Current Enzyme Inhibition - Volume 20, Issue 1, 2024

The main objective of this study was to select effective extracts for the anti-browning (anti-polyphenol oxidase and anti-peroxidase), and antioxidant activities of by-products of Phoenix dactylifera L., Ghars variety, from Algeria.

Hydro-methanolic extracts from the pedicel, perianth, and leaves of date palm were examined to evaluate the phenol and total flavonoid contents. Using spectrophotometric techniques, the antioxidant activities were assessed using 1, 1-diphenyl-2-picrylhydrazyl radical (DPPH^●), 2, 2’-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) radical (ABTS^●+) and Ferric Reducing Antioxidant Power (FRAP) assay, examined the enzyme inhibitory activity against polyphenol oxidase and peroxidase of Phoenix dactylifera L. extract.

The range of total phenolic and flavonoid contents was 12.29 to 48.98 mg gallic acid equivalent/g dry matter and 2.83 to 15.07 mg rutin equivalent/g dry matter, respectively. The pedicel extracts showed significant antioxidant activity in the DPPH and FRAP tests (IC50 = 0.0057 ± 0.0010 mg/ml and FEAC = 1.1961 ± 0.0647) compared to other extracts. However, in the ABTS assay, the leaf extract exhibited an interesting potency (IC50 = 0.0020 ± 0.0001mg/ml). The study on the anti-browning activity of date palm by-product extracts showed that it inhibited the activity of peroxidase enzyme from date palm fruit.

This work is the first time the potential of an extract from date palm by-products to enzymatically reduce the browning of date palms is presented. According to the results obtained, the different organs studied from the Ghars date palm, are a powerful natural antioxidant and may include natural compounds that retard browning by enzymes.

Calendula suffruticosa subsp. monardii (Boiss. & Reut.) Ohle, a medicinal plant from the Mediterranean region and, more precisely, from the extreme northeast of Algeria, is characterized by its wide use in the traditional medicine of the local population. This is what prompted us to investigate some pharmacological benefits such as anti-diabetes and Alzheimer's activities, in addition to anti-oxidant activity.

The effects of extraction methods and solvents on the amount of phenolic profiles and the biological activity of the different parts of this plant were studied, where the aim was to obtain a high extraction yield of bioactive compounds and consequently high biological activities.

In vitro standard procedures were used to assess enzyme inhibitory activity (AChE, BChE, α-Amylase and α-Glucosidase) of Calendula monadii, and the antioxidant activity was assessed using the DPPH, ABTS, CUPRAC, Reducing power and Ferrous ions assays.

When using ultrasound, a significant increase in the amounts of (TPC, TFC and TFlas) and antioxidant activity (DPPH, ABTS, CUPRAC, Reducing power and Ferrous ions cheating assay) in addition to the inhibitory activity of enzymes (AChE, BChE, α-Amylase α-Glucosidase) was found, compared to the results of conventional extraction. Furthermore, the aqueous solvent of ethanol 70% is the very effective solvent for extraction compared to methanol 70% aqueous solvent.

Based on these results, it can be said that this plant contains important biological activities, so it can be used in phytotherapy.

The imbalance between free radical formation and antioxidant defence leads to the development of oxidative stress. The search for substances that would mitigate or prevent the effects of oxidative stress remains relevant.

Our goal was to compare the antioxidant and mitigation effects of L-glutamic acid (L-Glu) and N-acetylcysteine (NAC) alone or in combination using a battery of biomarkers of oxidative stress such as reduced glutathione (GSH) superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione transferase (GST) and lipid peroxidation, determined as a content of lipid hydroperoxides (LOOH) and thiobarbituric acid reactive substances (TBARS). Histopathological examination of the liver was also performed.

Experimental rats were divided into five experimental groups. Exp.1: was treated with CCl4 only, Exp. 2: was treated with CCl4/L-Glu, Exp. 3: was treated with CCl4/Glu/NAC. Exp. 4: was treated with CCl4/NAC, Control 5: served as the control rats.

These findings suggest that the CCl4 leads to oxidative stress by depleting the antioxidant enzyme activities and increasing peroxidation products. The studied biochemical parameters were altered by the introduction of CCl4, which was normalised (to one degree or another) by L-Glu, L-Glu/NAC and NAC treatment.

The most remarkable protective effect was observed in groups of rats that were treated with L-Glu only. This conclusion was confirmed by histopathological findings which showed less severe hepatocellular necrosis, fibrosis and inflammation in CCl4/L- Glu and CCl4/L-Glu/NAC treated group, compared to the CCl4 group.

Existing drugs for the treatment of Alzheimer's disease do not meet the basic requirements. Therefore, it is necessary to search for fundamentally new targets for the discovery of drugs for Alzheimer's disease (AD). When creating approaches to stimulate neurogenesis, such a search is promising to conduct as part of the development of a strategy for targeted regulation of intracellular signal transduction in regeneration-competent cells (RCCs). Moreover, the participation of c-Jun N-terminal kinases (JNK) in the regulation of the functions of the nervous tissue and neuroglial cells is known.

