Inflammatory mediators, oxidative stress and genetic disturbance in rheumatoid arthritis rats supported by alfalfa seeds metabolomic constituents via blocking interleukin-1receptor.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by aggressive cartilage and bone erosion. This work aimed to evaluate the metabolomic profile of Medicago sativa L. (MS) (alfalfa) seeds and explore its therapeutic impact against RA in rats. Arthritis was induced by complete Freund's adjuvant (CFA) and its severity was assessed by the arthritis index. Treatment with MS seeds butanol fraction and interlukin-1 receptor antagonist (IL-1RA) were evaluated through measuring interlukin-1 receptor (IL-1R) type 1 gene expression, interlukin-1 beta (IL-1ß), oxidative stress markers, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2), caspase-3 (Cas-3), intracellular adhesion molecule-1 (ICAM-1), DNA fragmentation, and chromosomal damage. Total phenolics/ flavonoids content in the ethyl acetate, butanol fraction and crude extract of MS seeds were estimated. The major identified compounds were Quercetin, Trans-taxifolin, Gallic acid, 7,4'-Dihydroxyflavone, Cinnamic acid, Kudzusaponin SA4, Isorhamnetin 3-O-beta-D-2'',3'',4''-triacetylglucopyranoside, Apigenin, 5,7,4'-Trihydroxy-3'-methoxyflavone, Desmethylxanthohumol, Pantothenic acid, Soyasapogenol E, Malvidin, Helilandin B, Stigmasterol, and Wairol. Treatment with MS seeds butanol fraction and IL-1RA enhanced all the biochemical parameters and the histopathological features of the ankle joint. In conclusion, Trans-taxifolin was isolated for the first time from the genus Medicago. MS butanol fraction seeds extract and IL-1 RA were considered as anti-rheumatic agents.

Profiling of secondary metabolites and DNA typing of three different Annona cultivars grown in Egypt.

OBJECTIVES: Natural products are often efficacious and safe alternatives to synthetic drugs. This study explored secondary leaves and bark metabolites profiles in extracts of a new Egyptian hybrid, Annona cherimola × Annona squamosa, known as Abdel Razek. This hybrid exhibited 100% similarity with A. cherimola as evidenced by random amplified polymorphic DNA (RAPD) and inter-simple sequence repeat (ISSR) analyses. METHODS: Primary constituents in methanol extracts of different plant organs were identified. Extracts richest in alkaloids and polyphenolics were assessed for in vitro antioxidant activity and the most potent were further studied in vivo for treating gastric ulcer in rats. The latter activity was assessed histopathologically. RESULTS: Structural analysis with HPLC/ESI-MSn, and UPLC/HESI-MS/MS identified 63 metabolites, including seven amino acids, 20 alkaloids, 16 flavonoids, eight phenolics and other compounds. Severe stomach alteration was observed after ethanol induction in rats. Ulcer score, oxidative stress biomarkers, cell organelles biomarker enzymes, and gastrointestinal histological features improved to variable degrees after treatment with Annona Abdel Razek hybrid leaves and bark methanol extracts. CONCLUSION: Extracts of Annona Abdel Razek had showed in vitro antioxidant effect and may be promising for the treatment of gastric ulcers.

Chemical compositions of Commiphora opobalsamum stem bark to alleviate liver complications in streptozotocin-induced diabetes in rats: Role of oxidative stress and DNA damage.

