A Comparative Study of Chamomile Essential Oils and Lipophilic Extracts Obtained by Conventional and Greener Extraction Techniques: Chemometric Approach to Chemical Composition and Biological Activity

Bearing in mind the centuries-old traditional use of chamomile, but also the increasing demand for its products in modern industry, oriented toward sustainable development, there are increasing efforts for the efficient extraction of high-value compounds of this plant, as well as obtaining its products with added value. With that goal, conventional and contemporary separation techniques were applied in this work. Both hydrodistillation processes (HD), conducted in a traditional manner and coupled with microwave irradiation (MWHD), were used for essential oil isolation. In parallel with those procedures, chamomile lipophilic extracts were obtained by Soxhlet extraction applying organic solvents and using supercritical fluid extraction as a greener approach. The obtained extracts and essential oils were characterized in terms of chemical composition (GC analysis, contents of total phenolics and flavonoids) and biological potential. GC analysis revealed that oxygenated sesquiterpenes and non-terpene compounds were the dominant compounds. α-Bisabolol oxide A (29.71–34.41%) and α-bisabolol oxide B (21.06–25.83%) were the most abundant individual components in samples obtained by distillation while in supercritical and Soxhlet extracts, major compounds were α-bisabolol oxide A and pentacosane. The biological potential of essential oils and extracts was tested by applying a set of analyzes to estimate the inhibition of biologically important enzymes (amylase, glucosidase, acetylcholinesterase, butyrylcholinesterase, tyrosinase) and antioxidant capacity (DPPH, ABTS, CUPRAC, FRAP, chelating and total antioxidant capacity). The results suggested essential oils as better antioxidants, while the extracts were proven to be better inhibitors of the tested enzymes. Principal Component Analysis was conducted using the experimental results of the composition of extracts and EOs of chamomile obtained by different separation techniques, showing clear discrimination between methods applied in correlation with the chemical profile. Molecular docking was applied for the identification of the main active principles present in the essential oil, among which α-bisabolol-oxide B (cp3) showed a higher affinity for tyrosinase.

[1]  Abid Naeem,et al.  Bioactive substances and therapeutic potential of camellia oil: An overview , 2022, Food Bioscience.

[2]  G. Karimi,et al.  Cytotoxic activity of cis-(E)- and trans-(Z)-spiroethers isolated from various Arnebia species , 2021 .

[3]  I. Marrucho,et al.  Recovery of β-carotene from pumpkin using switchable natural deep eutectic solvents , 2021, Ultrasonics sonochemistry.

[4]  U. Rashid,et al.  Treating Hyperglycemia From Eryngium caeruleum M. Bieb: In-vitro α-Glucosidase, Antioxidant, in-vivo Antidiabetic and Molecular Docking-Based Approaches , 2020, Frontiers in Chemistry.

[5]  C. Bicchi,et al.  Bio-Guided Fractionation Driven by In Vitro α-Amylase Inhibition Assays of Essential Oils Bearing Specialized Metabolites with Potential Hypoglycemic Activity , 2020, Plants.

[6]  A. Fernie,et al.  Using an UPLC/MS-based untargeted metabolomics approach for assessing the antioxidant capacity and anti-aging potential of selected herbs , 2020, RSC advances.

[7]  D. Rakić,et al.  Antioxidant and enzyme-inhibitory activity of peppermint extracts and essential oils obtained by conventional and emerging extraction techniques. , 2020, Food chemistry.

[8]  S. Handunnetti,et al.  Topical Anti-Inflammatory Activity of Essential Oils of Alpinia calcarata Rosc., Its Main Constituents, and Possible Mechanism of Action , 2020, Evidence-based complementary and alternative medicine : eCAM.

[9]  M. Farzaei,et al.  Nanoformulations of natural products for management of metabolic syndrome , 2019, International journal of nanomedicine.

[10]  Meenakshi Gupta,et al.  Docking techniques in pharmacology: How much promising? , 2018, Comput. Biol. Chem..

[11]  Y. Bustanji,et al.  Inhibitory effects of methanol extracts of selected plants on the proliferation of two human melanoma cell lines , 2018, Tropical Journal of Pharmaceutical Research.

[12]  A. Mollica,et al.  In vitro and in silico perspectives on biological and phytochemical profile of three halophyte species-A source of innovative phytopharmaceuticals from nature. , 2018, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[13]  G. Zengin,et al.  In vitro enzyme inhibitory properties, antioxidant activities, and phytochemical profile of Potentilla thuringiaca , 2017 .

[14]  A. Mollica,et al.  Cytotoxic and Enzyme Inhibitory Potential of Two Potentilla species (P. speciosa L. and P. reptans Willd.) and Their Chemical Composition , 2017, Front. Pharmacol..

[15]  A. Mollica,et al.  Euphorbia denticulata Lam.: A promising source of phyto-pharmaceuticals for the development of novel functional formulations. , 2017, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[16]  A. Mollica,et al.  Functional constituents of wild and cultivated Goji (L. barbarum L.) leaves: phytochemical characterization, biological profile, and computational studies , 2017, Journal of enzyme inhibition and medicinal chemistry.

[17]  A. Mollica,et al.  Chemical and biological insights on Cotoneaster integerrimus: A new (-)- epicatechin source for food and medicinal applications. , 2016, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[18]  C. De Monte,et al.  Novel 1,3-thiazolidin-4-one derivatives as promising anti-Candida agents endowed with anti-oxidant and chelating properties. , 2016, European journal of medicinal chemistry.

[19]  G. Zengin,et al.  Screening of in vitro antioxidant and enzyme inhibitory activities of different extracts from two uninvestigated wild plants: Centranthus longiflorus subsp. longiflorus and Cerinthe minor subsp. auriculata , 2016 .