The aim of the work was to study the effect of the JNK inhibitor (IQ-1S) on exploratory behavior and cognitive functions in aged mice (16-month-old male C57BL/6 mice as a model of AD) in combination with the dynamics of shifts in the RCCs functioning (nervous tissue progenitors: neural stem cells (NSCs) and neuronal-committed progenitors (NCPs); neuroglial cells: astrocytes, oligodendrocytes, microglial cells).

The studies were carried out on male C57BL/6 mice aged 16 months as model of Alzheimer's disease. We studied the effect of the JNK inhibitor on exploratory behavior, conditioned reflex activity, and on the functioning of RCCs in the subventricular zone of the cerebral hemispheres (SVZ). NCPs and neuroglial cells of different types were obtained by immunomagnetic separation.

We observed significant changes in exploratory behavior and impaired conditioned reflex activity in aged C57BL/6 mice. The administration of the JNK inhibitor led to a significant correction of age-related behavioral and memory disorders in aged mice. At the same time, against the background of JNK inhibition-based therapy, an increase in mitotic activity and the content of both NSCs and NCPs in the SVZ was noted. However, these shifts were more pronounced in committed precursors. The phenomenon of the inhibition of NSC specialization under the influence of a pharmacological agent was also revealed. In addition, the JNK inhibitor caused an increase in the secretion of neurotrophic growth factors by oligodendrocytes and microglial cells.

The findings open up prospects for the development of JNK targeting-based approaches for the treatment of AD.

The neuroprotective effect of bioflavonoids has been demonstrated in epileptic disorder.

The objective of this study was to investigate the anticonvulsant and adjuvant effects of the bioflavonoid and explore behavioural responses of orientin (Ore) on kindled mice induced by pentylenetetrazole [PTZ].

Albino Swiss mice weighing 20-30 g were divided into nine groups [n=6]. Prior to the PTZ dose, alternatively, Ore [10 mg/kg, i.p.] was given for 7 days, dissolved in 6% w/v carboxymethylcellulose [CMC] salt. On the 7^th day, saline was solubilized with Lamotrigine [Lmt], Phenobarbital [Pb], and Gabapentin [Gbp] and administered as separate intraperitoneal [i.p.] injections 30 minutes prior to the PTZ dose. For the development of kindling seizures in mice, PTZ [30 mg/kg, i.p.] was delivered to all the mice for 12 days, alternatively until the animals appeared to develop full motor muscle jerking seizures. Mice who survived from complete motor seizures were selected for further experimentation.

Data showed that anticonvulsive activity was exhibited by the control. Ore [10 mg/kg] with PB [40 mg/kg, i.p.] was administered on the 12^th day and showed an increase in transfer delays [ITL and RTL].

Anti-seizure efficacy of drugs was investigated at the effective dose of Ore at 10 mg/kg + PB 40mg/kg in group 7^th and was found to have promising therapeutic outcomes and potency in therapeutic strategies and associated concerns.

Pterocarpus milbreadii (PM), called Rosewood in English, is a leafy vegetable used in preparing soup and has also proven medicinal.

This study aimed to evaluate the most abundant compounds in the ethylacetate fraction of PM using Gas Chromatography-Mass Spectrometry (GC-MS) and docking it against cyclooxygenase isoenzymes.

The PM leaves were extracted with ethylacetate using the cold maceration method. The extract was subjected to GC-MS assay. The spectra obtained were matched with NIST 17. AutoDock Vina was used to perform the molecular docking of the most abundant compound of PM and cyclooxygenase. Celecoxib was used as the standard ligand.

The results of the study revealed that the ethyl acetate leaf extract of PM contained different phytochemicals, with hexadecenoic acid being the most abundant, with an intensity count of 9.5 x 10⁸ CPS. Docking of hexadecenoic acid and Celecoxib with COX-2 yielded binding energies of -6.7 and -7.7 kcal/mol, respectively, while with COX-1, the binding energies of -6.3 and -9.8 kcal/mol were respectively recorded. Hexadecenoic acid interacted with both COX-1 and COX-2 largely via Van der Waals and pi-Alkyl bonds. Celecoxib made conventional hydrogen, carbon-hydrogen, halogen, pi-sigma, pi-alkyl interactions with the cyclooxygenase isoenzymes.

It was concluded that hexadecenoic acid was the predominant phytochemical in the ethylacetate leaf extract of PM. The hexadecanoic acid ligand produced a better inhibitory effect on COX-2 compared to COX-1.

Tyrosine kinases are of great importance nowadays in cancer treatment. As designing new inhibitors with more potency is an optimal goal of pharmaceutical companies, using previous improvements in this area would be beneficial. One of the most popular and widely used methods is creating a QSAR model. Another useful way is to build a pharmacophoric map to address important features of inhibitors.

Upon this, a large dataset of molecules was applied to create a QSAR model for the prediction of the inhibitory activity of molecules against the epidermal growth factor receptor. Using MOE software, molecular descriptors were calculated in 3d, and a model was built.

9 descriptors were selected, which describe the energy, shape, and hydrophobicity of the molecules. A pharmacophoric map was also created, and 3 important features were selected: Hydrophobic areas, H-bond acceptor regions, and Aromatic moieties.

These findings proved the results obtained result from the QSAR model.