Analysis of the Chemical Composition and Evaluation of the Antioxidant, Antimicrobial, Anticoagulant, and Antidiabetic Properties of Pistacia lentiscus from Boulemane as a Natural Nutraceutical Preservative

Pistacia lentiscus L. has traditionally been employed as a diuretic and stimulant in the treatment of hypertension. Our interest centered on analyzing the chemical profile of the plant’s leaves and its in vitro, in vivo, and in silico antioxidant, antimicrobial, anticoagulant, and antidiabetic effects in order to valorize this species and prepare new high-value products that can be used in the agro-food and pharmaceutical industries. When this species’ essential oil was hydrodistilled and subjected to GC-MS analysis, the results showed that the principal components were germacrene D (17.54%), spathulenol (17.38%), bicyclogermacrene (12.52%), and terpinen-4-ol (9.95%). The extraction of phenolic compounds was carried out by decoction and Soxhlet. The determination of total polyphenols, flavonoids, and tannins of aqueous and organic extracts by spectrophotometric methods demonstrated the richness of this species in phenolic compounds. Chromatographic analysis by HPLC/UV-ESI-MS of the aqueous extract of P. lentiscus revealed the presence of 3,5-di-O-galloyl quinic acid, gallic acid, and 3,4,5-tri-O-galloyl quinic acid specific to this species. The study of antioxidant activity by three methods (DPPH, FRAP, and Total Antioxidant Capacity) revealed that P. lentiscus is a very promising source of natural antioxidants. The antimicrobial activity of the essential oil and aqueous extract (E0) was studied by microdilution on the microplate. The results revealed the effectiveness of the aqueous extract compared to the essential oil against Gram-negative bacteria (K. pneumoniae, A. baumannii, E. aerogenes, E. cloacae, P. fluorescence, Salmonella sp., Shigella sp., and Y. enterolitica) and candidoses (C. krusei and C. albicans). The measurements of prothrombin time (PT) and activated partial thromboplastin time (aPTT) of the aqueous extract (E0) can significantly prolong these tests from concentrations of 2.875 and 5.750 mg/mL, respectively. The antihyperglycemic effect of the aqueous extract (E0) showed a strong in vitro inhibitory activity of α-amylase and α-glucosidase compared to acarbose. Thus, it significantly inhibited postprandial hyperglycemia in Wistar albino rats. The in-silico study of the major compounds of the essential oil and extract (E0) carried out using PASS, SwissADME, pkCSM, and molecular docking tools confirmed our in vitro and in vivo results. The studied compounds showed a strong ability to be absorbed by the gastrointestinal tract and to passively diffuse through the blood-brain barrier, a similarity to drugs, and water solubility. Molecular docking experiments deduced the probable mode of action of the identified compounds on their respective target proteins, such as NADPH oxidase, thrombin, α-amylase, and α-glucosidase. Furthermore, given the demonstrated antioxidant, antimicrobial, anticoagulant, and antidiabetic effects, we can affirm the richness of P. lentiscus in bioactive molecules and its use in traditional medicine as a source of preservative agent.

[1]  T. Zair,et al.  Phytochemistry and Biological Activities of Essential Oils from Six Aromatic Medicinal Plants with Cosmetic Properties , 2023, Antibiotics.

[2]  C. Vágvölgyi,et al.  Activity of Binary Combinations of Natural Phenolics and Synthetic Food Preservatives against Food Spoilage Yeasts , 2023, Foods.

[3]  Deepansh Sharma,et al.  Biosurfactants: Forthcomings and Regulatory Affairs in Food-Based Industries , 2023, Molecules.

[4]  N. Jullian,et al.  A Review of Pistacia lentiscus Polyphenols: Chemical Diversity and Pharmacological Activities , 2023, Plants.

[5]  N. Christodoulakis,et al.  Heat and Cold-Stressed Individuals of Pistacia lentiscus (Mastic Tree) Do Modify Their Secreting Profile , 2022, Plants.

