Anti-inflammatory and anti-rheumatic effects of Phoenix dactylifera L. (date palm) seed by controlling cytokines and inhibiting JAK1/STAT3 pathway on CFA-induced arthritis rat and its phytochemical profiling.

ETHNOPHARMACOLOGICAL RELEVANCE: Phoenix dactylifera L. (date palm) seed is widely used in Arabian traditional medicine to alleviate several health problems including inflammatory conditions. The herbal tea of date palm seed has been consumed by rheumatoid patients to relief their symptoms. AIM OF THE STUDY: The purpose of this study was to investigate the claimed beneficial use of P. dactylifera L. (Sewy variety) seed (PDS) in the treatment of rheumatoid arthritis (RA) and its mechanism of action as well as to study its phytoconstituents. MATERIALS AND METHODS: The anti-inflammatory and anti-oxidative properties of the non-polar and the polar extracts of PDS were studied using Complete Freund's adjuvant (CFA)-induced arthritis rat model. Paw edema, body weight, total nitrate/nitrite NOX content and cytokine markers were evaluated to monitor the progress of arthritis. Also, histological examination and thermal analysis were conducted. The phytoconstituent profiles of non-polar and polar extracts of PDS were investigated using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). The multiple reactions monitoring mode (MRM) of liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) was used to quantify phenolic phytoconstituents in both extracts. RESULTS: According to the findings, the polar and non-polar PDS extracts kept body weight comparable to those of healthy individuals while considerably lowering paw swelling, edema, and neutrophil infiltration. It also reduced the levels of Nuclear Factor Kappa B (NF-κB), Tumor Necrosis Factor Alpha (TNF-α), Interleukin 22, Interleukin 23, Interferon (IFN), Interleukin 17, Interleukin 1ß, Interleukin 6, Interleukin 36, Janus Kinase 1 (JAK1), and Signal Transducer and Activator of Transcription 3 (STAT3). They also reduced the degenerative alterations caused by RA. Thermal research gave additional support for these findings. 83 phytoconstituents were identified in the non-polar PDS extract and 86 phytoconstituents were identified in the polar PDS extract. 74 of the identified phytoconstituents were common in both extracts. 33 phytoconstituents were identified here from P. dactylifera for the first time as far as we know. In MRM-LC-ESI-MS/MS analysis, the major phenolics in both extracts were chlorogenic acid, naringenin, and vanillin. Catechin was only detected in the non-polar PDS extract. On the other hand, apigenin, kaempferol, and hesperetin were only detected in the polar PDS extract. Generally, the polar PDS extract showed higher concentrations of the identified phenolics than the non-polar extract. CONCLUSIONS: The PDS extracts especially the non-polar extract showed significant anti-inflammatory and anti-oxidative properties in the CFA-induced arthritis rat model. PDS might be used to produce RA medicines.

Ferulic acid nanoemulsion as a promising anti-ulcer tool: in vitro and in vivo assessment.

OBJECTIVE: Ferulic acid (FA) is a promising nutraceutical molecule which exhibits antioxidant and anti-inflammatory properties, but it suffers from poor solubility and bioavailability. In the presented study, FA nanoemulsions were prepared to potentiate the therapeutic efficacy of FA in prevention of gastric ulcer. METHODS: FA nanoemulsions were prepared, pharmaceutically characterized, and the selected nanoemusion was tested for its ulcer-ameliorative properties in rats after induction of gastric ulcer using ethanol, by examination of stomach tissues, assessment of serum IL-1ß and TNF-α, assessment of nitric oxide, prostaglandin E2, glutathione, catalase and thiobarbituric acid reactive substance in stomach homogenates, as well as histological and immunohistochemical evaluation. RESULTS: Results revealed that the selected FA nanoemulsion showed a particle size of 90.43 nm, sustained release of FA for 8 h, and better in vitro anti-inflammatory properties than FA. Moreover, FA nanoemulsion exhibited significantly better anti-inflammatory and antioxidant properties in vivo, and the gastric tissue treated with FA nanoemulsion was comparable to the normal control upon histological and immunohistochemical evaluation. CONCLUSION: Findings suggest that the prepared ferulic acid nanoemulsion is an ideal anti-ulcer system, which is worthy of further investigations.

Gastroprotective Chitosan Nanoparticles Loaded with Oleuropein: An In Vivo Proof of Concept.