CONTEXT: Hyperglycaemia plays an important role in the development of non-alcoholic fatty liver disease, which is a common complication in diabetics. OBJECTIVE: The present study aimed to investigate the chemical composition and the efficacy of Commiphora opobalsamum stem bark butanol fraction in ameliorating liver injury associated with diabetes induced by streptozotocin (STZ) in rats. MATERIALS AND METHODS: The butanol fraction was applied to high-performance liquid chromatography-mass spectrometry (HPLC/MSn) to identify the most bioactive metabolites. Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg body weight), while treatment with the plant extract was performed (100 mg/kg body weight) for three weeks after diabetic induction for one month. RESULTS: Thirty eight metabolites were tentatively identified from the butanol fraction of C. opobalsamum stem bark. Insulin, glutathione, superoxide dismutase, and high density lipoprotein levels in diabetic rats were significantly low (p < 0.05), while glucose, α-amylase, malondialdehyde, aspartate and alanine aminotransferases, cholesterol, triglycerides, low density lipoprotein, tumour necrosis factor-α, interleukin-6, and DNA fragmentation levels were significantly high. Treatment with the plant extract showed improvements in the seleced parameters by variable degrees. Conclusion: The plant extract is considered as a promising natural therapeutic agent against liver injury, hyperglycemia, oxidative stress, inflammation, hyperlipidaemia, and DNA damage.

Salvia hispanica L. seeds extract alleviate encephalopathy in streptozotocin-induced diabetes in rats: role of oxidative stress, neurotransmitters, DNA and histological indices.

CONTEXT: Diabetes mellitus (DM) is a metabolic disorder and may lead to cognitive dysfunctions. OBJECTIVE: The aim of this work is to evaluate the potency of Salvia hispanica L. seeds (S. hispanica L.) (chia seeds) petroleum ether extract in attenuating brain complications associated with streptozotocin (STZ) induced diabetes in rats. MATERIALS AND METHODS: Phytochemical composition of the seeds extract, macro and micro elements, vitamins, protein, carbohydrate and caloric values were estimated. Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg body weight (b.wt)). Glibenclamide as a reference drug was also evaluated. The biochemical evaluation was done by measuring levels of glucose, insulin, α- amylase, glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), dopamine (DA), serotonin (5-HD), noradrenaline (NE), acetylcholinesterase (AchE), tumour necrosis factor-α (TNF-α), DNA fragmentation pattern and the histopathological profile of the brain hippocampus region. RESULTS: Gas chromatography/mass spectrometry (GC/MS) analysis revealed the presence of twenty-five fatty acid esters and twenty-two compounds. Column chromatography led to the isolation of nine compounds. Treatment with the seeds extract revealed improvement of the measured parameters with variable degrees. CONCLUSION: Chia seeds extract succeeded to attenuate the neurodegeneration in diabetic rats. Thereafter, it had a therapeutic effect and could be potentially used as a new dietary supplement against diabetic encephalopathy.

Chromosomal aberrations, DNA damage, and biochemical disturbances induced by silver nanoparticles in mice: role of particle size and natural compounds treatment.

CONTEXT: Nanotechnology is widely used nowadays in several fields of industry, engineering, and medicine, the biological action mechanisms of AgNPs, which mainly involve the release of silver ions (Ag+), generation of reactive oxygen species (ROS). OBJECTIVE: The potential toxicity AgNPs of damages to hepatic cells, hesperidin, and naringin role for their protective effect against the increase of ROS due to AgNPs toxicity. They can be restored, most cellular biochemical parameters, genotoxicity, mutagenicity, and histopathological analysis. MATERIALS AND METHODS: Toxicity was induced by an oral dose of Ag NPs of (20-100 nm) for one month, after that treated with hesperidin, naringin (100 mg/kg) for three weeks, malondialdehyde (MDA) levels, nitric oxide (NO), glutathione (GSH) and catalase were estimated. Also, aminotransferases (AST and ALT), alkaline phosphatase (ALP), γ-glutamyltransferase (GGT), albumin, and total bilirubin were determined, following Chromosomal aberrations, DNA breaks, and histological analyses. RESULTS: hesperidin, and naringin treatment, recorded amelioration in most biochemical, genetic, and spermatogenesis disturbances Also, histological Investigations were improved. CONCLUSION: Their biological safety problems, such as potential toxicity on cells, tissue, and organs should be paid enough attention, hesperidin and naringin amelioration fundamental alterations, as hepatic architectural and DNA damage, related to its role as an antioxidant and anti-inflammatory agent.

