In addition, VEGF (in hippocampus) and NGF (in cortex and hippocampus) protein levels were also higher (P⩽0.05) in the VBSO group as compared to the VBS group. Our results indicate that the combined supplementation of vitamin B12 and n-3 PUFA improves NGF and maintains VEGF levels in the brain which may improve neurovascular function.

A combined supplementation of vitamin B12 and omega-3 fatty acids across two generations improves cardiometabolic variables in rats.

Our earlier studies indicate that micronutrients (vitamin B12, folic acid) and omega-3 fatty acids especially docosahexaenoic acid (DHA) are interlinked in one carbon cycle. The present study examines the effects of a sustained vitamin B12 deficiency/supplementation in the presence of omega-3 fatty acids across two generations on the pregnancy outcome and cardiometabolic profile [blood pressure, plasma lipid profile (cholesterol and triglycerides), plasma/liver fatty acid profile and hepatic lipid metabolism] in the second generation adult Wistar rat offspring. Two generations of animals were fed the following diets: control; vitamin B12 deficient; vitamin B12 supplemented; vitamin B12 deficient diet supplemented with omega-3 fatty acids; vitamin B12 and omega-3 fatty acid supplemented diets. Male offspring were sacrificed at 3 months of age. Vitamin B12 deficiency lowered the weight gain (p < 0.01) during pregnancy, increased systolic (p < 0.05) and diastolic (p < 0.01) blood pressure, and lowered the levels of plasma/liver DHA (p < 0.05 for both) but did not affect the lipid profile. Vitamin B12 supplementation showed weight gain, blood pressure and the fatty acid profile similar to the control. However, it increased (p < 0.05) the levels of plasma triglycerides. Omega-3 fatty acid supplementation to the vitamin B12 deficient group lowered the weight gain although the levels of cardiometabolic variables were comparable to the control. Omega-3 fatty acid supplementation in the presence of vitamin B12 improved the pregnancy outcome and all cardio-metabolic variables. Our study highlights the adverse effects of sustained vitamin B12 deficiency across two generations on the pregnancy outcome, fatty acid profile and blood pressure while a combined supplementation of vitamin B12 and omega-3 fatty acids is beneficial.

Effect of vitamin B12 and omega-3 fatty acid supplementation on brain neurotrophins and cognition in rats: A multigeneration study.

Vitamin B12 and omega-3 fatty acids are important nutrients required for neuronal functioning. We have demonstrated the beneficial effects of vitamin B12 and omega-3 fatty acid supplementation on brain neurotrophins and cognition in the first and second generation offspring. However, there is a need to examine if the effects are sustained in the third generation offspring. This study reports the effects of vitamin B12 and omega-3 fatty acid supplementation across three consecutive generations on brain neurotrophins like brain derived neurotrophic factor (BDNF); nerve growth factor (NGF) and cognitive performance in the third generation male offspring. Three successive generations of Wistar rats were assigned the following groups throughout pregnancy, lactation and adulthood: i) Control, ii) vitamin B12 deficient (BD), iii) vitamin B12 deficient + omega-3 fatty acid (BDO), iv) vitamin B12 supplemented (BS) and v) vitamin B12 supplemented + omega-3 fatty acid (BSO). The BD group demonstrated lower (p < 0.01) NGF in the cortex but not BDNF levels although the cognition was impaired (p < 0.01). In contrast, in the BDO group, higher NGF levels were observed in the hippocampus and animals demonstrated improved (p < 0.01) cognitive performance. Vitamin B12 supplementation showed comparable BDNF levels in the hippocampus while their levels were lower in the cortex as compared to the control (p < 0.05). These animals showed more reference and working memory errors (p < 0.01) as compared to the control group. A combined supplementation of vitamin B12 and omega-3 fatty acid showed higher (p < 0.01) levels of DHA and NGF in the hippocampus, higher BDNF in both hippocampus and cortex and improved cognitive performance. Our findings have implications for fortification of foods with vitamin B12 and omega-3 fatty acids in improving brain development.

Beneficial effects of omega-3 fatty acids and vitamin B12 supplementation on brain docosahexaenoic acid, brain derived neurotrophic factor, and cognitive performance in the second-generation Wistar rats.

