Chemical characterisation, hypoglycaemic and renoprotective effects of aqueous leaf extract of Limoniastrum guyonianum on fructose-induced metabolic syndrome in rats.

In the present study, we chemically characterised the aqueous leaf extract of Limoniastrum guyonianum by HPLC-TOF/MS and evaluated its effects on fructose-induced metabolic syndrome (MetS) in Wistar rats. MetS groups were given (10% w/v) fructose solution to drink ad libitum for 9 weeks, whereas, normal animals received ordinary water. LG extract was administrated to treated groups by gavage for the last 6 weeks of the experimental period. Fructose feeding as a liquid solution increased body weight, reduced insulin sensitivity, raised blood glucose level and provoked atherogenic dyslipidemia associated with renal oxidative stress and structural damage. Treating MetS rats with LG extract at doses of 100, 200 and 300 mg/kg b.w./day considerably ameliorated the fructose-induced alterations. From this study, it was concluded that aqueous leaf extract of L. guyonianum possesses hypoglycaemic, hypolipidemic, antioxidant and renoprotective abilities against fructose-induced metabolic syndrome in rats.

Protective activity of Hertia cheirifolia extracts against DNA damage, lipid peroxidation and protein oxidation.

CONTEXT: Hertia cheirifolia L. (Asteraceae), a perennial shrub widely distributed in Northern Africa, is traditionally used to treat inflammatory disorders. OBJECTIVE: The protective effect of methanol (Met E) and aqueous (Aq E) extracts of Hertia cheirifolia against DNA, lipid and protein oxidation was investigated. MATERIALS AND METHODS: Different concentrations (50-1000 µg/mL) of Hertia cheirifolia aerial part extracts were examined against DNA, lipid and protein oxidation induced by H2O2 + UV, FeSO4, and Fe3+/H2O2-ascorbic acid, respectively. The DPPH•, metal ion chelating, reducing power and ß-carotene bleaching tests were conducted. RESULTS: Both extracts were rich in polyphenols, flavonoids and tannins, and were able to scavenge DPPH• with IC50 values of 138 and 197 µg/mL, respectively. At 300 µg/mL, Aq E exerted stronger chelating effect (99%) than Met E (69%). However, Met E reducing power (IC50 = 61 µg/mL) was more than that of Aq E (IC50 = 193 µg/mL). Both extracts protected from ß-carotene bleaching by 74% and 94%, respectively, and inhibited linoleic acid peroxidation. The inhibitory activity of Aq E extract (64%) was twice more than that of Met E (32%). Interestingly, both extracts protected DNA against the cleavage by about 96-98%. At 1 mg/mL, Met E and Aq E restored protein band intensity by 94-99%. CONCLUSIONS: Hertia cheirifolia exhibits potent antioxidant activity and protects biomolecules against oxidative damage; hence, it may serve as potential source of natural antioxidant for pharmaceutical applications and food preservation. This is the first report on the protective activity of this plant against biomolecule oxidation.

Phenolic Content and Biomolecule Oxidation Protective Activity of Globularia alypum Extracts

ABSTRACT The protective activity of methanolic (Met E) and aqueous (Aq E) extracts of Globularia alypum L. (G. alypum) against DNA, lipid and protein oxidative damage was investigated. Moreover, the scavenging, chelating, and reducing power activities of the extracts were also evaluated. Phytochemical analysis was performed to determine phenolic compounds. Results showed that Met E and Aq E were rich in phenolic compounds, and were able to scavenge DPPH˙ with IC50 values of 48.61 µg/mL and 51.97 µg/mL, respectively. In addition, both extracts were able to chelate ferrous ions. At 300 μg/mL, the chelating activity was 97.53% and 91.02%, respectively. The reducing power of these extracts was also remarkable and concentration dependent. At 100 µg/mL, both extracts inhibited lipid peroxidatin by only 42.45% and 4.03%. However, the DNA oxidation damage was inhibited dose-dependently in the presence of G. alypum extracts. At 1 mg/mL, both extracts suppressed DNA cleavage by 83%-84%. The protein oxidation was also inhibited by G. alypum extracts. At 1 mg/mL, Aq E and Met E protected BSA fragmentation by 77%-99%. The overall results suggest that G. alypum extracts exerted antioxidant activity and protect biomolecules against oxidative damage; hence it may serve as a potential source of natural antioxidants.

Phytochemical screening and anti-inflammatory properties of Algerian Hertia cheirifolia methanol extract.