Phytochemical constituents and protective efficacy of Schefflera arboricola L. leaves extract against thioacetamide-induced hepatic encephalopathy in rats.

CONTEXT: Hepatic encephalopathy (HE) is a severe neuropsychiatric syndrome resulting from liver failure. OBJECTIVE: To evaluate the protective effect of Schefflera arboricola L. leaves methanol extract against thioacetamide (TAA) induced HE in rats. MATERIALS AND METHODS: GC/MS, LC-ESI-MS, and the total phenolic and flavonoid contents were determined. The methanol extract was orally administrated (100 and 200 mg/kg body weight) for 21 days. TAA (200 mg/kg body weight) was given intraperitoneally on day 19 and continued for three days. The evaluation was done by measuring alanine aminotransferase (ALT), alkaline phosphatase (ALP), ammonia, reduced glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO), tumour necrosis factor-alpha (TNF-α), toll-like receptor 4 (TLR4), interleukin-1 beta (IL-1ß), interlukin-6 (IL-6), cyclooxygenase 2 (COX2), B cell lymphoma 2 (BCL2), alpha-smooth muscle actin (α-SMA), and the cluster of differentiation 163 (CD163). The histological features of the liver and brain were conducted. RESULTS: Forty-five compounds were identified from the n-hexane fraction, while twenty-nine phenolic compounds were determined from the methanol extract. Pre-treatment with the plant extract returned most of the measurements under investigation to nearly normal. CONCLUSION: Due to its richness with bioactive compounds, Schefflera arboricola L. leaves methanolic extract succeeded to exert anti-fibrotic, anti-inflammatory, and antioxidants properties in TAA-induced HE in rats with more efficacy to its high protective dose.

Pulicaria crispa mitigates nephrotoxicity induced by carbon tetrachloride in rats via regulation oxidative, inflammatory, tubular and glomerular indices.

CONTEXT: Carbon tetrachloride (CCl4) induces oxidative stress in various tissues by altering antioxidants defense system. Recently, there has been a substantial use of phytotherapy to treat different diseases. OBJECTIVE: This study was designed to evaluate the curative effect of Pulicaria crispa (Forssk.) Benth et Hook (Family Asteraceae) aerial parts ethanol extract against CCl4 induced toxicity in rats kidneys. MATERIALS AND METHODS: Nephrotoxicity was induced by intraperitoneal injection with CCl4 in a dose of 0.5 mL/kg b.wt./twice a week for six consecutive weeks. Serum kidney function tests, oxidative stress markers, inflammatory cytokines, nephrotoxicity biomarkers and histopathological observation were evaluated. RESULTS: CCl4 increased serum kidney function parameters, malondialdehyde level, inflammatory cytokines, and nephrotoxicity markers, while decreased certain oxidative stress indices as superoxide dismutase and glutathione refereeing to the control group (p < 0.0001). Administration of P. crispa ethanol extract to CCl4 injured rats attenuated these changes with variable degrees. The results were confirmed through the observed amelioration of the renal histological architectures. CONCLUSION: P. crispa ethanol extract possesses potent curative effect against CCl4-induced nephropathy through improvement of kidney function, oxidative stress, inflammatory and nephrotoxicity index and the renal histopathological features. To establish the therapeutic and pharmacological applications of the plant, additional researches are required.

Bioactive compounds and therapeutic role of Brassica oleracea L. seeds in rheumatoid arthritis rats via regulating inflammatory signalling pathways and antagonizing interleukin-1 receptor action.

