High anti-inflammatory and antidiabetic activities of Hammada elegans (Bge.)Botsch (Chenopodiaceae) extracts: an in vivo assessment.

BACKGROUND: Several medicinal plants are used in the steep area of Algeria (Laghouat) for treatment of inflammation and diabetes. Furthermore, Hammada elegans Botsch. (Chenopodiaceae) a xerophytic plant popularly known as (Ajram) is widely spread perennial shrub in Laghouat region and it is traditionally used to treat inflammation and diabete. Then, the objective of this work is to study for the first time the in vivo anti-inflammatory, antidiabetic and acute toxicity effects of acetonic, methanolic and aqueous Hammada elegans Botsch extracts. METHODS: The acute toxicity test was performed according to the OECD method using single increasing doses (50-1500 mg/kg bw). The anti-inflammatory effect is investigated in Wistar rats by using the rat paw edema assay. The antidiabetic activity was evaluated in vivo using three tests: short-term test (in non-diabetic rats), starch-induced hyperglycemia test (in non-diabetic rats) and long-term alloxan test (experimental diabetes). RESULTS: The acute toxicity results show no deaths in rats and no clinical signs of toxicity. The anti-inflammatory effects showed that all extracts significantly inhibit rat paw edema (EC50 less than 345.51 ± 0.29 mg/kg bw). Therefore, the acetonic extract (EC50 = 157.45 ± 0.33 mg/kg bw) had the more active anti-inflammatory activity than that of the standard inhibitor "Ibuprofen". In addition, the evaluation of the antidiabetic activities by three tests shows that: in, in the short-term test, there was no important decrease in normal rats glucose rate, while in the starch-induced hyperglycemia test, the aqueous extract decreased significantly hyperglycemia (57.21 ± 1.24 mg AEAC / kg bw) compared to all tested extracts. While in the long-term test, the acetone extract significantly decreased hyperglycemia (9.18 ± 0.72 mg GEAC / kg bw) compared to all the tested extracts. CONCLUSIONS: Hammada elegans Botsch extracts seem to have therapeutic opportunities for the treatment of the inflammation and diabetes.

Molecular docking and two-dimensional quantitative structure-activity relationship studies of synthetic flavonoids on horseradish peroxidase compounds (I, II, and III).

For the first time, the enzymatic inhibition activity of 13 synthetic flavonoids was assessed by quantitative structure-activity relationship (QSAR) modeling and molecular docking with the three states of the enzyme horseradish peroxidase (HRP). The results show that apigenin, quercetin, kaempferol, fisetin, tricetin, and luteolin exerted a high competitive inhibition on HRP (Ki between 0.14 and 1.74 mM) compared with other flavonoids. The QSAR model of enzymatic activity (R2 = 0.95, RMSE = 5.48) showed that Ghose-Crippen octanol-water partition coefficient (Alog P) and lowest unoccupied molecular orbital's energy (εlumo ) correlated with 0.65 and 0.17, respectively, with Ki values. According to the docking results using Molegro Virtual Docker program, all the flavonoids have shown great binding affinity towards peroxidase. Apigenin has the largest MolDock score in the three states of HRP noting an increased affinity of these flavonoids between compound I and compound II by 2.26%. However, these affinities strongly decrease between compound II and compound III by 28.43% especially for luteolin whose MolDock score decreased by 74.7%. With the results of docking, the affinities of the flavonoids tested and translated by their Ki values are much more presentative of the inhibition of the first reaction states of HRP because their inhibitory effect is important.

Structure-activity relationships and molecular docking of thirteen synthesized flavonoids as horseradish peroxidase inhibitors.

For the first time, the structure-activity relationships of thirteen synthesized flavonoids have been investigated by evaluating their ability to modulate horseradish peroxidase (HRP) catalytic activity. Indeed, a modified spectrophotometrically method was carried out and optimized using 4-methylcatechol (4-MC) as peroxidase co-substrate. The results show that these flavonoids exhibit a great capacity to inhibit peroxidase with Ki values ranged from 0.14±0.01 to 65±0.04mM. Molecular docking has been achieved using Auto Dock Vina program to discuss the nature of interactions and the mechanism of inhibition. According to the docking results, all the flavonoids have shown great binding affinity to peroxidase. These molecular modeling studies suggested that pyran-4-one cycle acts as an inhibition key for peroxidase. Therefore, potent peroxidase inhibitors are flavonoids with these structural requirements: the presence of the hydroxyl (OH) group in 7, 5 and 4' positions and the absence of the methoxy (O-CH3) group. Apigenin contributed better in HRP inhibitory activity. The present study has shown that the studied flavonoids could be promising HRP inhibitors, which can help in developing new molecules to control thyroid diseases.

