{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T20:07:10Z","timestamp":1787170030454,"version":"build-2736575974"},"reference-count":88,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T00:00:00Z","timestamp":1603324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>Crocus sativus, a medicinally important herbaceous plant, has been traditionally used to cure coughs, colds, insomnia, cramps, asthma, and pain. Moreover, the therapeutic applications of saffron include its immunomodulatory and anticancer properties. The current experimental analysis was performed to explore the potential nutraceutical efficacy of corm, leaf, petal, and stigma of saffron ethanolic extracts as analgesic, anti-inflammatory, anticoagulant, and antidepressant using hot plate, carrageenan-induced paw edema, capillary tube and forced swim test, respectively in mice. The results indicated that among all the extracts, stigma ethanolic extract (SEE) represented maximum latency activity (72.85%) and edema inhibition (77.33%) followed by petal ethanolic extract (PEE) with latency activity and edema inhibition of 64.06 and 70.50%, respectively. Corm ethanolic extract (CEE) and leaf ethanolic extract (LEE) displayed mild analgesic activity of 22.40% and 29.07%, respectively. Additionally, LEE (53.29%) and CEE (47.47%) exhibited mild to moderate response against inflammation. The coagulation time of SEE (101.66 s) was almost equivalent to the standard drug, aspirin (101.66 s), suggesting a strong anticoagulant effect followed by PEE (86.5 s). LEE (66.83 s) represented moderate inhibitory effect on coagulation activity while CEE (42.83 s) showed neutral effect. Additionally, PEE and SEE also expressed itself as potential antidepressants with immobility time \u226476.66 s, while CEE (96.50 s) and LEE (106.83 s) indicated moderate to mild antidepressant efficacy. Based on the in vivo activities, saffron extract, particularly SEE and PEE, can be used as a potential nutraceutical and therapeutic agent due to its significant pharmacological activities.<\/jats:p>","DOI":"10.3390\/plants9111414","type":"journal-article","created":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T02:01:42Z","timestamp":1603418502000},"page":"1414","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Potential Nutraceutical Benefits of In Vivo Grown Saffron (Crocus sativus L.) As Analgesic, Anti-inflammatory, Anticoagulant, and Antidepressant in Mice"],"prefix":"10.3390","volume":"9","author":[{"given":"Asif","family":"Khan","sequence":"first","affiliation":[{"name":"Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nur Airina","family":"Muhamad","sequence":"additional","affiliation":[{"name":"Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8008-4595","authenticated-orcid":false,"given":"Hammad","family":"Ismail","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology, University of Gujrat, Gujrat 50700, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2339-3500","authenticated-orcid":false,"given":"Abdul","family":"Nasir","sequence":"additional","affiliation":[{"name":"Department of Molecular Science and Technology, Ajou University, Suwan 16499, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1450-5635","authenticated-orcid":false,"given":"Atif Ali Khan","family":"Khalil","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, National University of Medical Sciences, Rawalpindi 46000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3588-7361","authenticated-orcid":false,"given":"Yasir","family":"Anwar","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Faculty of Science, King Abdulaziz University, P.O. Box 54229, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahid","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Federal Urdu University of Arts Science and Technology, Karachi 75300, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amjad","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Botany, University of Malakand, Khyber Pakhtunkhwa 18800, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosna Mat","family":"Taha","sequence":"additional","affiliation":[{"name":"Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7137-6545","authenticated-orcid":false,"given":"Baker","family":"Al-Shara","sequence":"additional","affiliation":[{"name":"Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Latif","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4134-6636","authenticated-orcid":false,"given":"Bushra","family":"Mirza","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan"},{"name":"Lahore