CONTEXT: Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease characterized by aggressive and systematic polyarthritis. OBJECTIVE: The present study aimed to isolate and identify the phenolic constituents in Brassica oleracea L. (Brassicaceae) seeds methanolic extract and evaluates its effect against rheumatoid arthritis in rats referring to the new therapy; interleukin-1 receptor antagonist (IL-1RA). MATERIALS AND METHODS: The GC/MS profiling of the plant was determined. Arthritis induction was done using complete Freund's adjuvant. Arthritis severity was assessed by percentage of edema and arthritis index. IL-1 receptor type I gene expression, interleukin-1ß (IL-1ß), oxidative stress markers, protein content, inflammatory mediators, prostaglandin-E2 (PGE2), genetic abnormalities and the histopathological features of ankle joint were evaluated. RESULTS: For the first time twelve phenolic compounds had been isolated from the seeds extract. Treatment with extract and IL-1RA improved the tested parameters by variable degrees. CONCLUSIONS: RA is an irreversible disease, where its severity increases with the time of induction. Brassica oleracea L. seeds extract is considered as a promising anti-arthritis agent. IL-1 RA may be considered as an unusual therapeutic agent for RA disease. More studies are needed to consider the seeds extract as a nutraceutical agent and to recommend IL-1RA as a new RA drug.

Downregulation of fibrosis and inflammatory signalling pathways in rats liver via Pulicaria crispa aerial parts ethanol extract.

CONTEXT: Liver is a vital organ for the detoxification of toxic substances in the body, where fibrosis is the major cause of liver damage. Pulicaria crispa processes many therapeutic applications such as antioxidant, antimicrobial, anticancer and anti-ulcerative agent. OBJECTIVE: This study aimed to modulate the fibrosis and inflammatory signalling pathways in carbon tetrachloride (CCl4)-induced liver damage in rats via treatment with Pulicaria crispa aerial parts ethanol extract (PCEE). MATERIALS AND METHODS: CCl4 was intraperitoneally injected at a dose of 0.5 mL/kg b.wt./twice a week/six consecutive weeks, PCEE was orally allocated at a dose of 250 mg/kg b.wt./day/six weeks and silymarin was orally administrated at a dose of 100 mg/kg, b.wt/day/six weeks. The plant extract evaluation was done through measuring aspartate and alanine aminotransferases (AST& ALT), alkaline phosphatase (ALP), total lipids (TP), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low level glycoprotein-cholesterol (LDL-C), alpha fetoprotein (AFP), reduced glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), tumour necrosis factor-α (TNF-α) and interleukin 6 (IL-6). The liver architectures were also estimated. RESULT: The phytochemical analysis of the extract showed the presence of sterols and/or triterpenoids. Treatments with plant extract suppressed significantly (p < 0.0001) the levels of AST, ALT, ALP, TP, TG, TC, LDH-C, MDA, NO, AFP, TNF-α and IL-6, while increased (p < 0.0001) the levels of HDL-C, GSH and SOD. The histopathological features confirmed the therapeutic role of the plant extract. CONCLUSION: PCEE succeeded to exert anti-fibrotic, anti-inflammatory and anti- oxidants effects in CCl4-induced liver fibrosis.

Isolation and characterization of flavonoid compounds from Stachytarpheta jamaicensis (L.) Vahl and its role as anti-gastro ulcerative agent in rats.

CONTEXT: Stomach ulcer is one of the most common gastrointestinal problems in the world. OBJECTIVE: This study aimed to isolate flavonoid compounds from methanol extract of the aerial parts of Stachytarpheta jamaicensis (L.) Vahl. and evaluate its protective and therapeutic effects against gastric ulcer. MATERIALS AND METHODS: Chromatographic techniques were used for the identification of the isolated compounds. To explore the effects of the plant extract, it was administrated by oral gavage for one week either before or post-ethanol ulcer induction. Ranitidine was also evaluated as a reference drug. Stomach pH, gastric juice volume, lesions number, glutathione, superoxide dismutase, malondialdehyde, succinate dehydrogenase, lactate dehydrogenase, acid phosphatase, Interleukin-10, intracellular adhesion molecule-1, prostaglandin E2, and total protein levels were estimated in gastric tissue. Stomach histopathological features were also monitored. RESULTS: Six flavonoid compounds were isolated, where five of them were isolated for the first time (vitexin, isovitexin, apigenin 7,4'-dimethyl ether, 5,7,2'-trimethoxyflavone, and scutellarein), while apigenin was previously reported. Treatment with plant extract recorded amelioration in all the biochemical parameters. CONCLUSION: The methanol extract of plant aerial parts had prophylactic and treatment effects against gastric ulcer in rats, where its treatment effect exceeded its protective role. The extract recorded anti-inflammatory, and antioxidant effects due to the presence of flavonoid compounds.

