Renoprotective effect of Limonium duriusculum (de Girard) Kuntze via modulation of oxidative stress/ UPR markers and inflammation during cyclosporine-induced nephrotoxicity in rats.

Objectives: The present study aimed to explore the mechanisms underlying the potency of the renoprotective effect of the EtOAc fraction of Limonium duriusculum (EALD) (Plumbaginaceae) against cyclosporine A (CsA), in comparison to vitamin E (Vit. E). Materials and Methods: In the in-vivo experiment, a model of CsA-induced nephrotoxicity was established by dosing male Wistar rats with 25 mg/kg, for 14 days. The protective effect of EALD was investigated through pretreatment of rats with a dose of 200 mg/kg for 14 days, compared to the oral administration of Vit. E at 100 mg/kg. Renal function and markers of oxidative stress were then assessed. Furthermore, a complementary in-vitro study was carried out to evaluate CsA-induced endoplasmic reticulum stress (ERS) and inflammation on cell culture (3T3 cells and MCT cells) using western blot and quantitative RT-PCR.. Results: Pretreatment of rats with EALD significantly attenuated the elevated levels of renal dysfunction markers (BUN, creatinine) and suppressed malondialdehyde (MDA) levels; It also significantly regulated the changes in superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxydase (GPx), and glutathione S-transferase (GST) levels as compared to Vit. E, demonstrating a more effective recovery in renal tissues. Treatment of cells with CsA was linked to the expression of ERS and inflammatory markers activating transcription factor (ATF4), inositol-requiring enzyme 1α (IRE1α), binding immunoglobulin protein (BiP), and monocyte chemoattractant protein-1 (MCP1). In contrast, pretreatment of cells with EALD resulted in a significant decrease in both ERS and inflammatory markers. Conclusion: These findings indicate the renoprotective potential of L. duriusculum, as it demonstrated the ability to ameliorate CsA-induced renal dysfunction through its distinctive antioxidant properties.

The preventive effects of Centaurea maroccana Ball. extract against oxidative stress induced by cisplatin in mice brains: in vitro and in vivo studies.

Since antiquity, Centaurea species have been used in folk medicine to treat several diseases owing to their potential biological activities that distinguish this genus such as antioxidant, anticancer, and anti-inflammatory effect. The current study aimed to investigate the possible neuroprotective effects of the n-butanol extract of Centaurea maroccana (BECM) against cisplatin (CP) induced neurotoxicity in mice. BECM's potential neuroprotective properties were studied in vitro and in vivo models. Male Swiss albino mice were orally received BECM (200 mg/kg) for 10 days before a single intraperitoneal injection of cisplatin (8 mg/kg). Vitamin E (100 mg/kg) was given daily by gavage as a positive control. In vitro results revealed that BECM inhibited lipid peroxidation (LPO) levels and acetylcholinesterase (AChE) activity. In vivo findings showed that BECM pretreatment was able to regulate lactate dehydrogenase (LDH) levels and to improve CP-induced cholinergic dysfunction by inhibiting AChE activity in mice brains. Moreover, BECM attenuated CP-provoked oxidative stress by suppressing LPO levels, increasing total antioxidant capacity (TAC) and enhancing the activities of antioxidant enzymes (catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPx) and glutathione S-transferase (GST)) in both brain cytosolic and mitochondrial fractions. The histological analysis exhibited neurotoprotective effect of BECM by protecting the cerebral cortex and reducing the histomorphological alterations resulted by cisplatin. Interestingly, our extract achieved neuroprotection comparable to vitamin E in most evaluated parameters. It appears that protective potency of BECM against CP-induced neurotoxicity could be related to its richness in polyphenols confirmed by liquid-chromatography tandem mass spectrometry analysis (LC-MS/MS).

Neuroinflammation and Behavioral Deficit in Rotenone-Induced Neurotoxicity in Rats and the Possible Effects of Butanolic Extract of Centaurea africana.

