Neuroprotective effect of Morin via TrkB/Akt pathway against diabetes mediated oxidative stress and apoptosis in neuronal cells.

Long-term diabetes mellitus results in neuronal damage by increased intracellular glucose leading to oxidative stress. This condition is known as diabetic encephalopathy. Morin is a bioflavonoid, has significant antidiabetic, antioxidant and anti-inflammatory activities. The present study investigated whether the antioxidant properties of morin has beneficial effects on structural brain damage, neuronal apoptosis and dysregulation of TrkB/Akt signaling associated with diabetes. Adult male Sprague Dawley rats were induced diabetes by an intraperitoneal injection of 40 mg/kg of streptozotocin and kept untreated for 30 days to induce DE. Cognitive performance was assessed using the Morris water maze test followed by morin and metformin administration at the doses of 50 and 100 mg/kg, respectively, for 60 days. After 60 days of treatment, animals were subjected to the behavioral test and sacrificed to collect blood and brain and checked biochemical parameters. The treatment with morin could significantly reduce the escape latency time in Morris water maze test, blood glucose level, HbA1c, toxicity markers, lipid peroxidation products and protein carbonyl content, downregulated the expression of Bax, Caspase - 3 and Cytochrome C and upregulated Bcl-2, Bcl-XL, Akt, BDNF and TrkB expressions. Besides, enhanced the activities of antioxidant enzymes, and plasma insulin level. Histomorphological observations also confirmed the protective effect of morin on neuronal degeneration. Morin 50 mg once daily for 60 days was the most effective dose with a significant reduction in diabetes mediated complications in the brain associated with neuronal apoptosis and dysregulation of TrkB/Akt signaling.

Hibiscus rosa sinensis Linn. Petals Modulates Glycogen Metabolism and Glucose Homeostasis Signalling Pathway in Streptozotocin-Induced Experimental Diabetes.

The prevalence of diabetes mellitus is becoming more and more serious and reaches epidemic proportions worldwide. Scientific research is constantly looking for new agents that could be used as dietary functional ingredients in the fight against diabetes. The objective of the present study was to evaluate the effect of ethyl acetate fraction of Hibiscus rosa sinensis Linn. petals on experimental diabetes at a dose of 25 mg/kg body weight and it was compared with standard anti-diabetic drug metformin. The elevated levels of serum glucose (398.56 ± 35.78) and glycated haemoglobin (12.89 ± 1.89) in diabetic rats were significantly decreased (156.89 ± 14.45 and 6.12 ± 0.49, respectively) by Hibiscus rosa sinensis petals (EHRS) administration. Hepatotoxicity marker enzyme levels in serum were normalized. The fraction supplementation restored the glycogen content by regulating the activities of glycogen metabolizing enzymes. It significantly modulated the expressions of marker genes involved in glucose homeostasis signalling pathway. Histopathological analysis of liver and pancreas supported our findings. The overall effect was comparable with metformin. Hence, our study reveals the role of hibiscus petals for alleviation of diabetes complications, thus it can be propagated as a nutraceutical agent.

The regulatory effects of Cissus quadrangularis on some enzymes involved in carbohydrate metabolism in streptozotocin-induced diabetic rats.

CONTEXT: Diabetes mellitus (DM) is probably the single most important metabolic disease and is widely recognized as one of the leading causes of death and disability. Cissus quadrangularis Linn. (Vitaceae) is a medicinal food and is reported to possess hypoglycemic activity. OBJECTIVE: The present study evaluates the effect of ethyl acetate fraction of C. quadrangularis stem (CQSF) on carbohydrate metabolism in hepatic tissues of experimental diabetic rats. The phytochemical compounds present in the CQSF extract were identified by gas chromatography-mass spectrometry (GC-MS) analysis. MATERIALS AND METHODS: Diabetic animals were treated with CQSF (50, 100, and 200 mg/kg body weight) for 45 d. Several indices such as blood glucose, glycated hemoglobin (HbA1c), insulin, liver function tests, hepatic glycogen content, and the activities of carbohydrate-metabolizing enzymes were assayed after 45 d of extract treatment. RESULTS: A pronounced effect was observed with extract doses 100 and 200 mg/kg body weight. CQSF at a dose of 100 mg/kg body weight significantly decreased the altered levels of blood glucose by about 56%. CQSF also modulated the activities of carbohydrate-metabolizing enzymes by significantly increasing the activity of hexokinase (1.9-fold) and pyruvate kinase (2.2-fold) and significantly reducing the activity of glucose-6-phosphatase (41.23%), fructose-1,6-diphosphatase (29.43%), and glycogen phosphorylase (35.07%). GC-MS analysis revealed the presence of 10 chemical constituents, and N-methyl-1-adamantane acetamide was found to be the prevailing compound in the extract. DISCUSSION AND CONCLUSION: The current study suggests the antidiabetic potential of CQSF, mediated through the regulation of carbohydrate metabolic enzyme activities.