CONTEXT: Hertia cheirifolia L. (Asteraceae) is traditionally used in Northern Africa to treat various inflammatory infections. However, few studies on this plant have been reported. OBJECTIVE: The anti-inflammatory activity of methanol extract of H. cheirifolia leaves was investigated using different experimental models. MATERIALS AND METHODS: Phytochemical analysis was performed to determine phenolic compounds. Acute toxicity of the extract (2000 mg/kg) was examined in Swiss albino mice for 14 days, before croton oil-induced ear oedema in mice, carrageenan-induced paw oedema in Swiss albino rats, cotton pellet-induced granuloma in rats and carrageenan-induced air pouch in mice were conducted. The IL-1ß and TNF-α release from concanavalin A-stimulated monocytes was measured by ELISA. RESULTS: Methanol extract of H. cheirifolia is rich in polyphenols and flavonoids. Cinnamic acid and rutin represent the major constituents. Methanol extract up to 2000 mg/kg did not produce any toxic effects. Topical application of 2 mg/ear of the extract produced 78.7% of inhibition on ear swilling. Oral pre-treatment of rats with 200 and 400 mg/kg of the extract inhibited paw oedema by 70% and 89%, respectively. At 200 mg/kg, granuloma dry and wet weights were reduced by 41.85% and 61.72%, respectively. Moreover, the treatment with methanol extract at 1 mg/kg exerted 62.7% of inhibition on leucocytes migrated into the ear pouch. TNF-α and IL-1ß release was reduced by 69% and 78%, respectively, with 1 µg/mL of the extract. CONCLUSION: Methanol extract of H. cheirifolia possesses a strong anti-inflammatory activity and may be considered an interesting source of effective anti-inflammatory compounds.

Impaired intracellular signaling, myeloperoxidase release and bactericidal activity of neutrophils from patients with alcoholic cirrhosis.

BACKGROUND & AIMS: Myeloperoxidase exocytosis and production of hydrogen peroxide via the neutrophil superoxide-generating nicotinamide adenine dinucleotide phosphate (NADPH) oxidase contribute to efficient elimination of bacteria. Cirrhosis impairs immune functions and increases susceptibility to bacterial infection. We recently showed that neutrophils from patients with decompensated alcoholic cirrhosis exhibit a severe impairment of formylpeptide receptor (fPR)-mediated intracellular signaling and superoxide production. Here, we performed ex vivo studies with these patients' neutrophils to further investigate myeloperoxidase release, bactericidal capacity and signaling events following fPR stimulation by the formylpeptide formyl-met-leu-phe (fMLP). METHODS: Myeloperoxidase release was studied by measuring extracellular myeloperoxidase activity. Activation of signaling effectors was studied by Western blot and their respective contribution to myeloperoxidase release studied using pharmacological antagonists. RESULTS: fMLP-induced myeloperoxidase release was strongly impaired in patients' neutrophils whereas the intracellular myeloperoxidase stock was unaltered. The fMLP-induced phosphorylation of major signaling effectors, AKT, ERK1/2 and p38-MAP-Kinases, was also strongly deficient despite a similar expression of signaling effectors or fPR. However, based on effector inhibition in healthy neutrophils, AKT and p38-MAPK but not ERK1/2 upregulated fMLP-induced myeloperoxidase exocytosis. Interestingly, patients' neutrophils exhibited a defective bactericidal capacity that was reversed ex vivo by the TLR7/8 agonist CL097, through potentiation of the fMLP-induced AKT/p38-MAPK signaling axis and myeloperoxidase release. CONCLUSIONS: We provide first evidence that neutrophils from patients with decompensated alcoholic cirrhosis exhibit a deficient AKT/p38-MAPK signaling, myeloperoxidase release and bactericidal activity, which can be reversed via TLR7/8 activation. These defects, together with the previously described severe deficient superoxide production, may increase cirrhotic patients' susceptibility to bacterial infections.

Immunomodulatory effects of Santolina chamaecyparissus leaf extracts on human neutrophil functions.

