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Clinical manifestation of gastric ulcers is frequent, in addition to their costly drug regimens, warranting the development of novel drugs at lower costs. Although Bassia indica is well characterized for its anti-inflammatory and antioxidant potential, capacity of its ethanol extract (BIEE) to prevent stomach ulcers’ progression has not been reported. A nuclear protein termed high-mobility group box 1 (HMGB1) plays a key role in the formation of stomach ulcers by triggering a number of inflammatory responses. The main purpose of the current investigation was to evaluate the in vivo anti-inflammatory and anti-ulcerogenic capabilities of BIEE against ethanol-induced gastric ulcers in rats via the HMGB1/TLR-4/NF-B signaling pathway. HMGB1 and Nuclear factor kappa (NF-B) expression, IL-1β and Nrf2 contents showed an increase along with ulcer development, concurrent with an increase in immunohistochemical TLR-4 level. In contrast, pre-treatment with BIEE significantly reduced HMGB1 and Nuclear factor kappa (NF-B) expression levels, IL-1β and Nrf2 contents and ulcer index value. Such protective action was further confirmed based on histological and immunohistochemical TLR-4 assays. Untargeted analysis via UPLC-ESI–Qtof-MS has allowed for the comprehensive characterization of 40 metabolites in BIEE mostly belonged to two main chemical classes, viz., flavonoids and lipids. These key metabolites, particularly flavonoids, suggesting a mediation for the anti-inflammatory and anti-ulcerogenic properties of BIEE, pose it as a promising natural drug regimen for treatment of stomach ulcers.

Graphical abstract Dunaliella salina and its isolated Zeaxanthin mitigate counteract age related dementia via attenuating levels of inflammatory mediators in the brain, i.e. interlekin-1β and inducible nitric oxide synthase, as well as brain Aβ protein and myelin base protein. D. salina overcomes brain aging and thereby repairs age-related dementia, both for its modulating function in attenuating the Aβ protein and neurotransmitters (serotonin, norepinephrine & dopamine)., Highlights • D. salina as well as its isolated zeaxanthin showed marked recovery of the D-gal-induced effect on the escape latency time. • D. salina exerted an amelioration in the brain Aβ contents and an increase in the brain 5-HT, NE and DOP levels. • These effects were confirmed by histopathological increase in number of viable neurons in both cerebral cortex and hippocampus., Age-related deterioration of sensorimotor and cognitive abilities suggests that the brain undergoes regressive alterations with aging that compromise its function. Thus, the present study was designed to assess the efficacy of Dunaliella salina in counteracting D-galactose (D-gal)-induced dementia brain aging and its modulatory role in attenuating amyloid β (Aβ) protein and neurotransmitters. Aging associated dementia was generated by injection of D-gal (200 mg/kg; i.p) of rats for 8 weeks. D. salina biomass (250 mg/kg), polar (30 mg/kg), its carotenoid (30 mg/kg) fractions as well as the isolated zeaxanthin (250 μg/kg) were given orally simultaneously with D-gal for additional two weeks. Twenty-four hours after the last treatment dose; behavioral, biochemical and histopathological assessment were performed. Results showed that oral treatment of motor deficit rats with D. salina biomass and its isolated polar and carotenoid fractions showed amelioration in the motor coordination assessed by the rotarod test and in the memory and learning capabilities evaluated by Morris water maze test. D. salina also showed a reduction in brain levels of inflammatory indicators viz. interlekin-1β and inducible nitric oxide synthetase as well as brain contents of Aβ protein and myelin base protein. Likewise, oral treatment with D. salina biomass and its isolated polar and carotenoid fractions exhibited an increase in the rats’ brain neurotransmitters and their metabolites. Furthermore, histopathological investigations have confirmed all of these results. Our findings suggest that D. salina overcomes brain aging and thereby repairs age-related dementia, both for its modulating function in attenuating the Aβ protein and neurotransmitters.

Diabetes mellitus has been implicated in the exacerbation of cerebral ischemic injuries. Among the most promising therapeutic approaches is the combination of nutraceuticals and nanotechnology. Curcumin has been termed "the magic molecule", and it was proven to exert several therapeutic actions. Therefore, the aim of the presented work was to investigate the therapeutic effects of curcumin nanoemulsion (NC) administered orally on the middle cerebral artery occlusion and reperfusion (MCAO/Re)-induced cerebral damage in rats with streptozotocin-induced diabetes. The cerebral injury was induced in rats by MCAO/Re 6 weeks after single intraperitoneal STZ injection (50 mg/kg; i.p.). MCAO/Re diabetic rats were then treated with NC (50 and 100 mg/kg; bw; p.o.) for two consecutive weeks. The results of the present study showed that oral treatment of MCAO/Re diabetic rats with NC was associated with a marked attenuation of the neurological deficit score as well as the brain imbalance of the redox homeostasis. NC treatment was also associated with decline in the brain expression of tumor necrosis factor, interleukin-1β, COX-2, cleaved caspase-3, and nuclear factor kappa B. In addition, the expression of glucose transporter 1 proteins upon treatment was restored. PRACTICAL APPLICATIONS: From all these results, it can be concluded that oral supplementation of curcumin nanoemulsion (NC) in diabetic rats reduced the brain injury via augmentation of the expression of glucose transporter 1, as well as its antioxidant and anti-inflammatory properties. Therefore, NC could be delineated as a promising treatment option for cerebral ischemia in diabetic patients.