An overview on COVID-19: reality and expectation.

Recently, severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), commonly known as coronavirus disease-2019 (COVID-19) has rapidly spread across China and around the world. By the declaration of WHO, COVID-19 outbreak considered as a public health problem of international concern. The aim of this study is to provide a comprehensive view on COVID-19 and the future expectations to control virus progression. Patients with liver disease, diabetes, high blood pressure, and obesity are more susceptible to the incidence of COVID-19 infection. So, there is a rapid need for disease diagnosis, vaccine development, and drug discovery to detect, prevent, and treat this sudden and lethal virus. Real-time polymerase chain reaction (RT-PCR) is considered as a rapid, accurate, and specific tool for disease diagnosis. Under this emergency situation that the world facing against COVID-19, there are about 15 potential vaccine candidates tested globally based on messenger RNA, DNA-based, nanoparticle, synthetic, and modified virus-like particle. Certain drugs that are clinically approved for other diseases were tested against COVID-19 as chloroquine, hydroxychloroquine, ivermectin, favipiravir, ribavirin, and remdesivir. Convalescent plasma transfusion and traditional herbal medicine were also taken into consideration. Due to the absence of effective treatment or vaccines against COVID-19 so far, the precautionary measures according to WHO's strategic objectives are the only way to confront this crisis. Governments should adopt national medical care programs to reduce the risk of exposure to any future viral outbreaks especially to patients with pre-existing medical conditions.

Potential therapeutic effects of antagonizing adenosine A2A receptor, curcumin and niacin in rotenone-induced Parkinson's disease mice model.

Parkinson's disease (PD) is the second common age-related neurodegenerative disease. It is characterized by control loss of voluntary movements control, resting tremor, postural instability, bradykinesia, and rigidity. The aim of the present work is to evaluate curcumin, niacin, dopaminergic and non-dopaminergic drugs in mice model of Parkinson's disease through behavioral, biochemical, genetic and histopathological observations. Mice treated with rotenone rerecorded significant increase in adenosine A2A receptor (A2AR) gene expression, α synuclein, acetylcholinesterase (AchE), malondialdehyde (MDA), angiotensin-II (Ang-II), c-reactive protein (CRP), interleukin-6 (IL-6), caspase-3 (Cas-3) and DNA fragmentation levels as compared with the control group. While, significant decrease in dopamine (DA), norepinephrine (NE), serotonin (5-HT), superoxide dismutase (SOD), reduced glutathione (GSH), ATP, succinate and lactate dehydrogenases (SDH &LDH) levels were detected. Treatment with curcumin, niacin, adenosine A2AR antagonist; ZM241385 and their combination enhanced the animals' behavior and restored all the selected parameters with variable degrees of improvement. The brain histopathological features of hippocampal and substantia nigra regions confirmed our results. In conclusion, the combination of curcumin, niacin and ZM241385 recorded the most potent treatment effect in Parkinsonism mice followed by ZM241385, as a single treatment. ZM241385 succeeded to antagonize adenosine A2A receptor by diminishing its gene expression and ameliorating all biochemical parameters under investigation. The newly investigated agent; ZM241385 has almost the same pattern of improvement as the classical drug; Sinemet®. This could shed the light to the need of detailed studies on ZM241385 for its possible role as a promising treatment against PD. Additionally, food supplements such as curcumin and niacin were effective in Parkinson's disease eradication.

Chemical composition and protective role of Pulicaria undulata (L.) C.A. Mey. subsp. undulata against gastric ulcer induced by ethanol in rats.