College for Women University, Lahore 54000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2638-624X","authenticated-orcid":false,"given":"Yousef Abdal Jalil","family":"Fadladdin","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Faculty of Science, King Abdulaziz University, P.O. Box 54229, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isam Mohamed Abu","family":"Zeid","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Faculty of Science, King Abdulaziz University, P.O. Box 54229, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saed Ayidh","family":"Al-Thobaiti","sequence":"additional","affiliation":[{"name":"Department of Biology, University College Turabah, Taif University, Taif 21995, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.indcrop.2019.01.026","article-title":"Corm weight or number per unit of land: Which one is more effective when planting corm, based on the age of the field from which corms were selected?","volume":"131","author":"Koocheki","year":"2019","journal-title":"Ind. Crops Prod."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"109560","DOI":"10.1016\/j.scienta.2020.109560","article-title":"Saffron (Crocus sativus L.), the king of spices: An overview","volume":"272","author":"Cardone","year":"2020","journal-title":"Sci. Hortic."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"51","DOI":"10.14720\/aas.2018.111.1.06","article-title":"Effect of different concentrations of saffron corm and leaf residue on the early growth of arugula, chickpea and fenugreek under greenhouse conditions","volume":"111","author":"Fallahi","year":"2018","journal-title":"Acta Agric. Slov."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1007\/s11105-013-0608-x","article-title":"Cloning and Characterization of FLOWERING LOCUS T-Like Genes from the Perennial Geophyte Saffron Crocus (Crocus sativus)","volume":"31","author":"Tsaftaris","year":"2013","journal-title":"Plant Mol. Biol. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.btre.2016.03.006","article-title":"Influence of nutrient media on callus induction, somatic embryogenesis and plant regeneration in selected Turkish crocus species","volume":"10","author":"Verma","year":"2016","journal-title":"Biotechnol. Rep."},{"key":"ref_6","unstructured":"Ozturk, M., Hakeem, K.R., Ashraf, M., and Ahmad, M.S.A. (2018). An Expensive Spice Saffron (Crocus sativus L.): A Case Study from Kashmir, Iran, and Turkey. Global Perspectives on Underutilized Crops, Springer International Publishing."},{"key":"ref_7","unstructured":"Sarwat, M., and Sumaiya, S. (2020). Protecting Mechanisms of Saffron Extract Against Doxorubicin Toxicity in Ischemic Heart. Saffron: The Age-Old Panacea in a New Light, Elsevier."},{"key":"ref_8","first-page":"251","article-title":"Kaempferol from saffron petals","volume":"2","author":"Hadizadeh","year":"2010","journal-title":"Iran. J. Pharm. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.phytochem.2019.02.004","article-title":"Biologically active compounds and pharmacological activities of species of the genus Crocus: A review","volume":"162","author":"Mykhailenko","year":"2019","journal-title":"Phytochemistry"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Jos\u00e9 Bagur, M., Alonso Salinas, G.L., Jim\u00e9nez-Monreal, A.M., Chaouqi, S., Llorens, S., Mart\u00ednez-Tom\u00e9, M., and Alonso, G.L. (2018). Saffron: An Old Medicinal Plant and a Potential Novel Functional Food. Molecules, 23.","DOI":"10.3390\/molecules23010030"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1108\/PRT-11-2016-0107","article-title":"Identification of crocin, crocetin and zeaxanthin in Crocus sativus grown under controlled environment in Malaysia","volume":"47","author":"Anuar","year":"2018","journal-title":"Pigm. Resin Technol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Mzabri, I., Addi, M., and Berrichi, A. (2019). Traditional and Modern Uses of Saffron (Crocus Sativus). Cosmetics, 6.","DOI":"10.3390\/cosmetics6040063"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1002\/ptr.4784","article-title":"Avicenna\u2019s (Ibn Sina) the canon of medicine and saffron (Crocus sativus): a review","volume":"27","author":"Hosseinzadeh","year":"2013","journal-title":"Phytother. Res."