{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:06:01Z","timestamp":1791828361014,"version":"4.3.4"},"reference-count":47,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T00:00:00Z","timestamp":1645401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"King Saud University, Researchers Supporting Project","award":["RSP-2021\/118"],"award-info":[{"award-number":["RSP-2021\/118"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Euphorbia nivulia-Ham (EN) is a neglected medicinal plant traditionally used for a number of pathologies, but it has not been explored scientifically. In the current study, its various fractions were assessed for their phenolic and flavonoid content, radical scavenging, as well as its enzyme inhibitory potential. The hydro-alcoholic crude extract (ENCr) was subjected to a fractionation scheme to obtain different fractions, namely n-hexane (ENHF), chloroform (ENCF), n-butanol (ENBF), and aqueous fraction (ENAF). The obtained results revealed that the highest phenolic and flavonoid content, maximum radical scavenging potential (91 \u00b1 0.55%), urease inhibition (54.36 \u00b1 1.47%), and \u03b1-glucosidase inhibition (97.84 \u00b1 1.87%) were exhibited by ENCr, while the ENBF fraction exhibited the highest acetylcholinestrase inhibition (57.32 \u00b1 0.43%). Contrary to these, hydro-alcoholic crude as well as the other fractions showed no significant butyrylcholinestrases (BChE) and carbonic anhydrase inhibition activity. Conclusively, it was found that EN possesses a significant radical scavenging and enzyme inhibitory potential. Thus, the study may be regarded a step forward towards evidence-based phyto-medicine.<\/jats:p>","DOI":"10.3390\/life12020321","type":"journal-article","created":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:47:45Z","timestamp":1645476465000},"page":"321","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Investigation of Euphorbia nivulia-HAM for Enzyme Inhibition Potential in Relation to the Phenolic and Flavonoid Contents and Radical Scavenging Activity"],"prefix":"10.3390","volume":"12","author":[{"given":"Muhammad","family":"Younus","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan"},{"name":"Department of Pharmacognosy, Faculty of Pharmacy, University of Karachi, Sindh 75270, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Mohtasheem-ul-Hasan","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, University of Karachi, Sindh 75270, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0143-7429","authenticated-orcid":false,"given":"Shakeel","family":"Ijaz","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, The University of Dublin, D02 PN40 Dublin, Ireland"},{"name":"Department of Pharmaceutics, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0781-0332","authenticated-orcid":false,"given":"Muhammad","family":"Kamran","sequence":"additional","affiliation":[{"name":"School of Agriculture, Food and Wine, The University of Adelaide, Adelaide 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0788-8909","authenticated-orcid":false,"given":"Ambreen","family":"Maqsood","sequence":"additional","affiliation":[{"name":"Faculty of Agriculture, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bushra","family":"Saddique","sequence":"additional","affiliation":[{"name":"Faculty of Agriculture, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uzair","family":"Nisar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Ziauddin University, Karachi 75600, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Ashraf","sequence":"additional","affiliation":[{"name":"Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7796-8480","authenticated-orcid":false,"given":"Eman","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Department of Food Industries, Faculty of Agriculture, Damietta University, Damietta 34511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"El-Sabrout","sequence":"additional","affiliation":[{"name":"Department of Applied Entomology and Zoology, Faculty of Agriculture (EL-Shatby), Alexandria University, Alexandria 21545, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4476-2408","authenticated-orcid":false,"given":"Hosam","family":"Elansary","sequence":"additional","affiliation":[{"name":"Plant Production Department, College of Food & Agriculture Sciences, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3767\/000651909X474023","article-title":"EuphORBia: A global inventory of the spurges","volume":"54","author":"Esser","year":"2009","journal-title":"Blumea-Biodivers. Evol. Biogeogr. Plants"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.jep.2015.10.025","article-title":"Global medicinal uses of Euphorbia L.(Euphorbiaceae)","volume":"176","author":"Ernst","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1556\/034.61.2019.3-4.1","article-title":"Exploring the potential of four medicinal plants for antioxidant enzymes activity, proximate and nutritional composition","volume":"61","author":"Akhtar","year":"2019","journal-title":"Acta Bot. Hung."},{"key":"ref_4","first-page":"37","article-title":"Bioprospecting of Euphorbia nivulia Buch.-ham","volume":"2","author":"Mahajan","year":"2011","journal-title":"Int. J. Phytopharm."