Rumex dentatus L. phenolics ameliorate hyperglycemia by modulating hepatic key enzymes of carbohydrate metabolism, oxidative stress and PPARγ in diabetic rats

Rumex dentatus L. is a flowering plant with promising therapeutic effects. This study investigated the antioxidant efficacy of phenolic compounds isolated from R. dentatus L. in vitro and by conducting density function theory (DFT) studies to explore the mechanisms of action. The antioxidant, anti-inflammatory and antidiabetic effects of polyphenols-rich R. dentatus extract (RDE) were investigated in type 2 diabetic rats. Phytochemical investigation of the aerial parts of R. dentatus resulted in the isolation of one new and seven known compounds isolated for the first time from this species. All isolated phenolics showed in vitro radical scavenging activity. The antioxidant activity of the compounds could be oriented by the hydrogen atom transfer and sequential proton loss electron transfer mechanisms in gas and water phases, respectively. In diabetic rats, RDE attenuated hyperglycemia, insulin resistance and liver injury and improved carbohydrate metabolism. RDE suppressed oxidative stress and inflammation and upregulated PPARγ. In silico molecular docking analysis revealed the binding affinity of the isolated compounds toward PPARγ. In conclusion, the computational calculations were correlated with the in vitro antioxidant activity of R. dentatus derived phenolics. R. dentatus attenuated hyperglycemia, liver injury, inflammation and oxidative stress, improved carbohydrate metabolism and upregulated PPARγ in diabetic ratsThis work has DGI Project no. CTQ2015-63997-C2, a generous allocation of computing time at the Centro de Computación Científica of the UAM is also acknowledge

Toxicological Activity of Some Plant Essential Oils Against Tribolium castaneum and Culex pipiens Larvae

In the present work, essential oils (EOs) from Schinus terebinthifolius (ripe and unripe fruits and leaves), Origanum majorana (air-dried aerial parts), and Psidium guajava (leaves) were assayed for their insecticidal activity against red flour beetle (Tribolium castaneum) and Culex mosquito larvae (Culex pipiens). Several components were identified in the EOs using Gas chromatography–mass spectrometry (GC/MS), of which Δ-3-carene (25.9%), γ-terpinene (19.4), and γ-elemene (7.1%) were the major ones in S. terebinthifolius ripe fruits, α-pinene (48.9%), germacrene D (12.9%), and α-thujene (7.7%) in S. terebinthifolius unripe fruits, γ-elemene (11.7%), spathulenol (10.1%), β-elemene (9.2%), and p-cymene (9.1%) in S. terebinthifolius leaves, α-pinene (25.5%), (E)-caryophyllene (15.7%), (E)-nerolidol (16.7%), and cedran-8-ol (8.8%) in P. guajava leaves, and terpinen-4-ol (21.7%), γ-terpinene (16.5%), and sabinene (10.1%) in O. majorana air-dried aerial parts. The lethal concentration (LC50) was calculated for tested EOs at different time periods (after 6, 12, 24, 48, and 72 h). After 6 h of treatment, the LC50 was 33.3 and 6.8 µg/L air for S. terebinthifolius ripe and unripe fruits, respectively, and >40 µg/L air for EOs of S. terebinthifolius leaves, O. majoranaair-dried aerial parts, and P. guajava leaves. After 24 h of treatment, the LC50 was 4.2, <2, 5, >40, and 6.1 µg/L air for EOs of S. terebinthifolius ripe fruits and leaves, O. majorana leaves, and P. guajava leaves, respectively. On the other hand, the LC50 values decreased when the exposed period was increased to 72 h, and were <2 µg/L air for EOs of S. terebinthifolius ripe fruits, unripe fruits, and leaves along with P. guajava leaves, respectively, and 37.912 for EO of O. majorana leaves. The LC50 value after 24 h of exposure of S. terebinthifolius unripe fruit EO was under 2 µg/L air, which means that the EO of S. terebinthifolius ripe fruit had a strong effect on adult T. castaneum adults compared to other tested EOs using the fumigation method. The present data confirm that the EOs of O. majorana leaves and S. terebinthifolius unripe fruits and leaves were more effective as larvicide than the EOs of S. terebinthifolius ripe fruits and P. guajava leaves on C. pipiens at a higher concentration (100 mg/L) when applied by the dipping method. EOs from S. terebinthifolius unripe or ripe fruits and leaves and P. guajava leaves were more effective as adulticide than EO of O. majorana leaves against T. castaneum when applied by the fumigant method

Evaluation of Bifidobacteria and Lactobacillus Probiotics as Alternative Therapy for Salmonella typhimurium Infection in Broiler Chickens

