The Effects of Urtica dioica and Lamium album Extracts on the Expression Level of Cyclooxygenase-2 and Caspase-3 in the Liver and Kidney of Streptozotocin-Induced Diabetic Rats

Background: Diabetes seems to be associated with increased inflammation and induced apoptosis in several tissues. Urtica dioica and Lamium album have shown to possess a variety of beneficial properties like anti-inflammatory effects. In this experimental study, we tried to evaluate the effects of U. dioica and L. album extracts on the expression level of cyclooxygenase-2 (COX-2; as an inflammation marker) and caspase-3 (CASP-3; as an apoptotic marker) in the liver and kidney tissues of diabetic rats. Methods: Thirty-two male Wistar rats were randomly allocated to four groups: normal control, diabetic control, diabetic treated with U. dioica (100 mg/kg/daily), and diabetic treated with L. album (100 mg/kg/daily) for 28 days. At the end of the study, liver and kidney tissues were harvested and mRNA expression level of COX-2 and CASP-3 was determined by real-time PCR technique. Also, serum glucose was measured. Results: Liver COX-2 mRNA in diabetic rats was significantly higher than normal control rats (P=0.02). However, U. dioica and L. album caused significant decrease in mRNA expression of liver COX-2 in diabetic rats (P=0.015 and P=0.03, respectively). Also, in diabetic rats treated with both extracts, serum glucose was remarkably lower than diabetic control rats (P<0.0001 and P<0.01, respectively). Conclusion: It appears that U. dioica and L. album might decrease liver damage by decreasing the inflammatory effects of COX-2 in streptozocin-induced diabetic rats. Since these plant extracts may influence diabetes by several mechanisms, further research in this field is warranted

The Relationship Between Janus Kinase Pathways and MicroRNAs

Janus Kinase (JAK) family is a group of four signaling enzymes composing of four distinct domains and involved in the intracellular pathways of cytokine downstream signaling. There are two kinase domains at C-terminal of protein, one of which is regulatory and the other has the main functionality in phosphorylation of target proteins. JAKs involve in the critical physiological processes, including immune response, growth, and differentiation. Mutations or malfunction of JAKs gene can result in pathological conditions like immuno-inflammatory diseases and malignancies. Targeting of JAK enzymes has been considered as effective therapeutic approaches in immuno-inflammatory disorders and different types of hematopoietic cancers or solid tumors. Rather than cytokines that are the natural modulators and the small chemical inhibitors developed as the therapeutic modulators of JAK enzymes, miRNAs can exert regulatory activity on JAKs. miRNAs are valuable biomarkers and regulatory elements of different pathophysiological conditions, particularly cancers. The relationships between JAK enzymes and miRNA are bi-directional, as the JAKs activity through JAK-STAT pathway as well as some other non-STAT pathways, control the expressions of various genes. These connections help scientists to design and develop novel therapeutic agents and predict the prognosis of disease following therapeutic regimens, based on these two critical components of cell biology. HIGHLIGHTS•Janus kinase family consists of four signaling enzymes involved in cytokine signaling pathways.•Modifications of JAK enzymes resulted in various pathological conditions.•JAK2 modification is reported in several types of cancers.•JAK modulators have been approved by FDA for treatment of several immunological and neoplastic disorders

Development and stability comparison of targeted therapeutic nanomolecules of aptamer-miRNA conjugates using two methods of conjugation

