Effect of the Antibiotic Neomycin on the Toxicity of the Glycoside Vicine in Rats

Vicine is hydrolyzed by microflora to highly reactive free radical generating compound divicine which causes mortality and other adverse effects. This study in the rats established the effect of a broad spectrum and poorly absorbed antibiotic, neomycin sulfate on the toxicity of vicine. The results showed extremely decrease in mortality rate in the group pretreated with neomycin. Hemoglobin (Hb) concentration, hematocrit (Hct) value, and red blood cells (RBCs) count were significantly decreased after injection of vicine and the improvement of these values in the group pretreated with neomycin. The same results were observed in white blood cells (WBCs). The results showed a significant decrease in glucose level and returned to normal in group pretreated with neomycin. Glutathione (GSH) was significantly decreased in the vicine group and returned to normal value in the group pretreated with neomycin. Lipid peroxide (TBARs) was significantly increased in the group treated with vicine and neomycin pretreated group decreased to the normal level. Glucose-6-phosphate dehydrogenase (G6-PD) activity was significantly decreased and returned to normal level in rats pretreated with neomycin. Serum protein and globulin were significantly decreased but serum albumin showed insignificant decrease in vicine and neomycin groups compared to control. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly decreased in the vicine group. The group pretreated with neomycin showed significantly increased activities of AST and ALT compared with vicine group. In conclusion, neomycin pretreatment of rats injected with glycoside vicine decreased to a great extent of its toxic and mortality effects and is useful in favism and hemolytic anemia

POTENTIAL ANALGESIC AND ANTI-INFLAMMATORY EFFECT OF CUMINUM CYMINUM AND BORAGO OFFICINALIS IN RATS AND MICE

Objective: Our research aimed to study the potential therapeutic effect of Cuminum cyminum and Borago officinalis seed oil against inflammation induced by carrageenan as well as its central and peripheral analgesic effect. Methods: The anti-inflammatory effect was determined by measuring the edema rate and inhibition rate using Plethysmometer. Writhing test and hot plate test were used to determine the peripheral and central analgesic effect, respectively. Key Findings: Significant anti-inflammatory effects were witnessed for all the drugs at different dose levels in the results. Substantial analgesic effect against both peripheral and central pain induction was also incurred on administration of all doses of C. cyminum and B. officinalis seed oil. Conclusion: The C. cyminum and B. officinalis seed oil has potent anti-inflammatory and analgesic effects

Explicit mechanistic insights of Prosopis juliflora extract in streptozotocin-induced diabetic rats at the molecular level

Background: The Ancient system of medicine showed the limelight on the use of herbal remedies and was found to possess minimal side effects and acceptable therapeutic outcomes. In this context, Prosopis juliflora gained importance in managing chronic diseases such as cancer, dermatological diseases, and chronic inflammatory disorders. Hence, P. juliflora was selected for further investigation associated with diabetes and inflammation. Aim: The present study aimed to evaluate the anti-diabetic activity in chemically induced experimental rats and explore the nature of phytocomponents that may produce this activity. Methods: Experimentally, diabetes was induced by a single administration of streptozotocin at 50 mg/kg intraperitoneally in Wistar rats. The animals were treated orally with P. juliflora at low and high doses (200 and 400 mg/kg) for 10 days. Blood collected from the retro-orbital plexus was analyzed for parameters like blood glucose levels, insulin, adiponectin, Keap1 and Nrf2. PPAR-γ, AMPK and GLUT 2 levels were analyzed in the pancreatic tissue. Besides, at the end of the experiment, animals were sacrificed, and the pancreatic tissue sections were subjected for histopathological, morphometrical and immune histochemical exploration. The phytochemical composition of the plant was investigated by GC–MS. Results: The administration of P. juliflora higher dose showed a significant decrease (**p< 0.001) in blood glucose levels with a rise in adiponectin, PPARγ, Keap1, Nrf2, Glut 2, and AMPK significantly (**p< 0.001). The inflammatory cytokine TNFα was also estimated and was found to be lowered significantly (**p< 0.001) in test drug-treated animals. Furthermore, in the pancreatic tissue, the number of Islets, the area, and the number of β-cells were improved significantly with the sub-chronic treatment of P. juliflora extract. The structure and function of β-cells were also revamped. Conclusion: The study results demonstrated a significant effect of P. juliflora on glycemic status, inflammatory condition, and the architecture of pancreatic tissue. In the identification and isolation process by GC MS, it was noticed that P. juliflora contained few phytochemical constituents from which it might be considered a promising drug for type 2 diabetes mellitus