Oleuropein is the main constituent of olive leaf extract, and it has shown antioxidant and gastroprotective properties against gastric ulcers. Chitosan nanoparticles are known for their mucoadhesive abilities, and consequently, they can increase the retention time of drugs in the gastrointestinal tract. Therefore, loading oleuropein onto chitosan nanoparticles is expected to enhance its biological efficiency. Oleuropein-loaded chitosan nanoparticles were prepared and characterized for particle size, surface charge, in vitro release, and anti-inflammatory activity. Their in vivo efficacy was assessed by measuring specific inflammatory and protective biomarkers, along with histopathological examination. The optimum oleuropein chitosan nanoparticles were cationic, had a size of 174.3 ± 2.4 nm and an entrapment efficiency of 92.81%, and released 70% of oleuropein within 8 h. They recorded a lower IC50 in comparison to oleuropein solutions for membrane stabilization of RBCs (22.6 vs. 25.6 µg/mL) and lipoxygenase inhibition (7.17 vs. 15.6 µg/mL). In an ethanol-induced gastric ulcer in vivo model, they decreased IL-1ß, TNF-α, and TBARS levels by 2.1, 1.7, and 1.3 fold, respectively, in comparison to increments caused by exposure to ethanol. Moreover, they increased prostaglandin E2 and catalase enzyme levels by 2.4 and 3.8 fold, respectively. Immunohistochemical examination showed that oleuropein chitosan nanoparticles markedly lowered the expression of IL-6 and caspase-3 in gastric tissues in comparison to oleuropein solution. Overall, oleuropein chitosan nanoparticles showed superior gastroprotective effects to oleuropein solution since comparable effects were demonstrated at a 12-fold lower drug dose, delineating that chitosan nanoparticles indeed enhanced the potency of oleuropein as a gastroprotective agent.

Curcumin nanoemulsion ameliorates brain injury in diabetic rats.

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-1ß, 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.

Dunalialla salina microalgea and its isolated zeaxanthin mitigate age-related dementia in rats: Modulation of neurotransmission and amyloid-ß protein.

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 ß (Aß) 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-1ß and inducible nitric oxide synthetase as well as brain contents of Aß 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 Aß protein and neurotransmitters.

'Methyl palmitate attenuates adjuvant induced arthritis in rats by decrease of CD68 synovial macrophages.

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)-1ß 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-1ß. 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.

Synthesis of Hydroxybenzofuranyl-pyrazolyl and Hydroxyphenyl-pyrazolyl Chalcones and Their Corresponding Pyrazoline Derivatives as COX Inhibitors, Anti-inflammatory and Gastroprotective Agents.

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.

Impact of type III collagen on monosodium iodoacetate-induced osteoarthritis in rats.

Osteoarthritis (OA) is a degenerative chronic disease that affects various tissues surrounding the joints, such as the subchondral bone and articular cartilage. The purpose of the study was to investigate the impact of collagen type III (CIII; 10 mg/kg; p.o.) on OA evidenced by restoration of articular cartilage structural changes as well as inflammatory responses using an established rat model of OA. OA was induced in rats by a single intra-articular injection of monosodium iodoacetate (MIA) through the right knee of the rats. Oral administration of CIII was undergone for 14 consecutive days. Changes in joint volume were measured throughout the experiment period with one-week intervals. At the end of the experiment, the rats were placed in the activity cage, and their activities were counted. Oxidative stress and nitrosative biomarkers were assessed by measuring the serum levels of malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NOx). Moreover, inflammatory markers viz. interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and tumor necrosis nuclear factor-alpha (TNF-α) were measured. In addition, radiographic analysis and histopathological examination of the rat's knee were performed. The results of the current study revealed that oral treatment of MIA-induced osteoarthritic rats with CIII (10 mg/kg) for two weeks showed a marked decrease in the joint volume which led eventually to a prominent increase in the motor activity. Furthermore, treatment with CIII restored the serum levels of MDA, GSH, NOx, IL-6, IL-1ß and the TNF-α. Furthermore, CIII succeeded to ameliorate the detrimental effect of MIA on radiographic images and histopathological alterations of the joint. From these findings, it can be concluded that CIII has regenerative and anti-inflammatory properties, thus has the ability to counteract MIA-induced OA in rat. Finally, CIII is said to be a potential anti-osteoarthritic candidate.

Attenuation of Age-Related Hepatic Steatosis by Dunaliella salina Microalgae in Senescence Rats through the Regulation of Redox Status, Inflammatory Indices, and Apoptotic Biomarkers.

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 ß-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.

Protective effect of royal jelly against diclofenac-induced hepato-renal damage and gastrointestinal ulcerations in rats.

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.

Anti-inflammatory and phytochemical evaluation of Combretum aculeatum Vent growing in Sudan.

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-ß-glucoside, isovitexin and rutin, in addition to two previously isolated ones: ß-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-1ß 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.

Heamatococcus pluvialis ameliorates bone loss in experimentally-induced osteoporosis in rats via the regulation of OPG/RANKL pathway.

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-κß 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.

Synthesis, crystallographic characterization, molecular docking and biological activity of isoquinoline derivatives.

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-1ß [IL-1ß], cyclooxygenase-2 [COX-2] and prostaglandin E2 [PGE2] was observed in CFA rats.

Anti-inflammatory and gastroprotective potential of leaf essential oil of Cinnamomum glanduliferum in ethanol-induced rat experimental gastritis.

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.

Hypoglycemic activity of Gleditsia caspica extract and its saponin-containing fraction in streptozotocin-induced diabetic rats.

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.

Cu (I) catalyzed alkyne-azide 1,3-dipolar cycloaddition (CuAAC): Synthesis of 17α-[1-(substituted phenyl)-1,2,3-triazol-4-yl]-19-nor-testosterone-17ß-yl acetates targeting progestational and antipro-liferative activities.

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-17ß-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.

Prophylactic role of coenzyme Q10 and Cynara scolymus L on doxorubicin-induced toxicity in rats: Biochemical and immunohistochemical study.

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.

Thioacetamide-induced liver injury: protective role of genistein.

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.