Ethanol extract of Butea monosperma bark modulates dyslipidemia in streptozotocin-induced diabetic rats.

CONTEXT: Dyslipidemia is one of the major risk factors for cardiovascular disease in diabetes mellitus (DM). The availability of multiple lipid-lowering drugs and supplements provides new opportunities for patients to regulate lipid levels. OBJECTIVE: The present study was designed to evaluate the effect of Butea monosperma Lam. (Fabaceae) bark extract in diabetes-induced dyslipidemia. MATERIALS AND METHODS: A daily dose of B. monosperma bark extract (BMBE, 500 mg/kg body weight) was given orally to streptozotocin (STZ)-induced diabetic rats for 60 d. Several indices such as blood glucose, insulin, glycosylated hemoglobin, TC, TG, high-density lipoprotein-cholesterol (HDL-C), apo A1, apo B, activities of lipogenic enzymes in tissues, liver function tests, and histopathology of liver were analyzed to assess the modulation of STZ-induced diabetic dyslipidemia by B. monosperma bark. RESULTS: BMBE significantly reduced blood glucose (40.79%) and increased plasma insulin (37.5%) levels in diabetic rats. Altered levels of serum lipids, lipoproteins, and activities of lipogenic enzymes in tissues were partially restored upon the administration of BMBE in diabetic rats. Liver function tests and histopathological examination revealed that consumption of BMBE at a dose of 500 mg/kg body weight had no toxic effects in experimental rats. CONCLUSION: The findings suggest that BMBE supplementation could ameliorate dyslipidemia in DM.

Natural 3D Extra Cellular Matrix mimicking stem cells seeded decellularized scaffolds as a platform for tendon regeneration.

Achilles tendon, which connects the calf muscles to heel, is the strongest tendon in the body. Despite its strength, it is more prone to injury due to its limited blood supply. Tendon-related injuries are more common in sportspersons, people with labor-intensive work and the aged community. The currently available treatment mode is surgery which is expensive with chances of re-injury. Present study made an attempt to fabricate a tissue-engineered tendon product using decellularized tendon (DT) seeded with stem cells and bioactive components of Tinospora cordifolia extract (TCE). The bare DT tissue scaffold/substitute may also serve as a drug delivery platform for growth factors and cells with a new approach to promote tissue regeneration in clinical applications. DT construct showed good regenerative potential and easily promoted new tissue formation. Decellularization of the tendon was carried out by chemical method using tri (n-butyl) phosphate (TnBP). DT was physicochemically characterized by contact angle measurement, thermal gravimetric analysis (TGA), and mechanical testing. Rabbit adipose derived mesenchymal stem cells (RADMSCs) were isolated and phenotypically characterized by flow cytometry analysis, tri lineage differentiation, and so forth. Further, stem cell seeded DT scaffolds were prepared and found to be non-toxic by cytotoxicity, cell adhesion by scanning electron microscope (SEM) analysis, cell viability by live dead assays, and so forth. The findings of this study yield valid proof for the employability of cell-seeded DT construct as a natural scaffold in repairing injured tendons-the toughest chords of the skeleton. This is a cost effective method for the replacement of injured/damaged tendons for athletes, people in labor-intensive occupations, the elderly population, and so forth-a boon towards the repair of the tendon in damage/injury.

Antioxidant, antiglycation and inhibitory potential of Saraca ashoka flowers against the enzymes linked to type 2 diabetes and LDL oxidation.