Five new series of hydroxybenzofuranyl-pyrazolyl chalcones 3a,b, hydroxyphenyl-pyrazolyl chalcones 6a-c and their corresponding pyrazolylpyrazolines 4a, d, 7a-c and 8a-f have been synthesized and evaluated for their in vitro cyclooxygenase (COX)-1 and COX-2 inhibitory activity. All the synthesized compounds exhibited dual COX-1 and COX-2 inhibitory activity with obvious selectivity against COX-2. The pyrazolylpyrazolines 4a-d and 8a-f bearing two vicinal aryl moieties in the pyrazoline nucleus showed more selectivity towards COX-2. Within these two series, derivatives 4c, d and 8d-f bearing the benzenesulfonamide group were the most selective. Compounds 4a-d and 8a-f were further subjected to in vivo anti-inflammatory screening, ulcerogenic liability and showed good anti-inflammatory activity with no ulcerogenic effect. In addition compounds 4c and 8d as examples showed prostaglandin (PG)E2 inhibition % 44.23 and 51.4 respectively, tumor necrosis factor α (TNFα) inhibition % 33.48 and 41.41 respectively and gastroprotective effect in ethanol induced rodent gastric ulcer model. In addition, to explore the binding mode and selectivity of our compounds, 8d and celecoxib were docked into the active site of COX-1 and COX-2. It was found that compound 8d exhibited a binding pattern and interactions similar to that of celecoxib with COX-2 active site, while bitter manner of interaction than celecoxib to COX-1 active site.

Nonalcoholic fatty liver disease (NAFLD) is recognized globally as the leading cause of chronic liver diseases whose patients are asymptomatic and are diagnosed incidentally. It increases the rate of mortality which is usually related to cardiovascular events; however, scarce attention has been addressed to brain damage. This study was designed to investigate the impact of melatonin (MEL; 10 mg/kg) on overcoming the hepato and neuro-complications associated with high fat, high fructose (HFHF) diet induced-NAFLD in rats. NAFLD was induced by HFHF diet for 8 consecutive weeks. MEL was given orally for the last 10 days. Rats' general behavior was assessed by; open field test (OFT) and forced swimming test (FST). On biochemical level; serum levels of glucose, insulin, alanine transaminase and aspartate transaminase as well as the hepatic levels of triglycerides and total cholesterol were evaluated. Monoamines' brain levels, their metabolites in addition to the brain level of 8-hydroxyguanosine (8-OHdG) were evaluated. Moreover, the levels of tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NOx) were measured in both the liver and brain tissues. Oral treatment of NAFLD induced rats with MEL for ten consecutive days managed to increase the activity of the rats in the OFT and decrease the immobility period in the FST. Moreover, MEL reduced monoamines turnover and elevated brain 8-OHdG level. It also had the ability to counteract the elevated levels of GSH, NOx, MDA, and TNF- α in liver and brain tissues. MEL can be suggested to be a promising candidate for treating the neuronal side effects related to NAFLD.

Background and purpose: Diabetes mellitus is a disorder accompanied by oxidative and inflammatory responses, that might exacerbate vascular complications. The purpose of this study was to investigate the potential antioxidant and anti-inflammatory effects of melatonin (MLN) on streptozotocin (STZ)-induced diabetic rats subjected to middle cerebral artery occlusion followed by reperfusion (MCAO/Re). Experimental approach: Diabetes was induced in rats by a single injection of STZ (55 mg/kg; i.p.). The cerebral injury was then induced by MCAO/Re after six weeks. After 24 h of MCAO/Re the MLN (10 mg/kg) was administered orally for 14 days. Serum and tissue samples were extracted to determine malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), interleukin-1β (IL-1β), and the tumor necrosis factor-α (TNF-α). Part of the brain tissue was kept in formalin for pathological and immunohistochemical studies to determine nuclear factor kappa B (NF-kB) and cyclooxygenase-2 (COX-2) immune reactivity. Findings/Results: MCAO/Re in STZ-induced hyperglycaemic rats caused a decrease in brain GSH, an increase in brain MDA, and NO was increased in both serum and brain tissue. Rats showed a prominent increase in the serum and brain inflammatory markers viz. IL-1β and TNF-α. Oral treatment with MLN (10 mg/kg) for two weeks reduced the brain levels of MDA, NO, IL-1β, and TNF-α. Impressive amelioration in pathological findings, as well as a significant decrease in NF-kB and COX2 immune stained cells of the cerebral cortex, hippocampus, and cerebellum, occurred after treatment with MLN. It also succeeded to suppress the exacerbation of damage in the brain of hyperglycaemic rats. Conclusion and implications: Daily intake of MLN attenuates the exacerbation of cerebral ischemic injury in a diabetic state.

Aim and Objective:A series of new 2-pyrazoline analogues were synthesized. The structures of the synthesized compounds were elucidated by the analytical and spectroscopic data. Some selected compounds were screened for the anti-inflammatory activity by using animal model of carrageenan-induced paw edema in mice. Additionally, the analgesic and acute toxicity of these compounds were evaluated and exhibited reasonable results. The anti-oxidant and anti-inflammatory effects of these compounds were established by measuring the contents of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), and tumor necrosis factor alpha (TNF-α) in the edema paw tissue.Materials and Methods:All chemicals and reagents used in current study were of analytical grade. Melting points were determined using APP. Digital ST 15 melting point apparatus and are uncorrected. FT-IR spectra were recorded on a Pye-Unicam SP3-100 spectrophotometer in KBr pellet. All 1H and 13C NMR spectra were recorded on AVANCE-III (400 MHz) High Performance FT-NMR Spectrometer Brucker (Switzerland) and some 1H NMR spectra were recorded on Varian EM-360L NMR Spectrophotometer (60 MHz) (USA) in CDCl3 or DMSO-d6 as solvent. Chemical shifts are reported in δ units and the coupling constants (J) are reported in hertz. C, H, N and S analyses were performed with a Vario EL C, H, N, S Analyzer. Carrageenan (product number C1013) was obtained from Sigma-Aldrich (USA).Results:The structures of the compounds were confirmed by IR, 1H NMR, 13C NMR, and elemental analyses. The results of pharmacological activity revealed that compounds 5, 6, 7, and 15 could be recognized as potential multi-potent anti-inflammatory.Conclusion:A simple and suitable method for the synthesis of new pharmacophore was reported. We have designed nineteen heterocycles related to pyrazoline ring, and evaluated eleven of them for their antiinflammatory, analgesic and acute toxicity activities. Compounds 5, 6, 7, and 15 proved to be the interesting compounds, they have high anti-inflammatory activity. However, all the selected compounds show remarkable analgesic activity.

