Allium jesdianum Extract Induces Oxidative Stress and Necroptosis in Human Colorectal Cancer (HT-29) Cell Line

Abstract This study aimed to evaluate the toxic impact of hydro-alcoholic Allium jesdianum extract (AJE) on the growth of HT-29 human colorectal cancer cell line. Phytochemical analysis using gas chromatography and mass spectroscopy (GCMS) was done to determine the bioactive components of AJE. HT-29 cells exposed to 0 (control), 25, 50, and 100 ��g/mL of AJE for 48 hours. Cell survival, colony numbers, flow cytometry, oxidative stress, and gene expression were examined to evaluate the toxic impacts of the AJE. Twelve different phyto-constituents with peak areas were determined by the GCMS analysis. The major compounds were Allicin and α-Pinene. AJE considerably reduced the viability and colony numbers of the HT-29 cells. The AJE concentration-dependently increased necrosis, but not apoptosis in the HT-29 cells. AJE upregulated the expression of necroptosis-associated genes including RIPK1, RIPK3, and MLKL in a concentration-dependent manner. AJE also dose-dependently enhanced MDA contents and reactive oxygen species (ROS) level and diminished antioxidant enzyme level in the HT-29 cells. These data collectively indicated that AJE prevented the growth of the HT-29 cells by inducing oxidative stress, and activation necroptosis signaling pathways.

Anti-diabetic effect of betulinic acid on streptozotocin-nicotinamide induced diabetic male mouse model

ABSTRACT Diabetes is a metabolic disease caused by abnormal insulin secretion or action. In the present study, the effects of betulinic acid (BA, a triterpene) are evaluated on glucose, α-amylase and plasma insulin levels, insulin resistance and the histopathology of pancreatic islets in streptozotocin-nicotinamide (STZ-NA) diabetic mice. Seventy adult male NMRI mice were randomly divided into seven groups: control, sham, diabetic, diabetic treated with BA (10, 20 and 40 mg/kg) and diabetic treated with metformin (200 mg/kg). Diabetes was induced in mice by intraperitoneal injection of streptozotocin 50 mg/kg after a dose of nicotinamide 120 mg/kg. Two weeks after treatment with BA, blood samples were collected for measuring glucose, α-amylase and insulin levels, and the pancreas was isolated for histopathology evaluation. Diabetes reduced the number and diameter of pancreatic islets, and increased α-amylase and insulin resistance. BA treatment reduced blood glucose, α-amylase and improved insulin sensitivity as well as pancreas histopathology. In addition, BA showed stronger effects on the pancreatic histology and insulin resistance compared to the metformin group

Safety Assessment of a New Pigmented Safflower Seed Coat (A82) by a Feeding Study on Rat

ABSTRACT Safflower (Carthamus tinctorius L.) is an annual herbaceous plant, cultivated mainly for the seed which is used for edible oil extraction and bird feeding. This study was designed to evaluate the safety of a new pigmented variety of safflower (A82) seeds. The results showed that oral administration of A82 seeds significantly increased the body weight of male rats in a dose-dependent manner (p<0.05). Biochemical tests showed that A82 seeds significantly increased the serum levels of AST (Aspartate aminotransferase) (p<0.05), slightly reduced the serum levels of ALT (Alanine aminotransferase) and significantly reduced ALP (p<0.05) levels in a dose dependent manner. BUN (Blood Urea Nitrogen) and Cr (Creatinine) were not significantly changed in A82 seed treated groups. Also, testosterone levels were not significantly changed by administration of different doses of A82. However, Johnson scoring showed slightly decrease in experimental groups. No organ weight or histological changes were observed in liver, kidney, spleen, heart and brain of A82 seed treated animals. These results indicate that A82 seeds have not any toxic effects in Wistar rats. Future studies are required to clarify the exact mechanism by which A82 seeds alter AST levels and body weight in rat.

Exendin-4 effects on islet volume and number in mouse pancreas

The aim of this study was to evaluate Exendin-4 (EX-4) effects on islet volume and number in the mouse pancreas. Thirty-two healthy adult male NMRI mice were randomly divided into control and experimental groups. EX-4 was injected intraperitoneally (i. p.) at doses of 0.25 (E1 group), 0.5 (E2 group), and 1 µg/kg (E3 group), twice a day for 7 consecutive days. One day after the final injection, the mice were sacrificed, and the pancreas from each animal dissected out, weighed, and fixed in 10% formalin for measurement of pancreas and islet volume, and determination of islet number by stereological assessments. There was a significant increase in the weight of pancreases in the E3 group. Islet and pancreas volumes in E1 and E2 groups were unchanged compared to the control group. The E3 group showed a significant increase in islet and pancreas volume (P < 0.05). There were no significant changes in the total number of islets in all three experimental groups. The results revealed that EX-4 increased pancreas and islet volume in non-diabetic mice. The increased total islet mass is probably caused by islet hypertrophy without the formation of additional islets.

O objetivo deste estudo foi avaliar os efeitos do Exendin-4 (EX-4) sobre o volume e número de ilhotas no pâncreas. Trinta e dois camundongos NMRI machos saudáveis e adultos foram divididos ao acaso em grupos controle e grupos experimentais. EX-4 foi injetado intraperitonealmente (i. p.) nas doses de 0,25 (grupo E1), 0,5 (grupo E2) e 1 (grupo E3), duas vezes por dia durante 7 dias consecutivos. Um dia após a injeção final, os camundongos foram sacrificados e o pâncreas de cada animal foi dissecado, pesado e fixado em solução de formaldeído 10% para avaliação do volume do pâncreas e ilhotas e do número de ilhotas por métodos estereológicos. Observou-se aumento significativo no peso de pâncreas no grupo E3. O volume do pâncreas assim como das ilhotas não apresentou alterações nos grupos E1 e E2, quando comparados ao grupo controle No grupo E3 houve aumento significativo no volume do pâncreas e das ilhotas (P<0,05). Não se observaram alterações significativas no número de ilhotas nos três grupos experimentais. Os resultados revelaram que o EX-4 provoca aumento no volume do pâncreas, bem como no volume das ilhotas em camundongos não-diabéticos. O aumento no volume total de ilhotas deve-se, provavelmente, a hipertrofia das ilhotas sem a formação de ilhotas adicionais.