Introduction: An important issue in cancer therapy is the achievement of desired therapeutic response with the least adverse effects. To achieve this goal, targeted drug delivery systems were developed. Aptamers, mainly DNA/RNA aptamers, are the attractive affinity ligands for the cancer cell surface specific antigens. Besides, microRNAs are another type of therapeutic and diagnostic oligonucleotides that have been recently studied in various cancers. miRNAs are small double stranded RNAs with important roles in cell regulatory pathways. Profile changes of miRNAs can result in cancer development. External addition of miRNAs or their elimination using antagomiR can lead to the efficient treatment of related disease. Targeted delivery of therapeutic agents to the site of action with less adverse effects is the most challenging issue in anticancer chemotherapeutic agents as well as miRNA therapy. In addition, miRNAs stability in biological systems can be improved by targeting strategy. In this study, a cancer specific aptamer (anti-nucleolin aptamer) and a functional miRNA in cell growth and proliferation (miRNAlet-7d) were used in the development of targeted nano-molecules as an efficient anti-proliferative agent for cancer cells. &nbsp; Methods and Results: Sequences of A1411 aptamer and miRNA let-7d were extracted from related databanks and were chemically synthesized with amine and thiol modification in the 3' terminals or with a 17 nucleotides sticky extension at 3' terminal.&nbsp; The sequences were conjugated covalently using SM(PEG)2 hetero-bi-functional cross-linker or un-covalently by annealing the sticky ends. Conjugation was confirmed using polyacrylamide gel electrophoresis 15%. The serum stability of these two types of conjugates were evaluated using up to 48 h incubation of conjugates in human serum (AB+). Stability of covalent conjugate using SM(PEG)2 linker was at least two hours more than the un-covalent one. &nbsp; Conclusions: Remarkable advantages of this nano-molecule were targeted and relative stable delivery of miRNA as the therapeutic agent with probable synergistic effect of two oligonucleotides of miRNA and aptamer in the proliferation inhibition of cancer cells

LAMIUM ALBUM OR URTICA DIOICA? WHICH IS MORE EFFECTIVE IN DECREASING SERUM GLUCOSE, LIPID AND HEPATIC ENZYMES IN STREPTOZOTOCIN INDUCED DIABETIC RATS: A COMPARATIVE STUDY

Objectives: Diabetes mellitus, the most common endocrine disorder, is defined by hyperglycaemia. Urtica dioica or stinging nettle is known to have antidiabetic effects. Lamium album or non stinging nettle is shown to have some beneficial effects such as antioxidant, and cytoprotective properties. The purpose of this study was to compare the effects of hydroalchoholic extract of L. album and U. dioica on serum glucose, lipids and hepatic enzymes level in sterptozotocin induced diabetic rats. Methods: Thirty-two male Wistar rats were randomly assigned into four groups; normal control, diabetic control, diabetic treated with U. dioica (100 mg/kg/daily), diabetic treated with L. album (100 mg/kg/daily) for 28 days. Serum glucose, cholesterol, triglyceride (TG), alanin trasaminase (ALT), alkaline phosphatase (ALP) and aspartate transaminase (AST) were measured. Results: U. dioica and L. album extracts caused significant decrease (

The Effect of Fenugreek (Trigonella foenum-graecum) Seed and 17-β Estradiol on Serum Apelin, Glucose, Lipids, and Insulin in Ovariectomized Rats

Background: Menopause, a natural phenomenon, is defined by the fall of ovarian hormones mainly estrogens causing major problems such as insulin resistance. Fenugreek (Trigonella foenum-graecum) is known to have some useful properties such as insulin sensitizing effect. Apelin is an adipokine, which has several roles such as regulation of insulin secretion. Objectives: The objective of the present study was to evaluate the effect of fenugreek seed and 17-β estradiol on serum Apelin along with glucose, lipids and insulin in ovariectomized rats. Materials and Methods: Forty-nine adult female Wistar rats were randomly divided to seven groups: normal control, ovariectomized control, ovariectomized treated with ethanolic and hexanic extract of fenugreek seed (50 and 150 mg/kg/daily for each), and ovariectomized treated with 17-β estradiol (10 μg/kg/daily) for 42 days. Serum Apelin, glucose, lipids and insulin were measured. Results: Serum Apelin, glucose, lipids and insulin significantly increased in ovariectomized controls in comparison with normal controls (P < 0.05). Serum glucose, lipids and insulin in ovariectomized rats treated with fenugreek seed extract and 17-β estradiol were remarkably lower than ovariectomized controls (P < 0.05). Furthermore, 17-β estradiol caused a significant decrease (P < 0.05) in serum Apelin in ovariectomized rats. Conclusions: It appears that fenugreek seed might be effective against hyperglycemia, hyperlipidemia and insulin resistance in ovariectomized rats without impact on serum Apelin. Furthermore, 17-β estradiol could have similar effects along with possible inhibitory effects on serum Apelin. The complicated role of Apelin in menopause needs to be further explored. Keywords: Apelin-13; Trigonella Foenum-Graecum; 17 Beta-Estradiol; Ovariectomized; Insulin; Lipid

