Umbelliprenin shows antitumor,antiangiogenesis, antimetastatic,anti‐inflammatory,and immunostimulatory activities in 4T1 tumor‐bearing Balb/c mice

Umbelliprenin (UMB) has shown various pharmacological properties in vitro. We investigated the antineoplastic and immunostimulatory effects of UMB in 4T1 mammary‐tumor‐bearing mice. Two‐hundred microliter of UMB (12.5 mg/ml) was intraperitoneally administrated to healthy and tumor‐bearing female Balb/c mice for a period of 18 days. Data was analyzed using GraphPad Prism 5 software for Windows (version 5, La Jolla, CA). UMB caused a significant decrease in tumor size (P < 0.01). Serum interferon gamma (IFNγ) was augmented in both healthy and tumor‐bearing animals (P < 0.01), and IL‐4 declined in healthy animals (P < 0.01) treated with UMB. Expressions of Ki‐67, VEGF, CD31, MMP2, MMP9, VCAM1, and NF‐κB were significantly decreased in tumors from UMB‐treated animals (P < 0.001), whereas E‐Cadherin and TNFR1 expressions were markedly increased (P < 0.001). The rates of liver and lung metastases in UMB‐administrated animals were smaller compared to the control. UMB can potently inhibit tumor growth, angiogenesis, metastasis, and inflammation and potentiate an antitumor immune response in vivo. However, further investigations are required to evaluate the UMB mechanisms of action in cancerous cells.     

Possible molecular mechanisms of glucose-lowering activities of Momordica charantia (karela) in diabetes

Diabetes mellitus is a highly prevalent metabolic disorder which is characterized by impaired glucose tolerance, with a relative or absolute insulin deficiency and profound changes in the metabolism of macronutrients. Traditional and complementary medicine is therapeutic strategies that have both been applied to improving glycemic control. Momordica charantia is one of the plant-based, folk medicines that used for improving glycemic control. We aimed to review, the effects of M. charantia on blood glucose with a clarification of the molecular pathways involved. Of the compounds derived from the plants, the insulin-like peptide, charantin, and the alkaloid vicine, have been reported to have hypoglycemic effects. Different mechanisms contribute to the antidiabetic activities of M. charantia, these include increasing pancreatic insulin secretion, decreasing insulin resistance and increasing peripheral and skeletal muscle cell glucose utilization, inhibition of intestinal glucose absorption and suppressing of key enzymes in the gluconeogenic pathways.     

HHEX gene polymorphisms and type 2 diabetes mellitus: A case-control report from Iran

Genome-wide association studies indicated that hematopoietically-expressed homeobox (HHEX) gene is a remarkable candidate for type 2 diabetes (T2D) mellitus susceptibility in spite of the fact that the results are ambiguous in some cases. So, this study aimed to evaluate the possible correlation between HHEX gene polymorphisms and T2D development in a sample of the Iranian population. The rs1111875G/A, rs7923837A/G, and rs5015480C/T HHEX gene polymorphisms were genotyped in 250 cases and 250 matched (age and sex) healthy controls using tetra-amplification-refractory mutation system-polymerase chain reaction method. The finding revealed the all measured inheritance models of rs1111875G/A and of rs5015480C/T variants dramatically increase the risk of T2D while another polymorphism (rs7923837A/G) was not associated with risk/protective role in T2D. The results indicated that rs1111875G/A and rs5015480C/T may contribute to the enhancement of T2D risk in a sample of the southeast Iranian population.     