[20]  Jennifer L. Knight,et al.  OPLS3: A Force Field Providing Broad Coverage of Drug-like Small Molecules and Proteins. , 2016, Journal of chemical theory and computation.

[21]  J. Ríos,et al.  Natural Products for the Treatment of Type 2 Diabetes Mellitus , 2015, Planta Medica.

[22]  A. Cvetanović,et al.  Antioxidant and biological activity of chamomile extracts obtained by different techniques: perspective of using superheated water for isolation of biologically active compounds , 2015 .

[23]  M. Couladis,et al.  Antihyperalgesic and Antiedematous Activities of Bisabolol‐Oxides‐Rich Matricaria Oil in a Rat Model of Inflammation , 2014, Phytotherapy research : PTR.

[24]  G. Zengin,et al.  A comprehensive study on phytochemical characterization of Haplophyllum myrtifolium Boiss. endemic to Turkey and its inhibitory potential against key enzymes involved in Alzheimer, skin diseases and type II diabetes , 2014 .

[25]  Jianping Zhao,et al.  Hydroxylated bisabolol oxides: evidence for secondary oxidative metabolism in Matricaria chamomilla. , 2013, Journal of natural products.

[26]  G. Zengin,et al.  Antioxidant potentials and anticholinesterase activities of methanolic and aqueous extracts of three endemic Centaurea L. species. , 2013, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[27]  S. Rocha,et al.  In vitro and in vivo studies of natural products: A challenge for their valuation. The case study of chamomile (Matricaria recutita L.) , 2012 .

[28]  F. Bucar,et al.  Guaianolides and Volatile Compounds in Chamomile Tea , 2012, Plant Foods for Human Nutrition.

[29]  A. Mollica,et al.  Recent application of analytical methods to phase I and phase II drugs development: a review. , 2011, Biomedical chromatography : BMC.

[30]  B. Dijkstra,et al.  Crystal structure of Agaricus bisporus mushroom tyrosinase: identity of the tetramer subunits and interaction with tropolone. , 2011, Biochemistry.

[31]  A. Obmann “Pharmakognosie – Phytopharmazie” , 2010, Scientia Pharmaceutica.

[32]  J. Barnes Medicinal natural products , 2010 .

[33]  K. Alberti,et al.  Diagnosis and Classification of Diabetes Mellitus , 2009, Diabetes Care.

[34]  M. Kimura,et al.  Spiroethers of German chamomile inhibit production of aflatoxin G and trichothecene mycotoxin by inhibiting cytochrome P450 monooxygenases involved in their biosynthesis. , 2008, FEMS microbiology letters.

[35]  Ž. Knez,et al.  Supercritical fluid extraction of chamomile flower heads: Comparison with conventional extraction, kinetics and scale-up , 2007 .

[36]  Jeremy R. Greenwood,et al.  Epik: a software program for pKa prediction and protonation state generation for drug-like molecules , 2007, J. Comput. Aided Mol. Des..

[37]  Matthew P. Repasky,et al.  Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. , 2006, Journal of medicinal chemistry.

[38]  M. Loizzo,et al.  Comparative radical scavenging and antidiabetic activities of methanolic extract and fractions from Achillea ligustica ALL. , 2005, Biological & pharmaceutical bulletin.

[39]  T. Ogihara,et al.  Effect of two alpha-glucosidase inhibitors, voglibose and acarbose, on postprandial hyperglycemia correlates with subjective abdominal symptoms. , 2005, Metabolism: clinical and experimental.

[40]  A. Rosato,et al.  Chemical composition and antimicrobial activity of Myrtus communis , 2005 .

[41]  Farid Chemat,et al.  Solvent-free microwave extraction of essential oil from aromatic herbs: comparison with conventional hydro-distillation. , 2004, Journal of chromatography. A.

[42]  P. Schmidt,et al.  Supercritical carbon dioxide extraction of chamomile flowers: extraction efficiency, stability, and in-line inclusion of chamomile-carbon dioxide extract in beta-cyclodextrin. , 2004, Phytochemical analysis : PCA.

[43]  E. Stashenko,et al.  Comparison of different extraction methods for the analysis of volatile secondary metabolites of Lippia alba (Mill.) N.E. Brown, grown in Colombia, and evaluation of its in vitro antioxidant activity. , 2004, Journal of chromatography. A.

[44]  E. Stashenko,et al.  Analysis of volatile secondary metabolites from Colombian Xylopia aromatica (Lamarck) by different extraction and headspace methods and gas chromatography. , 2004, Journal of chromatography. A.

[45]  Erik Schmolz,et al.  Cuticular lipids as trail pheromone in a social wasp , 2003, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[46]  P Willett,et al.  Development and validation of a genetic algorithm for flexible docking. , 1997, Journal of molecular biology.

[47]  M. Perrault,et al.  [The antidiabetic drugs]. , 1965, La semaine des hopitaux : organe fonde par l'Association d'enseignement medical des hopitaux de Paris.

[48]  H. Vandendool,et al.  A GENERALIZATION OF THE RETENTION INDEX SYSTEM INCLUDING LINEAR TEMPERATURE PROGRAMMED GAS-LIQUID PARTITION CHROMATOGRAPHY. , 1963, Journal of chromatography.

[49]  F. Šorm,et al.  On terpenes. CI. Isolation and constitution of matricarin, another guaianolide from camomile ( Matricaria chamomilla L.) , 1959 .

[50]  F. Šorm,et al.  Über terpene LXXX. Die struktur von matricin, ein guajanolid aus der kamille ( Matricaria chamomilla L.) , 1957 .