The in vitro evaluation of antioxidative activity, α-glucosidase and α-amylase enzyme inhibitory of natural phenolic extracts.

Phenolic extracts from the medicinal parts of six traditional Algerian herbs were tested in screening experiments for the antioxidant, α-amylase and α-glycosidase inhibiting activities. UV-analysis of the extracts from the plants indicated that the total phenols content was ranged between 0.48 and 3.46 mg equivalent of gallic acid per gram of dry matter, whereas the flavonoids content expressed as rutin equivalent per gram of dry matter was ranged between 0.18 and 2.23 mg/g. The study of antioxidant activity by scavenging the hydroxyl radical (OH), the nitroxide radical (NO) and the stable radical cation (ABTS(+)) showed a high antioxidant power. Also, these extracts illustrated a significant reductive power of the Fe(3+)-TPTZ complex. Similarly, we have found that the phenolic extracts exhibit an imperative antioxidant status compared to synthetic antioxidants. The study of the extract effects shows that Anabasis articulata, Agatophora alopecuroide and Heliantheum kahiricum extracts have a powerful inhibiting capacity of the α-amylase and α-glycosidase with a Ki values less than 10 µM. Our study, for the first time, revealed the anti-diabetic potential of the six plants and the results of this study could be helpful to develop medicinal preparations or nutraceuticals and functional foods for diabetes.

Isolation and characterization of a new steroid derivative as a powerful antioxidant from Cleome arabica in screening the in vitro antioxidant capacity of 18 Algerian medicinal plants.

Hydromethanolic extracts from 18 Algerian medicinal plants were screened for their phenolic contents and radical scavenging activities. The phenolic extract of Cleome arabica (Capparaceae) was found to be the most active one. Purification of this extract by semi-preparative high performance liquid chromatography led to the isolation and identification of new steroid derivative. The structure of the active principle is proposed as (17-(4-hydroxy-1,5-dimethylhexyl)-2,3,7-(acetyloxy) gona-1,3,5(10)-trien-15-ol). Compared to six other standard antioxidants which were ascorbic acid, α-tocopherol, Trolox, (+) catechin, p-coumaric acid and gallic acid, the isolated compound was found to be significantly more active in the radical scavenging assay using 2,2-diphenyl-1-picrylhydrazyl (DPPH). Similar results were obtained in the hemolysis assay. The antioxidant capacities of the methanolic extract of C. arabica and its principle compound indicate that this plant may be an important source of chemopreventive and chemotherapeutic natural products activity.

Composition, antioxidant and antimicrobial activities of the essential oil of Marrubium deserti.

The essential oil from aerial part of Marrubium deserti De Noé (Lamiaceae), obtained by hydrodistillation was analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS), and evaluated for in vitro antimicrobial activity. The antioxidant activity was determined using three in vitro assays: scavenging effect on DPPH, the ABTS test and the phosphomolybdenum method. Thirty-seven compounds were identified in the oil, with germacrene D as the major component (45.7%). This oil was characterized by an important hydrocarbon fraction (78.1%) and by the predominance of sesquiterpenes (67.4%). M. deserti essential oil had no activity on the tested microorganisms (Staphylococcus aureus ATCC 25923, Echerichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Candida albicans and Aspergillus flavus). However the oil presented an antioxidant activity.

Isolation and characterization of a new hispolone derivative from antioxidant extracts of Pistacia atlantica.

The quantification of the total phenolic compounds of Pistacia atlantica showed that the different parts of the tree are rich in natural phenolic compounds. The antioxidant tests proved that the phenolic extracts have a strong antioxidant activity. The positive correlation between the Trolox equivalent antioxidant capacity (TEAC) and the amount of phenolic compounds confirms their contribution to the antioxidant activity. Among the various phenolic compounds isolated and characterized by spectroscopic methods, a new natural antioxidant 1 (methyl 5-(3,4-dihydroxyphenyl)-3-hydroxypenta-2,4-dienoate) derived from hispolone 2 has been isolated from the mushroom Inonotus hispidus growing on Pistacia atlantica. Hispolone 2 (6-(3,4-dihydroxyphenyl)-4-hydroxyhexa-3,5-dien-2-one) and hispidin 3 (6-(2-(3,4-dihydroxyphenyl)vinyl)-4-hydroxy-2H-pyran-2-one) have been also identified using spectroscopic methods, including 2D-NMR and EI-MS.