The study was designed to investigate the potential anti-arthritic effects of methyl palmitate in an adjuvant arthritis model in rats that shares many histopathological similarities with human RA. The underlying mechanism and its effect on CD68 macrophages were investigated, as a further argument to its possible efficacy in RA treatment. A normal control group was injected only with saline, arthritic group, and three treatment groups with CFA induced arthritis received methyl palmitate (MP) at three different doses (75, 150, 300 mg/kg/week for 3 weeks, intraperitoneal). The degree of ipsilateral paw swelling, ankle diameter, spleen index, thymus index and the expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β were measured. In addition, the underlying molecular mechanism was investigated using CD68 expression. Methyl palpitate significantly and dose dependently decreased the arthritic symptoms as measured by ipsilateral paw volume and ankle diameter. It showed no effect on body weight but significantly decreased splenic, thymus index, serum TNF-α and IL-1β. CD68 macrophages expression and the overall synovial inflammatory cellularity were halted. Methyl palmitate exhibits significant anti-inflammatory and exerts a potential anti-arthritic effect in a rat model of adjuvant induced arthritis. Furthermore, it inhibits expression of synovial CD68 macrophage that validate its therapeutic potential adjuvant arthritis.

BACKGROUND: Therapies for diabetes mellitus are still meeting failure in most cases, especially in the developed stages of the disease due to incredible associating complications. Hence, there is a need for continuous development of curative therapies for that stubborn disease. AIM: We aimed to investigate the antidiabetic effects of one of the most popular plants cultivated in Egypt, C. olitorius. METHODS: Phytochemical screening of total alcoholic extract of Corchorus olitorius leaves and its aqueous and chloroform fractions revealed the presence of flavonoids, saponins, carbohydrates, tannins, coumarins, and alkaloids. RESULTS: The gas chromatography-mass spectrometry analysis showed the presence of 12 and nine chemical compounds in aqueous and chloroform extracts, respectively. C. olitorius decreased serum glucose level and α-amylase activity. This effect was more pronounced in the total alcoholic extract and its chloroform fraction than the aqueous one. The extracts also adjusted the lipid profile, reduced liver injury parameters, and caused remarkable improvement and increase number, size, and density of functioning β-cells. CONCLUSION: The findings suggest the antihyperglycemic and antioxidant effects of C. olitorius besides its beneficial effect on diabetic complications such as hyperlipidemia and liver injury. The presence of some phytochemicals such as theophylline, trans-2, 3-dimethoxycinnamic acid, 7-hydroxy-4-methyl coumarin, apigenin 7-glucoside, and glycitein may contribute to such pharmacological effects.

Background. Hepatic steatosis is the most common type of chronic liver disease and is considered an established risk factor of major chronic diseases. Purpose. The present study aimed to investigate the effect of Dunaliella salina, a microalga and its isolated zeaxanthin on age-related hepatic steatosis as well as their underling mechanism. Study Design. Age-related hepatic steatosis was induced in rats by intraperitoneal injection of D-galactose (200 mg/kg/day) for eight consecutive weeks. D. salina biomass (BDS; 450 mg/kg), its polar fraction (PDS; 30 mg/kg), carotenoid fraction (CDS; 30 mg/kg), and isolated zeaxanthin heneicosylate (ZH; 250 μg/kg) were orally administered to D-galactose treated rats for two weeks. Methods. Blood samples were collected 24 hours after the last dose of D. salina treatments, animals were sacrificed, and liver tissues were isolated. Sera as well as hepatic tissue homogenates were used for further investigations. Liver tissues were also used for histopathological and immunohistochemical examinations. A computed virtual docking study for the biologically active candidates was performed to confirm the proposed mechanism of action. Results. Oral treatment of D-galactose-injected rats with BDS, PDS, CDS, or ZH ameliorated the serum hepatic function parameters as well as serum levels of adiponectin, apolipoprotein B 100, and insulin. Furthermore, D. salina decreased the hepatic lipid contents, redox status biomarkers, inflammatory cytokine, and showing antiapoptotic properties. Molecular docking of β-carotene and zeaxanthin on various receptors involved in the pathophysiological cascade of steatosis highlighted the possible mechanism underlying the observed therapeutic effect. Conclusion. D. salina carotenoids have beneficial effect on age-related hepatic steatosis in senescence rats through the regulation of redox status, inflammatory indices, and apoptotic biomarkers.

