Phytochemistry, Biological Activities, Therapeutic Potential, and Socio-Economic Value of the Caper Bush (Capparis Spinosa L.).

Capparis spinosa L., commonly known as the caper bush, is an aromatic plant growing in most of the Mediterranean basin and some parts of Western Asia. C. spinosa L. has been utilized as a medicinal plant for quite a long time in conventional phytomedicine. Polyphenols and numerous bioactive chemicals extracted from C. spinosa L. display various therapeutic properties that have made this plant a target for further research as a health promoter. This review is meant to systematically summarize the traditional uses, the phytochemical composition of C. spinosa L., and the diverse pharmacological activities, as well as the synthetic routes to derivatives of some identified chemical components for the improvement of biological activities and enhancement of pharmacokinetic profiles. This review also addresses the benefits of C. spinosa L. in adapting to climate change and the socio-economic value that C. spinosa L. brings to the rural economies of many countries.

Natural Bioactive Compounds Targeting Histone Deacetylases in Human Cancers: Recent Updates.

Cancer is a complex pathology that causes a large number of deaths worldwide. Several risk factors are involved in tumor transformation, including epigenetic factors. These factors are a set of changes that do not affect the DNA sequence, while modifying the gene's expression. Histone modification is an essential mark in maintaining cellular memory and, therefore, loss of this mark can lead to tumor transformation. As these epigenetic changes are reversible, the use of molecules that can restore the functions of the enzymes responsible for the changes is therapeutically necessary. Natural molecules, mainly those isolated from medicinal plants, have demonstrated significant inhibitory properties against enzymes related to histone modifications, particularly histone deacetylases (HDACs). Flavonoids, terpenoids, phenolic acids, and alkaloids exert significant inhibitory effects against HDAC and exhibit promising epi-drug properties. This suggests that epi-drugs against HDAC could prevent and treat various human cancers. Accordingly, the present study aimed to evaluate the pharmacodynamic action of different natural compounds extracted from medicinal plants against the enzymatic activity of HDAC.

Comparative Investigation of Chemical Constituents of Kernels, Leaves, Husk, and Bark of Juglans regia L., Using HPLC-DAD-ESI-MS/MS Analysis and Evaluation of Their Antioxidant, Antidiabetic, and Anti-Inflammatory Activities.

Leaves, husk, kernels, and bark methanolic extracts of Juglans regia L. were tested for their in vitro antidiabetic, anti-inflammatory, and antioxidant activities. For these purposes, α-amylase and α-glucosidase were used as the main enzymes to evaluate antidiabetic activities. Moreover, lipoxidase and tyrosinase activities were tested to estimate anti-inflammatory properties. Antioxidant properties of Juglans regia L., extracts were determined using three different assays. Leaves extract has an important radical scavenging activity and a-amylase inhibition. Similarly, husk extracts showed high total phenolic content (306.36 ± 4.74 mg gallic acid equivalent/g dry extract) with an important α-amylase inhibition (IC50 = 75.42 ± 0.99 µg/mL). Kernels exhibit significant tyrosinase (IC50 = 51.38 ± 0.81 µg/mL) correlated with antioxidant activities (p < 0.05). Husk and bark extracts also showed strong anti-lipoxidase activities with IC50 equal to 29.48 ± 0.28 and 28.58 ± 0.35 µg/mL, respectively. HPLC-DAD-ESI-MS/MS analysis highlights the phenolic profile of methanolic extracts of Juglans regia L. plant parts. The identified polyphenols were known for their antioxidant, antidiabetic (dicaffeoyl-quinic acid glycoside in kernels), and anti-inflammatory (3,4-dihydroxybenzoic acid in leaves) activities. Further investigations are needed to determine molecular mechanisms involved in these effects as well as to study the properties of the main identified compounds.

Recent Advances in Electrochemical Biosensors Based on Enzyme Inhibition for Clinical and Pharmaceutical Applications.

A large number of enzyme inhibitors are used as drugs to treat several diseases such as gout, diabetes, AIDS, depression, Parkinson's and Alzheimer's diseases. Electrochemical biosensors based on enzyme inhibition are useful devices for an easy, fast and environment friendly monitoring of inhibitors like drugs. In the last decades, electrochemical biosensors have shown great potentials in the detection of different drugs like neostigmine, ketoconazole, donepezil, allopurinol and many others. They attracted increasing attention due to the advantage of being high sensitive and accurate analytical tools, able to reach low detection limits and the possibility to be performed on real samples. This review will spotlight the research conducted in the past 10 years (2007-2017) on inhibition based enzymatic electrochemical biosensors for the analysis of different drugs. New assays based on novel bio-devices will be debated. Moreover, the exploration of the recent graphical approach in diagnosis of reversible and irreversible inhibition mechanism will be discussed. The accurate and the fast diagnosis of inhibition type will help researchers in further drug design improvements and the identification of new molecules that will serve as new enzyme targets.

Validation and screening of patulin in apple beverages marketed in Morocco.