In vegetarian population, vitamin B12 deficiency coexists with suboptimal levels of omega-3 fatty acids. Studies indicate a need for supplementation/fortification of vitamin B12 and omega-3 fatty acids to reduce the risk of brain disorders. We have described the effects of vitamin B12 and omega-3 fatty acid supplementation on brain development in F1 generation animals. The current study investigates the effects of vitamin B12 and omega-3 fatty acids supplementation on brain function and cognition. Pregnant Wistar rats were assigned the following groups: control, vitamin B12 deficient (BD), vitamin B12 deficient + omega-3 fatty acid (BDO), vitamin B12 supplemented (BS), vitamin B12 supplemented + omega-3 fatty acid (BSO). The same diets were continued for two generations. BDO group showed higher (P < 0.05) levels of BDNF (brain derived neurotrophic factor) and DHA (docosahexaenoic acid) in the cortex and hippocampus as compared with the BD group. The cognitive performance was also normalized in this group. BS showed comparable levels of DHA, BDNF (protein and mRNA), and CREB mRNA (cAMP response element-binding protein) to that of control group while Tropomyosin receptor kinase mRNA levels were higher. The combined vitamin B12 and omega-3 fatty acid supplementation further enhanced the levels of DHA (P < 0.05) and BDNF (P < 0.05) in the hippocampus and CREB mRNA (P < 0.01) in the cortex as compared with BS group. The cognitive performance of these animals was higher (P < 0.05) as compared with BS group. Our data indicates the beneficial effects of vitamin B12 and omega-3 fatty acid supplementation across two generations on brain development and function.

Maternal omega-3 fatty acids and micronutrients modulate fetal lipid metabolism: A review.

It is well established that alterations in the mother's diet or metabolism during pregnancy has long-term adverse effects on the lipid metabolism in the offspring. There is growing interest in the role of specific nutrients especially omega-3 fatty acids in the pathophysiology of lipid disorders. A series of studies carried out in humans and rodents in our department have consistently suggested a link between omega-3 fatty acids especially docosahexaenoic acid and micronutrients (vitamin B12 and folic acid) in the one carbon metabolic cycle and its effect on the fatty acid metabolism, hepatic transcription factors and DNA methylation patterns. However the association of maternal intake or metabolism of these nutrients with fetal lipid metabolism is relatively less explored. In this review, we provide insights into the role of maternal omega-3 fatty acids and vitamin B12 and their influence on fetal lipid metabolism through various mechanisms which influence phosphatidylethanolamine-N-methyltransferase activity, peroxisome proliferator activated receptor, adiponectin signaling pathway and epigenetic process like chromatin methylation. This will help understand the possible mechanisms involved in fetal lipid metabolism and may provide important clues for the prevention of lipid disorders in the offspring.

Vitamin B12 and omega-3 fatty acids together regulate lipid metabolism in Wistar rats.

Our recent study indicates that maternal vitamin B12 and omega-3 fatty acid status influence plasma and erythrocyte fatty acid profile in dams. The present study examines the effects of prenatal and postnatal vitamin B12 and omega-3 fatty acid status on lipid metabolism in the offspring. Pregnant dams were divided into five groups: Control; Vitamin B12 deficient (BD); Vitamin B12 supplemented (BS); Vitamin B12 deficient group supplemented with omega-3 fatty acids (BDO); Vitamin B12 supplemented group with omega-3 fatty acids (BSO). The offspring were continued on the same diets till 3 month of age. Vitamin B12 deficiency increased cholesterol levels (p<0.01) but reduced docosahexaenoic acid (DHA) (p<0.05), liver mRNA levels of acetyl CoA carboxylase-1 (ACC-1) (p<0.05) and carnitine palmitoyltransferase-1 (CPT-1) (p<0.01) in the offspring. Omega-3 fatty acid supplementation to this group normalized cholesterol but not mRNA levels of ACC-1 and CPT-1. Vitamin B12 supplementation normalized the levels cholesterol to that of control but increased plasma triglyceride (p<0.01) and reduced liver mRNA levels of adiponectin, ACC-1, and CPT-1 (p<0.01 for all). Supplementation of both vitamin B12 and omega-3 fatty acid normalized triglyceride and mRNA levels of all the above genes. Prenatal and postnatal vitamin B12 and omega-3 fatty acids together play a crucial role in regulating the genes involved in lipid metabolism in adult offspring.

Maternal omega-3 fatty acid supplementation to a vitamin B12 deficient diet normalizes angiogenic markers in the pup brain at birth.