Context: Nothing could be found in the literature concerning Cinnamomum glanduliferum (Wall) Meissn (Lauraceae) bark (CG) in Egypt. Objective: To investigate CG volatile oil chemically and its anti-inflammatory and gastroprotective effects. Materials and methods: Essential oils were investigated by GC-MS. Leaves oil was assessed at doses of 250, 500 and 1000 mg/kg for its anti-inflammatory effect against carrageenan-induced rat oedema model. Serum inflammation markers were measured. The gastro-protective effect of the same doses of the volatile oil was also tested in ethanol-induced non-ulcerative gastritis model in rats. Stomach oxidative stress markers were examined following 1 h after intragastric ethanol administration. Results: Twenty-five and 20 compounds were identified from leaf and branch oils, respectively (98.85 and 99.13%). The major ones were: eucalyptol (59.44%; 55.74%), sabinene (14.99%; 7.12%), α-terpineol (6.44%; 9.81%), α-pinene (5.27%; 4.71%). Following 4 h of treatment leaves volatile oil at doses of 250, 500 and 1000 mg/kg significantly reduced paw volume to 94, 82 and 69%, respectively. The same doses significantly reduced COX-2 activity to 73.8, 50.7 and 21.4 nmol/min/mL, respectively. A significant reduction of PGE2 concentration was observed (2.95 ± 0.2, 2.45 ± 0.15 and 1.75 ± 0.015 pg/mL). CG oil exhibited a significant modulatory effect on ethanol-induced gastritis in rats as the level of NO reduced to 32, 37 and 41 μM nitrate/g and also a significant inhibition of lipid peroxidation was observed via reduction of MDA concentration (1.15, 1.11 and 1.04 nmol/g). Conclusion: CG volatile oil exhibited an anti-inflammatory effect and protected against ethanol-induced non-ulcerative gastritis.

Backgrounds Osteoporosis prevailing in elderly involves a marked increase in bone resorption showing an initial fall in bone mineral density leading to a significant reduction in bone formation. Aim The present study aimed to investigate the effect of Heamatococcus pluvialis microalgae on osteoporosis in D-galactose-treated rats. The underlying mechanism was tracked targeting the osteoprotegerin (OPG)/ nuclear factor-κβ ligand (RANKL) pathway using micro-computed tomography scanning. Methods Osteoporosis was induced in rats by intraperitoneal injection of D-galactose (200 mg/kg/day) for eight consecutive weeks. Osteoporotic rats were orally treated with H. pluvialis biomass (BHP; 450 mg/kg), its polar (PHP; 30 mg/kg) and carotenoid (CHP; 30 mg/kg) fractions for the last 2 weeks of D-Gal injection. Twenty four hours after the last dose of the treatments, tibia bones of the rats were scanned using micro-computed tomography scanning for bone mineral density (BMD), bone volume fraction (BV/TV), trabecular thickness/separation/number (Tb.Th, Tb.Sp, Tb.N) evaluation, blood samples were withdrawn and sera were used for biochemical assessment. Moreover, femur bones were examined histopathologically using several stains. Results Induction of osteoporosis was associated with a marked reduction in BMD, BV/TV, Tb.Th, Tb.Sp, Tb.N and in serum levels of phosphorus and catalase. On the other hand, a significant elevation in serum levels of calcium, bone alkaline phosphatase (BALP) and interleukin-6 was observed. Moreover, up-regulation of OPG was detected in osteoporotic rats. Oral treatment with BHP, and PHP incremented tibia BMD and serum phosphorus level along with the decrease in serum levels of calcium, BALP, interleukin-6, OPG and RANKL. However, treatment with CHP almost restored all the fore mentioned parameters to normal values. Furthermore, the histopathological evaluation emphasized the biochemical outcomes. Conclusion H. pluvialis fractions rich in astaxanthin ameliorated bone loss in experimentally-induced osteoporosis in rats probably through the down-regulation of serum OPG in concurrence with up-regulation of serum RANKL.

Retinoids are essential during early cardiovascular morphogenesis. However, recent studies showed their important role in cardiac remodeling in rats with hypertension and following myocardial infarction. The present study aimed to investigate the effect of zeaxanthin heneicosylate (ZH), a carotenoid ester isolated from Dunaliella salina microalgae, on cardiac dysfunction ensuing d-galactose injection in rats. Rats injected with d-GAL (200 mg/kg, I.P) for 8 weeks were orally treated with ZH (250 &mu, g/kg) for 28 consecutive days. Results showed that d-GAL injection caused dramatic electrocardiographic changes as well as marked elevation in serum levels of homocysteine, creatinine kinase isoenzyme and lactate dehydrogenase. A reduction in the cardiac contents of glucose transporter-4 and superoxide dismutase along with the elevation of inducible nitric oxide synthetase and interleukin-6 was also noticed. Oral administration of ZH significantly improved the above mentioned cardiac aging manifestations, this was further emphasized through histopathological examinations. The effect of ZH is mediated through the interaction with retinoid receptor alpha (RAR-&alpha, ) as evidenced through a significant elevation of RAR-&alpha, expression in cardiac tissue following the lead of an in silico molecular docking study. In conclusion, zeaxanthin heneicosylate isolated from D. salina ameliorated age-associated cardiac dysfunction in rats through the activation of retinoid receptors.