Patulin is one of the mycotoxins frequently detected in apples and derivatives, representing a major food safety risk. This study aimed to validate a high-performance liquid chromatography (HPLC) method with an ultraviolet (UV) detector for patulin quantification and assess its occurrence in apple beverages marketed in Morocco. The validation parameters showed satisfactory results with adequate linearity (R > 0.997), a relative standard deviation below 2.5%, repeatability between 3.6 and 7.1%, reproducibility between 3.9 and 11.5%, a limit of quantification (LOQ) of 4 µg/L, and recoveries close to 100% for three levels. Analysis of 30 samples revealed patulin levels ranging from 0 to 16.36 µg/L, with 50% of samples showing negative levels. All positive results remained below the regulatory maximum limit of 50 µg/L. These findings affirm the efficacy of the HPLC proposed method in ensuring compliance with patulin regulations in apple beverages, underlining its importance in safeguarding food safety.

Phenolic Profile, Antioxidant, Antidiabetic, and Antigout Potential of Stem Extracts of Four Sweet Cherry Cultivars.

In order to highlight the activities of bioactive compounds present in the stem of sweet cherries, four different cultivars (Van, Burlat, Napoleon, and Cœur pigeon) were collected in Sefrou city in Morocco and were studied. Several assays were performed for this purpose, such as the quantification of phenolic compounds (TPC, TFC, and CTC) and the evaluation of the antioxidant activity using DPPH, ABTS, and FRAP assays. The phenolic profile of each extract was characterized by UHPLC-DAD/MS analysis. The antidiabetic (α-amylase inhibition) and antigout (xanthine oxidase inhibition) activities were also investigated. The results showed high levels of phenolic compounds, with the values of 340 ± 12.06, 244 ± 10.20, 232 ± 5.07, and 19 ± 3.10 mg gallic acid equivalent/g extract for the cultivars Napoleon, Coeur de pigeon, Van, and Burlat, respectively. According to the same order, the flavonoids showed amounts of 34.31 ± 2.08, 23.75 ± 1.02, 24.37 ± 1.20, and 23.31 ± 0.90 mg (rutin equivalent) RE/g extract. These values were correlated with the results of the antioxidant assays, where the Napoleon cultivar proved to be the most potent using the DPPH (IC50 = 2.51 µg/mL) and ABTS (IC50 = 55.38 µg/mL) assays. The phenolic profile of each extract resulted in the identification of twenty-two compounds belonging to five distinct groups. The major phenolic compounds identified were sakuranetin and dihydrowgonin with their glucosides. Antidiabetic activity assays showed that only stem extracts from Burlat and Napoleon cultivars were able to inhibit the α-amylase enzyme with values of 85.57 ± 1.09% and 68.01 ± 3.52%, respectively. All stem extracts proved their ability to inhibit the xanthine oxidase enzyme which is directly linked to the gout disease, with a high value for Van cultivar (40.63 ± 2.37%). These new findings could provide new opportunities for the valorization of cherry stems for the pharmaceutical application of their active phytochemicals.

Traditional Knowledge, Phytochemistry, and Biological Properties of Vachellia tortilis.

Vachellia tortilis is a medicinal plant of the Fabaceae family, widely distributed in arid and semi-arid regions of North, East and Southern Africa, the Middle East and the Arabian Peninsula. In traditional medicine. It's commonly used to treat certain ailments, including diabetes, asthma, hepatitis and burns. Different scientific search databases were used to obtain data on V. tortilis, notably Google Scholar, Scopus, Wiley Online, Scifinder, Web of Science, ScienceDirect, SpringerLink, and PubMed. The knowledge of V. tortilis was organized based on ethnomedicinal use, phytochemistry, and pharmacological investigations. Phytochemical studies revealed the presence of a variety of phytocompounds, including fatty acids, monosaccharides, flavonoids, chalcones, and alcohols. Essential oils and organic extracts prepared from V. tortilis showed several biological properties, specifically antibacterial, antifungal, antiparasitic, antioxidant, antiproliferative, anti-diabetic, and anti-inflammatory effects. Antimicrobial and antiparasitic activities are due to the disturbance of cellular membranes and ultra-structural changes triggered by V. tortilis phytochemicals. While physiological and molecular processes such as apoptosis induction, preventing cell proliferation, and inflammatory mediators are responsible for the anti-diabetic, anti-cancer, and anti-inflammatory activities. However, further investigations concerning pharmacodynamics and pharmacokinetics should be carried out to validate their clinical applications.

Health Benefits and Pharmacological Properties of Stigmasterol.