Pulicaria undulata subsp. undulata (Family; Asteraceae) is a medicinal plant used to treat inflammation. The objective of this study is to explore the protective effect of the ethanol extract of P. undulata subsp. undulata aerial parts against ethanol induced gastric ulcer in rats. The chemical composition of plant extract, the unsaponifiable matter and the fatty acid methyl esters were analyzed. The biological evaluation was carried out through measuring ulcer indices, oxidative stress markers, certain marker enzymes, inflammatory index and the histopathological assessment of the stomach in rats. The total unsaponifiable matter (94.29%) and the fatty acid methyl ester (82.96%) content were identified. Gastric ulcer recorded significant increase in gastric volume and lesion counts (p < 0.0001). Drastic changes in all biochemical parameters under investigation were observed. Protection with plant extract reversed the action of ethanol by variable degrees of improvement in comparison with the reference drug. The presence of carbohydrates and proteins that acted as a mucilage lining the stomach inner wall give its protective action. In conclusion, P. undulata subsp. undulata succeeded to have anti-ulcerative protective effect. The measured biomarkers served as a good mirror to predict gastric ulcer and the presence of carbohydrates, protein and fibers present in the plant extract acted as a mucilage lining the inner intestinal wall and protect against ethanol induced gastric ulcer. Future study will be carried out to identify the biologically active compounds responsible for plant protection against the gastric ulcer.

Pulicaria crispa mitigates gastric ulcer induced by ethanol in rats: role of treatment and auto healing.

Context: Stomach ulcers are the common gastrointestinal disorders worldwide. Objective: This study aimed to investigate the therapeutic impact of Pulicaria crispa aerial parts ethanol extract against gastric ulcer in rats. Materials and methods: Ulcer was induced by one oral dose of ethanol (0.5 ml/100g body weight) on 24 hours empty stomach, then the plant extract (500 mg/kg b.wt.) was orally administered daily for one week. Ranitidine (100 mg/kg b.wt.); as a reference drug was evaluated. Stomach acidity and volume, as well as lesion counts were measured. Levels of malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) were estimated. Assay of different marker enzymes; succinate dehydrogenase (SDH), lactate dehydrogenase (LDH), glucose-6-phosphatase (G-6-Pase), acid phosphatase (AP) and 5'-nucleotidase (5'NT) were determined. Interlukin-10 (IL-10), intracellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor alpha (TNF-α) were also determined. Stomach histopathological assessment was detected. Results: Gastric ulcer showed drastic changes in oxidative stress, cell organelles and inflammatory markers. These biomarkers served as good tools to identify the presence of gastric ulcer. Treatment with P. crispa recorded amelioration in most parameters exceeding the auto healing effect. Conclusion: Healing potency of P. crispa is possibly related to its content of glycosides, coumarins, flavonoids, tannins, sterols and triterpenes.

Hepatoprotective evaluation and isolation of the major secondary metabolites from the ethyl acetate extract of liquid culture filtrate of Chaetomium globosum.

The aim of the present study was to evaluate the hepatoprotective activity of ethyl acetate extract of the liquid culture filtrate of Chaetomium globosum fungus (family Chaetomiaceae). Rats were intraperitoneally injected by CCl4 (0.5ml/kg) twice a week for six consecutive weeks. Treatment tacks (250mg/kg) place at the same time of CCl4 induction and with the same duration. The evaluation was done through determination of liver function indices; aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total serum protein content. In addition, the oxidative stress markers; hepatic glutathione content (GSH), hepatic malondialdehyde (MDA), hepatic superoxide dismutase (SOD), and hepatic total protein were estimated. Moreover, the liver architectures were also examined. Isolation and identification of the main secondary metabolites were identified. Seven volatile compounds were identified from the plain chloroform fraction where, 1-Cyclopentyl-2,2-dimethyl-1-propanol (54.63%) was presented as the major compound. Eleven compounds were also identified from the fraction eluted by chloroform: methanol (85:15). 1,5,5-Trimethyl-6-methylene-1-cyclohexene (25.79%) and Norbornan-2-one (26.84%) are presented as the major compounds of this fraction. In conclusion, the extract recorded hepatoprotective effect by ameliorating the biochemical parameters under investigation. The liver histopathological pictures confirmed our results.