Two-spotted spider mite reared on resistant eggplant affects consumption rate and life table parameters of its predator,Typhlodromus bagdasarjani (Acari: Phytoseiidae)

The blue tick, Rhipicephalus microplus, threatens cattle production in most tropical and subtropical areas of the world. Delayed skin hypersensitivity reactions are thought to cause Nguni cattle to be more resistant to R. microplus than Bonsmara cattle yet the cellular mechanisms responsible for these differences have not been classified. Tick counts and inflammatory cell infiltrates in skin biopsies from feeding sites of adult R. microplus ticks were determined in 9-month-old Nguni and Bonsmara heifers to determine the cellular mechanisms responsible for tick immunity. Nguni heifers (1.7 ± 0.03) had lower (P < 0.05) tick counts than the Bonsmaras (2.0 ± 0.03). Parasitized sites in Nguni heifers had higher counts of basophils, mast and mononuclear cells than those in the Bonsmara heifers. Conversely, parasitized sites in Nguni heifers had lower neutrophil and eosinophil counts than those in the Bonsmara heifers. Tick count was negatively correlated with basophil and mast cell counts and positively correlated with eosinophil counts in both breeds. In the Bonsmara breed, tick count was positively correlated with mononuclear cell counts. Cellular responses to adult R. microplus infestations were different and correlated with differences in tick resistance in Nguni and Bonsmara cattle breeds. It is essential to further characterise the molecular composition of the inflammatory infiltrate elicited by adult R. microplus infestation to fully comprehend immunity to ticks in cattle.     

Effect of crocus sativus on gentamicin induced nephrotoxicity

Crocus sativus, known as saffron, is used in folk medicine for treatment of different types of diseases, and its anti-inflammatory and free radical scavenging activities have been demonstrated. The present study evaluated gentamicin nephrotoxicity in saffron treated rats. Male Wistar rats (200-250 g) were treated with saffron (40 or 80 mg/k/d) for 10 days, or saffron (40 or 80 mg/ kg/d) for 10 days and gentamicin 80 mg/kg/d for five days, starting from day 6. At the end of treatment, blood samples were taken for measurement of serum creatinine (SCr) and BUN. The left kidney was prepared for histological evaluation and the right kidney for Malondialdehyde (MDA) measurement. Gentamicin 80 (mg/k/d) increased SCr, BUN and renal tissue levels of MDA and induced severe histological changes. Saffron at 40 mg/k/d significantly reduced gentamicin-induced increases in BUN and histological scores (p<0.05). Gentamicin-induced increases in BUN, SCr and MDA and histological injury were significantly reduced by treatment with saffron 80 mg/k/d (p<0.05, p<0.001, p<0.05, and p<0.001 respectively). In conclusion, our results suggest that saffron treatment reduces gentamicin-induced nephrotoxicity and this effect seems to be dose dependent.     

Anticholinesterase activity of some major intermediates in carbacylamidophosphate synthesis: Preparation,spectral characterization and inhibitory potency determination

Carbacylamidophosphates with the general formula RC(O)NHP(O)R₁R₂ constitute organophosphorus compounds that are used as insecticides, pesticides and ureas inhibitors. In this work, we studied the inhibition potency of CCl₃C(O)NHP(O)Cl₂1, CHCl₂C(O)NHP(O)Cl₂2, CH₂ClC(O)NHP(O)Cl₂3 and CF₃C(O)NHP(O)Cl₂4, which are the major intermediates for carbacylamidophosphates synthesis towards human erythrocyte acetylcholinesterase (hAChe) activity using Ellman's modified kinetic method. Unexpectedly, it was observed that they were not only hydrolytically unstable but also inhibited hAChE in a similar manner to that produced by organophosphorus insecticides. Enzymatic data, bimolecular inhibition rate constants (k_i) and IC₅₀ values for inhibition of hAChE demonstrated that they are irreversible inhibitors and the inhibition potency of compound 2 (IC₅₀ = 88 μM) was the greatest in comparison with compounds 1, 3 and 4. Also the electropositivity of the phosphorus atom and the hydrophobicity of the compounds demonstrated that these two factors play an additional effect and different role in the inhibitory activity of these compounds. Hydrolytic stability of the compounds was determined by ³¹P NMR monitoring of the loss of the parent molecules with D₂O as a function of time. This study considers antiacetylcholinesterase activity according to the structural and the electronic aspects of compounds 1–4, according to IR, ¹H, ¹³C and ³¹P NMR spectral data.