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.jep.2007.04.004","article-title":"Ethnobotanical survey of plants used to treat asthma in Andhra Pradesh, India","volume":"113","author":"Savithramma","year":"2007","journal-title":"J. Ethnopharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Khare, C.P. (2004). Indian Herbal Remedies: Rational Western Therapy, Ayurvedic, and Other Traditional Usage, Botany, Springer Science & Business Media.","DOI":"10.1007\/978-3-642-18659-2"},{"key":"ref_7","first-page":"675","article-title":"Evaluation of anticonvulsant and antiepileptogenic activity of Euphorbia nivulia in PTZ-induced kindling model of epilepsy in mice","volume":"32","author":"Rehman","year":"2019","journal-title":"Pak. J. Pharm. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1080\/13880200490510658","article-title":"Antimicrobial activity of Euphorbia nivulia leaf extract","volume":"42","author":"Annapurna","year":"2004","journal-title":"Pharm. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1248\/cpb.51.431","article-title":"Glossary of Indian Medicinal Plants Glossary of Indian Medicinal Plants 114, 1956","volume":"51","author":"Ravikanth","year":"2003","journal-title":"Chem. Pharm. Bull. (Tokyo)"},{"key":"ref_10","unstructured":"Radcliffe-Smith, A. (2021, January 20). Euphorbiaceae Flora of Pakistan (Last Modified on 6\/3\/2011), Tropicos. org. Missouri Bot. Gard. Available online: http\/\/www.Trop.org\/Name\/12800166."},{"key":"ref_11","unstructured":"Patil, D.A. (2003). Flora of Dhule and Nandurbar Districts (Maharashtra), M\/S Bishen Singh Mahendra Pal Singh."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Khare, C.P. (2007). Indian Medicinal Plants: An Illustrated Dictionary, Springer.","DOI":"10.1007\/978-0-387-70638-2"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1007\/s00203-018-1487-1","article-title":"An overview of lectin\u2013glycan interactions: A key event in initiating fungal infection and pathogenesis","volume":"200","author":"Ballal","year":"2018","journal-title":"Arch. Microbiol."},{"key":"ref_14","first-page":"4","article-title":"Indian Journal of Pharmaceutical Science & Research","volume":"1","author":"Badgujar","year":"2011","journal-title":"Indian J. Pharm. Sci. Res."},{"key":"ref_15","first-page":"151","article-title":"Phytochemical investigations of some laticiferous plants belonging to Khandesh region of Maharashtra","volume":"2008","author":"Mahajan","year":"2008","journal-title":"Ethnobot. Leafl."},{"key":"ref_16","unstructured":"Badgujar, S.B. (2011). Proteolytic Enzymes of Some Latex Bearing Plants Belonging to Khandesh Region of Maharashtra. [Ph.D. Thesis, North Maharashtra University]."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/nrd892","article-title":"The druggable genome","volume":"1","author":"Hopkins","year":"2002","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e21995","DOI":"10.1002\/jbt.21995","article-title":"The impact of some natural phenolic compounds on carbonic anhydrase, acetylcholinesterase, butyrylcholinesterase, and \u03b1-glycosidase enzymes: An antidiabetic, anticholinergic, and antiepileptic study","volume":"31","author":"Taslimi","year":"2017","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1080\/14756366.2018.1543288","article-title":"Inhibition of acetylcholinesterase and butyrylcholinesterase with uracil derivatives: Kinetic and computational studies","volume":"34","author":"Cavdar","year":"2019","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.bios.2016.08.104","article-title":"Towards timely Alzheimer diagnosis: A self-powered amperometric biosensor for the neurotransmitter acetylcholine","volume":"87","author":"Moreira","year":"2017","journal-title":"Biosens. Bioelectron."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40035-017-0096-2","article-title":"Disease modification and Neuroprotection in neurodegenerative disorders","volume":"6","author":"Cummings","year":"2017","journal-title":"Transl. Neurodegener."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"613","DOI":"10.14348\/molcells.2017.0096","article-title":"Molecular and cellular basis of neurodegeneration in Alzheimer\u2019s disease","volume":"40","author":"Jeong","year":"2017","journal-title":"Mol. Cells"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ahmad, H.I., Nadeem, M.F., Khan, H.M.S., Sarfraz, M., Saleem, H., Khurshid, U., Locatelli, M., Ashraf, M., Akhtar, N., and Abidin, S.A.Z. (2021). Phytopharmacological Evaluation of Different Solvent Extract\/Fractions From Sphaeranthus indicus L. Flowers: From Traditional Therapies to Bioactive Compounds. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.708618"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2066","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":"ref_25","doi-asserted-by":"crossref","first-page":"310","DOI":"10.5530\/pj.2016.4.2","article-title":"Review of the phytochemical and pharmacological activities of Euphorbia hirta Linn","volume":"8","author":"Kausar","year":"2016","journal-title":"Pharmacogn. J."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Xavier, E., Trezzi, M.M., Oliveira, M.C., Vidal, R.A., and Brusamarello, A.P. (2018). Activity of antioxidant enzymes in Euphorbia heterophylla biotypes and their relation to cross resistance to ALS and Protox inhibitors. Planta Daninha, 36.","DOI":"10.1590\/s0100-83582018360100138"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"43","DOI":"10.2174\/157488909787002582","article-title":"Contemporary anticholinesterase pharmaceuticals of natural origin and their synthetic analogues for the treatment of Alzheimer\u2019s disease","volume":"4","author":"Orhan","year":"2009","journal-title":"Recent Patents CNS Drug Discov."