{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:55:01Z","timestamp":1791251701898,"version":"4.1.0"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,27]],"date-time":"2021-10-27T00:00:00Z","timestamp":1635292800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:italic>Sphaeranthus indicus<\/jats:italic> L. is a medicinal herb having widespread traditional uses for treating common ailments. The present research work aims to explore the in-depth phytochemical composition and <jats:italic>in vitro<\/jats:italic> reactivity of six different polarity solvents (methanol, <jats:italic>n<\/jats:italic>-hexane, benzene, chloroform, ethyl acetate, and <jats:italic>n<\/jats:italic>-butanol) extracts\/fractions of <jats:italic>S. indicus<\/jats:italic> flowers. The phytochemical composition was accomplished by determining total bioactive contents, HPLC-PDA polyphenolic quantification, and UHPLC-MS secondary metabolomics. The reactivity of the phenolic compounds was tested through the following biochemical assays: antioxidant (DPPH, ABTS, FRAP, CUPRAC, phosphomolybdenum, and metal chelation) and enzyme inhibition (AChE, BChE, \u03b1-glucosidase, \u03b1-amylase, urease, and tyrosinase) assays were performed. The methanol extract showed the highest values for phenolic (94.07\u00a0mg GAE\/g extract) and flavonoid (78.7\u00a0mg QE\/g extract) contents and was also the most active for \u03b1-glucosidase inhibition as well as radical scavenging and reducing power potential. HPLC-PDA analysis quantified rutin, naringenin, chlorogenic acid, 3-hydroxybenzoic acid, gallic acid, and epicatechin in a significant amount. UHPLC-MS analysis of methanol and ethyl acetate extracts revealed the presence of well-known phytocompounds; most of these were phenolic, flavonoid, and glycoside derivatives. The ethyl acetate fraction exhibited the highest inhibition against tyrosinase and urease, while the <jats:italic>n<\/jats:italic>-hexane fraction was most active for \u03b1-amylase. Moreover, principal component analysis highlighted the positive correlation between bioactive compounds and the tested extracts. Overall, <jats:italic>S. indicus<\/jats:italic> flower extracts were found to contain important phytochemicals, hence could be further explored to discover novel bioactive compounds that could be a valid starting point for future pharmaceutical and nutraceuticals applications.<\/jats:p>","DOI":"10.3389\/fphar.2021.708618","type":"journal-article","created":{"date-parts":[[2021,10,27]],"date-time":"2021-10-27T08:12:17Z","timestamp":1635322337000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Phytopharmacological Evaluation of Different Solvent Extract\/Fractions From Sphaeranthus indicus L. Flowers: From Traditional Therapies to Bioactive Compounds"],"prefix":"10.3389","volume":"12","author":[{"given":"Hafiz Ibtesam","family":"Ahmad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Faisal","family":"Nadeem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haji Muhammad","family":"Shoaib Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Sarfraz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hammad","family":"Saleem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umair","family":"Khurshid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Locatelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Ashraf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naveed","family":"Akhtar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syafiq Asnawi","family":"Zainal Abidin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adel","family":"Alghamdi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,27]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"22","DOI":"10.26538\/tjnpr\/v3i1.5","article-title":"Evaluation of the analgesic potential of Basella alba (L.) leaves (Basellaceae)","volume":"3","author":"Abioye","year":"2019","journal-title":"Trop. J. Nat. Product. Res."