Rasha R. Ahmed

Synthesis and anti-tumor activities of some new pyridines and pyrazolo (1,5-a)pyrimidines

Cyclocondensation of cyanoacetamide, cyanothioacetamide and 3-aminopyrazols with sodium salt of 3-hydroxy-1-(2-naphthyl)prop-2-en-1-one gives pyridin-2-one, pyridin-2(1H)-thione, and pyrazolo[1,5-a]pyrimidine derivatives. These derivatives showed potent anti-tumor cytotoxic activity in vitro using different human cancer cell lines.

Limiting prolonged inflammation during proliferation and remodeling phases of wound healing in streptozotocin-induced diabetic rats supplemented with camel undenatured whey protein

BackgroundImpaired diabetic wound healing occurs as a consequence of excessive reactive oxygen species (ROS) and inflammatory cytokine production. We previously found that whey protein (WP) was able to normally regulate the ROS and inflammatory cytokines during the inflammatory phase (first day) in streptozotocin (STZ)-diabetic wound healing. This study was designed to assess the effect of WP on metabolic status, the inflammation and anti-inflammation response, oxidative stress and the antioxidant defense system during different phases of the wound healing process in diabetic rats. WP at a dosage of 100 mg/kg of body weight, dissolved in 1% CMC, was orally administered daily to wounded normal (non-diabetic) and STZ-induced diabetic rats for 8 days starting from the 1st day after wounding.ResultsThe data revealed that WP enhanced wound closure and was associated with an increase in serum insulin levels in diabetic rats and an alleviation of hyperglycemic and hyperlipidemic states in diabetic animals. The increase in insulin levels as a result of WP administration is associated with a marked multiplication of β-cells in the core of islets of Langerhans. WP induced a reduction in serum TNF-α, IL-1β and IL-6 levels and an increase in IL-10 levels, especially on the 4th day after wounding and treatment. WP also suppressed hepatic lipid peroxidation and stimulated the antioxidant defense system by increasing the level of glutathione and the activity of glutathione-S-transferase, glutathione peroxidase and superoxide dismutase (SOD) in wounded diabetic rats.ConclusionsWP was observed to enhance wound closure by improving the diabetic condition, limiting prolonged inflammation, suppressing oxidative stress and elevating the antioxidant defense system in diabetic rats.

Anti-Proliferative and Apoptotic Efficacies of Ulvan Polysaccharides against Different Types of Carcinoma Cells In Vitro and In Vivo

Objective: This study was designed to assess the anti-proliferative and apoptotic effects of ulvan polysaccharides in vivo using Ehrlich ascites carcinoma (EAC)-bearing mice model and in vitro using hepatocarcinoma cell lines (HepG2) and colon carcinoma cell lines (HCT116). Methods: In vivo, ulvan polysaccharide was orally administered to EAC-bearing mice at dose level of 100 mg/ kg b. w. for 2 weeks beginning from the 1st day of EAC-intraperitoneal transplantation and compared with a control given a vehicle. The expressed anti-apoptotic protein Bcl2, proapoptotic mediator p53 and DNA fragmentation marker TdT were detected by TUNEL assay. Plasma and ascites total sialic acid was determined. In vitro, the anti-tumor effect of ulvan polysaccharide against HepG2 and HCT116 was tested at 0, 12.5, 25, 50 and 100 μg/ml and IC50 was determined. Results: The data revealed that EAC-aliquot volume, EAC-total and alive cell numbers were potentially decreased while dead cell number and percent were profoundly increased as a result of treatment with ulvan polysaccharide. The EAC-cells exhibited phenotypic signs of apoptosis after treatment with ulvan polysaccharide. The expression of proapoptotic and cell cycle arrest protein p53 in cytoplasm and nuclei and the amount of TdT in the nuclei of EAC-cells in mice treated with ulvan polysaccharide were remarkably increased while the antiapoptotic protein Bcl-2 expression was decreased. The treatment of EAC-bearing mice with ulvan polysaccharides successfully decreased plasma and ascites total sialic acid level. In vitro, the ulvan polysaccharide induced potential anti-proliferative and anti-tumor cytotoxic effects against EAC-cells, hepatoma (HepG2) and colon carcinoma (HCT116) human cell line. Conclusion: Taken together, this study may provide evidence for the anti-tumor effects of ulvan polysaccharides which may be mediated by induction of apoptosis and suppression of cell division.