BACKGROUND: Many studies have used rotenone (ROT) to create an experimental animal model of Parkinson's disease (PD) because of its ability to induce similar behavioral and motor deficits. PD is the most common age-related motoric neurodegenerative disorder. Neuroinflammation and apoptosis play an important role in the pathogenesis of this disease. OBJECTIVE: This study investigated the effect of butanolic (n-BuOH) extract of Centaurea africana (200 mg/kg, 16 days) on a ROT-induced neurotoxicity model in male Wistar albino rats. METHODS: Estimation of Tumor Necrosis Factor (TNF-α) and Nitric Oxide (NO) levels along with the myeloperoxidase (MPO) activity in brains was carried out in order to evaluate neuro-inflammation. Oxidative stress, Caspase 3 activity (apoptosis), and behavioral alterations were also evaluated. RESULTS: In behavior assessment, using Ludolph Movement Analysis Scale, all ROT treated animals showed a decreased locomotor activity. The mitochondrial dysfunction induced by ROT was expressed by a decreased activity of complex I of the mitochondrial respiratory chain and increased lipid peroxidation and caspase 3. Co-treatment with the n-BuOH extract significantly restored the activity of complex I (65.41 %) compared to treatment with ROT alone. The n-BuOH extract also reduced the neuroinflammation in rat brains by reducing MPO activity (75.12 %), NO levels (77.43 %), and TNF-α (71.48 %) compared to the group treated with ROT. CONCLUSION: The obtained results indicated that C. africana n-BuOH extract exhibited a protective effect in rats.

Chemical constituents, in vitro anti-inflammatory, antioxidant and hemostatic activities of the n-butanol extract of Hyacinthoides lingulata (Poir.) Rothm.

The phytochemical profile obtained from LC-ESI-MS/MS analysis of the n-butanol extract (BEHL) from the North African endemic plant Hyacinthoides lingulata (Poir.) Rothm. brought about the identification of ten glycosylated derivatives of apigenin and luteolin flavones. For the same plant extract, in vitro anti-inflammatory (hypotonic induced hemolysis and heat induced haemolysis assay) and antioxidant (DPPH and ß-Carotene) activities were evaluated observing high inflammatory inhibition by protecting membrane stability of erythrocyte in both heat (84.70 ± 0.24%) and hypotonic induced hemolysis (79.45 ± 0.12%). A remarkable hemostatic effect was also established by measuring the coagulation time (15.95 ± 1.05 s at a dose of 1 mg/mL) of decalcified plasma related to its phytochemical content. It is the first report on combined chemical components and biological evaluation of this specific plant.

Antioxidant, Anti-Inflammatory and Cytotoxic Properties of Centaurea africana Lamk var. [Bonnet] M].

BACKGROUND: In Algerian traditional medicine, Centaurea species are well known in traditherapy. Centaurea africana has been used in folk medicine for the treatment of several inflammatory disorders. OBJECTIVE: This study aims to examine the antioxidant, anti-inflammatory and anti-proliferative potential of both n-Butanol (BECA) and ethyl acetate (EAECA) extracts of Centaurea africana. METHODS: The phytochemical analysis of both BECA and EAECA were explored and the antioxidant activities were investigated by measuring the DPPH° scavenging effect, the reducing power and the inhibition of lipid peroxidation (LPO) induced by by Fe2+/ ascorbic acid system. The antiinflammatory properties were determined by measuring the NO° scavenging effect and by using carrageenan-induced rat paw oedema. The antiproliferative activity was studied on HT29 (human colorectal adenocarcinoma), OV2008 (human ovarian cancer) and C6 (Rattus norvegicus brain glioma) cell lines using the Sulforhodamine B assay. RESULTS: The total polyphenol contents (TPC) of EAECA and BECA are recorded at 125.24±10.14 and 53.03±2.50 mgGAE/g extract, respectively. Both extracts revealed the antioxidant activity in a concentration-dependent manner; this effect is more pronounced with EAECA. The BECA exhibited a higher anti-inflammatory activity. This anti-inflammatory activity was reflected in a reduction of swelling of carrageenan-evoked edemas (48.45 %), inhibition of nitric oxide (84.7 %), effective decrease in myeloperoxidase activity (58.82 %) and malondialdehyde level (65.58 %). The cytotoxic effect of BECA was found to be more pronounced against C6 cell lines (IC50 value: 131.93 µg/mL) while the cytotoxic activity of EAECA was more effective against HT29 and OV2008 cell lines. CONCLUSION: The obtained results indicated that EAECA exhibited a high antioxidant activity, while BECA has significant anti-inflammatory activity. Both extracts showed cytotoxic effects against cancer cell lines at certain concentrations in a cell-specific manner.

Anti-inflammatory and hemostatic effects of Linaria reflexa Desf.