Vitamin B12 and omega-3 fatty acids are critical for normal brain development and function and their deficiencies during pregnancy could have adverse effects on cognitive performance in children. Our earlier studies indicate that both maternal vitamin B12 and omega-3 fatty acids influence brain development by regulating the levels of neurotrophins. Literature suggests that there exists a cross talk between neurotrophins like nerve growth factor (NGF) and angiogenic factors like vascular endothelial growth factor (VEGF). It remains to be established whether maternal nutrients like vitamin B12 and omega-3 fatty acids influence the levels of angiogenic markers like VEGF and NGF in the brain of the offspring. Therefore the present study examines the effect of maternal vitamin B12 and omega-3 fatty acids on protein and mRNA levels of VEGF, HIF-1 alpha (hypoxia inducible factor alpha) and NGF in the pup brain at birth. Pregnant Wistar rats were divided into five dietary groups (n=8 each): control, vitamin B12 deficient, vitamin B12 deficient+omega-3 fatty acid, vitamin B12 supplemented, vitamin B12 supplemented+omega-3 fatty acid. At birth the pups were dissected to collect the brain tissue. Maternal vitamin B12 deficiency showed lower (p<0.05) pup brain mRNA and protein levels (p<0.01) of VEGF, higher (p<0.01) HIF-1 alpha protein levels, lower (p<0.05) NGF protein levels while NGF mRNA levels were not altered. Omega-3 fatty acid supplementation to a vitamin B12 deficient group normalized the VEGF mRNA levels, NGF protein levels and HIF-1 alpha protein levels. Vitamin B12 supplementation showed similar protein and mRNA levels of VEGF and NGF as well as HIF-1 alpha protein levels as compared to control. Omega-3 fatty acid supplementation to the vitamin B12 supplemented group showed higher (p<0.01) protein and mRNA levels of NGF but the protein and mRNA levels of VEGF were comparable to control. In conclusion maternal vitamin B12 and omega-3 fatty acids both influence the levels and expression of neurotrophins and angiogenic factors in the offspring brain suggesting a possible benefit of combined maternal supplementation of these vital nutrients.

Aqueous extract of some indigenous medicinal plants inhibits glycation at multiple stages and protects erythrocytes from oxidative damage-an in vitro study.

Azadirachta indica, Emblica officinalis, Syzygium cumini and Terminalia bellirica are common in Indian system of traditional medicine for the prevention of diabetes and its complications. The aim of the present study was to comprehensively and comparatively investigate the antiglycation potential of these plant extracts at multiple stages and their possible protective effect against glycated albumin mediated toxicity to erythrocytes. Antiglycation activities of these plant extracts was measured by co-incubation of plant extract with bovine serum albumin-fructose glycation model. The multistage glycation markers- fructosamines (early stage), protein carbonyls (intermediate stage) and AGEs (late stage) are investigated along with measurement of thiols and ß aggregation of albumin using amyloid-specific dyes-Congo red and Th T. Protection of erythrocytes from glycated albumin induced toxicity by these plant extracts was assessed by measuring erythrocytes hemolysis, lipid peroxidation, reduced glutathione and intracellular antioxidant capacity. Total phenolics, reducing power and antioxidant activities of the plant extracts were also measured. In vitro glycation assays showed that plant extracts exerted site specific inhibitory effects at multiple stages, with T. bellirica showing maximum attenuation. In erythrocytes, along with the retardation of glycated albumin induced hemolysis and lipid-peroxidation, T. bellirica considerably maintained cellular antioxidant potential. Significant positive correlations were observed between erythrocyte protection parameters with total phenolics. These plant extracts especially T. bellirica prevents glycation induced albumin modifications and subsequent toxicity to erythrocytes which might offer additional protection against diabetic vascular complications.

Nutraceutical properties of dietary plants extracts: prevention of diabetic nephropathy through inhibition of glycation and toxicity to erythrocytes and HEK293 cells.

CONTEXT: Glycated albumin is reported to elicit pathobiologic effects in diabetic nephropathy and abrogating its biologic effects has novel therapeutic potential. OBJECTIVE: This study examines the effects of dietary plants extracts (Laurus nobilis, Carum carvi, Coccinia grandis, Mentha arvensis, Phaseolus vulgaris) against albumin glycation and its toxicity to erythrocytes and HEK293 cells. MATERIALS AND METHODS: Albumin (10 mg/ml) was incubated with fructose (250 mM) in PBS along with aqueous plant extracts (1% w/v) for 4 d. After incubation, the antiglycation potential of extracts was estimated by measuring AGEs, fructosamine, amyloids, carbonyls, free amino groups, and antioxidant potential of albumin. The glycation extent of the treated samples was determined by boronate affinity chromatography. Effect of extracts against glycation induced cytotoxicity in erythrocytes and HEK 293 cells was assessed by estimating viability, glutathione, and antioxidant capacity. Plant extracts were tested for their phenolic content and antioxidant potential (reducing potential, DPPH, ABTS, NO, and H2O2 radical scavenging activities). RESULTS: Plant extracts significantly decreased the AGEs formation and amyloid aggregation in glycated BSA (p < 0.001). Further, fructosamine and carbonyls were reduced to 55-72% and 83-89%, respectively. Free amino group and antioxidant activity of albumin were also preserved by 1.25-1.40-fold and 1.75-1.8-fold, respectively. Further, co-incubation of extracts with glycated albumin, protected erythrocytes, and HEK293 cells as they inhibited cellular hemolysis/toxicity (p < 0.001) by upregulating cellular antioxidants. DISCUSSION AND CONCLUSION: Plant co-incubation reversed many modifications in albumin glycation, cellular dysfunction indicating that dietary sources with antiglycating and antioxidant potential could be considered for the effective management of diabetic nephropathy.