Fermented Rooibos tea (Aspalathus linearis) Ameliorates Sodium Fluoride-Induced Cardiorenal Toxicity, Oxidative Stress, and Inflammation via Modulation of NF-κB/IκB/IκKB Signaling Pathway in Wistar Rats.

High dose of fluoride intake is associated with toxic effects on kidney and cardiac tissues. This study evaluated the potential protective effect of fermented rooibos tea (RTE) on sodium fluoride (NaF)-induced cardiorenal toxicity in rats. Male Wistar rats (n = 56) were randomly allocated into one of seven equal groups: control, NaF (100 mg/kg orally), NaF + RTE (2%, w/v), NaF + RTE (4%, w/v), NaF + lisinopril (10 mg/kg orally), 2% RTE, and 4% RTE. The experiment lasted for 14 days and RTE was administered to the rats as their sole source of drinking fluid. NaF induced cardiorenal toxicity indicated by elevated level of urea, creatinine, LDH, creatinine kinase-MB, and cardiac troponin I in the serum, accompanied by altered histopathology of the kidney and heart. Furthermore, levels of H2O2, malondialdehyde, and NO were elevated, while GSH level was depleted in the kidney and heart due to NaF intoxication. Protein levels of c-reactive protein, TNFα, IL-1B, and NF-κB were increased by NaF in the serum, kidney, and heart. RTE at 2% and 4% (w/v) reversed cardiorenal toxicity, resolved histopathological impairment, attenuated oxidative stress and inhibited formation of pro-inflammatory markers. RTE at both concentrations down-regulates the mRNA expression of NF-κB, and upregulates the mRNA expression of both IκB and IκKB, thus blocking the activation of NF-κB signaling pathway. Taken together, these results clearly suggest that the protective potential of rooibos tea against NaF-induced cardiorenal toxicity, oxidative stress, and inflammation may be associated with the modulation of the NF-κB signaling pathway.

Anacardium occidentale leaves extract and riboceine mitigate hyperglycemia through anti-oxidative effects and modulation of some selected genes associated with diabetes.

Background: Diabetes mellitus (DM) is one of the leading causes of death globally and complications of DM have become a major health concern. Anacardium occidentale is a plant widely recognized for its hypoglycemic properties and traditionally used in developing nations as remedy for DM treatment. Riboceine is a supplement that enhances production of glutathione and known for its vital role in supporting cellular function. This study was designed to evaluate the antidiabetic and antioxidant potential of riboceine and ethanolic extract of A. occidentale leaves in streptozotocin (STZ)-induced diabetic rats. Method: Twenty-nine adult male Wistar rats were induced with DM intraperitoneally using a single dose of STZ (70 mg/kg). The STZ-induced rats were divided into groups and administered the same dose (100 mg/kg) of A. occidentale leaves extract and riboceine via gastric gavage at the dose (100 mg/kg) for seventeen days while metformin (40 mg/kg) was used as positive control. Fasting blood glucose and weight of the model rats were examined periodically. Activities of total protein, creatinine, urea, antioxidants (SOD, GSH and GPX), and level of serum insulin were determined. Expression of diabetes related genes including pancreas (Insulin, pdx-1, P16NK4A, and Mki-67), Liver (FAS, ACC, and GFAT) and KIM-1 genes were also determined. Results: Data showed that treatment of STZ-induced diabetic rats with A. occidentale and riboceine at the same dose significantly (p < 0.05) ameliorated hyperglycemic effects by improving hepatic and renal functions and antioxidants, preventing hepatic fat accumulation by downregulation of ACC, FAS and GFAT expression, improving ß-cell functions through up-regulation of pancreatic insulin, P16NK4A, Mki-67 and pdx-1 expression. Induction of diabetes upregulated mRNA expression of KIM-1, which was ameliorated after treatment of the rats with A. occidentale and riboceine. Conclusion: The results obtained in this study demonstrate significant antidiabetic properties of ethanolic extract of A. occidentale and riboceine.

Hepatoprotective Effect of Morin Hydrate in Type 2 Diabetic Wistar Rats Exposed to Diesel Exhaust Particles.