OBJECTIVE: The present study investigated the antioxidant, antiglycation and inhibitory potential of flavonoid fraction of Saraca ashoka flowers (SAF) against alpha-glucosidase and alpha-amylase (the enzymes linked to type 2 diabetes) and LDL oxidation. MATERIALS AND METHODS: Antioxidant capacity of SAF was evaluated by estimating total antioxidant activity (TAA) and its protective effects against the oxidative stress induced by H2O2 on C2C12 cells. Cytotoxicity by MTT assay and markers of oxidative stress: reduced glutathione (GSH), malondialdehyde (MDA) and reactive oxygen species (ROS) were measured. RESULTS: Pre-treatment of C2C12 cells with SAF prevented the increased formation of MDA and depletion of GSH induced by H2O2. The increased ROS generation induced by H2O2 was also reduced by a pretreatment with SAF. Significant inhibitory potential against alpha-glucosidase and alpha-amylase enzymes revealed the therapeutic potential of SAF as an antihyperglycemic agent. SAF also demonstrated potent antiglycation property and inhibited LDL oxidation under in vitro conditions. CONCLUSIONS: The overall results demonstrate that SAF can be used as an ideal natural remedy for preventing oxidative stress and other complications associated with diabetes.

Seroprevalence of SARS-CoV 2 antibodies & its determinants in children of 5-to-18-year age group in an urban setting, Kerala.

Background: There were limited data on the true burden of COVID 19 infection in children since the majority of the infections are asymptomatic or paucisymptomatic. This study aimed to measure the prevalence of SARS CoV2 antibodies in children of the 5-to-18 years age group. Methods: A community-based cross-sectional study was conducted in the field practice area attached to a tertiary care hospital in Kerala. Two hundred four children of the 5-to-18 year age group were enrolled in our study. The data regarding sociodemographic details, symptoms suggestive of COVID 19, exposure to confirmed COVID 19 cases and history of COVID 19 positivity were collected from the study participants. 2 ml venous blood was collected from each participant, and the seroprevalence of SARS CoV2 combined antibodies was assessed using WANTAI antibody test kit. Results: The seroprevalence of SARS Cov2 antibodies in children of 5-to-18 years age group was 41.7% (95% CI,34.9% to 48.43%). The seroprevalence was high in the 13-to-15 year age group, almost similar in both gender and socio-economic groups. The seropositivity was significantly associated with history of confirmed COVID 19 positivity, children with a history of symptoms suggestive of COVID 19 and the presence of positive contact in the household (P < 0.05). Seroprevalence was also significantly high in children whose mothers were health care workers. Conclusion: Approximately 41.7% of children showed seropositivity to COVID 19 infection. More than 50% of the children remain susceptible. Among seropositive, 56.5% were asymptomatic. Thus there is a need to test even asymptomatic children in COVID 19 positive households.

A Study Comparing Gait and Lower Limb Muscle Activity During Aquatic Treadmill Running with Different Water Depth and Land Treadmill Running.

Aquatic treadmill running is a partial weight-bearing exercise for rehabilitation. The purpose of this study was to investigate the surface electromyography activities of the rectus femoris, tibialis anterior, biceps femoris and medial head of gastrocnemius, and gait kinematics during aquatic treadmill running in water levels at waist, mid-thigh and mid-shin and on land. Seventeen healthy subjects (9 males and 8 females) were recruited by convenience sampling. Participants performed 2-min aquatic treadmill running at a specific speed for each water depth. The test speed was selected based upon the speed that elicited 110 steps per min. The surface electromyography data of lower limb muscles and the joint angles at three different water depths and on land were collected to evaluate the muscle activity and gait kinematics using a waterproofed surface electromyography system and inertial measurement unit for each muscle. Results showed that rectus femoris electromyography was different between depths during the swing and stance phases. Likewise, biceps femoris and tibialis anterior electromyography were different between depths for the swing phase. However, it was not the case for gastrocnemius electromyography. Peak flexion angles in both left and right hips were different between depths. A significant increase in a stance/swing ratio was observed with rising water depths. Water depth influenced muscle activity as well as kinematics. Aquatic treadmill running in the mid-thigh level should be further evaluated for its effectiveness, training value and applicability.

Corrigendum to "Protective role of Moringa oleifera leaf extract on cardiac antioxidant status and lipid peroxidation in streptozotocin induced diabetic rats" [Heliyon 5, (12), (December 2019), e02935].