[6]  G. Zengin,et al.  Pharmacological insights into the multifaceted biological properties of quinic acid. , 2022, Biotechnology & genetic engineering reviews.

[7]  H. Grajeta,et al.  Hypersensitivity Reactions to Food Additives—Preservatives, Antioxidants, Flavor Enhancers , 2022, International journal of environmental research and public health.

[8]  M. Bouachrine,et al.  Computational investigation of pyrrolidin derivatives as novel GPX4/MDM2–p53 inhibitors using 2D/3D-QSAR, ADME/toxicity, molecular docking, molecular dynamics simulations, and MM-GBSA free energy , 2022, Structural Chemistry.

[9]  Amina Maalej,et al.  Pistacia lentiscus L. Distilled Leaves as a Potential Cosmeceutical Ingredient: Phytochemical Characterization, Transdermal Diffusion, and Anti-Elastase and Anti-Tyrosinase Activities , 2022, Molecules.

[10]  Karina Moslova,et al.  Selective synthesis of novel quinolones-amino esters as potential antibacterial and antifungal agents: Experimental, mechanistic study, docking and molecular dynamic simulations , 2021 .

[11]  C. Tringali,et al.  Valorization of Agri-Food Waste from Pistachio Hard Shells: Extraction of Polyphenols as Natural Antioxidants , 2021, Resources.

[12]  T. Zair,et al.  Ethnobotanical investigation of herbal food additives of Morocco used as natural dyes , 2021, Ethnobotany Research and Applications.

[13]  F. Berrekhis,et al.  Correlation of Total Polyphenolic Content with Antioxidant Activity of Hydromethanolic Extract and Their Fractions of the Salvia officinalis Leaves from Different Regions of Morocco , 2021 .

[14]  A. Alam,et al.  In vitro antioxidant and anti-inflammatory activities of green cardamom essential oil and in silico molecular docking of its major bioactives , 2021, Journal of Taibah University for Science.

[15]  A. Ziyyat,et al.  Inhibitory effect of roasted/ unroasted Argania spinosa seeds oil on α- glucosidase, α-amylase and intestinal glucose absorption activities , 2020 .

[16]  V. Dragović-Uzelac,et al.  Evaluation of Polyphenolic Profile and Antioxidant Activity of Pistacia lentiscus L. Leaves and Fruit Extract Obtained by Optimized Microwave-Assisted Extraction , 2020, Foods.

[17]  A. Chiaravalle,et al.  Sulfites in meat: Occurrence, activity, toxicity, regulation, and detection. A comprehensive review. , 2020, Comprehensive reviews in food science and food safety.

[18]  A. Das,et al.  A comprehensive review on antioxidant dietary fibre enriched meat-based functional foods , 2020 .

[19]  T. Pires,et al.  Vaccinium myrtillus L. Fruits as a Novel Source of Phenolic Compounds with Health Benefits and Industrial Applications - A Review , 2020, Current pharmaceutical design.

[20]  F. Chemat,et al.  Extraction of aromas from Pistacia lentiscus L. leaves using alternative solvents: COSMO-RS-assisted solvent screening and GC-MS metabolites profiling , 2020, Separation Science and Technology.

[21]  M. Halabalaki,et al.  Traditional uses, phytochemistry and pharmacology of Chios mastic gum (Pistacia lentiscus var. Chia, Anacardiaceae): A review. , 2020, Journal of ethnopharmacology.

[22]  H. Daoud,et al.  Antimicrobial and Antioxidant Activities of Flavonoids Extracted from Pistacia lentiscus L., Leaves , 2020 .

[23]  B. Hammouti,et al.  Total phenolic content, antioxidant and antimicrobial activities of extracts from Pistacia lentiscus leaves , 2019 .

[24]  M. Ramchoun,et al.  Effect of extraction methods on antioxidant and anticoagulant activities of Thymus atlanticus aerial part , 2019, Scientific African.