Novel CoQ10 antidiabetic mechanisms underlie its positive effect: modulation of insulin and adiponectine receptors, Tyrosine kinase, PI3K, glucose transporters, sRAGE and visfatin in insulin resistant/diabetic rats.

As a nutritional supplement, coenzyme Q10 (CoQ10) was tested previously in several models of diabetes and/or insulin resistance (IR); however, its exact mechanisms have not been profoundly explicated. Hence, the objective of this work is to verify some of the possible mechanisms that underlie its therapeutic efficacy. Moreover, the study aimed to assess the potential modulatory effect of CoQ10 on the antidiabetic action of glimebiride. An insulin resistance/type 2 diabetic model was adopted, in which rats were fed high fat/high fructose diet (HFFD) for 6 weeks followed by a single sub-diabetogenic dose of streptozotocin (35 mg/kg, i.p.). At the end of the 7(th) week animals were treated with CoQ10 (20 mg/kg, p.o) and/or glimebiride (0.5 mg/kg, p.o) for 2 weeks. CoQ10 alone opposed the HFFD effect and increased the hepatic/muscular content/activity of tyrosine kinase (TK), phosphatidylinositol kinase (PI3K), and adiponectin receptors. Conversely, it decreased the content/activity of insulin receptor isoforms, myeloperoxidase and glucose transporters (GLUT4; 2). Besides, it lowered significantly the serum levels of glucose, insulin, fructosamine and HOMA index, improved the serum lipid panel and elevated the levels of glutathione, sRAGE and adiponectin. On the other hand, CoQ10 lowered the serum levels of malondialdehyde, visfatin, ALT and AST. Surprisingly, CoQ10 effect surpassed that of glimepiride in almost all the assessed parameters, except for glucose, fructosamine, TK, PI3K, and GLUT4. Combining CoQ10 with glimepiride enhanced the effect of the latter on the aforementioned parameters.These results provided a new insight into the possible mechanisms by which CoQ10 improves insulin sensitivity and adjusts type 2 diabetic disorder. These mechanisms involve modulation of insulin and adiponectin receptors, as well as TK, PI3K, glucose transporters, besides improving lipid profile, redox system, sRAGE, and adipocytokines. The study also points to the potential positive effect of CoQ10 as an adds- on to conventional antidiabetic therapies

Isolation of Antiosteoporotic Compounds from Seeds of <i>Sophora japonica</i>

<div><p>Chemical investigation of <i>Sophora japonica</i> seeds resulted in the isolation of seven metabolites identified as: genistin (<b>1</b>), sophoricoside (<b>2</b>), sophorabioside (<b>3</b>), sophoraflavonoloside (<b>4</b>), genistein 7,4’-di-<i>O</i>-<i>β</i>-D-glucopyransoide (<b>5</b>), kaempferol 3-<i>O</i>-<i>α</i>–L-rhamnopyranosyl(1→6)<i>β</i>-D-glucopyranosyl(1→2)<i>β</i>-D-glucopyranoside (<b>6</b>) and rutin (<b>7</b>). Compounds <b>1</b>, <b>2</b> and <b>5</b> showed significant estrogenic proliferative effect in MCF-7 cell in sub-cytotoxic concentration range. Compounds <b>1</b> and <b>2</b> showed minimal cell membrane damaging effect using LDH leakage assay. Accordingly, compound <b>2</b> (sophoricoside, (SPH)) was selected for further <i>in-vivo</i> studies as a potential anti-osteoporosis agent. The anti-osteoporotic effect of SPH was assessed in ovarectomized (OVX) rats after oral administration (15 mg/kg and 30 mg/kg) for 45 days compared to estradiol (10 µg/kg) as a positive control. Only in a dose of 30 mg/kg, SPH regained the original mechanical bone hardness compared to normal non-osteoporotic group. However, SPH (15 mg/kg) significantly increased the level of alkaline phosphatase (ALP) to normal level. Treatment with SPH (30 mg/kg) increased the level of ALP to be higher than normal group. SPH (15 mg/kg) did not significantly increase the serum level of osteocalcin (OC) compared to OVX group. On the other hand, treatment with SPH (30 mg/kg) significantly increased the level of OC to 78% higher than normal non-ovarectomized animals group. In addition, SPH (15 mg/kg) decreased the bone resorption marker, acid phosphatase (ACP) to normal level and SPH (30 mg/kg) further diminished the level of serum ACP. Histopathologically, sophoricoside ameliorated the ovarectomy induced osteoporosis in a dose dependent manner. The drug showed thicker bony trabeculae, more osteoid, and more osteoblastic rimming compared to OVX group.</p></div

