Aqueous extract of Ceratonia siliqua L. leaves elicits antioxidant, anti-inflammatory, and AChE inhibiting effects in amyloid-ß42-induced cognitive deficit mice: Role of α7-nAChR in modulating Jak2/PI3K/Akt/GSK-3ß/ß-catenin cascade.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder attributed to several etiological factors including cholinergic dysregulation, neuroinflammation, oxidative stress, ß-amyloidogenesis, and tauopathy. This demands the search for multitarget drugs, especially of natural sources owing to their pleiotropic activities and low adverse effects. The present study was conducted to investigate the cognitive-improving potential of Ceratonia siliqua L. (Cs) extract compared with donepezil, an acetylcholinesterase inhibitor, on AD-like pathological alterations induced by single intracerebroventricular amyloid-ß42 (Aß42) injection in mice. Aß42-injected mice were treated with Cs (100 mg/kg/day, po) with or without methyllycaconitine (MLA; 1 mg/kg/day, ip), an α7-nAChR antagonist. Aß42-injected animals demonstrated an elevation of hippocampal Aß42, p-Tau, and acetylcholinesterase. They also showed a decline in phosphorylated levels of Jak2, PI3K, Akt, and GSK-3ß, leading to induction of neuroinflammation and oxidative stress. Noteworthy, Cs improved the histopathological and behavioral variables in addition to mitigating AD hallmarks. It also exerted neuroprotection by reducing NF-κBp65 and TNF-α, while elevating Nrf2 and HO-1, along with stabilizing ß-catenin under the impact of Jak2/PI3K/Akt/GSK-3ß signaling. These beneficial effects of Cs were abrogated by MLA co-administration signifying the α7-nAChR involvement in Cs-mediated effects. Therefore, Cs can ameliorate Aß42-induced neurodegeneration by modulating Jak2/PI3K/Akt/GSK-3ß/ß-catenin axis in an α7-nAChR-dependent manner.

Phytochemical profile and antioxidant capacity, α-amylase and α-glucosidase inhibitory activities of Oxalis pes-caprae extracts in alloxan-induced diabetic mice.

Diabetes and its complications are closely correlated with chronic hyperglycemia, causing severe oxidative stress and leading to glycation reaction with formation of advanced glycation end products. However, medicinal plants are still a source of inspiration for the discovery of new treatments of several diseases, including diabetes. The present study was aimed to evaluate the antioxidant and antidiabetic properties of Oxalis pes-caprae flowers extract in alloxan-induced diabetic mice. The phytochemical and antioxidant activities of both aqueous and methanolic extracts were assessed by in-vitro testing such as free radical scavenging assays (DPPH and ABTS+), ferrous ions (Fe2+) chelating activity and reducing power assay. Additionally, the detection of Amadori products and advanced glycation end products was used to determine the antiglycation potential. α-glucosidase and α-amylase inhibitory assessment was employed to determine the antidiabetic effect, while alloxan-induced diabetic mice were used to measure the in-vivo activities of antioxidants and carbohydrates enzymes. The effect of the methanolic extract on body weight and blood glucose level of extract-treated diabetic mice were also investigated. Among the tested extract, the methanolic extract was the richest in phenolic compounds which is directly related with their remarkable antioxidant, enzyme inhibitory and antiglycation activity. The oral administration of the two doses of Oxalis pes-caprae flowers (150 mg/kg and 250 mg/kg) daily for 3 weeks resulted in hypoglycemic effect compared to the reference drug, glibenclamide (10 mg/kg). Furthermore, the extract was shown to significantly increase the activities of antioxidants and glycolysis enzymes in the liver, kidney and spleen of diabetic mice, compared to diabetic control group. Therefore, Oxalis pes-caprae extract effectively exhibited hypoglycemic and antidiabetic effects as indicated by in-vitro and in-vivo studies, confirming the protective effects on hyperglycemia and oxidative damage.

Determination of the polyphenolic content of Ammodaucus leucotrichus Cosson and Durieu by liquid chromatography coupled with mass spectrometry and evaluation of the antioxidant and antiglycation properties.