Ethnopharmacological relevance Combretum aculeatum Vent was traditionally used in Sudan, Eretria and Ethiopia as anti-inflammatory in case of skin inflammation, catarrh, wounds, scorpion stings and snake bites. Nevertheless, there is no scientific information regarding this activity. Aim of study The present study aimed to evaluate the phytochemical constituents and the scientific basis for the traditional use of Combretum aculeatum Vent through studying its anti-inflammatory properties for the first time to illustrate the putative mechanisms behind this bioactivity. Materials and methods the ethanolic extract was partitioned by petroleum ether, methylene chloride, ethyl acetate, and n-butanol saturated with water. The petroleum ether fraction was saponified and the saponifiable and unsaponifiable fractions were analyzed on GC/MS. The different fractions were subjected to phytochemical investigation to isolate pure compounds. In-vivo anti-inflammatory activity of the ethanolic extract was evaluated using carrageenan induced rat paws edema method at doses of 200, 400 and 600 mg/kg and proved based on histopathological and biochemical parameters. Results Five known compounds were isolated for the first time from the aerial parts of Combretum aculeatum Vent: quercetin, vitexin, isorhamnetin 3-O-β-glucoside, isovitexin and rutin, in addition to two previously isolated ones: β-sitosterol and its glucoside. The ethanolic extract evidenced in-vivo anti-inflammatory activity by oral intake of 400 mg/kg of the ethanolic extract significantly (P ≥ 0.05) decreased the paw edema (only 32±1.9% increase in paw weight after 4 h) compared to indomethacin (28.6±2.5%). Moreover, it significantly suppressed the serum malondialdehyde (MDA) and nitric oxide (NO) and increased the GSH to be 11.76±0.85, 5.13±0.62 μmol/mL and 5.66±0.28 μM/mL, respectively. It diminished the serum cytokines TNF-α, IL-6 and IL-1β levels to be 39.1±1.2, 32.6±1.1 and 37.5±1.2 pg/mL, respectively. Results are accompanied by histopathological examination. Conclusion Overall, the results herein presented significant anti-inflammatory properties traditionally ascribed to Combretum aculeatum Vent. Moreover, the biochemical mechanisms associated to this action were highlighted, introducing new prospects for the development of effective anti-inflammatory herbal medicinal products.

The highly selective serotonin reuptake inhibitors are successful in the treatment of depression mood and anxiety disorders. The objective of this study is to investigate the effect of fluexotine and buspirone when given orally in three dose levels (5, 10 and 15 mg/ kg) not only for eight weeks on gastric lesions and oxidative markers in normal rats' mucosal integrity, but also for four weeks on gastric mucosal lesions in rats treated with indomethacin- induced ulcers. The results of this study showed that in normal rats, the administration of fluoxetine induced gastric lesions while buspirone caused no lesions. The indomethacin administration resulted in the development of gastric mucosal lesions. Furthermore, co-administration of fluoxetine and indomethacin enhanced the development of gastric mucosal lesions that were coupled with disturbance in antioxidant status. Buspirone, in contrast, significantly decreased the development of gastric mucosal lesions in rats treated with indomethacin. In conclusion, fluoxetine caused the development of gastric mucosal lesions and aggravate the effect of indomethacin to induce ulcer, however, buspirone had a protective effect that may be attributed to its antioxidant properties. Key words: Fluoxetine, buspirone, peptic ulcer, indomethacin-induced ulcer, oxidative stress.

The fruits of Gleditsia species (Fabaceae) have been known in traditional medicine as a saponin-rich herbal medicine. The present study aimed to investigate the effects of the total methanolic extract of Gleditsia caspica (MEGC) and its saponin-containing fractions (SFGC) on hyperglycemia in streptozotocin (STZ)-induced diabetic rats. A single intraperitoneal injection of STZ (55 mg/kg body weight) was used to induce hyperglycemia in male albino rats. MEGC (15, 30 and 60 mg/kg, p.o.) and SFGC (15, 30 and 60 mg/kg, p.o.) were administered to the diabetic rats daily for 14 days. The anti-diabetic drug gliclazide (10 mg/kg, p.o.) was used as a positive control. Blood samples were collected from overnight fasted rats for the evaluation of the antihyperglycemic, antihyperlipidemic and antioxidant activities. The levels of glucose, triglycerides (TG), cholesterol (TC) and malondialdehyde (MDA) were increased significantly, whereas the levels of α-amylase, insulin and reduced glutathione (GSH) were decreased in the experimental diabetic rats. Pancreas and liver of the diabetic rats exhibited significant changes in the histopathology, morphology and DNA content. Administration of MEGC or SFGC led to a decrease in the levels of glucose, TG, TC and MDA. In addition, the levels of α-amylase, insulin and GSH were increased in MEGC and SFGC treated diabetic rats. Also, the histopathological and morphological changes, as well the changes in DNA were significantly reversed by the extracts. Thus, MEGC and SFGC exhibited potent hypoglycemic and hypolipidemic activities in STZ- induced diabetic rats.

Objective To investigate some pharmacological effects including gastroprotective, anti-inflammatory, analgesic, antipyretic and in vitro antioxidant effects of Artemisia herba-alba extract in different experimental models. Methods Inflammation was induced in rat paw by subcutaneous injection of 1% (v/v) carrageenan solution. Writhes was induced in mice by intraperitoneal injection of 0.6% (v/v) acetic acid solution. Pyrexia was induced using Brewer's yeast suspension. Gastric lesion was induced in rats by oral administration of 99% ethanol. The anti-inflammatory, analgesic, antipyretic and gastroprotective activities of Artemisia herba-alba extract were investigated respectively. In vitro antioxidant effect was investigated using DPPH free radical. Results The plant extract showed anti-inflammatory effect in carrageenan-induced paw edema in rats, analgesic effect against acetic acid-induced writhing, and antipyretic activity in Brewer's yeast model of pyrexia. Besides, it was shown to be a gastroprotective agent against ethanol-induced gastric ulcers. The plant also exhibited a free radical scavenging potential in an in vitro antioxidant study using DPPH. Conclusions The results validate the use of the investigated plant in traditional medicine for different ailments.

