Molecular docking studies, chemical composition, antioxidant, cytotoxicity, antibacterial and antifungal activities of Globularia alypum extract

Background: Globularia alypum L. is a Mediterranean plant of the Globulariaceae family which has been used in folk medicine to cure several diseases. Different studies have been done in vitro and in vivo using diverse G. alypum extracts to understand this traditional use. Methods: In this study, Tunisian G. alypum leaf methanol extract (GAME) was chemically identified using LC-ESI-MS, then examined in vitro for its antioxidant, antibacterial, and antifungal activities. Besides, a molecular docking study was also conducted. Results: Nineteen phenolic compounds were detected, with trans-cinnamic acid (45.14%) and luteolin 7-O-glucoside (19.82%) being the dominant ones. The GAME demonstrated important antioxidant activities, especially against 2, 2-diphenyl-l-1-picrylhydrazil (DPPH) radical (IC50 = 16.1±1.1 μg.ml−1) and exhibited an anti-proliferative effect against Vero cells with (IC50 2091 ± 177 μg.ml−1)). Data also reveals that the GAME inhibited the growth of oral bacteria, in particular Streptococcus oralis (MICs value ranged from 2560 to 20480 μg.ml−1)). In addition, GAME has a significant antifungal action, especially against Candida albicans ATCC 90028 (MIC=2560 µg.ml−1)). Docking study identified one of the major molecules (luteolin 7-O-glucoside) present in the GAME extract, displaying a good interaction with tyrosinase (docking score −9.6 kcal.mol−1)) and other antibacterial (tyrosyl-tRNA synthetase, gyrase, deformylase) and antifungal (n-myristoyl-transferase, chitinase) target proteins. Conclusion: This study illustrates that GAME has potent sources of antioxidants and antimicrobials useful in combating oral bacteria. Hence GAME can be of reasonable use in food technology, processing, as well as the medical field.

The antioxidant and anti-inflammatory effect of Globularia alypum aqueous extract in hypercholesterolemic rats

Globularia alypum (G. alypum) is a medicinal plant commonly used intradi-tional pharmacopoeias. In this study, the antioxidant and anti-inflammatory activities of G. alypum lyophilized aqueous extract were evaluated. Male Wistar rats (n=24) weighing 232±10g were divided into 4 groups (n=6). Two control groups were fed a standard-diet (St-D) supplemented (C-Ga) or not (C) with 1.66% G. alypum extract. The two others were fed enriched choles-terol diet (EC-D) for 15 days, which contains the St-D plus 1% of cholesterol and 0.5% of cholic acid (HC) with the same amount of G. alypum (HC-Ga). At d28, EC-D leads to increase TBARS concentrations in plasma, lipoproteins (VLDL-LDL, HDL), tissues (liver, heart, kidney and adipose tissues) and ery-throcytes (p<0.05) in HC vs C and HC-Ga vs C-Ga. While, in HC vs C group, antioxidant defenses were decreased in tested tissues, except in kidney and heart for GSH and SOD (p<0.05). Whereas, treatment with G. alypum indu-ced a reduction of lipid peroxidation (p<0.05) in HC vs C and HC-Ga vs C-Ga by enhancing CAT and GSH-Px activities in all tissues (p<0.05); GSH and SOD activities were increased in liver, adipose tissue and erythrocytes in HC-Ga vs HC (p<0.05). Also, an increase in the concentration of IL-6 and TNF-α was noted in HC vs C group (p<0.05). Moreover, the concentration of these pro-inflammatory cytokines was diminished in HC-Ga vs HC group (p<0.05). Our findings showed that G. alypum lyophilized aqueous extract presented anti-oxidant and anti-inflammatory potential in hypercholosterolemic rats and can be explored in patients with hypercholesterolemia.