[This corrects the article DOI: 10.1016/j.heliyon.2019.e02935.].

Protective role of Moringa oleifera leaf extract on cardiac antioxidant status and lipid peroxidation in streptozotocin induced diabetic rats.

Moringa oleifera is a medicinal plant with great therapeutic potential. The leaves of Moringa oleifera are used by Indians in herbal medicines to treat diabetes. The present study is aimed to determine the protective role of Moringa oleifera in cardiac tissues under diabetic conditions. Diabetic rats were treated orally with methanolic extract of Moringa oleifera leaves at a dose of 300 mg/Kg body weight for 60 days. The effect of extract on serum glucose, glycated hemoglobin, plasma insulin and the levels of thiobarbituric acid reactive substances (TBARS), hydroperoxides (HP), conjugated dienes (D), activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-reductase (GRD) and reduced glutathione content (GSH) were estiated. Metformin and atorvastatin were used as standard drugs. A significant increase in plasma insulin, activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-reductase (GRD) and reduced glutathione content (GSH) and a significant decrease in serum glucose, glycated hemoglobin, thiobarbituric acid reactive substances (TBARS), hydroperoxides (HP) and conjugated dienes (CD) were observed in the treated groups. This study evaluated the antioxidant potential of methanolic extract of Moringa oleifera leaves. These findings suggest the protective role of Moringa oleifera against oxidative stress in the heart of diabetic rats.

Attenuation of high glucose induced apoptotic and inflammatory signaling pathways in RIN-m5F pancreatic ß cell lines by Hibiscus rosa sinensis L. petals and its phytoconstituents.

ETHNOPHARMACOLOGICAL RELEVANCE: Hibiscus rosa sinensis petals possess wide range of pharmacological properties, with remarkable nutritional values. Diabetes is one of the most devastating diseases affecting the world today. A few side effects associated with the use of insulin and oral hypoglycemic agents prompted us to search new bioactive principles from antidiabetic plants used in traditional medicine. AIM OF THE STUDY: The anti-diabetic therapeutic potential of the flavonoids rich ethyl acetate fraction of Hibiscus rosa sinensis petals (EHRS) was evaluated. MATERIALS AND METHODS: High glucose (25 mM) induced apoptotic model of diabetes in RIN-m5F pancreatic ß-cells was used for the study. RESULTS: EHRS elevated the release of insulin in pancreatic cells and modulated apoptotic signaling cascades. It significantly reduced NF-κB nuclear translocation, thereby down-regulated the expressions of major inflammatory cytokines and up-regulated expressions of pancreatic ß-cell functional genes such as, foxO-1, Ucn-3, Pdx-1, MafA and Nkx6.1. On comparison with its constituent phytochemicals, superior protective effect shown by EHRS may be due to the additive action of these phytoconstituents. CONCLUSIONS: Results of the present study suggest hibiscus petals as a natural source and functional food of potential therapeutics to protect pancreatic ß-cells in experimental diabetes mellitus.

Data analysis on the level of exposure to pollutions in industrial zone: A case study of Ewekoro and Ota Township.

This study focused on a comparative analysis of exposure to pollution in Ota and Ewekoro Township where we have concentration of industries that emits pollutant to the air. This was with a view to proffer solution to the negative effects of industrial activities on residents within industrial location. The study involved empirical observation and interview of residents. About 652 questionnaires were administered randomly on the residents. Analysis involved descriptive statistical tools including chi-square techniques. The results suggest that air pollution was most frequently reported in Ewekoro and Ota and this can help in the prediction of stringent factor in which industrial activities could pose to society.

Averrhoa bilimbi fruits attenuate hyperglycemia-mediated oxidative stress in streptozotocin-induced diabetic rats.