Objective Evaluation of traditionally used royal jelly (RJ) for the management of hepato-renal damage and gastrointestinal ulcerations caused by diclofenac. Methods Forty adult male Wistar rats were allocated into four groups. Rats of the 1st group received only saline and served as normal group. The remaining 3 groups received diclofenac (50 mg/kg/day, I.P.) for 7 days. Group 2 served as diclofenac-control group. Groups 3 and 4 received RJ (150 and 300 mg/kg/day, P.O.) respectively for 30 days. Twenty-four hours after the last treatment, blood samples were collected, rats were sacrificed, and livers, kidneys, stomachs & intestines were harvested. Stomachs and intestines were tested for ulcer counts. Serum levels of AST, ALT, creatinine and urea were investigated. Hepatic, renal, gastric and intestinal tissue contents of myeloperoxidase (MPO) and prostaglandin-E2 (PGE2) were measured. Histopathological examinations were also performed followed by immunohistochemical determination of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression. Results Diclofenac administration caused significant deterioration of all the above mentioned parameters. RJ improved hepatic and renal functions. Gastric and intestinal ulcer counts were significantly ameliorated. Hepatic, renal, gastric and intestinal tissue PGE-2 contents and COX-2 expression were significantly elevated. RJ also significantly reduced MPO content and iNOS expression as compared to diclofenac-control group. Improvements of the histopathological pictures of hepatic, renal, gastric and intestinal tissues were also apparent. Conclusion The study demonstrates promising protective effects of RJ against diclofenac-induced hepato-renal damage and gastrointestinal ulceration in rats., Royal jelly; Diclofenac; Hepatic; Renal; Gastrointestinal; Inflammation; Rats; Pharmaceutical science; Biochemistry; Molecular biology; Gastrointestinal system; Renal system; Pathology; Pharmacology; Toxicology

Context: Mango is a valuable plant with vital economic importance; the leaves of its cultivars show several morphological similarities. Aims: Full differentiation of the leaves of eight Mangifera indica L. cultivars depending on genetic, chemical, and biological bases. Settings and Design: Chemometric analysis was applied to fully distinguish the diversity among cultivars; also, their gastroprotective activity was studied. Subjects and Methods: DNA fingerprinting of eight mango cultivars using random amplified polymorphic DNA–polymerase chain reaction technique and high-performance liquid chromatography (HPLC) analysis of phenolic compounds and flavonoids were compared using chemometric analysis. Furthermore, estimation of total polyphenolics and flavonoids and gastroprotective activity was studied.Statistical Analysis Used: One-way analysis of variance was used, followed by Tukey's post hoc test. Results: Primers OPA-O7 and OPA-O8 showed 100% polymorphism. Total polyphenolics and flavonoids concentrations varied greatly (14.58 in Tommy atkins to 29.54 in Fagrklan g gallic acid equivalent/100 g extract and 22.49 in Tommy atkins to 93.40 in Fagrklan g rutin equivalent/100 g extract, respectively). HPLC quantification revealed that Kent had relatively high mangiferin content (732.446 mg/kg), and caffeic acid was recorded in the tested cultivars (2266.66 in Keitt to 1106.94 mg/kg in Naaomy). Pylorus ligation model in rats was used to assess gastroprotective potential at a dose of 200 mg/kg using standard ranitidine. High percentage protection was observed in Kent (65.62%), whereas Keitt showed the lowest percentage protection (45.31%). No direct correlation could be deduced between concentration of detected metabolites and the gastroprotective effect, so this activity might be attributed to synergistic effect between all secondary metabolites. Conclusions: This study spots the light on the great variation among the tested extracts; in addition, it provides effective techniques that pave the way for complete discrimination of these mango cultivars.

The main objective of this work was to synthesize novel compounds with a benzo[de][1,2,4]triazolo[5,1-a]isoquinoline scaffold by employing (dioxo-benzo[de]isoquinolin-2-yl) thiourea as a building block. Molecular docking was conducted in the COX-2 active site to predict the plausible binding mode and rationalize the structure–activity relationship of the synthesized compounds. The structures of the synthesized compounds were confirmed by HREI-MS, and NMR spectra along with X-ray diffraction were collected for products 1 and 5. Thereafter, anti-inflammatory effect of molecules 1–20 was evaluated in vivo using carrageenan-induced paw edema method, revealing significant inhibition potency in albino rats with an activity comparable to that of the standard drugs indomethacin. Compounds 8, 9, 15 and 16 showed the highest anti-inflammatory activity. However, thermal sensitivity-hot plat test, a radiological examination and motor coordination assessment were performed to test the activity against rheumatoid arthritis. The obtained results indicate promising anti-arthritic activity for compounds 9 and 15 as significant reduction of the serum level of interleukin-1β [IL-1β], cyclooxygenase-2 [COX-2] and prostaglandin E2 [PGE2] was observed in CFA rats. Electronic supplementary material The online version of this article (doi:10.1186/s13065-017-0321-1) contains supplementary material, which is available to authorized users.

The progestational potency and selectivity of synthetic steroidal agonists can be enhanced by even larger chemical moieties at 17α-position of the steroid backbones. Hereby a series 5a-c and 6a-c of novel 17α-[1-(substituted phenyl)-1,2,3-triazol-4-yl]-19-nortestosterone-17β-yl acetates were designed and synthesized using click chemistry approach searching progestogenic derivatives with potential anticancer activity. Compounds 5a , b and 6a , c have affected to different extents the three histopatho-logical parameters considered for evaluation of their progestational activity. The compounds 5a , b and 6a , c showed modifications in rat uterus at 35.7–34.8 nM levels with privileged endometrial thickening effect and least change of uterine weight relative to NEA at 52.9 nM level. Up to 40 mg/kg dose compounds 5b and 6c were non-toxic. Molecular docking of the ligands in PR showed in the majority of cases a conformational fitting into the active site different from that of the reference steroid NEA. Compound 6b revealed about 46.4% growth inhibition of CNS cancer SNB-75 cell line, 56% growth inhibition of renal cancer A498 cell line and 56.7% growth inhibition of prostate cancer PC-3 cell line which was mediated by cell cycle arrest. Drugability of the screened compounds showed tolerated results after being challenged to diverse physicochemical parameters.