CONTEXT: Santolina chamaecyparissus L. (Asteraceae) is an aromatic plant wide spread in the Mediterranean region. It is used in folk medicine for its anti-inflammatory properties. OBJECTIVE: The effects of S. chamaecyparissus aqueous extract (SCAE) and polyphenolic extract (SCPE) on human polymorphonuclear neutrophil (PMN) degranulation, chemotaxis, phagocytosis, and microbicidal capacity were examined in vitro. MATERIALS AND METHODS: Aqueous and polyphenolic extracts were prepared from S. chamaecyparissus leaves. The elastase release was used as a marker for measuring PMN degranulation, while chemotaxis was performed using a 48-microwell chemotaxis chamber. The phagocytosis and the microbicidal capacity were evaluated using fresh cultures of Candida albicans. RESULTS: The treatment of neutrophils with different concentrations (10-200 µg/ml) of SCAE and SCPE caused a significant (p < 0.001) and dose-dependent inhibitory effect on elastase release in fMLP/Cytochalasin B (CB)-stimulated neutrophils. Indeed, 100 µg/ml of SCAE exerted an inhibitory effect of 51.97 ± 6.2%, whereas SCPE at the same concentration abolished completely PMN degranulation. Moreover, both extracts inhibited markedly (p < 0.01) fMLP-induced chemotactic migration. At 200 µg/ml, SCAE and SCPE exerted an inhibitory effect of 54.61 ± 7.3% and 57.71 ± 7.44%, respectively. In addition, a decline in both phagocytosis and microbicidal capacity against Candida albicans was observed when PMNs were exposed to 100 and 200 µg/ml of SCAE or SCPE. CONCLUSION: The exerted effects on neutrophil functions support the anti-inflammatory activity and show new mechanisms of action and effectiveness of S. chamaecyparissus leaf extracts. This plant may be considered as an interesting source of anti-inflammatory and immunomodulatory agents.

Cleome arabica leaf extract has anticancer properties in human cancer cells.

CONTEXT: Cleome arabica L. (Capparidaceae) is a desert plant widely distributed in the North part of Africa whose leaves are used in traditional medicine as a sedative for abdominal and rheumatic pains. OBJECTIVES: The anticancer activity of methanol Cleome arabica leaf extracts (CALE) is investigated in different human cancer cell lines. MATERIALS AND METHODS: Five different human cancer cell lines, representative of the most common cancers in Western countries (i.e., breast adenocarcinoma, colon carcinoma, neuroblastoma, hepatoma, cervix carcinoma) were treated with different concentrations of CALE (i.e., 1, 5, 10, 25, 50, 100 and 200 µg/ml). Cell viability and cell cycle were measured by using a hemocytometer chamber and a cytofluorimeter, respectively. Epidermal growth factor (EGF) was used as a positive control. Western blots were performed to evaluate the CALE effects on pathways involved in cell growth regulation and on apoptotic cascade activation. RESULTS AND CONCLUSION: Our results confirm that CALE has a high content of polyphenolic compounds (i.e., 32.21 ± 3.44%), mainly as flavonoids (24.56 ± 4.67%). In all tested cell lines CALE treatment reduces cell number in a dose-dependent manner (ED50 = 175 ± 30 µg/ml). CALE (100 and 200 µg/ml) increases by three-fold the activation of the apoptotic cascade involving caspase-3 activation and the cleavage of its substrate poly(ADP-ribose) polymerase (PARP). Intriguingly, CALE treatment (200 µg/ml) also blocks EGF-induced cell growth by preventing the growth factor-triggered AKT and ERK phosphorylation. As a whole, these data strongly suggest that CALE possesses anticancer effects in all tested cancer cell lines.

Anti-inflammatory, free radical-scavenging, and metal-chelating activities of Malva parviflora.

CONTEXT: Malva parviflora L. (Malvaceae) is widely distributed throughout Africa. It has several uses in traditional medicinal practice. Leaves of this plant are used in the treatment of some inflammatory disorders. OBJECTIVE: The anti-inflammatory and the antioxidant activities of the methanol extract (Met. E) and aqueous extract (Aq. E) of M. parviflora leaves were investigated. MATERIALS AND METHODS: Croton oil-induced ear edema and acetic acid-induced vascular permeability were applied as acute inflammatory models to evaluate the anti-inflammatory activity of the extracts. The antioxidant effects were evaluated using the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical assay and the measurement of the metal-chelating activity. RESULTS: Results demonstrated that Met. E inhibited the croton oil-induced ear edema by 57%. In contrast, the Aq. E did not show any activity. Furthermore, Met. E and Aq. E inhibited significantly the acetic acid-induced vascular permeability by 36 and 40%, respectively. However, Met. E and Aq. E exerted a strong scavenging activity with IC(50) values of 89.03 ± 2.65 and 76.67 ± 0.29 µg/mL, respectively. Moreover, Met. E and Aq. E were able to chelate ferrous ions in a concentration-dependent manner. DISCUSSION AND CONCLUSION: These findings demonstrate that M. parviflora leaf extracts possess anti-inflammatory and antioxidant activities and thus have great potential as an interesting source for natural health products.