},{"key":"B2","first-page":"242","article-title":"Phytochemical Screening, Antioxidant Activity of Pure Syringin in Comparison to Various Solvents Extracts of Musa Paradisiaca (Banana) (fruit and Flower) and Total Phenolic Contents","volume":"7","author":"Ahmad","year":"2015","journal-title":"Int. J. Pharm. Pharm. Sci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/14786419.2019.1648463","article-title":"Phenolic, Flavonoid Content and Radical Scavenging Activity of Smilax China with its Inhibitory Potential against Clinically Important Enzymes","volume":"35","author":"Ahmad","year":"2019","journal-title":"Nat. Prod. Res."},{"key":"B4","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1002\/jsfa.3959","article-title":"Antioxidant Properties, Radical Scavenging Activity and Biomolecule protection Capacity of Flavonoid Naringenin and its Glycoside Naringin: a Comparative Study","volume":"90","author":"Cavia\u2010Saiz","year":"2010","journal-title":"J. Sci. Food Agric."},{"key":"B5","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1016\/j.fct.2017.05.009","article-title":"Inhibition on Cholinesterase and Tyrosinase by Alkaloids and Phenolics from Aristotelia Chilensis Leaves","volume":"109","author":"Cespedes","year":"2017","journal-title":"Food Chem. Toxicol."},{"key":"B6","first-page":"4","article-title":"The Wealth of India","volume":"10","author":"Chadha","year":"1976","journal-title":"Publications Inf. Directorate"},{"key":"B7","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.cbi.2005.10.013","article-title":"Polyethylene Glycosylation Prolongs the Circulatory Stability of Recombinant Human Butyrylcholinesterase","author":"Chilukuri","year":"2005","journal-title":"Chem. Biol. Interact"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/14786419.2019.1684285","article-title":"Quinic Acid Esters from Erycibe Obtusifolia with Antioxidant and Tyrosinase Inhibitory Activities","volume":"35","author":"Choi","year":"2019","journal-title":"Natl. Product. Reserch"},{"key":"B9","first-page":"1097","article-title":"A New Source for Developing Multi\u2010functional Products: Biological and Chemical Perspectives on Subcritical Water Extracts of","volume":"93","author":"Cvetanovi\u0107","year":"2018","journal-title":"Sambucus Ebulus L."},{"key":"B10","doi-asserted-by":"publisher","first-page":"7313","DOI":"10.3390\/molecules15107313","article-title":"Plant Phenolics: Extraction, Analysis and Their Antioxidant and Anticancer Properties","volume":"15","author":"Dai","year":"2010","journal-title":"Molecules"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0163130","article-title":"Extracts of Morus Nigra L. Leaves Standardized in Chlorogenic Acid, Rutin and Isoquercitrin: Tyrosinase Inhibition and Cytotoxicity","volume":"11","author":"De Freitas","year":"2016","journal-title":"Plos One"},{"key":"B12","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1093\/qjmed\/hcn026","article-title":"Predicting Outcome Using Butyrylcholinesterase Activity in Organophosphorus Pesticide Self-Poisoning","volume":"101","author":"Eddleston","year":"2008","journal-title":"QJM"},{"key":"B13","doi-asserted-by":"publisher","first-page":"247","DOI":"10.4103\/0974-7788.76790","article-title":"Sphaeranthus indicus Linn.: A Phytopharmacological Review","volume":"1","author":"Galani","year":"2010","journal-title":"Int. J. Ayurveda Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.diabres.2019.03.024","article-title":"Treatment of Type 2 Diabetes Mellitus Worldwide: Baseline Patient Characteristics in the Global DISCOVER Study","volume":"151","author":"Gomes","year":"2019","journal-title":"Diabetes Res. Clin. Pract."},{"key":"B15","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1016\/j.phytol.2017.03.005","article-title":"In Vitro enzyme Inhibitory Properties, Antioxidant Activities, and Phytochemical Profile of Potentilla Thuringiaca","volume":"20","author":"Grochowski","year":"2017","journal-title":"Phytochemistry Lett."