The work presented here was aimed to investigate the in vivo anti-inflammatory and in vitro hemostatic activities of Linaria reflexa extract and to establish the relationship between its bioactivity and chemical composition. Twenty-three secondary metabolites were identified, most of them are good anti-inflammatory agents, in line with data by carrageenin-induced rat paw edema assays of the n-butanol extract showing high anti-inflammatory inhibition (63.90%) of edema swelling in the rat paw at the dose 200 mg/kg after 4 h. Furthermore, both extent of inflammatory response and tissue injury were prevented keeping the levels of rate myeloperoxidase (60.16%) and of malondialdehyde, which is the final product of lipid peroxidation generated by free radicals (58.58%). The same extract showed also a remarkable hemostatic effect established by measuring the coagulation time of decalcified plasma (45 s), related to its flavonoid glycosides content.

Apigenin rich-Limonium duriusculum (de Girard) Kuntze promotes apoptosis in HCT116 cancer cells.

The pro-apoptotic property of n-BuOH extract of Limonium duriusculum (BEL) and its major isolated components [apigenin (APG1) and apigenin7-O-ß-D-(6''-methylglucuronide) (APG2)] were tested. The anti-proliferative IC50 of BEL and APG1 was quantified as 7.60 µg/mL and 25.74 µM respectively, while APG2 did not affect cell proliferation in HCT116 p53 wild type cells. Growth inhibition by BEL treatment was associated with reduced signaling from the MAP kinase, activation of the p53 response pathway and PARP cleavage. The multi-effect of Limonium duriusculum could be due through their major apigenin compounds and the other bioactive constituents that may possibly act in synergy to exercise the most favorable anti-tumor activities.

Limonium duriusculum (de Girard) Kuntze Exhibits Anti-inflammatory Effect Via NF-κ B Pathway Modulation

HIGHLIGHTS L. duriusculum n-BuOH extract reduces inflammatory responses both in vitro and in vivo. L. duriusculum n-BuOH extract inhibits NF-κB-dependent transcriptional responses. L. duriusculum n-BuOH extract decreases the expression of TNF-α and IL-6 genes.

Abstract Limonium duriusculum is used in folk medicine to treat inflammatory disorders and has gained attention due to its richness in apigenin. The present investigation was performed to evaluate and confirm its anti-inflammatory properties, in cell lines and animal models. The potential anti-inflammatory properties of n-butanol (n-BuOH) extract of L. duriusculum (BEL) and isolated apigenins were examined on NF-κB transcriptional activity in TNFα- or LPS-stimulated cells, and on in vivo acute inflammatory models (carrageenan induced paw edema and peritonitis). BEL treatment was able to inhibit the activity of an NF-κB reporter gene in HCT116 cells both in the absence and in the presence of exogenous TNFα, used as NF-κB pathway inducer. This anti-inflammatory effect was even more potent compared to Apigenin (APG1) and was confirmed using monocyte-derived THP-1 cells treated with LPS to stimulate NF-κB-dependent transcription of IL-6 and TNFα mRNAs. Apigenin7-O-β-(6''-methylglucuronide) (APG2) was instead inactive both in HCT116 and THP-1 cells. BEL (oral, 200 mg/kg) led to paw swelling inhibition, vascular permeability and peritoneal leukocyte and PN migration diminution. Apigenins (intraperitoneal, APG1, APG2: 20 mg/kg) also evoked a significant anti-edema effect, early vascular permeability and leukocyte influx reduction. Collectively, this study demonstrates for the first time the effectiveness of L. duriusculum to inhibit NF-κB-dependent transcriptional responses in HCT116 and THP-1 cells. In vivo studies also established that L. duriusculum possesses a potential anti-inflammatory effect, confirm its traditional, empirical use, that could be attributed to its richness in apigenin.

Chemical composition, in vitro antiparasitic, antimicrobial and antioxidant activities of Frankenia thymifolia Desf.

This study was performed on the derived fractions [chloroform (FT-C), ethyl acetate (FT-E) and n-butanol (FT-B)] of the 70% ethanol extract prepared from Frankenia thymifolia, endemic to North Africa. The fractions showed high total phenolic and flavonoid contents particularly FT-E. These results agreed with their antioxidant effects. Indeed, all the fractions were able to scavenge 1,1-diphenyl-2-picrylhydrazyl radical, with a better power of FT-E. These results were supported by the inhibition of ß-carotene oxidation assay. The fractions showed moderate activity against Acanthamoeba castellanii and Leishmania amazonensis with a better activity of FT-E against A. castellanii. Moreover, FT-B exhibited an interesting antimicrobial activity against all tested bacteria. The phytochemical investigation of the most active fractions (FT-E and FT-B) led to the isolation and structural determination of six compounds. The observed biological activities may be associated with the presence of quercetin and its derivatives found in the chemical composition of these fractions.