Phytochemical study on the methanolic extract of Sansevieria cylindrica aerial parts lead to the isolation, characterization and structure elucidation of a new steroidal saponin, 1β-hydroxy-kryptogenin-1- O -α- l -rhamnopyranosyl-(1 → 2)-α- l -arabinopyranoside ( 1 ), a new homoisoflavanone, (3S)-3,7-dihydroxy-8-methoxy-3-(3′,4′-methylenedioxybenzyl) chroman-4-one ( 2 ) and the known saponin alliospiroside A ( 3 ). To the best of our knowledge, the genin 1β-hydroxy-kryptogenin is reported here for the first time. The structures of the new compounds were determined by UV, IR, EIMS, HRESIMS together with 1D ( 1 H and 13 C) and 2D (HSQC and HMBC) NMR spectral analysis. The isolated compounds 1–3 were tested for their radical scavenging activity (DPPH). Compound 2 exhibited activity compared to that of ascorbic acid as a standard. The cytotoxicity of the isolated compounds and the standard doxorubicin was tested against the three human tumor cell lines HT116, MCF-7 and PC-3. The results showed that the isolated compounds were inactive.

Haloperidol (HP) is a classic antipsychotic drug known for its propensity to cause extrapyramidal side effects. HP is known to induce oxidative stress due to increased turnover of dopamine. The aim of the present study was to investigate the effect of sucrose (1 and 5 mg/kg; p.o.) and grape seed extract (GSE; 100, 200 and 400 mg/kg; p.o.) on the oxidative stress induced in rats by HP (1 mg/kg; p.o.) in the liver and the brain tissues. Oxidative stress was induced by injection of HP for 14 consecutive days which was concurrently administered with sucrose and GSE. Liver and brain levels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (nitrite) levels were determined in the brain and liver. Results of the present study revealed that HP-treated rats showed elevated levels of NO in the brain and MDA in the brain and liver. HP-treated rats showed also decreased levels of NO levels in the liver and GSH in the brain and liver. Treatment of HP-treated rats with GSE reversed all the oxidative stress markers in both the brain and liver due to its potent antioxidant property. On the other hand, sucrose attenuates the levels of NO in the brain and liver and the brain levels of MDA and GSH. It can be concluded that both GSE (a potent anti-oxidant) and sucrose (as a source of energy) have beneficial impacts on the brains of HP-treated rats. However, GSE is more potent in alleviating the oxidative stress associated with HP in the liver.

This study aimed to investigate the possible protective effects of genistein (GEN), a phytoestrogen, on the liver injury induced in rats by thioacetamide (TTA; 200.0 mg·(kg body mass)–1; administered 3 times a week by intraperitoneal injection). GEN (0.5, 1.0, or 2.0 mg·(kg body mass)–1; by subcutaneous injection) was concurrently administered on a daily basis for 8 weeks, and its effects were evaluated 24 h after the administration of the last dose. The results from this study revealed that TTA-induced liver injury was associated with massive changes in the serum levels of liver biomarkers, oxidative stress markers, and liver inflammatory cytokines. Treatment of TAA-induced liver injury in rats with GEN decreased the elevated serum levels of aspartate aminotransferase, alanine aminotransferase, and total and direct bilirubin, and increased the serum level of albumin. GEN also restored the liver levels of malondialdehyde and reduced glutathione, as well as tumor necrosis factor-alpha, interleukin-6, and their modulator nuclear factor kappa-light-chain-enhancer of activated B cells. From our results, it can be concluded that GEN attenuates the liver injury-induced in rats with TAA, and this hepatoprotective role is attributed to its anti-inflammatory and antioxidant properties.

Within the global context of increasing poverty in the developing countries, natural products are important in devising new drugs. Vicia ervilia L. Willd., unlike several fabaceae seeds, is not used for human consumption till now. We aim to discover any possible medicinal use of the seed. Analgesic, anti-inflammatory, antiulcerogenic and antihyperglycemic activities were evaluated using hot plate, carrageenan-induced rat paw edema, ethanol-induced ulcer model and alloxan-induced diabetes methods, respectively. Antiviral activity was evaluated using Methylthiazol Tetrazolium assay. V. ervilia seeds ethanol (70%) extract had significant anti-inflammatory, analgesic, antiulcerogenic, antihyperglycemic and antiviral activities. It is of excellent choice for treatment of several illnesses in developing countries due to its diverse resource, easy accessibility, affordability and its newly proved significant wide range of biological activities.

Due to toxic and adverse side effects of synthetic drugs, traditional herbal medicine has the potential as a source of new bioactive molecules. That is why we investigated this research, searching new anti-inflammatory drugs from plants growing around us. The anti-inflammatory effect of the mixture of different plants used in traditional medicine (Alkanna tinctoria, Rubia tinctorum and Artemisia herba alba) were studied using carrageenan-induced paw edema (oil mixture extract 100 mg/kg and 200 mg/kg). These material reduces carrageenan-induced inflammation in rats and shows inhibition after 4 h especially at a concentration 200 mg/ kg. Oil mixture extract were investigated by capillary GC and GC-MS in combination with retention indices revealed the presence of about 17 compounds: artemisol, epiglobulol and α-bisabolol are the main constituents as well as volatile oil and other triterpenes: taraxasterol, stigmasterol, ursan-12-ene, olean-12-ene, betulin, germincol, lupeol acetate and lupeol. Other heterocyclic compounds: moropholine and piperidinol were also identified