Exploring the Antimicrobial and Antitumor Potentials of Streptomyces sp. AGM12-1 Isolated from Egyptian Soil

The occurrence of extensive antibiotics resistant bacteria increased the demands for mining out new sources of antimicrobial agents. Actinomycetes, especially Streptomyces sp. have grasped considerable attention worldwide due to production of many useful bioactive metabolites. In the present study, a total of 52 actinomycetes were isolated from agricultural soil samples in Beni-Suef, Egypt. All isolates were characterized based on colony morphology, mycelium coloration, and pigment diffusion. They were screened for their capabilities to show antimicrobial activities against different indicator microorganisms, and only 20 isolates have shown significant antimicrobial activities against at least one of the tested indicator microorganisms. The isolate AGM12-1 was active against all tested microorganisms and showed a marked antitumor activity with IC50 3.3 and 1.1 μg/ml against HCT-116 and HepG-2 cell lines respectively. It was genotypically characterized as Streptomyces sp. with the presence of PKS Π biosynthetic gene cluster. Mannitol, ammonium sulfate, pH 7, 2% inoculum size and incubation for 11 days at 30°C were the optimum conditions that used to maximize the production and hence allowed purification of one active antimicrobial compound to homogeneity using high performance liquid chromatography with a molecular mass of m/z 488.05. Nuclear magnetic resonance structural elucidation showed that this compound was a diketopiperazine derivative.

Ruta graveolens and its active constituent rutin protect against diethylnitrosamine-induced nephrotoxicity through modulation of oxidative stress -

Article history: The current study was designed to evaluate the possible protective effects of Ruta graveolens (Rue) and its active phenolic constituent rutin against diethylnitrosamine (DEN)-induced nephrotoxicity in rats. A single dose of DEN (200 mg/kg body weight) was intraperitoneally injected. Two-weeks after DEN administration, rats received 0.05 % phenobarbital in drinking water for 12 weeks. Ruta graveolens (50 mg/kg) and rutin (50 mg/kg) were orally administered from the first day of experiment. DEN administration induced kidney injury evidenced by histological alterations as well as significant increase in serum urea (P<0.01), creatinine (P<0.001) and uric acid (P<0.001), and renal lipid peroxidation levels. On the other hand, renal glutathione content and activity of superoxide dismutase, glutathione peroxidase and glutathione-s-transferase were significantly declined. Concomitant supplementation with either R. graveolens extract or rutin markedly alleviated the altered biochemical and histopathological features. In conclusion, the current findings provide evidence tha t R. graveolens and its active phenolic component rutin could protect against DEN-induced renal damage through abolishment of oxidative stress and potentiation of the antioxidant defense system.

Antidiabetic and Antioxidant Effects of Newly Synthesized Pyrimido[1,6-A] Pyrimidine Derivatives in Neonatal Streptozotocin-Induced Diabetic Rats

Synthesis of some novel pyrimido[1,6-a]pyrimidine derivatives 4, 8 and 10 was described through the respective reactions of sodium salts of formyl ketones 1, 7 and 9 with 6-aminothiouracil. The characterization of the reaction products was confirmed by using the available elemental analysis and spectral data. One of these derivatives ( 4b), 1-thioxo-1,2,7,8,9,10-hexahydro-3H-pyrimido[1,6-a]quinazolin-3-one, was tested using sublethal dose level (10 mg/kg b. w./day for 3 weeks) and was found to have potent antihyperglycemic, antihyperlipidemic and antioxidant properties in neonatal streptozotocin-induced (n-STZ) diabetic male and female albino rats.

Quercetin and low level laser therapy promote wound healing process in diabetic rats via structural reorganization and modulatory effects on inflammation and oxidative stress

This study aimed to evaluate the effect of quercetin and the photo-stimulatory effect of low energy 632.8 nm laser irradiation on excisional wound healing in non-diabetic and diabetic rats. Streptozotocin (45 mg/kg body weight) was intraperitoneally applied for diabetes induction. A full-thickness skin wound (2 × 2 cm2) was aseptically created with a scalpel in non-diabetic and diabetic rats on the shaved back of the animals. The wounded non-diabetic and diabetic rats were treated every other day with quercetin by oral gavage at dose 25 mg/kg body weight and/or with low level laser therapy (LLLT) for 14 days. The wound closure percent calculated during the course of the experiment at days 1, 7 and 14 was remarkably increased as a result of treatment of non-diabetic and diabetic wounded rats with quercetin and LLLT; the treatment with both was the most potent. The elevated blood glucose and the lowered serum insulin levels were significantly improved in diabetic wounded rats treated with quercetin and LLLT as compared to the diabetic wounded control. The histological findings indicated that the wounded skin showed a marked increase in collagen fibers which become well oriented in sub-epidermal tissue, intact epidermis and presence of hyperplasia covering well-developed granulation tissue in the wounded rats treated with quercetin and LLLT as compared to the corresponding wounded control. The elevated levels of serum pro-inflammatory cytokines, IL-1β and TNF-α, as well as PGE-2 and LTB-4 were decreased in non-diabetic and diabetic wounded rats with quercetin and LLLT while the lowered level of serum anti-inflammatory cytokine, IL-10, was increased. The augmented oxidative stress represented by increased serum lipid peroxides level was decreased and the serum level of non-enzymatic anti-oxidant glutathione was increased as a result of treatment with quercetin and LLLT. Thus, it can be suggested that the improvements in glycemic state, cytokines involved in inflammation and antioxidant defense system as well as structural reorganization after treatment with quercetin and LLLT may play pivotal roles in promoting the wound healing process. The study also concluded that the treatment with quercetin in association with LLLT was better in improving wound healing in non-diabetic and diabetic rats than the use of either of each.