[25]  Xin Yan,et al.  Systematic Studies on the Protocol and Criteria for Selecting a Covalent Docking Tool , 2019, Molecules.

[26]  G. Zengin,et al.  Phytochemical profiling, in vitro biological properties and in silico studies on Caragana ambigua stocks (Fabaceae): A comprehensive approach , 2019, Industrial Crops and Products.

[27]  M. Grusch,et al.  Gallic acid, a common dietary phenolic protects against high fat diet induced DNA damage , 2018, European Journal of Nutrition.

[28]  M. Sakly,et al.  Pistacia lentiscus oil attenuates memory dysfunction and decreases levels of biomarkers of oxidative stress induced by lipopolysaccharide in rats , 2018, Brain Research Bulletin.

[29]  Jun Zhang,et al.  Role of ROS and Nutritional Antioxidants in Human Diseases , 2018, Front. Physiol..

[30]  Andreas Eckert,et al.  ProTox-II: a webserver for the prediction of toxicity of chemicals , 2018, Nucleic Acids Res..

[31]  T. Szekeres,et al.  Gallic Acid Improves Health‐Associated Biochemical Parameters and Prevents Oxidative Damage of DNA in Type 2 Diabetes Patients: Results of a Placebo‐Controlled Pilot Study , 2018, Molecular nutrition & food research.

[32]  B. Sritularak,et al.  New Biflavonoids with α-Glucosidase and Pancreatic Lipase Inhibitory Activities from Boesenbergia rotunda , 2017, Molecules.

[33]  J. Sindelar,et al.  Effects of Nitrite and Erythorbate on Clostridium perfringens Growth during Extended Cooling of Cured Ham. , 2017, Journal of food protection.

[34]  R. Carle,et al.  Determination of pistachio (Pistacia vera L.) hull (exo- and mesocarp) phenolics by HPLC-DAD-ESI/MSn and UHPLC-DAD-ELSD after ultrasound-assisted extraction , 2017 .

[35]  Charles L. Brooks,et al.  CHARMM‐GUI ligand reader and modeler for CHARMM force field generation of small molecules , 2017, J. Comput. Chem..

[36]  A. Sartoratto,et al.  Encapsulated thyme (Thymus vulgaris) essential oil used as a natural preservative in bakery product. , 2017, Food research international.

[37]  Olivier Michielin,et al.  SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules , 2017, Scientific Reports.

[38]  G. Oboh,et al.  Phenolic constituents and modulatory effects of Raffia palm leaf (Raphia hookeri) extract on carbohydrate hydrolyzing enzymes linked to type-2 diabetes , 2017, Journal of traditional and complementary medicine.

[39]  Y. Mabkhot,et al.  Phytochemical, ethnomedicinal uses and pharmacological profile of genus Pistacia. , 2017, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[40]  K. Shimizu,et al.  Antiplatelet and Anticoagulant Activities of Angelica shikokiana Extract and Its Isolated Compounds , 2017, Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis.

[41]  V. Morsch,et al.  Effects of gallic acid on delta - aminolevulinic dehydratase activity and in the biochemical, histological and oxidative stress parameters in the liver and kidney of diabetic rats. , 2016, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[42]  Yen Hoang,et al.  Sodium Benzoate and Potassium Sorbate in Processed Meat Products Collected in Ho Chi Minh City, Vietnam , 2016 .

[43]  A. Gramza-Michałowska,et al.  Effect of Plant Extracts on Lipid Oxidation and Changes in Nutritive Value of Protein in Frozen‐Stored Meat Products , 2016 .

[44]  M. Balouiri,et al.  Methods for in vitro evaluating antimicrobial activity: A review☆ , 2015, Journal of pharmaceutical analysis.

[45]  Abeer A. Alhadi,et al.  Understanding the chemistry behind the antioxidant activities of butylated hydroxytoluene (BHT): a review. , 2015, European journal of medicinal chemistry.

