Phytochemical Analysis, Antioxidant, and Antihyperglycemic Activities of Crataegus monogyna Jacq Aqueous Extract

Objective This study aims to evaluate the phytochemical composition, antioxidant, and antihyperglycemic (in vivo, in vitro, and in silico) activities and acute toxicity of Crataegus monogyna Jacq (C monogyna) aqueous extracts. Methods The study analyzed the aqueous extract of C monogyna through various methods such as phytochemical screening, and the high-performance liquid chromatography-ultraviolet (HPLC-UV)-visible analysis. The extract was also tested for antioxidant potential, acute toxicity, antihyperglycemic effect, and inhibitory effect on the pancreatic α-amylase enzyme. Additionally, the study used the molecular docking approach to identify the most potent ligands in the extract. Results The phytochemical screening of the aqueous extract of C monogyna showed the presence of flavonoids, tannins, coumarins, sterol, and triterpene. The extract was rich in total polyphenols (1.65 ± 0.04 mg gallic acid equivalent per gram of extract [GAE/g] DM), total flavonoids (0.33 ± 0.03 EQ/g DM), and condensed tannins (0.28 ± 0.01 EC/mg DM). HPLC-UV-visible analysis identified 9 phenolic compounds, with high levels of gallic acid and caffeic acid. The C monogyna extract has a high antioxidant activity with an IC50 of 9.23 ± 0.01 mg/mL by DPPH and 8.32 ± 0.02 mg/mL by FRAP. The aqueous extract of C monogyna was not toxic to albino mice. The glucose tolerance test showed a significant antihyperglycemic effect, with an IC50 of 0.070 ± 0.008 mg/mL for the inhibition of pancreatic α-amylase activity by the aqueous extract of C monogyna. The in vivo inhibitory effect of the extract on the pancreatic α-amylase enzyme was confirmed. Two flavonoids, catechin, and rutin, were identified as potent inhibitors of the activity of α-amylase in the in silico part of the study, compared to the native ligand, Acarbose. Conclusion The study found that C monogyna has significant antioxidant and antihyperglycemic properties. The presence of catechin and rutin may contribute to these effects. The results suggest that C monogyna could be used as a dietary supplement to prevent and treat diabetes.

[1]  T. Zair,et al.  Chemical Composition, Antioxidants, Antibacterial, and Insecticidal Activities of Origanum elongatum (Bonnet) Emberger & Maire Aerial Part Essential Oil from Morocco , 2023, Antibiotics.

[2]  N. Bencheikh,et al.  Nephroprotective and Antioxidant Effects of Flavonoid-Rich Extract of Thymelaea microphylla Coss.et Dur Aerial Part , 2022, Applied Sciences.

[3]  Y. D. Vankar,et al.  Synthesis of (5,6 & 6,6)-Oxa-Oxa Annulated Sugars as Glycosidase Inhibitors from 2-Formyl Galactal using Iodocyclization as a Key Step , 2022, Arkivoc.

[4]  J. Lorenzo,et al.  Phytochemical Analysis, α-Glucosidase and α-Amylase Inhibitory Activities and Acute Toxicity Studies of Extracts from Pomegranate (Punica granatum) Bark, a Valuable Agro-Industrial By-Product , 2022, Foods.

[5]  Christophe Hano,et al.  Antibacterial and Antioxidant Activity of Dysphania ambrosioides (L.) Mosyakin and Clemants Essential Oils: Experimental and Computational Approaches , 2022, Antibiotics.

[6]  S. Mandal,et al.  Ethnobotanical, pharmacological, phytochemical, and clinical investigations on Moroccan medicinal plants traditionally used for the management of renal dysfunctions. , 2022, Journal of ethnopharmacology.

[7]  F. Guarino,et al.  Botanical, Phytochemical, Anti-Microbial and Pharmaceutical Characteristics of Hawthorn (Crataegus monogyna Jacq.), Rosaceae , 2021, Molecules.

[8]  A. Piras,et al.  Chemical composition, antioxidant and antibacterial activity of Crataegus monogyna leaves’ extracts , 2021, Natural product research.