Hyperglycemia-mediated oxidative stress plays a major role in the development of diabetic complications. Averrhoa bilimbi Linn. (Oxalidaceae) is a medicinal plant with fruits reported to possess antidiabetic activity. This study evaluated the beneficial effects of the ethyl acetate fraction of A. bilimbi fruit (ABAEE) on the antioxidant/oxidant status in diabetes mellitus. Diabetic rats were treated orally with the ethyl acetate fraction of A. bilimbi fruits at a dose of 25 mg/kg body weight for 60 days. Serum glucose, glycated hemoglobin, plasma insulin, hepatic toxicity markers, antioxidant enzymes, lipid peroxidation products, and liver histopathology were assayed checked after 60 days of extract treatment. Diabetic rats administered ABAEE showed a significant decline in serum glucose, glycated hemoglobin, and also significantly increases the level of plasma insulin, as well as a notable attenuation in thiobarbituric acid-reactive substances, conjugated dienes, and hydroperoxides. ABAEE also modulated hepatic antioxidant potential by significantly increasing the activities of catalase, glutathione peroxidase, glutathione reductase, superoxide dismutase, and reducing glutathione content. The results associated with ABAEE were more significant than those observed following treatment with the standard drug metformin. Histopathological observations showed that ABAEE effectively rescued hepatocytes from oxidative damage without affecting cellular function and structural integrity. High-performance liquid chromatography analysis of ABAEE indicated the presence of phenolic compound, quercetin, indicating that the antidiabetic effect of the extract might be related to quercetin. These results demonstrated the potential beneficial effect of ABAEE on streptozotocin-induced diabetes in rats.

Ensete superbum ameliorates renal dysfunction in experimental diabetes mellitus.

OBJECTIVES: Hyperglycemia mediated oxidative stress plays a key role in the pathogenesis of diabetic complications like nephropathy. In the present study, we evaluated the effect of ethanolic extract of Ensete superbum seeds (ESSE) on renal dysfunction and oxidative stress in streptozotocin-induced diabetic rats. MATERIALS AND METHODS: Glucose, HbA1c, total protein, albumin, renal function markers (urea, uric acid and creatinine), and lipid peroxidation levels were evaluated. Renal enzymatic and non-enzymatic antioxidants were examined along with renal histopathological study. RESULTS: ESSE (400 mg/kg BW t) administration reduced glucose and HbA1c, and improved serum total protein and albumin in diabetic rats. ESSE in diabetic rats recorded decrement in renal function markers and renal lipid peroxidation products along with significant increment in enzymatic and non-enzymatic antioxidants. Renal morphological abnormalities of diabetic rats were markedly ameliorated by E. superbum. CONCLUSION: These results suggest that the antioxidant effect of E. superbum could ameliorate oxidative stress and delay/prevent the progress of diabetic nephropathy in diabetes mellitus.

Ethyl acetate fraction of Cissus quadrangularis stem ameliorates hyperglycaemia-mediated oxidative stress and suppresses inflammatory response in nicotinamide/streptozotocin induced type 2 diabetic rats.

BACKGROUND: Cissus quadrangularis is a plant with great medicinal value and different parts of the plant is traditionally used for the treatment of skin infections, constipation, piles, anaemia, asthma, irregular menstruation, burns and wounds. The stems and leaves of Cissus quadrangularis has been traditionally consumed as a vegetable. OBJECTIVE: The current study was hypothesized to investigate the beneficial effects of ethyl acetate fraction of Cissus quadrangularis stem (CQSF) on hyperglycaemia-mediated oxidative stress and inflammatory responses in nicotinamide/streptozotocin induced diabetes mellitus. MATERIALS AND METHODS: Experimental diabetes was induced by intraperitoneal injection of 110 mg/kg body weight nicotinamide 15 min prior to the injection of 45 mg/kg body weight streptozotocin. Diabetic rats were administered with a daily oral dose of 100 mg/kg CQSF for 60 days after diabetes induction. RESULTS: Diabetic control rats showed significant (p < 0.05) increase in blood glucose, HbA1c, liver toxicity markers, inflammatory markers and lipid peroxidation products and reduction in the activities of antioxidant enzymes. The mRNA expressions of TNF-α, IL-6 and NF-κB in adipose tissue were significantly (p < 0.05) increased in diabetic group. Nuclear translocation of NF-κB p65 subunit level was greater in diabetic rats. CQSF administration significantly reversed these alterations. Histopathological alterations of liver and pancreas were also restored by CQSF treatment. The results were compared with the standard oral hypoglycaemic drug metformin. In addition, the ESI-MS and GC-MS analysis of CQSF confirmed the presence of quercetin and phenol, 2,4-bis(1,1-dimethylethyl)- respectively. CONCLUSIONS: The present study demonstrates that CQSF exerts antidiabetic activity by potentiating the antioxidant defense system and suppressing inflammatory responses.

