Biomedical Research and Therapy

Orally administered fisetin as an immuno-modulatory and therapeutic agent in a mouse model of chronic allergic airway disease

2019-07-17T11:33:16+00:00

Introduction: Allergic asthma is a prevalent disorder, in which eosinophilic inflammation is involved in the lungs. Asthma affects people all over the world, regardless of the country's level of development. Chronic allergen-induced fibrotic damage of the lungs is stimulated in 55 days, which results in significant tissue destruction constitutive to pulmonary tissues, in addition to extensive oxidative & inflammation-induced damage of small and large airways. To date, there is no cure for asthma, and symptoms are controlled using corticosteroids, which may cause systemic side effects. Flavonoids, like fisetin, are a class of secondary metabolites produced by plants, which are known to have numerous beneficial effects. Previous report demonstrated that fisetin has beneficial effects against various diseases such as cancers, tumors, diabetes, and alcohol-induced liver injury.

Methods: In the present study, chronic allergic disease (asthma) was developed in C57BL/6J mice, using intraperitoneal injection of ovalbumin for 54 days together with orally administered fisetin as a treatment strategy. Fisetin was administered 1 hour before intratracheal treatment. On day 55, treated animals were sacrificed, and tissues were collected for various assays.

Results: Fisetin was found to reduce the symptoms of asthma significantly. Reduction in total cell infiltration, eosinophil count, and the levels of serum IgE were observed. There was a down regulation in CD3⁺CD4⁺ TH cells, and a decrease in the deposition of collagen in the lung and airways.

Conclusion: From these observations, we conclude that fisetin is effective in the treatment of asthma, and a pathway by which fisetin acts was hypothesized.

Prevention and treatment of brain damage in streptozotocin induced diabetic rats with Metformin, Nigella sativa, Zingiber officinale, and Punica granatum

2019-07-17T11:33:14+00:00

Introduction: Diabetes mellitus (DM) is well-known metabolic disorder, which causes serious effects on human health with its complications. Many mechanisms has been postulated to cause DM related complications. One of the main complications is neuronal damage, for which no proper preventive and curative therapies are available.

Methods: In this study the effects of Ginger, Nigella sativa, Punica granatum and Metformin were seen on the prevention and treatment of brain damage caused by diabetes mellitus in streptozotocin (STZ)- induced diabetes in rats. 50 adult Wistar albino male rats were used in the study, the rats were divided in 10 study groups. The body weight, serum glucose levels were measured, and histopathological examination was performed.

Results: In comparison to the diabetic control rats, significant increase in weight was found in animals of all the studied groups. Serum glucose levels reduced significantly in comparison to the STZ induced diabetic rats in all the animals. Histopathological examination showed prevention from brain damage and repair of the neuronal tissues by Ginger, Nigella sativa, Punica granatum and Metformin.

Conclusion: The studied substances were observed to possess preventive and curative effects on the brain damage caused by diabetes mellitus.

Low levels of serum complement factor H is associated with increasing progression of bronchiectasis

2019-07-17T11:33:13+00:00

Introduction: Complement Factor H (CFH) is the major soluble regulatory protein that monitors activation and/or amplification of the complement system. Here, we assess serum levels of complement factor H (CFH) among patients, who were diagnosed with bronchiectasis.

Methods: 115 subjects of 80 patients and 35 healthy volunteers were recruited for the study. Blood samples were collected and subjected to centrifugation in order to obtain the serum. The sensitive sandwich ELISA technique, specific for CFH was used for evaluation of CFH in the serum.

Results: The age and Body Mass Index (BMI) (expressed as Mean+/-SEM (range)) of the observed bronchiectasis patients and healthy volunteers were 66+/-1.13, (30-86) years, 54+/-2.37 (27-84) years and 26.14 kg/m2, 27.4 kg/m² respectively. CFH was detected in 27.0% of all subjects examined. It was found to be more common among bronchiectasis patients (18.26%) compared to healthy volunteers (8.70%) (F=0.9362; df=1; p<0.05). Mean CFH concentration was 17.0pg/ml and 9.0pg/ml in bronchiectasis patients and healthy volunteers respectively. FEV1% Pre. FEV1/VC% and CFH levels were found to decrease with increasing severity of bronchiectasis. The association between lung function, CFH levels and severity of disease among bronchiectasis patients was negative, strongly linear (r= -0.9316, r² =0.8678) and statistically significant (p<0.0001).