Objective: To investigate the possible protective and/or therapeutic potentials of Dunaliella salina (D. salina) biomass, its carotenoid and polar fractions on cardiac dysfunction associated with D-galactose (D-GAL) induced aging in rats. Methods: Aging associated cardiac dysfunction was induced in rats by injection of D-GAL (200 mg/kg; i.p) for 8 weeks. D-GAL injected rats were treated with two regimens; protective regimen where D. salina biomass (250 mg/kg), its carotenoid (250 μg/kg) and polar (250 μg/kg) fractions were given orally for two weeks concurrently with D-GAL injection as well as treatment regimen where the three treatments were given orally for 28 consecutive days after D-GAL injection. Results: D-GAL injection for 8 weeks was accompanied with dramatic electrocardiographic changes as well as profound elevation in serum levels of homocysteine, creatinine kinase isoenzyme and lactate dehydrogenase in addition to the reduction of the cardiac content of glucose trasporter 4. D-GAL also induced reduction in cardiac superoxide dismutase activity and elevation of inducible nitric oxide synthetase and interleukin-6. On the other hand, oral administration of D. salina carotenoid fraction as well as the total biomass significantly attenuated the D-GAL-induced disturbances in the above mentioned parameters where the protective regimen appeared more successful in controlling the manifestations of cardiac dysfunction. The histopathological examination further emphasized the promising results. Besides, the HPLC analysis of the carotenoid fraction of D. salina revealed the presence of 2.31% β -carotene. Conclusions: D. salina carotenoid fraction as well as the total biomass ameliorate D-GAL-induced aging associated cardiac dysfunction which is attributed to the potent antioxidant activity of β -carotene.

Objective: The study aims to evaluate the protective effects of coenzyme Q10 (CoQ10) and Cynara scolymus L (CS) on doxorubicin (dox)-induced toxicity.Materials and Methods: Sixty male rats were divided into six groups. Group 1 as a control. Group 2 received dox (10 mg/kg) intraperitoneally. Group 3 received CoQ10 (200 mg/kg). Group 4 received CS (500 mg/kg). Group 5 received CoQ10 (200 mg/kg) and dox (10 mg/kg). Group 6 received CS (500 mg/kg) and dox (10 mg/kg). The rats were then evaluated biochemically and immunohistochemically.Results: Dox produced a significant deterioration of hepatic and renal functional parameters. Moreover, an upsurge of oxidative stress and nitrosative stress markers. The expression of alpha-smooth muscle actin (α-SMA) was increased and proliferating cell nuclear antigen (PCNA) expression was decreased. Administration of CoQ10 and CS resulted in a significant improvement of hepatic and renal functional parameters, and an improvement of both α-SMA and PCNA.Conclusion: It is concluded that pretreatment with CoQ10 and CS is associated with up-regulation of favorable protective enzymes and down-regulation of oxidative stress. That can be advised as a supplement to dox-treated patients. Keywords: Alpha-smooth muscle actin, doxorubicin, nitrosative, oxidative, proliferating cell nuclear antigen

Background: Diabetes mellitus has been treated orally with herbal remedies based on folk medicine since ancient times. The current study investigates the protective effect of Artemisia herba alba (Ah) against experimentally-induced type 1 diabetes mellitus and its complications. Methods: Diabetes was induced in adult male Wister rats by administration of (Streptozotocin; STZ) at a dose of 52.5 mg/kg, i.p. Animals with diabetes were treated with either Ah ethanolic extract or gliclazide (10mg/kg, p.o.) for 14 days. Biochemical analysis was done such as glucose, insulin, homocysteine, lipid profile (cholesterol, triglyceride), liver function tests (T.bilirubin, AST and ALT), kidney function tests (BUN, sr. creatinine) and oxidative stress biomarkers. In addition, pancreas, liver, kidney, heart and aorta tissues were dissected out for pathological examination. Immuno histochemical study was done on pancreatic tissues for determination of insulin and glucagon immune reactivities. Liver tissues were also separated for genetic analysis. Results: Oral administration of Ah ethanolic extract at a concentration of 400, 200and 100 mg/kg daily for 14 days results in decreased fasting blood glucose and homocysteine levels as well as enhancement of plasma insulin level as compared with STZ-treated rats. The extract improved lipid profile, liver and kidney function tests. It also increased hepatic and renal contents of GSH, diminished lipid peroxidation, and inhibited pathological alterations induced in the different organs. Treatment with Ah extract increased insulin expression while decreased glucagon immunoreactivity and DNA band polymorphism. Conclusion: Thus, our results show that Ah possesses a promising antihyperglycemic effect that is comparable with gliclazide.

The benzofuran-morpholinomethyl-pyrazoline hybrids 4a-e, 5a-e and 6a-j were synthesized via reaction of α,β-unsaturated carbonyl compounds 3a-e with hydrazine hydrate, semicarbazide or thiosemicarbazide. Applying the Mannich reaction to 5-(5-aryl-4,5-dihydro-1H-pyrazol-3-yl)-4-methoxybenzofuran-6-ols 7a-e with morpholine hydrochloride and paraformaldehyde afforded positional isomeric 7-morpholinomethyl derivatives 4a-e and N-morpholinomethyl derivatives 8a-e. All the synthesized compounds showed significant vasodilatation properties in isolated thoracic aortic rings of rats precontracted using the standard norepinephrine hydrochloride technique. Compounds 3d, 3e, 5a-c, 6b, 6c, 6f, 6h and 6i exhibited activity (IC50 0.3185-0.4577 mM) superior to that of prazocin (IC50 0.487 mM), while 5d, 6j and 8c showed comparable activity (IC50 0.4789-0.4951 mM). The quantitative structure-activity relationship study revealed a correlation between the observed vasorelaxant activities of the newly synthesized compounds and their different physicochemical parameters, especially solubility, in addition to structure connectivity and energetic quantities calculated from stored three dimensional (3D) conformations. Absorption, distribution, metabolism and elimination (ADME) evaluation showed good agreement with the biological results obtained.