Chicken Salmonella enterica serovars are enteric bacteria associated with massive public health risks and economic losses. There is a widespread antimicrobial resistance among S. enterica serotypes, and innovative solutions to antibiotic resistance are needed. We aimed to use probiotics to reduce antibiotic resistance and identify the major probiotic players that modify the early interactions between S. enterica and host cells. One-day-old cobb broiler chicks were challenged with S. typhimurium after oral inoculation with different probiotic strains for 3 days. The adherence of different probiotic strains to Caco-2 intestinal epithelial cells was studied in vitro. Lactobacillus (Lacticaseibacillus) casei ATTC334 and Bifidobacterium breve JCM1192 strains attached to Caco-2 cells stronger than B. infantis BL2416. L. casei ATTC334 and B. breve JCM1192 reduced S. typhimurium recovery from the cecal tonsils by competitive exclusion mechanism. Although B. infantis BL2416 bound poorly to Caco-2 epithelial cells, it reduced S. typhimurium recovery and increased IFN-γ and TNF-α production. L. casei ATTC334, B. breve JCM1192 and B. infantis BL2416 improved body weight gain and the food conversion rate in S. typhimurium-infected broilers. B. longum Ncc2785 neither attached to epithelial cells nor induced IFN-γ and TNF-α release and consequently did not prevent S. typhimurium colonization in broiler chickens. In conclusion, probiotics prevented the intestinal colonization of S. typhimurium in infected chickens by competitive exclusion or cytokine production mechanisms

Impact of garlic (Allium sativum) oil on cisplatin-induced hepatorenal biochemical and histopathological alterations in rats

International audienceCisplatin (cis-diamminedichloridoplatinum II [CDDP]) is a chemotherapeutic agent used for treating different cancers types. However, its usage is limited because it induces harmful toxicities in multiple organs, including nephrotoxicity and hepatotoxicity. Garlic oil (GO) has several pharmacological activities, including antioxidant activity. The aim of the study is to evaluate the protective and antioxidant effects of GO against CDDP-induced acute liver and kidney injuries in male rats. CDDP-treated rats showed increased serum ALT, AST, ALP, LDH, uric acid, urea, creatinine, and IL-6 levels. Moreover, CDDP-treated rats showed significantly increased MDA and NO levels and decreased GSH level and T.SOD and CAT activities in hepatic and renal tissues compared with control rats. GO administration, especially at a dose of 100 ml/kg, alleviated CDDP-induced adverse biochemical and histopathological alterations and restored them to their normal values. These results suggest that GO reverses CDDP-induced hepatorenal damage by exerting antioxidant and anti-inflammatory effects

Preconditioning human natural killer cells with chorionic villous mesenchymal stem cells stimulates their expression of inflammatory and anti-tumor molecules

Abstract Background Mesenchymal stem cells derived from the chorionic villi of human placentae (pMSCs) produce a unique array of mediators that regulate the essential cellular functions of their target cells. These properties make pMSCs attractive candidates for cell-based therapy. Here, we examined the effects of culturing human natural killer (NK) cells with pMSCs on NK cell functions. Methods pMSCs were cultured with IL-2-activated and non-activated NK cells. NK cell proliferation and cytolytic activities were monitored. NK cell expression of receptors mediating their cytolytic activity against pMSCs, and the mechanisms underlying this effect on pMSCs, were also investigated. Results Our findings show that IL-2-activated NK cells, but not freshly isolated NK cells, efficiently lyse pMSCs and that this response might involve the activating NK cell receptor CD69. Interestingly, although pMSCs expressed HLA class I molecules, they were nevertheless lysed by NK cells, suggesting that HLA class I antigens do not play a significant role in protecting pMSCs from NK cell cytolytic activity. Co-culturing NK cells with pMSCs also inhibited NK cell expression of receptors, including CD69, NKpG2D, CD94, and NKp30, although these co-cultured NK cells were not inhibited in lysing cancer cells in vitro. Importantly, co-cultured NK cells significantly increased their production of molecules with anti-tumor effects. Conclusions These findings suggest that pMSCs might have potential applications in cancer therapy

Protective effects of thymoquinone against acrylamide-induced liver, kidney and brain oxidative damage in rats

International audienceAcrylamide (AA), an industrial monomer, may cause multi-organ toxicity through induction of oxidative stress and inflammation. The antioxidant properties of thymoquinone (TQ), an active constituent of Nigella sativa, have been established before. Theaim of the current study was to assess the protective effects of TQ against AA-induced toxicity in rats. Forty-eight male Wistarrats were divided into six groups each of eight rats. The first group acted as a negative control and received normal saline. GroupsII and III were administered TQ orally at doses of 10 and 20 mg/kg b.wt., respectively, for 21 days. The four group received AA(20 mg/kg b.wt.) for 14 days. The five and six groups were given TQ at either dose for 21 days, starting seven days before AAsupplementation (for 14 days). Acrylamide intoxication was associated with significant (p < 0.05) increases in serum levels ofliver injury biomarkers (alanine transferase, aspartate transferase, and alkaline phosphatase), renal function products (urea,creatinine), DNA oxidative damage biomarker (8-oxo-2′-deoxyguanosine), and pro-inflammatory biomarkers (interleukin-1β,interleukin-6, and tumor necrosis factor-α). Moreover, AA intoxication was associated with increased lipid peroxidation andnitric oxide levels, while reduced glutathione concentration and activities of glutathione peroxidase, superoxide dismutase, andcatalase in the liver, kidney, and brain. TQ administration normalized AA-induced changes in most serum parameters andenhanced the antioxidant capacity in the liver, kidney, and brain tissues in a dose-dependent manner. In conclusion, the currentexperiment showed that TQ exerted protective and antioxidant activities against AA-induced toxicity in mice