},{"key":"B16","volume-title":"Phytochemical Methods a Guide to Modern Techniques of Plant Analysis","author":"Harborne","year":"1998"},{"key":"B17","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.jep.2006.04.029","article-title":"Antioxidant Activity of Caffeoyl Quinic Acid Derivatives from the Roots of Dipsacus Asper Wall","volume":"108","author":"Hung","year":"2006","journal-title":"J. Ethnopharmacology). Antioxidant activity caffeoyl quinic acid derivatives roots Dipsacus asper Wall"},{"key":"B18","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1080\/22311866.2014.983977","article-title":"In vitroAntioxidant and Antimicrobial Activities ofSphaeranthus indicusL","volume":"5","author":"Kavitha","year":"2015","journal-title":"J. Biologically Active Prod. Nat."},{"key":"B19","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.indcrop.2019.01.044","article-title":"Phytochemical Profiling, In Vitro Biological Properties and In Silico Studies on Caragana Ambigua Stocks (Fabaceae): A Comprehensive Approach","volume":"131","author":"Khan","year":"2019","journal-title":"Ind. Crops Prod."},{"key":"B20","doi-asserted-by":"publisher","first-page":"111861","DOI":"10.1016\/j.indcrop.2019.111861","article-title":"Phytochemical Composition and In Vitro Pharmacological Investigations of Neurada Procumbens L. (Neuradaceae): A Multidirectional Approach for Industrial Products","volume":"142","author":"Khurshid","year":"2019","journal-title":"Ind. Crops Prod."},{"key":"B21","doi-asserted-by":"crossref","DOI":"10.5962\/bhl.title.137025","volume-title":"Indian Medicinal Plants","author":"Kirtikar","year":"1918"},{"key":"B22","volume-title":"Preliminary Phytochemical Analysis. Practical Pharmacognosy","author":"Kokate","year":"1986"},{"key":"B23","doi-asserted-by":"publisher","first-page":"3929","DOI":"10.2174\/092986711803414395","article-title":"Coumarins as Antioxidants","volume":"18","author":"Kostova","year":"2011","journal-title":"Cmc"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1418","DOI":"10.1080\/24701556.2017.1322613","article-title":"Synthesis, Characterization and Antiurease Activities of a Novel Mannich Base 1-[(4-Methoxyphenyl)(2-Methylidenecyclohexyl)methyl]pyrrolidine (MMP) and its Complexes with Cu (II), Ni (II), Co (II), and Fe (II) Ions","volume":"47","author":"Liaqat","year":"2017","journal-title":"Inorg. Nano-Metal Chem."},{"key":"B25","volume-title":"Introduction to Volume Rendering","author":"Lichtenbelt","year":"1998"},{"key":"B26","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1016\/j.foodchem.2010.11.041","article-title":"Investigation of \u03b1-glucosidase Inhibitory Activity of Wheat Bran and Germ","volume":"126","author":"Liu","year":"2011","journal-title":"Food Chem."},{"key":"B27","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/1472-6882-14-12","article-title":"Glucosidase Inhibitory Activity and Antioxidant Activity of Flavonoid Compound and Triterpenoid Compound from Agrimonia Pilosa Ledeb","volume":"14","author":"Liu","year":"2014","journal-title":"BMC Complement. Altern. Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1080\/14756366.2016.1235041","article-title":"Multicomponent Pattern and Biological Activities of Seven Asphodeline Taxa: Potential Sources of Natural-Functional Ingredients for Bioactive Formulations","volume":"32","author":"Locatelli","year":"2017","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"B29","doi-asserted-by":"publisher","first-page":"223","DOI":"10.3390\/antibiotics10020223","article-title":"Pharmacological Potential and Chemical Characterization of Bridelia Ferruginea Benth.-A Native Tropical African Medicinal Plant","volume":"10","author":"Mahomoodally","year":"2021","journal-title":"Antibiotics (Basel)"},{"key":"B30","doi-asserted-by":"publisher","first-page":"171","DOI":"10.3923\/ijp.2011.171.179","article-title":"Sphaeranthus indicus: A Review of its Chemical, Pharmacological and Ethnomedicinal Properties","volume":"7","author":"Makhija","year":"2011","journal-title":"Int. J. Pharmacol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1016\/j.indcrop.2018.12.041","article-title":"Phytochemical and Biological Activities of Silene Viridiflora Extractives. Development and Validation of a HPTLC Method for Quantification of 20-hydroxyecdysone","volume":"129","author":"Mamadalieva","year":"2019","journal-title":"Ind. Crops Prod."