Ammodaucus leucotrichus Cosson and Durieu, known as Sahara cumin, is a plant belonging to the Apiaceae family with a very strong smell of anise growing in the maritime sands in the countries of North Africa. The present work aims to study the polyphenolic profile of its seeds hydroalcoholic extract along with the determination of the antioxidant and antiglycation properties. The phytochemical screening revealed the presence of 16 compounds, out of which 15 have been detected in this extract for the first time. Luteolin-glucoside turned out to be the most abundant one (281.32 ± 0.34 mg/kg), followed by apigenin-hexoside (235.06 ± 0.29 mg/kg) and luteolin (202.41 ± 0.40 mg/kg). In terms of antioxidant activity, a half-maximal inhibitory concentration value as high as 0.39 ± 0.003 mg AAE/ml (w/v) was attained. Further, the antiglycation activity was determined to yield interesting results: at a concentration of 1.5 mg/ml, the extract showed an antiglycation activity (%I) of 61.86 compared to metformin as a positive control (%I = 84.01); on the other hand, increasing the concentration to 10 mg/ml, the inhibition activity switched to advanced glycation end products formation activation (%I = 41.71).

Dittrichia viscosa L. Leaves: A Valuable Source of Bioactive Compounds with Multiple Pharmacological Effects.

This work focused on the leaves of Dittrichia viscosa, a plant used in Mediterranean folk medicine. Compared to water extract, the methanolic extract had higher antioxidant effects. Moreover, this extract showed potent in vitro inhibitory activity against α-amylase and α-glucosidase and showed an interesting antiglycation effect. Additionally, the evaluation of the cytotoxic activity of the methanolic extract against two human breast cancer cell lines, MCF-7 and MDA-MB-468, was very promising, with no cytotoxicity towards normal cells (peripheral blood mononuclear cells (PBMCs). The antibacterial effect was also assessed and showed potent inhibitory activity against Proteus mirabilis and Bacillus subtilis. On the other hand, Dittrichia viscosa leaves were rich in macro-elements containing appropriate micro-elements and high levels of phenolics and flavonoids such as caffeic acid derivatives. Taken together, the results obtained in this study indicate that Dittrichia viscosa could constitute a valuable source of bioactive molecules and could be used either on the preventive side or for therapeutic applications without toxicity.

Promising effects of Rosa damascena petal extracts as antioxidant and antibacterial agents.

In the present work, the antioxidant properties of methanolic (MeOH), ethyl acetate (EtOAc) and chloroformic (CHCl3) fractions of Rosa damascena petals were evaluated. Antioxidant capacity was assessed by free radical scavenging assays (DPPH•) and ferrous ions (Fe2+) chelating activity. Antibacterial activity was evaluated using minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and IC50. Qualitative analysis of chemical composition was carried out by HPLC and showed variability in the chemical constituents with a richness in flavonones and phenolic acids. Acute toxicity study and hemolysis test were also assessed. The MeOH and EtOAc fractions are of real and potential interest by their antioxidant activities. Furthermore, the microbiological study of the fractions showed a high activity of the EtOAc fraction which possesses bactericidal properties, followed by a moderate activity of the methanolic MeOH. The most sensitive strains were S. aureus and B. cereus while the most resistant were P. aeruginosa and E. coli (R). On the other side, no cytotoxicity was observed towards erythrocytes isolated from human blood and on a warm-blooded animal model. Therefore, the R. damascena petals constitute a promising source of molecules for clinical use without cytoxicity.

The Aqueous Extract from Ceratonia siliqua Leaves Protects Against 6-hydroxydopamine in Zebrafish: Understanding the Underlying Mechanism.