Revisiting the Amyloid Cascade Hypothesis : From Anti-A beta Therapeutics to Auspicious New Ways for Alzheimer's Disease

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder related to age, characterized by the cerebral deposition of fibrils, which are made from the amyloid-beta (A beta), a peptide of 40-42 amino acids. The conversion of A beta into neurotoxic oligomeric, fibrillar, and protofibrillar assemblies is supposed to be the main pathological event in AD. After A beta accumulation, the clinical symptoms fall out predominantly due to the deficient brain clearance of the peptide. For several years, researchers have attempted to decline the A beta monomer, oligomer, and aggregate levels, as well as plaques, employing agents that facilitate the reduction of A beta and antagonize A beta aggregation, or raise A beta clearance from brain. Unluckily, broad clinical trials with mild to moderate AD participants have shown that these approaches were unsuccessful. Several clinical trials are running involving patients whose disease is at an early stage, but the preliminary outcomes are not clinically impressive. Many studies have been conducted against oligomers of A beta which are the utmost neurotoxic molecular species. Trials with monoclonal antibodies directed against A beta oligomers have exhibited exciting findings. Nevertheless, A beta oligomers maintain equivalent states in both monomeric and aggregation forms; so, previously administered drugs that precisely decrease A beta monomer or A beta plaques ought to have displayed valuable clinical benefits. In this article, A beta-based therapeutic strategies are discussed and several promising new ways to fight against AD are appraised

Emerging Promise of Cannabinoids for the Management of Pain and Associated Neuropathological Alterations in Alzheimer's Disease

Alzheimer's disease (AD) is an irreversible chronic neurodegenerative disorder that occurs when neurons in the brain degenerate and die. Pain frequently arises in older patients with neurodegenerative diseases including AD. However, the presence of pain in older people is usually overlooked with cognitive dysfunctions. Most of the times dementia patients experience moderate to severe pain but the development of severe cognitive dysfunctions tremendously affects their capability to express the presence of pain. Currently, there are no effective treatments against AD that emphasize the necessity for increasing research to develop novel drugs for treating or preventing the disease process. Furthermore, the prospective therapeutic use of cannabinoids in AD has been studied for the past few years. In this regard, targeting the endocannabinoid system has considered as a probable therapeutic strategy to control several associated pathological pathways, such as mitochondrial dysfunction, excitotoxicity, oxidative stress, and neuroinflammation for the management of AD. In this review, we focus on recent studies about the role of cannabinoids for the treatment of pain and related neuropathological changes in AD

Spirulina platensis ameliorates the sub chronic toxicities of lead in rabbits via anti-oxidative, anti- inflammatory, and immune stimulatory properties

International audienceLead acetate (Pb) is an oldest and widespread environmental toxicant that led to cumulative injury in humans and all living organisms through induction of oxidative stress. Spirulina platensis (SP) is a cyanobacteria with strong antioxidant, anti-inflammatory, and immune stimulatory effects. In this study, the ameliorative effect of SP was evaluated against the dietary sub chronic lead toxicities in rabbits. A total number of 75 male New Zealand rabbits were allocated randomly into 5 groups; the first group feed on basal diet alone and served as control group, the second group feed on basal diet + 100 mg Pb /kg diet, the third, fourth, and the fifth groups feed on basal diet + 100 mg Pb /kg diet + SP (0.5, 1, or 1.5 g/kg diet; respectively), the experiment was extended for 8 weeks. Results revealed a significant improvement in some of growth parameters like final body weight and daily weight gain, blood parameters in rabbits treated with SP at level 1.5 g/kg diet followed by those receiving SP 1g /kg diet. However, a significant decrease in blood parameters, liver function, renal parameters, lipid profiles, oxidative parameters (malondialdehyde and protein carbonyl), heart indices (creatine phosphokinase, creatine kinase-muscle/brain, lactate dehydrogenase), total Pb residues in muscles, and area percent of nuclear factor kappa b immune expression were reported in groups supplemented with different levels of SP. Pathologic analysis of liver, kidneys, and heart revealed moderate to severe degenerative and necrotic changes in Pb- exposed rabbits, which is ameliorated with supplementation of SP in different levels. Conclusively, dietary supplementation of SP at different levels attenuated the cumulative effect of lead in rabbits in dose-dependent manner; this attenuation may be attributed to its anti-oxidative, anti-inflammatory, as well as its immune stimulant effect