},{"key":"ref_14","first-page":"19","article-title":"Effects of extraction solvent\/technique on the antioxidant and antimicrobial activity of spring saffron (Crocus vernus (L.) Hill)","volume":"49","year":"2020","journal-title":"Acta Med. Salin."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.biopha.2018.01.042","article-title":"Crocin improves the proliferation and cytotoxic function of T cells in children with acute lymphoblastic leukemia","volume":"99","author":"Zhang","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"10685","DOI":"10.1021\/acs.jafc.0c04076","article-title":"Novel Insight into Utilization of Flavonoid Glycosides and Biological Properties of Saffron (Crocus sativus L.) Flower Byproducts","volume":"68","author":"Sun","year":"2020","journal-title":"J. Agric. Food Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.aoas.2019.10.002","article-title":"Saffron extract stimulates growth, improves the antioxidant components of Solanum lycopersicum L., and has an antifungal effect","volume":"64","author":"Khoulati","year":"2019","journal-title":"Ann. Agric. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1002\/ptr.5622","article-title":"Antiinflammatory, Antioxidant, and Immunomodulatory Effects of Crocus sativus L. and its Main Constituents","volume":"30","author":"Boskabady","year":"2016","journal-title":"Phytother. Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Yousefi, F., Arab, F.L., Rastin, M., Tabasi, N.S., Nikkhah, K., and Mahmoudi, M. (2020). Comparative assessment of immunomodulatory, proliferative, and antioxidant activities of crocin and crocetin on mesenchymal stem cells. J. Cell. Biochem., 1\u201314.","DOI":"10.1002\/jcb.29826"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.jtcme.2014.10.009","article-title":"Crocus sativus L. (saffron) for cancer chemoprevention: A mini review","volume":"5","author":"Bhandari","year":"2015","journal-title":"J. Tradit. Complement. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1177\/2156587215583756","article-title":"Effects of a topical saffron (Crocus sativus L.) gel on erectile dysfunction in diabetics: A randomized, parallel-group, double-blind, placebo-controlled trial","volume":"20","author":"Nazari","year":"2015","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.fitote.2006.04.012","article-title":"Evaluation of the antitussive effect of stigma and petals of saffron (Crocus sativus) and its components, safranal and crocin in guinea pigs","volume":"77","author":"Hosseinzadeh","year":"2006","journal-title":"Fitoterapia"},{"key":"ref_23","first-page":"36","article-title":"Comparative Antitussive Effects of Medicinal Plants and Their Constituents","volume":"24","author":"Saadat","year":"2018","journal-title":"Altern. Ther. Health Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"A90","DOI":"10.1089\/acm.2014.5237.abstract","article-title":"Potential Effect of Saffron as an Antiplatelet Drug in Patients with Autoimmune Diseases","volume":"20","author":"Arimitsu","year":"2014","journal-title":"J. Altern. Complement. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1089\/acm.2017.0173","article-title":"Effects of Saffron on Cognition, Anxiety, and Depression in Patients Undergoing Coronary Artery Bypass Grafting: A Randomized Double-Blind Placebo-Controlled Trial","volume":"24","author":"Abbasi","year":"2018","journal-title":"J. Altern. Complement. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.rmed.2018.10.016","article-title":"An evaluation of the effect of saffron supplementation on the antibody titer to heat-shock protein (HSP) 70, hsCRP and spirometry test in patients with mild and moderate persistent allergic asthma: A triple-blind, randomized placebo-controlled trial","volume":"145","author":"Hosseini","year":"2018","journal-title":"Respir. Med."},{"key":"ref_27","first-page":"75","article-title":"Comparison of the Effects of Crocus Sativus and Mefenamic Acid on Primary Dysmenorrhea","volume":"4","author":"Azimi","year":"2018","journal-title":"J. Pharm. Care"},{"key":"ref_28","first-page":"1760","article-title":"Comparison of Saffron versus Fluoxetine in Treatment of Women with Premenstrual Syndrome: A Randomized Clinical Trial Study","volume":"14","author":"Mohammad","year":"2020","journal-title":"Indian J. Med. Forensic Med. Toxicol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.4103\/1673-5374.274325","article-title":"Beneficial effects of saffron (Crocus sativus L.) in ocular pathologies, particularly neurodegenerative retinal diseases","volume":"15","author":"Salazar","year":"2020","journal-title":"Neural Regen. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jff.2016.03.032","article-title":"Polyphenol composition and in vitro antiproliferative effect of corm, tepal and leaf from Crocus sativus L. on human colon adenocarcinoma cells (Caco-2)","volume":"24","author":"Polissiou","year":"2016","journal-title":"J. Funct. Foods"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Wali, A.F., Pillai, J.R., Al Dhaheri, Y., Rehman, M.U., Shoaib, A., Sarheed, O., Jabnoun, S., Razmpoor, M., Rasool, S., Paray, B.A., and Ahmad, P. (2020). Crocus sativus L. Extract Containing Polyphenols Modulates Oxidative Stress and Inflammatory Response against Anti-Tuberculosis Drugs-Induced Liver Injury. Plants, 9.","DOI":"10.3390\/plants9020167"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Wali, A.F., Alchamat, H.A.A., Hariri, H.K., Hariri, B.K., Menezes, G.A., Zehra, U., Rehman, M.U., and Ahmad, P. (2020). Antioxidant, Antimicrobial, Antidiabetic and Cytotoxic Activity of Crocus sativus L. Petals. Appl. Sci., 10.","DOI":"10.3390\/app10041519"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Hoshyar, R., Hosseinian, M., Naghandar, M.R., Hemmati, M., Zarban, A., Amini, Z., Valavi, M., Beyki, M.Z., and Mehrpour, O. (2016). Anti-dyslipidemic properties of Saffron: Reduction in the associated risks of atherosclerosis and insulin resistance. Iran Red Crescent Med. J., 18.","DOI":"10.5812\/ircmj.36226"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.pnpbp.2006.11.010","article-title":"Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of depressed outpatients: A pilot double-blind randomized trial","volume":"31","author":"Basti","year":"2007","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_35","first-page":"1091","article-title":"Saffron (Crocus sativus) petal as a new pharmacological target: A review","volume":"21","author":"Hosseini","year":"2018","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_36","first-page":"113","article-title":"Chemical characterization, antioxidant and antibacterial activity of Moroccan Crocus sativus L. petals and leaves","volume":"9","author":"Jadouali","year":"2018","journal-title":"J. Mater. Environ. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e5705","DOI":"10.1002\/aoc.5705","article-title":"Green synthesis, characterization, and biological activities of saffron leaf extract-mediated zinc oxide nanoparticles: A sustainable approach to reuse an agricultural waste","volume":"34","author":"Rahaiee","year":"2020","journal-title":"Appl. Organomet. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.indcrop.2012.02.028","article-title":"In vitro antioxidant and metal chelating properties of corm, tepal and leaf from saffron (Crocus sativus L.)","volume":"39","year":"2012","journal-title":"Ind. Crops Prod."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.sajb.2015.03.194","article-title":"Phytochemical analysis and antioxidant activity of different tissue types of Crocus sativus and oxidative stress alleviating potential of saffron extract in plants, bacteria, and yeast","volume":"99","author":"Baba","year":"2015","journal-title":"S. Afr. J. Bot."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Esmaeelian, M., Jahani, M., Feizy, J., and Einafshar, S. (2020). Effects of Ultrasound-Assisted and Direct Solvent Extraction Methods on the Antioxidant and Antibacterial Properties of Saffron (Crocus sativus L.) Corm Extract. Food Anal. Methods.","DOI":"10.1007\/s12161-020-01855-8"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1021\/jf990735r","article-title":"Purification and Characterization of a Mannan-Binding Lectin Specifically Expressed in Corms of Saffron Plant (Crocus sativus L.)","volume":"48","author":"Escribano","year":"2000","journal-title":"J. Agric. Food Chem."