Ginseng alleviates folliculogenesis disorders via induction of cell proliferation and downregulation of apoptotic markers in nicotine-treated mice

Abstract Background Ginseng is a powerful phytoestrogen with high antioxidant properties. Objective This study aimed to evaluate the effect of Panax Ginseng (PG) on folliculogenesis, proliferation, and apoptosis in the ovary impaired by nicotine. Methods Forty adult mice were divided into five groups. Control, sham, and nicotine groups, and co-treated groups of nicotine and ginseng in doses of 0.5 and 1 g/kg. Folliculogenesis was assessed via histopathology and serum evaluation of estradiol, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) by ELISA. Lipid peroxidation and antioxidant enzyme activities both in homogenate tissue and serum were assayed by colorimetric analysis. Apoptotic markers of cytochrome c (Cyt c), Bax, and Bcl-2 were evaluated by RT-PCR. Proliferative index was studied by the Ki-67 immunostaining procedure. Results In comparison to the control or sham groups, nicotine significantly reduced the levels of FSH, LH, and estradiol hormones. An insignificant reduction was observed in the progesterone hormone. Nicotine reduced all healthy follicle numbers, except primordial (P = 0.001). Malondialdehyde (MDA) was increased in tissue and serum in the nicotine group (P = 0.01). Serum catalase (CAT) and enzymatic activity of superoxide dismutase (SOD) both were reduced in tissue and the serum, in the nicotine group. Nicotine induced a reduction in the proliferative indexes of granulosa and theca cells in pre-antral and antral follicles (P = 0.001). However, its effect on the proliferative index of stroma cells was not significant. Apoptotic markers were elevated in the nicotine group (P = 0.001). Co-treatment with ginseng elevated all sex hormones, increased healthy follicles, and reduced tissue or serum lipid peroxidation, compared with the nicotine group (p < 0.05). Co-Treatment with ginseng also reduced the expression of apoptotic markers and increased the proliferative indexes in granulosa and theca cells in pre-antral and antral follicles and also in stroma cells, in comparison to the nicotine group (P = 0.001). All above-mentioned alterations following treatment with ginseng were remarkable, especially in the dose of 1 g/kg. Conclusion This study showed ginseng protects folliculogenesis via alteration of hypothalamic- pituitary–gonadal (HPG) axis, induction of proliferation in ovarian somatic cells, reduction of lipid peroxidation, and downregulation of apoptotic markers in the mouse ovary, treated with nicotine

Potential anti-inflammatory effect of Lamium album extract through caspase-3 and cyclooxygenase-2 genes expression in a rat model of middle cerebral artery occlusion

Introduction: Stroke is one of the most common causes of death worldwide. Inflammation and apoptosis play an important role in the cascade of ischemic stroke. Aim: The aim of the present study was to evaluate the pretreatment effects of Lamium album (L. album) extract on caspase-3 and cyclooxygenase-2 (COX-2) expression, infarct volume, and neurological deficit score in a rat model of middle cerebral artery occlusion (MCAO). Materials and methods: Wistar male rats were randomly divided into three groups: 1) MCAO group (1 h after MCAO, reperfusion was allowed for 24 h by retracting the thread); 2) L. album + MCAO group [receiving L. album extract (100 mg/kg via intraperitoneal) for a week before MCAO]; 3) sham group. The expression level of caspase-3 and COX-2 in the core, penumbra, and subcortex regions was measured by real time-PCR technique. Infarct volume and neurological deficit score were also assessed. Results: The mRNA expression of caspase-3 in the core, penumbra, and subcortex regions in L. album group was significantly reduced compared to MCAO group (p<0.05). Expression level of COX-2 in the subcortex of the rats exposed to L. album was statistically decreased relative to MCAO group (p<0.05). Infarct volume in the core, penumbra, and subcortex was significantly reduced in the L. album group compared with MCAO group (p<0.001, p<0.001, p<0.05, respectively). Neurological deficit score was remarkably decreased in the L. album group in comparison with the MCAO group (p<0.05). Conclusions: It appears that pretreatment with L. album extract may attenuate brain tissue damage after ischemic stroke. The potential protective effects of this plant extract against this condition might be in part attributed to its anti-inflammatory and anti-apoptotic activities