Conclusion: As such, it can be inferred that low level of compliment factor H is related to the progression of bronchiectasis.

Therapeutic efficacy of Boerhaavia diffusa (Linn.) root methanolic extract in attenuating streptozotocin-induced diabetes, diabetes-linked hyperlipidemia and oxidative-stress in rats

2019-07-17T11:33:12+00:00

Introduction: We have previously demonstrated that sequentially extracted methanolic fractions of Boerhaavia diffusa (Linn.) showed marked antioxidant, antidiabetic and oxidative-DNA damage protective properties in vitro. The present study was undertaken to evaluate the beneficial effects of B.diffusa (Linn.) methanolic root extract and its partially purified bioactive fraction on streptozotocin (STZ)-induced hyperglycemia and hyperlipidemia in rats.

Methods: The diabetic rats were treated for fourteen weeks either with methanolic extract of B. diffusa root (D-MT1, D-MT2, and D-MT3 : doses of 50, 150, and 300 mg/rat/day, respectively), partially isolated bioactive fraction (DBT: 0.5 mg/rat/day), or glibenclamide (D-GT: 0.5 mg/rat/day).

Results: The level of fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) were significantly alleviated in D-MT- and D-BT treated groups after fourteen weeks of administration. Moreover, plasma lipid profile, free fatty acids (FFAs), phospholipids (PLs), HMG-CoA reductase (HMG-R) activity, conjugated diene (CD), lipid hydroperoxide (LOOH), and malondialdehyde (MDA) were also markedly ameliorate d in all treatment groups. In addition, the activity of antioxidant enzymes, e.g., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (Gred), and glutathione-S-transferase (GST), were also significantly restored by D-MT — and D-BT — treated groups. Furthermore, histologically, all the unseemly features of nephropathy were extensively regressed and normalized by the administration of B. diffusa and its bioactive fraction.

Conclusions: Our results demonstrate a strong antidiabetic and hypolipidemic impact of B. diffusa extract an ideal alternative therapeutic agent in the prevention and treatment of diabetes as well as diabetes-linked hyperlipidemia.

Apolipoprotein E gene polymorphism influenced glycemic status among Malaysians

2019-07-17T11:33:10+00:00

Aim: In the last decade Apolipoprotein E (APOE) gene polymorphism has been identified as one of the risk factors of type 2 diabetes mellitus (T2DM). Though more than 11% population of Malaysia are suffering from T2DM, there is inadequate data on the correlation between the APOE gene polymorphism and pathogenesis of diabetes among Malaysians. Hence, in this study we aimed to find out the association between the frequencies of APOE allele and fasting blood glucose (FBG) concentration among subjects with T2DM.

Methods: A total of 102 subjects were recruited into two distinct groups, 51 in diabetes (cases) and 51 in non-diabetes (control) group. Their fasting blood sample was tested for FBG, while APOE genotyping was carried out using restriction fragment length polymorphism technique. Predictive Analytics Software (PASW) statistics, version 18.0, was used for statistical analyses.

Results: There was no association between APOE alleles and T2DM; odd ratios for the e2, e3 and e4 alleles were 1.51 (95%CI: 0.615-3.706), 0.77 (95%CI: 0.431-1.375) and 1.12 (95%CI: 0.584-2.131) respectively. The highest mean FBG was found in subjects with e2 alleles, followed by e4 and e3 alleles in both cases and control groups. Both e2 and e4 alleles were significantly linked to higher mean FBG (p=0.03 and 0.04 for the respectively) compared to e3 allele in diabetes group.

Conclusions: Although the APOE gene was not found to be associated with T2DM, it may influence glycemic status among subjects.