Toxicity of titanium dioxide nanoparticles: Effect of dose and time on biochemical disturbance, oxidative stress and genotoxicity in mice.

The toxic impact of titanium dioxide nanoparticles (TiO2NPs) on human health is of prime importance owing to their wide uses in many commercial industries. In the present study, the effect of different doses and exposure time durations of TiO2NPs (21nm) inducing oxidative stress, biochemical disturbance, histological alteration and cytogenetic aberration in mice liver and bone marrow was investigated. Different doses of (TiO2NPs) (50, 250 and 500mg/kg body weight) were each daily intrapertioneally injected to mice for 7, 14 and 45days. Aspartate and alanine aminotransferases (AST &ALT), gamma glutamyl transpeptidase (GGT), total protein, total antioxidant capacity (TAC), malondialdehyde (MDA), glutathione (GSH), catalase (CAT) and nitric oxide (NO) levels were measured. The work was extended to evaluate the liver histopathological pattern and the chromosomal aberration in mice spinal cord bone marrow. The results revealed severe TiO2NPs toxicity in a dose and time dependent manner with positive correlation (r=0.98) for most investigated biochemical parameters. The same observation was noticed for the histological analysis. In case of cytogenetic study, chromosomal aberrations were demonstrated after injection of TiO2NPs with 500mg/kg b. wt. for 45days. In conclusion, the selected biochemical parameters and the liver architectures were influenced with dose and time of TiO2NPs toxicity, while the genetic disturbance started at the high dose of exposure and for long duration. Further studies are needed to fulfil the effect of TiO2NPs on pharmaceutical and nutritional applications.

A Therapeutic Insight of Niacin and Coenzyme Q10 Against Diabetic Encephalopathy in Rats.

Diabetes mellitus (DM) is characterized by hyperglycemia due to insulin inactivity or insufficiency with increasing risk of developing specific complications, including retinopathy, nephropathy, neuropathy, and atherosclerosis. The aim of the present study is to evaluate the efficacy of coenzyme Q10 (CoQ10), niacin, as well as their combination in ameliorating brain disorders associated with streptozotocin (STZ)-induced diabetes in rats. Glibenclamide, a reference diabetic drug, and donepezil, an acetylcholine inhibitor drug, were also evaluated. Diabetes was induced by single intraperitoneal injection of STZ (60 mg/kg body weight (b.wt)). One-month diabetic rats were treated with the selected drugs daily for another two consecutive weeks. The evaluation was done through the estimation of the levels of blood glucose, serum insulin, and oxidative stress markers: malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH); neurotransmitters: acetylcholinesterase (AchE) and dopamine (DA); vasoconstrictor indices: intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1(VCAM-1), and angiotensin II (Ang II); and apoptosis markers: tumor necrosis factor-α (TNF-α) and caspase-3 as well as the histopathological picture of the cerebellum region of the brain. The results revealed that the combination of niacin and CoQ10 improved most of the measured parameters with variable degrees. In conclusion, niacin and CoQ10 are promising dietary supplements in the management of diabetic encephalopathy.

Chemical Composition of Golden Berry Leaves Against Hepato-renal Fibrosis.