[9]  A. Ziyyat,et al.  Opuntia dillenii (Ker Gawl.) Haw., Seeds Oil Antidiabetic Potential Using In Vivo, In Vitro, In Situ, and Ex Vivo Approaches to Reveal Its Underlying Mechanism of Action , 2021, Molecules.

[10]  A. Ziyyat,et al.  Phenolic Content and Antioxidant, Antihyperlipidemic, and Antidiabetogenic Effects of Opuntia dillenii Seed Oil , 2020, TheScientificWorldJournal.

[11]  Susana Ferreira,et al.  Phytochemical Characterization, Bioactivities Evaluation and Synergistic Effect of Arbutus unedo and Crataegus monogyna Extracts with Amphotericin B , 2020, Current Microbiology.

[12]  Duangjai Tungmunnithum,et al.  Lights triggered differential accumulation of antioxidant and antidiabetic secondary metabolites in callus culture of Eclipta alba L. , 2020, PloS one.

[13]  S. Cosmulescu,et al.  Content in organic acids of Mespilus spp. and Crataegus spp. genotypes , 2020 .

[14]  Gregory P. Forlenza,et al.  MiniMed 670G hybrid closed loop artificial pancreas system for the treatment of type 1 diabetes mellitus: overview of its safety and efficacy , 2019, Expert review of medical devices.

[15]  A. Ziyyat,et al.  Antidiabetic effect of Opuntia dillenii seed oil on streptozotocin-induced diabetic rats , 2019, Asian Pacific Journal of Tropical Biomedicine.

[16]  E. Fernandes,et al.  Evaluation of a flavonoids library for inhibition of pancreatic α-amylase towards a structure–activity relationship , 2019, Journal of enzyme inhibition and medicinal chemistry.

[17]  Y. D. Vankar,et al.  A Stereoselective Synthesis of an Imino Glycal: Application in the Synthesis of (-)-1-epi-Adenophorine and a Homoimindosugar , 2018, European Journal of Organic Chemistry.

[18]  K. Khokhlova,et al.  Chromatographic characterization on flavonoids and triterpenes of leaves and flowers of 15 crataegus L. species , 2018, Natural product research.

[19]  Z. Xiu,et al.  Dietary Flavonoids and Acarbose Synergistically Inhibit α-Glucosidase and Lower Postprandial Blood Glucose. , 2017, Journal of agricultural and food chemistry.

[20]  Y. D. Vankar,et al.  Conversion of glycals into vicinal-1,2-diazides and 1,2-(or 2,1)-azidoacetates using hypervalent iodine reagents and Me3SiN3. Application in the synthesis of N-glycopeptides, pseudo-trisaccharides and an iminosugar , 2017 .

[21]  S. Weisnagel,et al.  Strawberry and cranberry polyphenols improve insulin sensitivity in insulin-resistant, non-diabetic adults: a parallel, double-blind, controlled and randomised clinical trial , 2017, British Journal of Nutrition.

[22]  F. Thong,et al.  Caffeic acid methyl and ethyl esters exert potential antidiabetic effects on glucose and lipid metabolism in cultured murine insulin-sensitive cells through mechanisms implicating activation of AMPK , 2017, Pharmaceutical biology.

[23]  Joana L. C. Sousa,et al.  α-Glucosidase inhibition by flavonoids: an in vitro and in silico structure–activity relationship study , 2017, Journal of enzyme inhibition and medicinal chemistry.

[24]  Legseir Belgacem,et al.  Ethnobotanical study close to the population of the extreme north east of Algeria: The municipalities of El Kala National Park (EKNP) , 2016 .

[25]  Zhuang Fengqing,et al.  Patients’ Responsibilities in Medical Ethics , 2016 .

[26]  M. P. Gómez-Serranillos,et al.  Geographic origin influences the phenolic composition and antioxidant potential of wild Crataegus monogyna from Spain , 2016, Pharmaceutical biology.