[46]  D. Atmani,et al.  Antioxidant, cytoprotective, anti-inflammatory and anticancer activities of Pistacia lentiscus (Anacardiaceae) leaf and fruit extracts , 2015 .

[47]  Douglas E. V. Pires,et al.  pkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures , 2015, Journal of medicinal chemistry.

[48]  R. Giriprasad,et al.  Fruit-based Natural Antioxidants in Meat and Meat Products: A Review , 2015, Critical reviews in food science and nutrition.

[49]  K. Msaada,et al.  Variations in composition and antioxidant activity of Tunisian Pistacia lentiscus L. leaf essential oil , 2015 .

[50]  Olivier Michielin,et al.  iLOGP: A Simple, Robust, and Efficient Description of n-Octanol/Water Partition Coefficient for Drug Design Using the GB/SA Approach , 2014, J. Chem. Inf. Model..

[51]  C. Wiley,et al.  Coxsackievirus B4 myocarditis and meningoencephalitis in newborn twins , 2014, Neuropathology : official journal of the Japanese Society of Neuropathology.

[52]  Vladimir Poroikov,et al.  Prediction of the Biological Activity Spectra of Organic Compounds Using the Pass Online Web Resource , 2014, Chemistry of Heterocyclic Compounds.

[53]  M. Bijak,et al.  Polyphenol compounds belonging to flavonoids inhibit activity of coagulation factor X. , 2014, International journal of biological macromolecules.

[54]  J. Kamdem,et al.  Influence of gallic acid on oxidative stress-linked streptozotocin-induced pancreatic dysfunction in diabetic rats , 2014, Journal of basic and clinical physiology and pharmacology.

[55]  M. Bijak,et al.  Thrombin inhibitory activity of some polyphenolic compounds , 2013, Medicinal Chemistry Research.

[56]  A. Segura‐Carretero,et al.  A metabolite-profiling approach allows the identification of new compounds from Pistacia lentiscus leaves. , 2013, Journal of pharmaceutical and biomedical analysis.

[57]  Da Thompson,et al.  Effect of emulin on blood glucose in type 2 diabetics. , 2013, Journal of medicinal food.

[58]  Teresa Cristina Castilho Gorayeb,et al.  Synthesis, characterization and antifungal activity of quaternary derivatives of chitosan on Aspergillus flavus. , 2013, Microbiological research.

[59]  Muhammad Rashid Khan,et al.  Antioxidant activity, total phenolic and total flavonoid contents of whole plant extracts Torilis leptophylla L , 2012, BMC Complementary and Alternative Medicine.

[60]  Udo Albus,et al.  Book Review: Guide for the Care and use of Laboratory Animals , 1998 .

[61]  S. Sayadi,et al.  Hypoglycemic and antioxidant effects of leaf essential oil of Pelargonium graveolens L’Hér. in alloxan induced diabetic rats , 2012, Lipids in Health and Disease.

[62]  Chris Morley,et al.  Open Babel: An open chemical toolbox , 2011, J. Cheminformatics.

[63]  S. Jaoua,et al.  Chemical composition, cytotoxicity effect and antimicrobial activity of Ceratonia siliqua essential oil with preservative effects against Listeria inoculated in minced beef meat. , 2011, International journal of food microbiology.

[64]  M. Mezei,et al.  Molecular docking: a powerful approach for structure-based drug discovery. , 2011, Current computer-aided drug design.

[65]  P. Stanely Mainzen Prince,et al.  Protective effects of gallic acid on hepatic lipid peroxide metabolism, glycoprotein components and lipids in streptozotocin‐induced type II diabetic wistar rats , 2011, Journal of biochemical and molecular toxicology.

[66]  P. S. Mainzen Prince,et al.  Effects of gallic acid on brain lipid peroxide and lipid metabolism in streptozotocin‐induced diabetic Wistar rats , 2011, Journal of biochemical and molecular toxicology.