Effect of 2 weeks daily oral administration of CoQ10 (10 mg/kg) and/or glimepiride (0.5 mg/kg) on serum level of reduced glutathione (GSH), malondialdehyde (MDA), adiponectin, visfatin and soluble receptor of advanced glycated end product (sRAGE) in HFFD/STZ diabetic rats.

<p>Values are means ± S.E of 8–10 animals. As compared with normal control (*), diabetic control (^#), glimepiride treated (^$) and CoQ10 treated (^{<a href="mailto:@" target="_blank">@</a>}) groups (one-way ANOVA followed by Tukey-Kramer post hoc test), <i>P</i><0.05.</p

Effect of diabetes and 2 weeks oral administration of CoQ10 (20 mg/kg) and/or glimepiride (0.5 mg/kg) on the hepatic (A) and muscular (C) glucose transporters [ng/mg protein], and (B, D) myeloperoxidase activity [MPO, U/mg].

<p>Values are means of 8–10 animals ± S.E.M. As compared with normal control (*), diabetic control (^#), glimepiride treated (^$) and CoQ10 treated (^{<a href="mailto:@" target="_blank">@</a>}) groups (one-way ANOVA followed by Tukey-Kramer post hoc test), <i>P</i><0.05.</p

The assessment of food and fructose/water intake, and body weight of the rats before and at the end of the HFFD.

<p>Values are presented as means <b>±</b> S.E.M. (n = 70–80). Animals were fed high fat diet [HFD] and were allowed free access to 20% fructose in water throughout the 6 weeks. Diet manipulation was stopped after the STZ injection on day 1 of the 7^th week. During this week animals received normal fat diet [NFD] and water. Caloric intake for NFD = food intake (g) × 3.15 kcal, caloric intake for HFD = food intake (g) × 5.3 kcal and caloric intake for 20% fructose = 0.6 kcal/ml. As compared with 1^st week (^*), and 7^th week (^#) (one-way ANOVA followed by Tukey-Kramer post hoc test), <i>P</i><0.05.</p

The glucose tolerance curve depicts the changes in glucose (2 g/kg, p.o) response in serum of normal control group (NFD) and non-treated insulin-resistant rats (HFFD), after 6 weeks of food manipulation at 0, 30, 60, 90, and 120 min.

<p>Values are means ± S.E of 6 animals; as compared to the normal control group (*) (one-way ANOVA followed by Tukey-Kramer post hoc test), <i>P</i><0.05.</p

Effect of diabetes and 2 weeks oral administration of CoQ10 (20 mg/kg) and/or glimepiride (0.5 mg/kg) on the hepatic (A, B) and muscular (C, D) insulin receptor isoforms (high affinity, [HAIR, fmol/mg protein] and low affinity [LAIR, pmol/mg protein] insulin receptor).

<p>Values are means of 8–10 animals ± S.E.M. As compared with normal control (*), diabetic control (^#), glimepiride treated (^$) and CoQ10 treated (<a href="mailto:@" target="_blank">@</a>) groups (one-way ANOVA followed by Tukey-Kramer post hoc test), <i>P</i><0.05.</p