[27]  Li Ye,et al.  The Traditional Medicine and Modern Medicine from Natural Products , 2016, Molecules.

[28]  F. Luan,et al.  Development of cleaved amplified polymorphic sequence markers and a CAPS-based genetic linkage map in watermelon (Citrullus lanatus [Thunb.] Matsum. and Nakai) constructed using whole-genome re-sequencing data , 2016, Breeding science.

[29]  J. Namieśnik,et al.  LC–MS/MS analysis, antioxidant and anticholinergic properties of galanga (Alpinia officinarum Hance) rhizomes , 2015 .

[30]  S. Nabavi,et al.  Role of quercetin as an alternative for obesity treatment: you are what you eat! , 2015, Food chemistry.

[31]  S. Nabavi,et al.  Modulation of human miR-17-3p expression by methyl 3-O-methyl gallate as explanation of its in vivo protective activities. , 2014, Molecular nutrition & food research.

[32]  Ö. Yılmaz,et al.  The investigation of some bioactive compounds and antioxidant properties of hawthorn (Crataegus monogyna subsp. monogyna Jacq). , 2014 .

[33]  R. Nieto-Ángel,et al.  Flavonoids and antioxidant activity of flowers of Mexican Crataegus spp. , 2013, Natural product research.

[34]  S. Nabavi,et al.  In vivo protective effects of quercetin against sodium fluoride-induced oxidative stress in the hepatic tissue , 2012 .

[35]  G. Fleet,et al.  Iminosugars as therapeutic agents: recent advances and promising trends. , 2011, Future medicinal chemistry.

[36]  Ana Maria Carvalho,et al.  Comparing the composition and bioactivity of Crataegus Monogyna flowers and fruits used in folk medicine. , 2011, Phytochemical analysis : PCA.

[37]  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.

[38]  E. Ernst.  Pharmacognosy: Phytochemistry, Medicinal Plants , 2010 .

[39]  R. Tundis,et al.  Natural Products as α-Amylase and α-Glucosidase Inhibitors and their Hypoglycaemic Potential in the Treatment of Diabetes: An Update , 2010 .

[40]  P. Haddad,et al.  Structural constraints and the importance of lipophilicity for the mitochondrial uncoupling activity of naturally occurring caffeic acid esters with potential for the treatment of insulin resistance. , 2010, Biochemical pharmacology.

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

[42]  N. Malleshi,et al.  Composition and enzyme inhibitory properties of finger millet (Eleusine coracana L.) seed coat phenolics: Mode of inhibition of α-glucosidase and pancreatic amylase , 2009 .

[43]  Arthur J. Olson,et al.  AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading , 2009, J. Comput. Chem..

[44]  T. Hase,et al.  A Catechin‐rich Beverage Improves Obesity and Blood Glucose Control in Patients With Type 2 Diabetes , 2009, Obesity.

[45]  V. Venkataraman,et al.  Probing the role of aromatic residues at the secondary saccharide-binding sites of human salivary alpha-amylase in substrate hydrolysis and bacterial binding. , 2008, Journal of molecular biology.

[46]  C. Lee,et al.  Relative antioxidant and cytoprotective activities of common herbs , 2008 .

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

[48]  A. María.,et al.  Etnobotánica del Parque Natural de Montesinho plantas, tradición y saber popular en un territorio del Nordeste de Portugal , 2005 .

[49]  P. Mishra,et al.  Human salivary alpha-amylase Trp58 situated at subsite -2 is critical for enzyme activity. , 2004, European journal of biochemistry.

[50]  L. Ascensão,et al.  An ethnobotanical study of medicinal and aromatic plants in the Natural Park of "Serra de São Mamede" (Portugal). , 2003, Journal of ethnopharmacology.

[51]  M. Strnad,et al.  Changes in sugars, organic acids and amino acids in medlar (Mespilus germanica L.) during fruit development and maturation , 2003 .

[52]  H. J. Dorman,et al.  Antioxidant properties and composition of aqueous extracts from Mentha species, hybrids, varieties, and cultivars. , 2003, Journal of agricultural and food chemistry.