The antifibrogenic effect of etanercept on development of liver cirrhosis induced by thioacetamide in rats

ABSTRACT Liver cirrhosis is an elevating cause of morbidity and mortality worldwide. TNF-α/TNF-R1 signal is implicated in progression of many liver diseases. This study provides histological and ultrastructural view that clarifies the effect of etanercept, a TNF-α inhibitor, on development of thioacetamide (TAA)-induced liver cirrhosis and the accompanied hemosiderosis in rats, highlighting the implication and distribution pattern of hepatic TNF-R1. Sixty male albino rats (Rattus norvegicus) were equally randomized into three groups. Group I served as the control. Liver cirrhosis was triggered in the other two groups by intraperitoneal injection of TAA twice a week for five months. Group II received TAA only, while group III subcutaneously injected with etanercept one hour before TAA, along five months. At the end of the experiment, blood was collected for biochemical analysis and livers were excised for histological, immunohistochemical, and electron microscopical preparations. Rats treated with TAA only developed hepatic cirrhosis accompanied by massive deposition of hemosiderin; strong and widespread expression of hepatic TNF-R1 in sinusoidal endothelial cells (SECs), Kupffer cells (KCs), and many hepatocytes; and frequent appearance of fibrogenic, plasma, and mast cells, at the ultrastructural level. By contrast, administration of etanercept diminished the expression of TNF-R1, attenuated the accumulation of collagen and hemosiderin, and preserved the hepatic histoarchitecture. In conclusion, TNF-α signal via TNF-R1 may be implicated in the mechanism of fibrogenesis and the associated hemosiderosis. Etanercept may provide a promising therapeutic approach not only for attenuating the progression of fibrogenesis, but also for hepatic iron overload-associated disorders.

Hepatoprotective effects of parsley, basil, and chicory aqueous extracts against dexamethasone-induced in experimental rats.

Aim: The objective of this study is to investigate the hypoglycemic, hypolipidemic, and hepatoprotective effects of the aqueous extract of parsley, basil, and chicory whole plant in normal and dexamethasone (Dex) rats. Materials and Methods: 50 female albino rats were used in this study and divided into 5 groups (for each 10). Group (1) fed basal diet and maintained as negative control group. Group (2) received Dex in a dose of (0.1 mg/kg b. wt.). Groups 3, 4, and 5 were treated with Dex along with three different plant extracts of parsley, basil, and chicory (2 g/kg b. wt.), (400 mg/kg b. wt.), and (100 mg/kg b. wt.), respectively. Results: All these groups were treated given three times per week for 8 consecutive weeks. Dex-induced alterations in the levels of serum glucose, triglyceride, cholesterol, low-density lipoprotein-cholesterol levels and cardiovascular indices and serum alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities, liver thiobarbituric acid (TBARS) levels increased, while high-density lipoprotein-cholesterol, total protein, albumin, and liver glutathione (GSH) levels decreased. On the other hand, plant extracts succeeded to modulate these observed abnormalities resulting from Dex as indicated by the reduction of glucose, cholesterol, TBARS, and the pronounced improvement of the investigated biochemical and antioxidant parameters. Conclusions: It was concluded that probably, due to its antioxidant property, parsley, basil, and chicory extracts have hepatoprotective effects in Dex-induced in rats.

A Review on Glucocorticoids Induced Osteoporosis: Pathogenesis, Diagnosis and Management by Some Natural Plants.

million person the all over the world affected by osteoporosis as it is most common metabolic bone disorder. The general reason of bone loss are age and menopause, and the rates of bone loss variable between individuals. Physical activity and environmental factors as nutrition can contribute to bone health as they modify both peak bone mass and following bone loss. Medications embrace both antire- sorptive and anabolic types. Antiresorptive medications acts by reducing rates of bone remodeling like estrogens, selective estrogen receptor modulators (raloxifene), bisphosphonates (alendronate, risedronate, and ibandronate) and calcitonins. Para- thyroid hormone is the only anabolic medication. The nonmedical treatment must be used with pharmacologic treatment to maximize outcomes for osteoporotic patient. Some plant-derived natural products, mostly phytoestrogens (isoflavones, lignans, coumestanes, stilbenes) and many more novel estrogen-like compounds in plants have been greatly used to prevent depletion in bone mineral density. In this review an attempt has been made out to compile the mechanisms of glucocorticoids induced osteoporosis, the medicinal plants which are commonly utilized in osteoporosis with their prominent chemical ingredients and certain phar- macological actions.