},{"key":"B32","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1007\/s10669-007-9024-9","article-title":"Review of the Methods Used for Isolating Pharmaceutical lead Compounds from Traditional Medicinal Plants","volume":"27","author":"Mcrae","year":"2007","journal-title":"Environmentalist"},{"key":"B33","doi-asserted-by":"publisher","first-page":"2288","DOI":"10.3390\/12102288","article-title":"A Novel Flavonoid C-Glycoside from Sphaeranthus indicus L. (Family Compositae)","volume":"12","author":"Mishra","year":"2007","journal-title":"Molecules"},{"key":"B34","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1080\/14756366.2016.1222585","article-title":"Enzymatic Assays and Molecular Modeling Studies of Schisandra Chinensis Lignans and Phenolics from Fruit and Leaf Extracts","volume":"31","author":"Mocan","year":"2016","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"B35","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.lfs.2015.11.030","article-title":"Effect of Apigenin-7-Glucoside, Genkwanin and Naringenin on Tyrosinase Activity and Melanin Synthesis in B16F10 Melanoma Cells","volume":"144","author":"Nasr Bouzaiene","year":"2016","journal-title":"Life Sci."},{"key":"B36","first-page":"1003","article-title":"Bridelia Ferruginea Leaf Fractions Ameliorates Helminth Infections","volume":"1","author":"Oladejo","year":"2019","journal-title":"Clin. Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.foodres.2007.12.004","article-title":"Updated Methodology to Determine Antioxidant Capacity in Plant Foods, Oils and Beverages: Extraction, Measurement and Expression of Results","volume":"41","author":"P\u00e9rez-Jim\u00e9nez","year":"2008","journal-title":"Food Res. Int."},{"key":"B38","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.jep.2017.12.003","article-title":"Ethnomedicinal Plant Diversity in Thailand","volume":"214","author":"Phumthum","year":"2018","journal-title":"J. Ethnopharmacology"},{"key":"B39","doi-asserted-by":"publisher","first-page":"9809","DOI":"10.3390\/ijms15069809","article-title":"Inhibitors of Acetylcholinesterase and Butyrylcholinesterase Meet Immunity","volume":"15","author":"Pohanka","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"B40","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1016\/j.foodchem.2017.07.098","article-title":"Phenolic Profiles and Antioxidant Activity of Defatted Camelina and sophia Seeds","volume":"240","author":"Rahman","year":"2018","journal-title":"Food Chem."},{"key":"B41","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.micpath.2016.12.019","article-title":"Evaluation of Anti-cholinesterase, Antibacterial and Cytotoxic Activities of green Synthesized Silver Nanoparticles Using from Millettia Pinnata Flower Extract","volume":"103","author":"Rajakumar","year":"2017","journal-title":"Microb. Pathog."},{"key":"B42","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.jep.2006.02.022","article-title":"Healing Potential of Cream Containing Extract of Sphaeranthus indicus on Dermal Wounds in Guinea Pigs","volume":"107","author":"Sadaf","year":"2006","journal-title":"J. Ethnopharmacol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"105","DOI":"10.2307\/1484100","article-title":"Upper Cretaceous and Lower Tertiary Foraminifera from Northern Sinai, Egypt","volume":"2","author":"Said","year":"1956","journal-title":"Micropaleontology"},{"key":"B44","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/s0074-7696(08)60169-2","article-title":"Follicular Atresia in the Ovaries of Nonmammalian Vertebrates","volume":"54","author":"Saidapur","year":"1978","journal-title":"Int. Rev. Cytol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1016\/j.fct.2018.11.016","article-title":"Biological, Chemical and Toxicological Perspectives on Aerial and Roots of Filago Germanica (L.) Huds: Functional Approaches for Novel Phyto-Pharmaceuticals","volume":"123","author":"Saleem","year":"","journal-title":"Food Chem. Toxicol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.jpba.2019.01.007","article-title":"Investigations into the Therapeutic Effects of Aerial and Stem Parts of Buxus Papillosa C.K. Schneid.: In Vitro Chemical, Biological and Toxicological Perspectives","volume":"166","author":"Saleem","year":"","journal-title":"J. Pharm. Biomed. Anal."