Phytochemical Screening and Antibacterial Activity of Libyan Globularia alypum

Aims. The aim of this study was to assess the phytochemical screening and antibacterial effect of the aerial parts of G. alypum cultivated in Libya. Methods. The methanolic extract of G. alypum (at concentrations 100 mg/ml, 300 mg/ml, 500 mg/ml and 700 mg/ml) were tested against 13 different strains of standard bacteria (ATCC) by four different methods; paper disc diffusion method, well diffusion method, broth dilution method and finally study the effect of extract on growth curve of bacterial cell were studied. Results. The results of phytochemical screening revealed the presence of flavonoids, phenols, reducing sugars, tannins, saponins, coumarins, steroids, terpenoids, carotenoids, antraquinones and glycosides. While the results of antibacterial tests showed remarkable inhibition of the bacterial growth, with maximum inhibition on growth of Methicillin Resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus. Moderate effect on growth of Enterococcus faecalis, Bacillus subtilis, Aeromonas hydrophila and Salmonella poona. While, the lowest inhibition showed in Yersinia enterocolitica and Listeria monocytogenes. However, the extract did not have any effect on Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, Salmonella typhimurium and Klabsiella pneumonia. Conclusion. The methanolic extract of Globularia alypumaerial parts contain the most important constituents with positive results during phytochemical screening, and have antibacterial activity against gram positive and gram-negative bacteria.

Phytochemical Investigation and Antioxidant Activity of Globularia alypum L.

The Moroccan flora is rich in medicinal plants that are commonly used in folk medicine for the treatment of various diseases. The present study was designed to investigate the total phenolic and flavonoid contents, as well as the antioxidant properties of leaves extracts from Globularia alypum L. colected from the Taza region in northeast Morocco. Additionally, the individual phenolics and volatiles of the extracts were also evaluated. The organic extracts of this plant were obtained by Soxhlet extraction using two different solvents, namely ethyl acetate and chloroform. The antioxidant capacity of leaves extracts was measured using DPPH, ABTS and FRAP assays; the phenolic profile was determined by HPLC-DAD/ESI-MS analysis, whereas the volatile composition was elucidated by GC-MS. The ethyl acetate extract analysis showed a total of 20 phenolic compounds and the determination of phenolic contents showed a significant value of 56.5 ± 0.61 µg GAE/mg of extract in comparison with the chloroform extract (18.9 ± 0.48 µg GAE/mg of extract). Also, the determination of the flavonoid contents revealed that the ethyl acetate extract contained the highest value (30.2 ± 0.55 µg CE/mg of extract) in comparison with the chloroform extract (18.0 ± 0.36 µg CE/mg of extract). Concerning the antioxidant properties, interesting values were attained for the ethyl acetate extract which exhibited higher antioxidant activity, namely IC50 = 12.3 ± 3.83 µg/mL and IC50 = 37.0 ± 2.45 µg/mL for the DPPH and ABTS assays, respectively, whereas a value of 531.1 ± 17.08 (mg AAE/g DW) was obtained for the FRAP assay. Concerning the volatile profile, a total of 73 compounds were positively detected and among them n-hexadecanoic acid (13.5%) was the most abundant one. The results achieved confirm the important role of this plant as a source of natural antioxidants.

Favorable effects of Globularia alypum on cardiometabolic markers in high fructose-fed rats