Stigmasterol is an unsaturated phytosterol belonging to the class of tetracyclic triterpenes. It is one of the most common plant sterols, found in a variety of natural sources, including vegetable fats or oils from many plants. Currently, stigmasterol has been examined via in vitro and in vivo assays and molecular docking for its various biological activities on different metabolic disorders. The findings indicate potent pharmacological effects such as anticancer, anti-osteoarthritis, anti-inflammatory, anti-diabetic, immunomodulatory, antiparasitic, antifungal, antibacterial, antioxidant, and neuroprotective properties. Indeed, stigmasterol from plants and algae is a promising molecule in the development of drugs for cancer therapy by triggering intracellular signaling pathways in numerous cancers. It acts on the Akt/mTOR and JAK/STAT pathways in ovarian and gastric cancers. In addition, stigmasterol markedly disrupted angiogenesis in human cholangiocarcinoma by tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor receptor-2 (VEGFR-2) signaling down-regulation. The association of stigmasterol and sorafenib promoted caspase-3 activity and down-regulated levels of the anti-apoptotic protein Bcl-2 in breast cancer. Antioxidant activities ensuring lipid peroxidation and DNA damage lowering conferred to stigmasterol chemoprotective activities in skin cancer. Reactive oxygen species (ROS) regulation also contributes to the neuroprotective effects of stigmasterol, as well as dopamine depletion and acetylcholinesterase inhibition. The anti-inflammatory properties of phytosterols involve the production of anti-inflammatory cytokines, the decrease in inflammatory mediator release, and the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Stigmasterol exerts anti-diabetic effects by reducing fasting glucose, serum insulin levels, and oral glucose tolerance. Other findings showed the antiparasitic activities of this molecule against certain strains of parasites such as Trypanosoma congolense (in vivo) and on promastigotes and amastigotes of the Leishmania major (in vitro). Some stigmasterol-rich plants were able to inhibit Candida albicans, virusei, and tropicalis at low doses. Accordingly, this review outlines key insights into the pharmacological abilities of stigmasterol and the specific mechanisms of action underlying some of these effects. Additionally, further investigation regarding pharmacodynamics, pharmacokinetics, and toxicology is recommended.

Origanum compactum Benth., from traditional use to biotechnological applications.

Origanum compactum Benth., is a Moroccan medicinal plant known by its local name as Zaatar. In Morocco, it has various traditional applications such as the use to treat diabetes, metabolic disorders, digestive, and respiratory problems. In this review, we critically highlighted current investigations on the ethnopharmacological studies, the phytochemistry, pharmacological investigations, biotechnological applications, and future perspective of O. compactum. A bibliometric electronic search in worldwide accepted scientific databases such as ScienceDirect, PubMed, SpringerLink, Web of Science, Scopus, Wiley Online, and Google Scholar was carried out to gather on O. compactum. Chemical analysis using GC-MS and/or HPLC allowed the identification of several bioactive compounds such as terpenoids and phenolic acids. Furthermore, O. compactum extracts and essential oils have been tested for various biological activities such as antibacterial, antioxidant, antiparasitic, antifungal, and anticancer effects. Moreover, an alignment between traditional use and biological effects was demonstrated, in particular for the antimicrobial activity. These properties are related to O. compactum bioactive components, especially the volatile compounds such as thymol and carvacrol. The pharmacological mechanisms involve several cellular and molecular targeted actions. Moreover, the biological potential of this species had led some laboratories to apply the biotechnological tools for its regeneration. PRACTICAL APPLICATIONS: Origanum compactum is applied as traditional drug against different illnesses and for food preservation. Scientific investigations proved the application of O. compactum essential oils in food industries as antioxidants and antimicrobials. These volatile compounds could be applied also in pharmaceutical industries, in particular as antibacterial, antifungal, and antileishmanial drugs. Moreover, further investigations concerning toxicological evidences and pharmacokinetic as well as pharmacodynamic mechanistic targets and clinical trials could develop anticancer, antimalaria and anti-inflammatory, and antidiabetic drugs. Finally, the results of the findings of these purposes encourage other research groups to carry out further investigations on the pharmacological properties of O. compactum.

Investigation of sulfonamides inhibition of carbonic anhydrase enzyme using multiphotometric and electrochemical techniques.

Two approaches for sulfonamides (SA's) determination, based on carbonic anhydrase enzyme inhibition have been investigated in this work. In the first method, nine different SA's have been screened using simultaneous multiphotometric measurement in multiwell plates. The sulfanilamide (SAD) showed significant inhibition compared to other sulfonamides. The carbonic anhydrase (CA) kinetic interactions reveal noncompetitive binding of SAD. Interferences from other inhibitors with enzyme were studied and the results showed very good selectivity toward SAD. In the second approach, an electrochemical enzyme inhibition biosensor, based on CA entrapped in a carbon paste electrode using carbon black nanoparticles and solid paraffin, was successfully applied to SAD measurements. Results from the quantitative analysis of SAD are discussed in terms of detection limit, linear range and sensitivity using multiphotometric and biosensor-based methods The biosensor developed was successfully applied to the determination of SAD at submicromolar levels and it is recommended for application for in situ analysis.

Enzyme inhibition-based biosensors for food safety and environmental monitoring.

Analytical technology based on sensors is an extremely broad field which impacts on many major industrial sectors such as the pharmaceutical, healthcare, food, and agriculture industries as well as environmental monitoring. This review will highlight the research carried out during the last 5 years on biosensors that are based on enzyme inhibition for determination of pollutants and toxic compounds in a wide range of samples. Here the different enzymes implicated in the inhibition, different transducers forming the sensing devices, and the different contaminants analyzed are considered. The general application of the various biosensors developed, with emphasis on food and environmental applications, is reviewed as well as the general approaches that have been used for enzyme immobilization, the enzyme catalysis, and the inhibition mechanism.