Ceratonia siliqua L. is a Mediterranean medicinal plant traditionally cultivated for its ethnopharmacological benefits, such as antidiarrheal, antidiabetic, enhance acetylcholine, antioxidant, antiatherosclerotic, and for its possible anti-neurodegenerative potential. The aim of the present study was to evaluate the chemical composition, as well as the cognitive-enhancing, anxiolytic, and antioxidant activities of the aqueous extract from C. siliqua (CsAE) leaves against 6-hydroxydopamine (6-OHDA) zebrafish Parkinson's disease (PD) model. CsAE (0.1, 0.3, and 1 mg/L) was administered by immersion to zebrafish (Danio rerio) for eight consecutive days and one hour before each behavioral test of each day, while 6-OHDA (250 µM) treatment was supplied one day before the novel tank diving test (NTT). Qualitative and quantitative analyses were performed by the ultra-high-performance liquid chromatography (UHPLC) analysis. The memory performance was evaluated through the NTT and Y-maze tests. Additionally, the in vitro and in vivo antioxidant status and acetylcholinesterase (AChE) activity was also assessed. Our finds demonstrated that CsAE presented positive antioxidant and anti-AChE activities, which contributed to the improvement of cognitive function in the 6-OHDA zebrafish PD model.

Glucose-mediated protein glycation: Contribution of methanolic extract of Ceratonia siliqua L. in protection and in vitro potential inhibition of acetylcholinesterase.

Chronic hyperglycemia presents the major etiology of diabetes mellitus and related complications mainly Alzheimer's disease, via the protein glycation and toxic products generated. In the current study, we investigated the eventual protective effect of the methanolic extract of Ceratonia siliqua L. (CsME) against glucose-mediated glycation in serum bovine albumin. The multi-stage glycation markers, namely fructosamines and advanced glycation end products (AGEs) levels were monitored along with measurement of thiol groups; moreover, the in vitro acetylcholinesterase (AChE) inhibition potential was carried out. HPLC was also assessed. Rutin was the main phenolic compound found in CsME. CsME showed a good capacity to inhibit AGEs, fructosamines and protected thiol groups against glycation. CsME exhibited a great AChE inhibition activity. In the present study, CsME prevented glucose-induced protein glycation, it also exhibited a good inhibition of AChE, suggesting its DM complications such as memory troubles related to AD. PRACTICAL APPLICATIONS: Neurodegenerative disorders ranging from memory troubles to Alzheimer's disease present the most diabetes mellitus complications and mainly attributed to protein glycation process. Currently, there is a strong trend to search for efficient natural sources of glycation and acetylcholinesterase inhibitors to replace the synthetic ones, whose secondary effects were shown. The present article tries to justify scientifically the wide use of Ceratonia siliqua L. in Moroccan folk medicine, demonstrating that the methanolic extract of leaves from this species presents a promising source of new natural compounds inhibiting acetylcholinesterase and acting in vitro against glycation generated compounds. Furthermore, for the first time, Rutin was the main phenolic compound found in this extract, these encouraging results should be coupled with further studies to integrate it in pharmaceutical formulations. As such, this paper should be of interest to a broad readership, including those interested in Biochemistry, Phytochemistry, pharmacology, and neurosciences.

Phytochemical Characterization, Antioxidant and In Vitro Cytotoxic Activity Evaluation of Juniperus oxycedrus Subsp. oxycedrus Needles and Berries.

In order to evaluate the antioxidant properties of aqueous and methanol extracts of needles and berries of Juniperus oxycedrus subsp. oxycedrus (Joo) species, various antioxidant capacity assessment tests (free radical scavenging assays (DPPH• and ABTS•+ tests), ferrous ions (Fe2+) chelating activity and reducing power assay (FRAP) were conducted. In all of the tests, the extracts exhibited strong antioxidant activity. Furthermore, in-vitro cytotoxic activity assays of the methanolic extracts showed potent cytotoxic effects against two breast cancer cell lines (MDA-MB-468 and MCF-7), with no cytotoxicity towards normal cells (PBMCs). Reactive oxygen species generation was presumed to be a potential reason for the observed cytotoxic effects. According to all the above, and considering its appropriate composition of mineral elements and phenolic compounds, Joo could offer a beneficial and natural source of bioactive compounds that can be either used on the preventive side as it could potentially be used in the clinic without toxicity.