[67]  T. Talou,et al.  Composition and insecticidal activity of essential oil from Pistacia lentiscus L. against Ectomyelois ceratoniae Zeller and Ephestia kuehniella Zeller (Lepidoptera: Pyralidae) , 2010 .

[68]  I. Kosalec,et al.  Evaluation of antioxidant activities and phenolic content of Berberis vulgaris L. and Berberis croatica Horvat. , 2010, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[69]  Koffi N'Guessan,et al.  Screening phytochimique de quelques plantes médicinales ivoiriennes utilisées en pays Krobou (Agboville, Côte-d'Ivoire) , 2009 .

[70]  David S. Goodsell,et al.  AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility , 2009, J. Comput. Chem..

[71]  Peter A. Williams,et al.  'Natural' claims on foods: a review of regulations and a pilot study of the views of Australian consumers , 2009 .

[72]  M. Yin,et al.  Anti-inflammatory and anti-coagulatory activities of caffeic acid and ellagic acid in cardiac tissue of diabetic mice , 2009, Nutrition & metabolism.

[73]  Bin Wang,et al.  Flavonoids intake and risk of lung cancer: a meta-analysis. , 2009, Japanese journal of clinical oncology.

[74]  E. Ehile,et al.  Étude ethnobotanique et screening phytochimique de Caesalpinia benthamiana (Baill.) Herend. et Zarucchi (Caesalpiniaceae) , 2008 .

[75]  Tatjana Kadifkova Panovska,et al.  Antioxidant and antimicrobial activities of the Pistacia lentiscus and Pistacia atlantica extracts , 2008 .

[76]  Chin-Lin Hsu,et al.  Effect of gallic acid on high fat diet-induced dyslipidaemia, hepatosteatosis and oxidative stress in rats. , 2007, The British journal of nutrition.

[77]  A. Bakhrouf,et al.  The chemical composition and biological activity of clove essential oil, Eugenia caryophyllata (Syzigium aromaticum L. Myrtaceae): a short review , 2007, Phytotherapy research : PTR.

[78]  J. Abrini,et al.  Investigation of the mutagenic and antimutagenic effects of Origanum compactum essential oil and some of its constituents. , 2007, Mutation research.

[79]  Camila Delarmelina,et al.  Activity of essential oils from Brazilian medicinal plants on Escherichia coli. , 2007, Journal of ethnopharmacology.

[80]  I. Chkhikvishvili,et al.  Effect of Blueberin on fasting glucose, C-reactive protein and plasma aminotransferases, in female volunteers with diabetes type 2: double-blind, placebo controlled clinical study. , 2006, Georgian medical news.

[81]  S. Kafkas Phylogenetic analysis of the genus Pistacia by AFLP markers , 2006, Plant Systematics and Evolution.

[82]  M. Yousfi,et al.  ANTIOXIDANT ACTIVITY OF SOME ALGERIAN MEDICINAL PLANTS EXTRACTS CONTAINING PHENOLIC COMPOUNDS , 2006 .

[83]  A. Jedinák,et al.  Inhibition activities of natural products on serine proteases , 2006, Phytotherapy research : PTR.

[84]  L. Chekir‐Ghedira,et al.  New study of the essential oil from leaves of Pistacia lentiscus L. (Anacardiaceae) from Tunisia , 2005 .

[85]  A. Sartoratto,et al.  Composition and antimicrobial activity of essential oils from aromatic plants used in Brazil , 2004 .

[86]  F. Shahidi,et al.  Extraction and analysis of phenolics in food. , 2004, Journal of chromatography. A.

[87]  Zhenjiang Li,et al.  Personal Experience with Four Kinds of Chemical Structure Drawing Software: Review on ChemDraw, ChemWindow, ISIS/Draw, and ChemSketch , 2004, J. Chem. Inf. Model..

[88]  Nihorimbere Venant,et al.  Antioxidant power of phytochemicals fromPsidium guajava leaf , 2004, Journal of Zhejiang University. Science.

[89]  H. Ogedegbe An Overview of Hemostasis , 2002 .