Studies have shown that exposure to air pollutants such as diesel exhaust particles (DEP) exacerbate diabetes complications. Morin hydrate (MH), a plant bioflavonoid, provides hepatoprotection due to its diverse pharmacological properties. This study examines the hepatoprotective effects of MH in Wistar rats with type 2 diabetes exposed to diesel exhaust (DE). Procured male Wistar rats (n = 60) were separated into 12 groups of five rat each. Type 2 diabetes was induced following oral therapy with fructose solution and one-time injection of 45 mg/kg of streptozotocin (STZ). The DEP extract was administered by nasal instillation, whereas MH was administered via oral gavage. Biochemical assays were used to determine the effect of MH on diabetic rats and DEP-exposed diabetic rats with respect to liver function indices (AST and ALT), liver antioxidants (SOD, CAT, Gpx, and GSH), lipid profile, and oxidative stress marker (conjugated diene and lipid peroxidation). The mRNA expression of PI3K/AKT/GLUT4 and AMPK/GLUT4 signaling pathways were quantified using RT-PCR. The results show that normal rats, diabetic rats, and diabetic rats exposed to DEP exhibited a substantial decrease in oxidative stress indicators, serum lipid profile, and levels of AST and ALP, as well as an increase in liver natural antioxidants following oral administration of MH. The gene expression study demonstrated that MH promotes the activation of the insulin signaling pathways which facilitates the uptake of glucose from the blood. This study suggests that MH offered hepatoprotection in type 2 diabetic rats and DEP exposed diabetic rats.

Morin hydrate protects type-2-diabetic wistar rats exposed to diesel exhaust particles from inflammation and oxidative stress.

Background: Studies have demonstrated that exposure to diesel exhaust particle (DEP) aggravates diabetes condition by inducing oxidative and pro-inflammatory effects. Morin hydrate (MH), a flavonol found in common guava, among others has been demonstrated to possess a variety of biological activities. The present study was designed to investigate the effects of morin hydrate (MH) on the pancreas of type-2 diabetic (T2D) wistar rats exposed to DEP. Methods: Rats were induced with type 2 diabetes by oral fructose therapy for 14 days followed by injection of streptozotocin (45 mg/kg). These rats were pre-treated with DEP (0.4 mg/kg and 0.5 mg/kg) through nasal instillation prior to receiving oral MH (30 mg/kg).This study determined oxidative stress parameters using biochemical assay, and some pancreatic genes involved in oxidative stress, inflammation and glucose uptake were quantified using RT-polymerase chain reaction (PCR). Results: The results indicate that MH reverses oxidative stress in T2D rats exposed to DEP via substantial increase in superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity and reduced glutathione (GSH) levels, but a decrease in malondialdehyde (MDA) and conjugated diene (CD) levels. Moreover, PCR assay showed that MH mitigate inflammation and oxidative stress but promote glucose uptake by increasing the mRNA expression of IL-10, HO-1, and GLUT 4; decreasing mRNA expression of IL-1 and modulating AKT/PI3K/GLUT4 and AMPK/GLUT4 signaling. Histopathological examination revealed that MH reverses DEP induced pancreatic fibrosis and necrosis. Conclusion: The results suggest that MH alleviate inflammation and oxidative stress and promote glucose uptake in the pancreas of type-2 diabetic rats, either in the presence or absence of DEP.

Newly designed compounds from scaffolds of known actives as inhibitors of survivin: computational analysis from the perspective of fragment-based drug design.

Survivin is an apoptosis suppressing protein linked to different forms of cancer. As it stands, there are no approved drugs for the inhibition of survivin in cancer cells despite a number of promising compounds in clinical trials. This study designed a new set of compounds from fragments of active survivin inhibitors to potentiate their binding with survivin at BIR domain. Three hundred and five (305) fragments made from eight potent inhibitors of survivin were reconstructed to form a new set of compounds. The compounds were optimized using R group enumeration and bioisostere replacement after extensive docking analysis. The optimised compounds were filtered by a validated pharmacophore model to reveal how well they are aligned to the pharmacophore sites. Molecular docking of the well aligned compounds revealed the top-scoring compounds; and these compounds were compared with the eight inhibitors used as template for fragment-based design on the basis of binding affinity (rigid and flexible docking), predicted pIC50 and intermolecular interactions. The electronic behaviours (global descriptors, HOMO/LUMO, molecular electrostatic potential and Fukui functions) of newly designed compounds were calculated to investigate their reactivity and atomic sites prone to neutrophilic/electrophilic attack. The nine newly designed compounds had better rigid and flexible docking scores, free energy of binding and intermolecular interactions with survivin at BIR domain than the eight active inhibitors. Based on frontier molecular orbitals, OPE-3 was found to be the most reactive and less stable compound (0.13194 eV), followed by OPE-4 and OPE-9. The global descriptive parameters showed that OPE-3 had highest softness value (7.5245 eV) while OPE-8 recorded the maximum hardness value (0.08486 eV). The well-validated QSAR model also showed that OPE-3, OPE-7 and OPE-8 had the most significant bioactivity of all the inhibitors. This study thus provides new insight into the design of compounds capable of modulating the activity of survivin. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-021-00108-8.