Synthesis and spectral studies of metal complexes of a Schiff base derived from (2-amino-5-chlorophenyl)phenyl methanone.

Some new complexes of Mn(II), Co(II), Ni(II), Cu(II), Zn(II), and Fe(III) with the Schiff base 5-chloro-2-(furan-2-yl methylamino)phenyl)phenyl methanone has been synthesized and characterized by elemental analysis, spectroscopic data including FT-IR, (1)H NMR, Electronic, ESI mass, Mössbauer & ESR. It has been found that the Schiff base behaves as a neutral bidentate N, O donor which chelates with the metal ions in 1:2 stoichiometry. Magnetic moment and electrolytic conductance data confirms this. The Schiff base and selected complexes were screened for antimicrobial activity. The complexes and the Schiff base were subjected to antioxidant study. The antitumor activity of Co(II) complex was tested by MTT assay. The result indicates the viability of the complex against tested cell lines.

Anticancer activity of galactoxyloglucan polysaccharide-conjugated doxorubicin nanoparticles: Mechanistic insights and interactome analysis.

Toxicity associated with chemotherapeutic drugs such as doxorubicin (Dox), is one of the major obstacles that is currently affecting patients. PST-Dox (Galactoxyloglucan, PST001-conjugated Dox) nanoparticles were synthesized by encapsulating Dox with polysaccharide PST001, isolated from Tamarindus indica (Ti) by ionic gelation with tripolyphosphate (TPP). Herein, we demonstrate a detailed mechanistic and interactome network analysis that is specific to PST-Dox action in cancer cells and normal lymphocytes. Our results show that PST-Dox is superior to its parental counterparts, exhibiting a greater cytotoxicity by the induction of apoptosis against a wide variety of cancers by enhanced cellular uptake of Dox from the nanoparticle conjugates. Also, PST-Dox nanoparticles were non-toxic to normal lymphocytes with limited immunostimulatory effects up to certain doses. Elucidation of molecular mechanism by whole genome microarray in cancer cells and lymphocytes revealed that a large number of genes were dysregulated specifically in cancer cells. Specifically, a unique target gene EGR1, contextually determined translational activation of P53 in the cancerous and non-cancerous cells. Most of the key downregulated genes were tyrosine kinases, indicating the potential inhibitory action of PST-Dox on tyrosine kinase oncogenic pathways. Western blotting of proteins corresponding to the genes that were altered at the genomic level was very well correlated in the majority of them, except in a few that demonstrated post-transcriptional modifications. The important findings and highly disciplined approaches highlighted in the present study will speed up the therapeutic potential of this augmented nanoparticle formulation for more robust clinical studies and testing in several cancers.

Progressive nephropathy associated with mitochondrial tRNA gene mutation.

Mitochondrial DNA plays a crucial role in oxidative production of energy. Thus, defects in mitochondrial DNA can affect virtually all organ systems. The point mutation A --> G at position 3243 in the mitochondrial tRNAleu(UUR) gene is the cause of several distinct types of mitochondrial cytopathy and several clinical phenotypes, including encephalomyopathy with lactic acidosis and stroke-like episodes and maternally inherited diabetes and deafness. This mutation has been recently described also in association with kidney disease, mainly focal and segmental glomerulosclerosis. At present, little is known about the prevalence of this mitochondrial nephropathy, its clinical course and the pathogenesis of glomerular damage. We describe 2 unrelated patients, who presented with proteinuria and progressed to end-stage renal failure. Other clinical features were short stature, severe headache, hearing loss, diabetes mellitus and hypertrophic cardiomyopathy. The main histological finding was an increased number of abnormal mitochondria in tubular cells and podocytes. Analysis of mitochondrial DNA from leukocytes and urine sediment revealed heteroplasmy for the A3243G mutation in tRNAleu(UUR) gene in both patients. Recognition of the characteristic clinical and histological features of the mitochondrial A3243G mutation-associated glomerulopathy will enable correct diagnosis and better management of a disease which is likely to be underdiagnosed.