Effects of gold nanoparticles on oxidative stress status in bladder cancer 5637 cells

Introduction: Nanomedicine has recently been known as an emerging research area with promising applications in cancer diagnosis and treatment. Aside from this, gold nanoparticles (AuNPs), as one of the important components of nanomedicine, have attracted considerable attention due to their special physicochemical properties and lower toxicity than other nanoparticles. Despite the impressive advantages of AuNPs, it has not been yet determined whether oxidative stress contributes to the toxicity of AuNPs on bladder cancer. Aim: The aim of this study was to address this issue by conducting experiments in order to investigate the effects of 20 nm AuNPs on human bladder cancer 5637 cells. Materials and methods: The viability of 5637 cells was evaluated upon 24 hour exposure to different concentrations of AuNPs (0-50 µg/ml) by 3-(4, 5-dimethylthiazol, 2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. In order to evaluate oxidative stress status, total antioxidant capacity (TAC), total oxidant status (TOS), malondialdehyde (MDA) and also activities of antioxidant enzymes including glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) were all determined by colorimetric assay kits. Results: The results from our experiment showed that the cytotoxicity caused by AuNPs was dose-dependent and the IC50 value was found to be 43.14 µg/ml after 24-hour exposure. Furthermore, MDA and TOS levels were significantly increased in treated cells compared to untreated cells (p<0.05). In contrast, TAC level and the activities of SOD, GPx, CAT were significantly decreased in AuNPs-treated groups as compared with the untreated cells (p<0.05). Conclusions: Overall, AuNPs decrease the cell viability and increase oxidative stress in bladder cancer 5637 cells

Effect of Lamium Album on Mitochondrial Oxidative Stress in Diabetic Rats

Background: Diabetes mellitus (DM) is characterized by the presence of hyperglycemia. It has been documented that oxidative stress and reactive oxygen species (ROS) production have a key role in the pathogenesis of diabetes and its complications. Neutrophils as a part of immune system produce ROS, neutrophils function might be altered in diabetes. Lamium album is known to have antioxidant, and free radical scavenging actions. The aim of the present study was to evaluate the potential effect of L. album on mitochondrial ROS production from circulating neutrophils in diabetic rats. Materials and Methods: Twenty-one male Wistar rats were randomly divided into three groups: normal control rats receiving daily saline; diabetic control rats receiving daily saline; and diabetic rats treated daily with hydroalcoholic extract of L. album (100 mg/kg) for 28 days. On the 28thday of treatment, whole blood samples were obtained and mitochondrial ROS of neutrophils were measured by dihydrorhodamine (DHR) flow cytometric method. Also, fasting blood sugar (FBS) was measured. Results: Mitochondrial ROS didn&rsquo;t show any significant differences among diabetic rats treated with L. album extract, diabetic control rats, and normal control rats (P=0.8). Serum glucose in diabetic control was significantly higher than normal control rats (P=0.0001). However, L. album caused a remarkable decrease in serum glucose of diabetic rats (P=0.03). Conclusion: According to the present findings, it seems that L. album at a dose of 100 mg/kg could not decrease mitochondrial ROS production from neutrophils in diabetic rats. Further studies considering higher concentrations of L. album are appreciated to evaluate its impact on the production of mitochondrial ROS along with extracellular ROS in diabetes condition