Purpose This study aims to examine whether Globularia alypum (Ga) lyophilized aqueous leaves extract treatment improves cardiometabolic syndromes such as hyperglycemia, lipid profiles and oxidative damage resulting from a high-fructose diet induced in hypertriglyceridemic rats. Design/methodology/approach A total of 24 male Wistar rats weighing 80 ± 5 g were first randomly divided into 2 groups. A total of 12 control rats (C) were fed a standard-diet (St-D) and 12 high fructose (HF) rats were fed a high-fructose diet (HF-D) containing St-D in which cornstarch was substituted by fructose (61.4%). After 15 weeks of feeding, body weight (BW) was about 320 ± 20 g and hypertriglyceridemia was noted in HF vs C group (2.69 ± 0.49 mmol/L) vs (1.25 ± 0.33 mmol/L). Each group of rats was then divided into two equal groups (n = 6) and fed during four weeks either a St-D or HF-D, treated or not with 1% of Ga extract (C-Ga) and (HF-Ga). After 28 days, fasting rats were anesthetized and blood and tissues were removed to measure biochemical parameters. Findings The results showed no significant differences in BW and insulinemia between all groups. Ga extract supplementation reduced glycemia (−36%), glycosylated hemoglobin (−37%), Homeostasis Model of Assessment-Insulin Resistance index (−34%) and triacylglycerol’s contents in plasma (−33%), very low density lipoproteins–low density lipoproteins (VLDL-LDL) (−48%), liver (−52%) and aorta (−39%); total cholesterol concentrations in aorta was 3.7-fold lower in HF-Ga vs HF group. Ga treatment reduced lipid peroxidation in plasma, VLDL-LDL, red blood cells (RBC), liver, muscle and kidney by improving superoxide dismutase (SOD) activity and glutathione peroxidase (GPx) in RBC and catalase (CAT) activity in kidney (p < 0.05). Moreover, Ga ameliorates glutathione (GSH) production in RBC (+41%) and kidney tissues (+35%). Originality/value Ga extract ameliorated cardiometabolic syndrome by its hypotriglyceridemic effect and prevented development of insulin resistance. It reduces lipid peroxidation by enhancing non-enzymatic (GSH) and enzymatic (SOD, GPx and CAT) antioxidant defense systems in high-fructose hypertriglyceridemic rats. Therefore, supplementation of Ga leaves extract as an adjuvant could be used for the treatment of hypertriglyceridemia and the prevention and/or the management of cardio-metabolic adverse effects.

Antihypercholesterolemic and anti-atherogenic effects of lyophilized aqueous extract of Globularia alypum leaves in rats fed a high-cholesterol diet

Purpose This paper aims to investigate the preventive effects of a concomitant supplementation of a lyophilized aqueous extract of Globularia alypum (Ga) leaves in a high cholesterol-diet (HC-D) on lipid profile and lecithin cholesterol acyltransferase (LCAT) activity in hypercholesterolemic rats. Design/methodology/approach Twenty-four male Wistar rats weighing 232 ± 10 g were divided into four groups (n = 6). Two control groups were fed a standard-diet (St-D) supplemented (C-Ga) or not (C) with 1.66% Ga leaf extract. The two others experimental groups were fed HC-D, which contains the St-D plus 1% of cholesterol and 0.5% of cholic acid supplemented (HC-Ga) or not (HC) with the same amount of Ga. At d28, feces were collected and fasting rats were anesthetized; bloods and livers were removed to measure biochemical parameters. Findings In hypercholesterolemic (HC) rats, Ga supplementation in HC-D induced a significant reduction in ALT (−64%, p = 0.002) and AST (−71%; p = 0.005) activities, in plasma TC (−55%; p = 0.03) and TG (−54%; p = 0.01) concentrations, in cholesterol contents of atherogenic lipoproteins VLDL (−78%; p = 0.004) and LDL-HDL1 (−64%; p = 0.003) and inversely, an increase in those of anti-atherogenic HDL2 (+14%; p = 0.002). Feeding the HC-D-Ga exhibited a reduction in atherogenic index Apo B/Apo A-I (−72%; p = 0.002), an increase in faecal lipids, cholesterol excretion and in plasma apo A-I (+60%; p = 0.002) and HDL2-cholesteryl esters (+32%, p = 0.04) and then improved LCAT activity (+31%; p = 0.03). Originality/value In hypercholesterolemic rats, Globularia alypum extract was effective in preventing lipid disorders by its hypolipidemic action, had an anti-atherogenic potential and a protective effect against cardiovascular risk by enhancing LCAT activity.