[90]  A. Reunanen,et al.  Flavonoid intake and risk of chronic diseases. , 2002, The American journal of clinical nutrition.

[91]  A. Akrout,et al.  Analysis of the essential oil of Artemisia campestris L. , 2001 .

[92]  M. Heinonen,et al.  Antioxidant activity of plant extracts containing phenolic compounds. , 1999, Journal of agricultural and food chemistry.

[93]  L. Gerschenson,et al.  Sorbate–nitrite reactions in meat products , 1998 .

[94]  F. Lombardo,et al.  Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings , 1997 .

[95]  A. Rapisarda,et al.  In vitro antimicrobial activity of Pistacia lentiscus L. extracts: preliminary report. , 1996, Journal of chemotherapy.

[96]  L. Butler,et al.  A critical evaluation of the vanillin reaction as an assay for tannin in sorghum grain , 1978 .

[97]  Justin A. Lemkul Pairwise-additive and polarizable atomistic force fields for molecular dynamics simulations of proteins. , 2020, Progress in molecular biology and translational science.

[98]  M. Shanmugasundaram,et al.  Advances in Meat Preservation and Safety , 2020 .

[99]  L. Hoffman,et al.  Effect of Moringa oleifera leaf powder on drying kinetics, physico‐chemical properties, ferric reducing antioxidant power, α‐tocopherol, β‐carotene, and lipid oxidation of dry pork sausages during processing and storage , 2019 .

[100]  R. Liu,et al.  Comparison of phytochemical profiles and health benefits in fiber and oil flaxseeds (Linum usitatissimum L.). , 2017, Food chemistry.

[101]  T. Zair,et al.  Phytochemical Study , Antibacterial and Antioxidant Activities of Extracts of Capparis spinosa L . , 2017 .

[102]  A. Soyer,et al.  Effect of plant extracts on lipid and protein oxidation of mackerel (Scomber scombrus) mince during frozen storage , 2017, Journal of Food Science and Technology.

[103]  Fergal J. Duffy,et al.  Computational approaches to developing short cyclic peptide modulators of protein-protein interactions. , 2015, Methods in molecular biology.

[104]  F. Afifi,et al.  In vitro inhibitory effects of Sardinian Pistacia lentiscus L. and Pistacia terebinthus L. on metabolic enzymes: Pancreatic lipase, α-amylase, and α-glucosidase , 2015 .

[105]  K. Miyatake,et al.  Total phenolic compounds and antioxidant capacity of wheat graded flours by polishing method , 2009 .

[106]  S. A. Wright Principles of Food Toxicology , 2008 .

[107]  P. Kefalas,et al.  Carob Pods (Ceratonia siliqua L.) as a Source of Polyphenolic Antioxidants , 2004 .

[108]  A. Badoc,et al.  Screening phytochimique d'une endémique ibéro-marocaine, Thymelaea lythroides , 2003 .

[109]  Hans-Joachim Hbschmann Handbook of GC/MS , 2001 .

[110]  R. B. Willis Improved method for measuring hydrolyzable tannins using potassium iodate , 1998 .

[111]  C. Berset,et al.  Use of a Free Radical Method to Evaluate Antioxidant Activity , 1995 .

[112]  J. Tian,et al.  [Antithrombotic and antiplatelet effects of rosmarinic acid, a water-soluble component isolated from radix Salviae miltiorrhizae (danshen)]. , 1993, Yao xue xue bao = Acta pharmaceutica Sinica.

[113]  M. Oyaizu Studies on products of browning reaction--antioxidative activities of products of browning reaction prepared from glucosamine , 1986 .

[114]  V. L. Singleton,et al.  Colorimetry of Total Phenolics with Phosphomolybdic-Phosphotungstic Acid Reagents , 1965, American Journal of Enology and Viticulture.

[115]  Hepatoprotective and antidiabetic effects of Pistacia lentiscus leaf and fruit extracts , 2022 .