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"113477","DOI":"10.1016\/j.jpba.2020.113477","article-title":"Phenolic compounds analysis of three Euphorbia species by LC-DAD-MSn and their biological properties","volume":"189","author":"Mahomoodally","year":"2020","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"78","DOI":"10.4103\/pr.pr_113_18","article-title":"Euphorbia hirta methanolic extract displays potential antioxidant activity for the development of local natural products","volume":"11","author":"Ismail","year":"2019","journal-title":"Pharmacognosy Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1016\/j.foodchem.2006.10.030","article-title":"Antioxidant and anticholinesterase evaluation of selected Turkish Salvia species","volume":"103","author":"Orhan","year":"2007","journal-title":"Food Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.3390\/molecules18021916","article-title":"Anti-oxidative and cholinesterase inhibitory effects of leaf extracts and their isolated compounds from two closely related Croton species","volume":"18","author":"Ndhlala","year":"2013","journal-title":"Molecules"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1538703","DOI":"10.1155\/2016\/1538703","article-title":"Biological activities of aerial parts extracts of Euphorbia characias","volume":"2016","author":"Pisano","year":"2016","journal-title":"BioMed Res. Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8373","DOI":"10.3390\/molecules19068373","article-title":"\u03b1-Glucosidase inhibitory activity of polyphenols from the burs of Castanea mollissima Blume","volume":"19","author":"Zhang","year":"2014","journal-title":"Molecules"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1219367","DOI":"10.1155\/2018\/1219367","article-title":"Selected enzyme inhibitory effects of Euphorbia characias extracts","volume":"2018","author":"Fais","year":"2018","journal-title":"Biomed Res. Int."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Gulati, V., Harding, I.H., and Palombo, E.A. (2012). Enzyme inhibitory and antioxidant activities of traditional medicinal plants: Potential application in the management of hyperglycemia. BMC Complement. Altern. Med., 12.","DOI":"10.1186\/1472-6882-12-77"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1248\/cpb.51.719","article-title":"First natural urease inhibitor from Euphorbia decipiens","volume":"51","author":"Ahmad","year":"2003","journal-title":"Chem. Pharm. Bull."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.jep.2016.06.032","article-title":"Anti-ulcer mechanisms of polyphenols extract of Euphorbia umbellata (Pax) Bruyns (Euphorbiaceae)","volume":"191","author":"Minozzo","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"395","DOI":"10.3109\/14756366.2011.593176","article-title":"Inhibition of carbonic anhydrase isozymes I and II with natural products extracted from plants, mushrooms and honey","volume":"27","author":"Sahin","year":"2012","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/S0378-8741(98)00143-3","article-title":"Euphorbia hirta leaf extracts increase urine output and electrolytes in rats","volume":"65","author":"Johnson","year":"1999","journal-title":"J. Ethnopharmacol."},{"key":"ref_40","first-page":"96","article-title":"Phytochemical screening and Extraction: A Review","volume":"1","author":"Tiwari","year":"2011","journal-title":"Int. Pharm. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.cj.2015.04.004","article-title":"Total phenolic, flavonoid content, and antioxidant activity of flour, noodles, and steamed bread made from different colored wheat grains by three milling methods","volume":"3","author":"Li","year":"2015","journal-title":"Crop J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1021\/jf00018a005","article-title":"Antioxidative properties of xanthan on the autoxidation of soybean oil in cyclodextrin emulsion","volume":"40","author":"Shimada","year":"1992","journal-title":"J. Agric. Food Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/0006-2952(61)90145-9","article-title":"A new and rapid colorimetric determination of acetylcholinesterase activity","volume":"7","author":"Ellman","year":"1961","journal-title":"Biochem. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1093\/clinchem\/24.2.208","article-title":"p-Nitrophenol-\u03b1-D-glucopyranoside as substrate for measurement of maltase activity in human semen","volume":"24","author":"Pierre","year":"1978","journal-title":"J. Clin. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1021\/ac60252a045","article-title":"Phenol-hypochlorite reaction for determination of ammonia","volume":"39","author":"Weatherburn","year":"1967","journal-title":"Anal. Chem."},{"key":"ref_46","first-page":"64","article-title":"Screening of selected medicinal plants for urease inhibitory activity","volume":"2","author":"Tahseen","year":"2010","journal-title":"Biol. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.arabjc.2015.02.024","article-title":"Alpha-glucosidase and carbonic anhydrase inhibition studies of Pd (II)-hydrazide complexes","volume":"10","author":"Ashiq","year":"2017","journal-title":"Arab. J. Chem."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/2\/321\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:24:06Z","timestamp":1760135046000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/2\/321"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,21]]},"references-count":47,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["life12020321"],"URL":"https:\/\/doi.org\/10.3390\/life12020321","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,21]]}}}