},{"key":"B47","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1055\/s-2000-11113","article-title":"Inhibition of Tyrosinase by Flavonoids, Stilbenes and Related 4-substituted Resorcinols: Structure-Activity Investigations","volume":"66","author":"Shimizu","year":"2000","journal-title":"Planta Med."},{"key":"B48","first-page":"993","article-title":"Vitro Antioxidant Studies of Sphaeranthus indicus. Linn)","volume":"44","author":"Shirwaikar","year":"2006","journal-title":"Indian J. Exp. Bio."},{"key":"B49","doi-asserted-by":"publisher","first-page":"92","DOI":"10.3164\/jcbn.40.92","article-title":"Ferulic Acid: Therapeutic Potential through its Antioxidant Property","volume":"40","author":"Srinivasan","year":"2007","journal-title":"J. Clin. Biochem. Nutr."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40816-020-00172-1","article-title":"Comparative Assessment of Antimicrobial and Antioxidant Activity between Whole Plant and Parts of Sphaeranthus indicus Linn.(Asteraceae)","volume":"6","author":"Tandon","year":"2020","journal-title":"Clin. Phytoscience"},{"key":"B51","first-page":"26","article-title":"Hepatoprotective and Antioxidant Effect of Sphaeranthus indicus against Acetaminophen-Induced Hepatotoxicity in Rats","volume":"1","author":"Tiwari","year":"2009","journal-title":"Internet J. Trop. Med."},{"key":"B52","first-page":"321","article-title":"The Antioxidant Studies of Two Medicinal Plants","volume":"12","author":"Vijayalakshmi","year":"2019","journal-title":"Sphaeranthus indicus and Psophocarpus tetragonolobus"},{"key":"B53","first-page":"61","article-title":"A Pharmacognostic Study on Sphaeranthus indicus","volume":"8","author":"Vikani","year":"2008","journal-title":"J. Nat. Remedies"},{"key":"B54","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1021\/jf020782a","article-title":"Antioxidant Activity of Apple Peels","volume":"51","author":"Wolfe","year":"2003","journal-title":"J. Agric. Food Chem."},{"key":"B55","doi-asserted-by":"publisher","first-page":"10572","DOI":"10.1021\/jf303393n","article-title":"Molecular Docking, Kinetics Study, and Structure-Activity Relationship Analysis of Quercetin and its Analogous as Helicobacter pylori Urease Inhibitors","volume":"60","author":"Xiao","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1016\/j.lwt.2007.06.010","article-title":"In Vitro antioxidant Properties of Rutin","volume":"41","author":"Yang","year":"2008","journal-title":"LWT - Food Sci. Technology"},{"key":"B57","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1016\/j.indcrop.2018.11.027","article-title":"Phenolic Profiling and In Vitro Biological Properties of Two Lamiaceae Species (Salvia Modesta and Thymus Argaeus): A Comprehensive Evaluation","volume":"128","author":"Zengin","year":"2019","journal-title":"Ind. Crops Prod."},{"key":"B58","doi-asserted-by":"publisher","first-page":"195","DOI":"10.15835\/nbha44110259","article-title":"Total Phenolics, Flavonoids, Condensed Tannins Content of Eight Centaurea Species and Their Broad Inhibitory Activities against Cholinesterase, Tyrosinase, \u03b1-Amylase and \u03b1-Glucosidase","volume":"44","author":"Zengin","year":"2016","journal-title":"Not Bot. Horti Agrobo"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.708618\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,27]],"date-time":"2021-10-27T08:12:29Z","timestamp":1635322349000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.708618\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,27]]},"references-count":58,"alternative-id":["10.3389\/fphar.2021.708618"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2021.708618","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,27]]},"article-number":"708618"}}