[53]  M. Eddouks,et al.  Ethnopharmacological survey of medicinal plants used for the treatment of diabetes mellitus, hypertension and cardiac diseases in the south-east region of Morocco (Tafilalet). , 2002, Journal of ethnopharmacology.

[54]  Z. Zuo,et al.  Hawthorn , 2002, Journal of clinical pharmacology.

[55]  B. V. Sweet,et al.  Hawthorn: pharmacology and therapeutic uses. , 2002, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.

[56]  L. D. Bari,et al.  Antioxidant principles from Bauhinia tarapotensis. , 2001, Journal of natural products.

[57]  A. Aganga,et al.  Tannin content, nutritive value and dry matter digestibility of Lonchocarpus capassa, Zizyphus mucronata, Sclerocarya birrea, Kirkia acuminata and Rhus lancea seeds , 2001 .

[58]  L. Holmberg,et al.  Fruit, vegetables, dietary fiber, and risk of colorectal cancer. , 2001, Journal of the National Cancer Institute.

[59]  H. Lebovitz,et al.  Type 2 diabetes: an overview. , 1999, Clinical chemistry.

[60]  B. Marjanović,et al.  Flavonoids as Antioxidants , 1994 .

[61]  J M Blaney,et al.  Molecular modeling software and methods for medicinal chemistry. , 1990, Journal of medicinal chemistry.

[62]  I. Koshiyama,et al.  Antioxidative Properties of Procyanidins B-1 and B-3 from Azuki Beans in Aqueous Systems , 1988 .

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

[64]  G. Dubois,et al.  Nonnutritive sweeteners: taste-structure relationships for some new simple dihydrochalcones. , 1977, Science.

[65]  M. Serafini,et al.  Endemic Plants of Italy and Their Peculiar Molecular Pattern , 2016 .

[66]  Belhattab Rachid,et al.  Antioxidant activity of aqueous extracts from Crataegus oxyacantha leaves , 2015 .

[67]  Sunil Kumar,et al.  α-glucosidase inhibitors from plants: A natural approach to treat diabetes , 2011, Pharmacognosy reviews.

[68]  B. D. Montmollin,et al.  Zones importantes pour les plantes en Méditerranée méridionale et orientale : sites prioritaires pour la conservation , 2011 .

[69]  B. Odhav,et al.  Screening of African traditional vegetables for their alpha-amylase inhibitory effect. , 2010 .

[70]  W. Bouzid.  Etude de l’Activité Biologique des Extraits du Fruit de Crataegus monogyna Jacq , 2009 .

[71]  T. El-Elimat,et al.  Antioxidant activity and total phenolic content of selected Jordanian plant species , 2007 .

[72]  E. Ernst,et al.  Adverse-Event Profile of Crataegus Spp. , 2006, Drug safety.

[73]  H. Bouriche,et al.  Anti-inflammatory effect of rutin on rat paw oedema, and on neutrophils chemotaxis and degranulation. , 2003, Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie.

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

[75]  A. Marfak.  Radiolyse gamma des flavonoïdes : étude de leur réactivité avec les radicaux issus des alcools : formation de depsides , 2003 .

[76]  A. Gosselin,et al.  INFLUENCE DE LA CULTURE HYDROPONIQUE DE QUELQUES PLANTES MÉDICINALES SUR LA CROISSANCE ET LA CONCENTRATION EN COMPOSÉS SECONDAIRES DES ORGANES VÉGÉTAUX , 2001 .

[77]  T. Bahorun.  SUBSTANCES NATURELLES ACTIVES: LA FLORE MAURICIENNE, UNE SOURCE D'APPROVISIONNEMENT POTENTIELLE , 1997 .

[78]  Z. Jia,et al.  Flavonoids as superoxide scavengers and antioxidants. , 1990, Free radical biology & medicine.

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

[80]  E. Fischer,et al.  ALPHA-AMYLASES AS CALCIUM-METALLOENZYMES. II. CALCIUM AND THE CATALYTIC ACTIVITY. , 1964, Biochemistry.