Effect of Cleome arabica leaf extract treated by naringinase on human neutrophil chemotaxis.

The leaves of Cleome arabica L. (Capparaceae), which contain a number of glucosylated and rhamnosylated flavonols, possess anti-inflammatory activity and are used for the treatment of abdominal and rheumatic pains. In this study, we examine the effects of C. arabica leaf extracts (CALE) treatment with naringinase on selected properties of polymorphonuclear leukocytes (PMNs). Chemotaxis of these cells was investigated in the presence of either CALE or CALE treated with naringinase. Results showed that CALE reduced the directed movement of PMNs induced by fMet-Leu-Phe in a dose-dependent manner. A previous treatment of CALE with naringinase enhanced this effect. We conclude that deglycosylation of flavonoids in CALE by naringinase improves the beneficial effect of this plant extract on PMNs. The ability of C. arabica leaf extract treated with naringinase to reduce chemotaxis in human neutrophils may be an important therapeutic factor in the treatment of chronic diseases.

Differential effects of flavonols on inactivation of alpha1-antitrypsin induced by hypohalous acids and the myeloperoxidase-hydrogen peroxide-halide system.

Alpha1-antitrypsin is well known for its ability to inhibit human neutrophil elastase. Pretreatment of alpha1-antitrypsin with hypohalous acids HOCl and HOBr as well as with the myeloperoxidase-hydrogen peroxide-chloride (or bromide) system inactivated this proteinase. The flavonols rutin, quercetin, myricetin, and kaempferol inhibited the inactivation of alpha1-antitrypsin by HOCl and HOBr with rutin having the most pronounced effect. In contrast, these flavonols did not remove the proteinase inactivation by the myeloperoxidase-hydrogen peroxide-halide system. Taurine did not protect against the inactivation of alpha1-antitrypsin by HOCl, HOBr, or the myeloperoxidase-hydrogen peroxide-halide system, while methionine was efficient in all systems. A close association between myeloperoxidase and alpha1-antitrypsin was revealed by native gel electrophoresis and in-gel peroxidase staining. In addition, alpha1-antitrypsin binds to the myeloperoxidase components transferred after SDS-PAGE on a blotting membrane. With this complex formation, myeloperoxidase overcomes the natural antioxidative protective system of plasma and prevents the inactivation of alpha1-antitrypsin.

Anti-inflammatory effect of rutin on rat paw oedema, and on neutrophils chemotaxis and degranulation.

BACKGROUND: Rutin, a natural flavone derivative, is known for its pharmacological properties. We have previously reported that this flavonol exerted a potent inhibitory effect on respiratory burst of fMet-Leu-Phe-stimulated neutrophils, as well as on phosphoinositide 3-kinase gamma activity in a cell free system. In the present study, the anti-inflammatory effect of rutin was investigated in vivo and in vitro. METHODS: rutin or aspirin (100 mg/kg, body weight) were given orally to rats 1 hour before paw oedema induction, using lambda-carrageenan 1%. The rat paw volume was measured by mean of plethysmometer, initially and during 6 hours. The chemotaxis of neutrophils towards 10(-7) M fMet-Leu-Phe was performed using 48-well chemotaxis chamber. Neutrophils that migrated through 5 microm pore size polycarbonate filter, in presence or in absence of rutin, were counted microscopically. Elastase exocytosis of either phorbol 12-myristate 13-acetate or fMet-Leu-Phe/cytochalasin B-stimulated neutrophils was assessed in absence or in presence of rutin using the synthetic substrate N-Suc-Ala-Ala-Ala-p-nitroanilide. The absorbance of released p-nitroaniline was measured at 405 nm using microplate reader. RESULTS: The maximal swelling in placebo group was observed at 5 hours, after lambda-carrageenan injection. Oral administration of rutin reduced rat paw swelling starting 2 hours after lambda-carrageenan injection. Rutin reduced significantly (p < 0.05) and in a dose-dependant manner the polymorphonuclear neutrophils chemotaxis to fMet-Leu-Phe. Furthermore, elastase exocytosis, induced by both stimuli, was partially inhibited by rutin up to 25 microM. CONCLUSION: The present study revealed that rutin possesses anti-inflammatory properties.