The role of Physalis peruviana (golden berry) as functional food against hepato-renal fibrosis induced by carbon tetrachloride (CCl4) was evaluated. The chemical composition of leaves referred the presence of withanolides and flavonoids. Two compounds, ursolic acid and lupeol, were isolated and their structures were elucidated by different spectral analysis techniques. The biological evaluation was conducted on different animal groups; control rats, control orally treated with plant extract (500 mg/kg body weight twice a week for six consecutive weeks), CCl4 (0.5 ml/kg body weight diluted to 1:9 (v/v) in olive oil and injected intraperitoneally) group, CCl4 treated with plant extract and CCl4 treated with silymarin as a reference herbal drug. The evaluation was done through measuring oxidative stress markers; malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO). Liver function indices; aspartate and alanine aminotransferases (AST & ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), bilirubin and total hepatic protein were also estimated. Kidney disorder biomarkers; creatinine, urea and serum protein were also evaluated. The results revealed plant safety and decrease in NO, MDA, IgG, ALP, tissue protein, bilirubin, creatinine and urea levels. Increase in SOD, AST, ALT, GGT and serum protein levels were observed. Improvement in liver and kidney histopathological architectures were also seen. In conclusion, Physalis peruviana recorded a significant protective role in liver and kidney against fibrosis. Further studies are needed to evaluate its isolated compounds and its use in pharmacological applications and clinical uses.

Combination of melatonin and certain drugs for treatment of diabetic nephropathy in streptozotocin-induced diabetes in rats.

Diabetic nephropathy is a major complication of diabetes and a leading cause of end-stage renal failure in many developed countries. The study aimed to evaluate the efficiency of certain drugs and melatonin in the treatment of nephropathy secondary to diabetes. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (50 mg/kg body weight). Three days after induction of diabetes (460-500 mg/dl), rats were treated daily for 60 days with Rowatinex, melatonin, Rowatinex + melatonin, Amosar (Losartan Potassium) (LSP) and LSP + melatonin. The evaluations were made by measuring blood urea nitrogen (BUN), serum uric acid, serum creatinine, urine creatinine, creatinine clearance, nitric oxide, malondialdehyde, superoxide dismutase, glutathione, total antioxidant capacity, kidney injury molecule-1, heat shock protein-70, caspase-3, transforming growth factor ß1, and DNA degradation by comet assay and total protein contents. The histopathological picture of the kidneys and pancreases was confirmed in our results. Diabetic rats showed drastic changes in all the measured parameters. Treatment with melatonin and the selected drugs revealed amelioration levels with variable degrees. In conclusion, the combination of LSP and melatonin had the most potent effect on treating the deleterious action of diabetes on rat kidney.

Phytochemical composition, protective and therapeutic effect on gastric ulcer and α-amylase inhibitory activity of Achillea biebersteinii Afan.

Three sesquiterpene lactones [two germacranolides (micranthin and sintenin) and one guaianolide (4ß,10α-dihydroxy-5ß,7ß,8ßH-guaia-1,11(13)dien-12,8α-olide)] and four derivatives of 3-methoxy flavones (santin, quercetagetin-3,6,3'-trimethyl ether, quercetagetin-3,6-dimethyl ether, and 5,7 dihydroxy 3,3',4'-trimethoxy flavone) were isolated from the ethyl acetate extract (EAE) of the aerial parts of Achillea biebersteinii Afan. (Asteraceae). Evaluation of protective and therapeutic effects of EAE against ethanol-induced gastric ulcer in rats was carried. Antiulcer activity evaluation was done through measuring ulcer indices, stomach acidity, gastric volume and lesion counts. Oxidative stress markers; malondialdehyde, glutathione and superoxide dismutase were also estimated. The work was extended to determine the histopathological assessment of the stomach. Gastric ulcer exhibited a significant elevation of the ulcer index and oxidative stress markers. The extract attenuated these increments and recorded protective and therapeutic effects against gastric ulcer. Hyperglycaemia increases the mucosal susceptibility to ulcerogenic stimuli and predisposes gastric ulceration. In vitro α-amylase inhibitory assay was applied to evaluate the post prandial antihyperglycaemia activity. The result showing that the EAE has the ability to reduce starch-induced postprandial glycaemic excursions by virtue of potent intestinal α-amylase inhibitory activity. These findings demonstrated the remarkable potential of A. biebersteinii as valuable source of antiulcer agent with post prandial hyperglycaemia lowering effect.