Assessment of water quality at the largest dam in Algeria (Beni Haroun Dam) and effects of irrigation on soil characteristics of agricultural lands.

Beni Haroun Dam is a vital water resource for both potable water and irrigation in eastern Algeria. This study assessed water quality at the dam and investigated the impacts of this water on some soil characteristics of irrigated lands. The physicochemical parameters of the water were measured monthly at eight sites and related to soil characteristics sampled from six irrigated areas, which were compared to non-irrigated soils. The chemical facies of the water were chloride sulfate and calcium magnesium. The water had low levels of cadmium (8.9 µg/L) and lead (4.55 µg/L), excessive contents of chloride and bicarbonate, while pH ranged between 6.5 and 8.4. High levels of electrical conductivity were measured in 39% of samples that exceeded standard for irrigation use. Richard diagram identified four classes of water: (i) C3S1 with 61.5% of samples having moderate or poor quality, (ii) C4S1 (30.2%) having poor or bad quality, (iii) C4S2 (5.2%) having very bad quality, and (iv) C5S3 (3.1%) determined unsuitable for irrigation. A Wilcox diagram revealed that 58% of samples had good quality while 42% were inappropriate for irrigation. Soil pH, EC and OM increased in irrigated soils, particularly in the surface horizon, compared to the control sites; whereas total CaCO3 decreased at all soil depths measured. High levels of bioavailable lead (35.82 µg/g) and cadmium (0.22 µg/g) were recorded in the surface soil. The study suggests that adequate protection measures with appropriate guidelines for various water and soil parameters are needed to minimize the detrimental effects of irrigation water on agricultural lands.

Iridoids and anti-inflammatory properties of n-butanol extract of Linaria tingitana Boiss. & Reut.

The analysis of the n-butanol extract of Linaria tingitana (BELT) by HPLC-DAD-ESI/MS allowed the identification of four iridoids structurally confirmed by NMR and ESI-MS/MS extensive experiments data. The subjection of BELT to the anti-inflammatory activity showed that it exhibited a concentration dependent stabilisation of HRBC membrane, inhibition of protein denaturation and nitric oxide scavenging effect in the in vitro process. These results were confirmed in the in vivo experiments which showed that BELT was found to be most pronounced at 200 mg/kg after carrageenan injection which significantly reduced the swelling in both early and late phases of carrageenan-evoked oedema, as well as a significant reduce at the accumulation of infiltrating cells, inhibition of the myeloperoxidase activity and suppressed the lipid peroxidation. These results were supported by the histological analysis which revealed the reduction of oedema and cells infiltration, this might be influenced by the synergistic action of the above isolated compounds.

Glycosyl flavonoid profile, in vivo antidiabetic and in vitro antioxidant properties of Linaria reflexa Desf.

Aerial parts of Linaria reflexa, used in North African folk medicine for treating certain skin diseases, were investigated by HPLC-DAD-ESI/MS technique able to identify the glycosyl flavonoids pectolinarin (1), isolinariin A (2), isolinariin B (3), linariin (4), isolinariin D (5) and isolinariin E (6) as the most abundant components in both hydroalcoholic (HAE) and ultrasound-assisted (UAE) extracts profiles. Metabolite 5, isolated and fully characterised by extensive nuclear magnetic resonance (NMR) analysis, has been very recently reported from L. japonica together with the compound 6. Good antioxidant activities (DPPH radical scavenging, ß-carotene bleaching and reducing power assays) were observed for the extracts. The remarkable antidiabetic activity displayed by UAE (300 mg/kg) has yielded the most marked decrease in blood glucose levels of the alloxan diabetic rats (-72.09%), greater than the effects by the drug glybenclamide (-63.29%). This study reports the first correlation of antidiabetic activity of Linaria sp. extracts with their chemical composition.

Exploring the Bioactive Terpenoid Content of an Algerian Plant of the Genus Pulicaria: The ent-Series of Asteriscunolides.

Chemical analysis of the chloroform extract of the aerial parts of the Algerian plant Pulicaria undulata exhibiting anti-inflammatory activity resulted in the isolation of 10 new humulene sesquiterpenoids, 1-10, belonging to the asteriscunolide family of compounds. The structure and relative configuration have been defined by NMR data, whereas the absolute configuration has been established by ECD analysis. Compounds 1-10 include enantiomers of the known asteriscunolides A-D and tetrahydroasteriscunolide previously reported from the genera Asteriscus and Nauplius. Compounds 1 and 10 showed in vitro anti-inflammatory activity by inhibiting heat-induced albumin denaturation with IC50 values of 23.76 and 220.42 µM.