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Mohajeri, S.A., Hedayati, N., and Bemani-Naeini, M. (2020). Available saffron formulations and product patents. Saffron, Elsevier.","DOI":"10.1016\/B978-0-12-818638-1.00034-4"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1002\/hep.24433","article-title":"Saffron: a potential candidate for a novel anti-cancer drug against hepatocellular carcinoma","volume":"54","author":"Amin","year":"2011","journal-title":"Hepatology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"103677","DOI":"10.1016\/j.jff.2019.103677","article-title":"Anti-cancer potential of polysaccharide extracted from hawthorn (Crataegus.) on human colon cancer cell line HCT116 via cell cycle arrest and apoptosis","volume":"64","author":"Ma","year":"2020","journal-title":"J. Funct. Foods"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S0378-8741(02)00299-4","article-title":"Effects of Crocus sativus petals\u2019 extract on rat blood pressure and on responses induced by electrical field stimulation in the rat isolated vas deferens and guinea-pig ileum","volume":"84","author":"Fatehi","year":"2003","journal-title":"J. Ethnopharmacol."},{"key":"ref_46","first-page":"1","article-title":"Gynura procumbens Standardised Extract Reduces Cholesterol Levels and Modulates Oxidative Status in Postmenopausal Rats Fed with Cholesterol Diet Enriched with Repeatedly Heated Palm Oil","volume":"2019","author":"Fauzi","year":"2019","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_47","first-page":"1","article-title":"Effect of saffron (Crocus sativus L.) and endurance training on mitochondrial biogenesis, endurance capacity, inflammation, antioxidant, and metabolic biomarkers in Wistar rats","volume":"43","author":"Najafi","year":"2019","journal-title":"J. Food Biochem."},{"key":"ref_48","unstructured":"Hosseinzadeh, H., and Younesi, H.M. (2002). Antinociceptive and anti-inflammatory effects of Crocus sativus L. stigma and petal extracts in mice. BMC Pharmacol., 2."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"112349","DOI":"10.1016\/j.jep.2019.112349","article-title":"Anti-nociceptive and anti-inflammatory effects of the ethanol extract of Arenga pinnata (Wurmb) Merr. fruit","volume":"248","author":"Li","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_50","first-page":"203","article-title":"Protective effects of aqueous and ethanolic extracts of saffron stigma and petal on liver toxicity induced by carbon tetrachloride in mice","volume":"1","author":"Iranshahi","year":"2011","journal-title":"Pharmacologyonline"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/0304-3835(95)04067-6","article-title":"Crocin, safranal and picrocrocin from saffron (Crocus sativus L.) inhibit the growth of human cancer cells in vitro","volume":"100","author":"Escribano","year":"1996","journal-title":"Cancer Lett."},{"key":"ref_52","first-page":"943","article-title":"Acute and sub-acute toxicity of crocin, a constituent of Crocus sativus L. (Saffron), in mice and rats","volume":"2","author":"Hosseinzadeh","year":"2010","journal-title":"Pharmacologyonline"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.neubiorev.2020.03.004","article-title":"The search for translational pain outcomes to refine analgesic development: where did we come from and where are we going?","volume":"113","author":"Tejada","year":"2020","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"284","DOI":"10.3389\/fnmol.2017.00284","article-title":"Methods used to evaluate pain behaviors in rodents","volume":"10","author":"Deuis","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.jff.2013.01.001","article-title":"Suppressive effect of carotenoid extract of Dunaliella salina alga on production of LPS-stimulated pro-inflammatory mediators in RAW264. 7 cells via NF-\u03baB and JNK inactivation","volume":"5","author":"Yang","year":"2013","journal-title":"J. Funct. Foods"},{"key":"ref_56","first-page":"97","article-title":"Crocin alleviates the local paw edema induced by histamine in rats","volume":"2","author":"Tamaddonfard","year":"2012","journal-title":"Avicenna J. Phytomed."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Gupta, A.K., Parasar, D., Sagar, A., Choudhary, V., Chopra, B.S., Garg, R., and Khatri, N. (2015). Analgesic and anti-inflammatory properties of gelsolin in acetic acid induced writhing, tail immersion and carrageenan induced paw edema in mice. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0135558"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.jep.2012.04.041","article-title":"In vivo anti-inflammatory activities of Ocimum suave in mice","volume":"142","author":"Masresha","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2892","DOI":"10.1016\/j.jksus.2020.07.014","article-title":"Hot methanol extract of Leea macrophylla (Roxb.) manages chemical-induced inflammation in rodent model","volume":"32","author":"Hossain","year":"2020","journal-title":"J. King Saud Univ. Sci."},{"key":"ref_60","first-page":"1","article-title":"Phytochemical Screening and Anti-inflammatory activity of Murraya koenigii & Ficus lacor roots in Carrageenan, Histamine and Serotonin induced paw edema in albino Wistar rats","volume":"6","author":"Pandey","year":"2020","journal-title":"Int. J. Rec. Adv. Sci. Technol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Miyasaka, M., and Takatsu, K. (2016). Prostaglandins in Chronic Inflammation. Chronic Inflammation: Mechanisms and Regulation, Springer.","DOI":"10.1007\/978-4-431-56068-5"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"96","DOI":"10.4103\/0253-7613.15109","article-title":"Pharmacological investigations of Sapindus trifoliatus in various in vitro and in vivo models of inflammation","volume":"37","author":"Arulmozhi","year":"2005","journal-title":"Indian J. Pharmacol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"112216","DOI":"10.1016\/j.ejmech.2020.112216","article-title":"Development of a novel nitric oxide (NO) production inhibitor with potential therapeutic effect on chronic inflammation","volume":"193","author":"Yang","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_64","first-page":"11","article-title":"Effect of water extract of saffron (Crocus sativus) on chronic phase of formaline test in female mice","volume":"14","author":"Arbabian","year":"2009","journal-title":"Kowsar Med. J."},{"key":"ref_65","first-page":"27","article-title":"Evaluation of anti-inflammatory potential of petal extracts of Crocus sativus \u201ccashmerianus\u201d","volume":"3","author":"Kumar","year":"2012","journal-title":"Int. J. Phytopharm."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1186\/1476-511X-12-115","article-title":"The anti-inflammatory effect of kaempferol on early atherosclerosis in high cholesterol fed rabbits","volume":"12","author":"Kong","year":"2013","journal-title":"Lipids Health Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1309\/50UQ-GUPF-W6XW-1X7B","article-title":"An overview of hemostasis","volume":"33","author":"Ogedegbe","year":"2002","journal-title":"Lab. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1177\/039463201302600402","article-title":"Anti-Hemorrhagic Agents in Oral and Dental Practice: An Update","volume":"26","author":"Scarano","year":"2013","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1155\/2010\/896819","article-title":"Ankaferd Blood Stopper for controlling gastrointestinal bleeding due to distinct benign lesions refractory to conventional antihemorrhagic measures","volume":"24","author":"Kurt","year":"2010","journal-title":"Can. J. Gastroenterol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2017\/7849501","article-title":"Five indigenous plants of Pakistan with Antinociceptive, anti-inflammatory, antidepressant, and anticoagulant properties in Sprague Dawley rats","volume":"2017","author":"Ismail","year":"2017","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/0168-9452(85)90051-2","article-title":"A high molecular weight platelet aggregating factor in Crocus sativus","volume":"40","author":"Sinakos","year":"1985","journal-title":"Plant Sci."},{"key":"ref_72","first-page":"103","article-title":"Characterization of the platelet aggregation inducer and inhibitor isolated from Crocus sativus","volume":"22","author":"Skubas","year":"1990","journal-title":"Biochem. Int."},{"key":"ref_73","first-page":"196","article-title":"Pharmacological studies of glycosides of saffron Crocus (Crocus sativus). II. Effects on blood coagulation, platelet aggregation and thromobosis","volume":"30","author":"Ma","year":"1999","journal-title":"Chin. Trad. Herbal Drugs"},{"key":"ref_74","first-page":"374","article-title":"Effect of crocetin on platelet aggregation in rats","volume":"5","author":"Yang","year":"2007","journal-title":"Chin. J. Nat. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"9429","DOI":"10.1021\/jf802027a","article-title":"Involvement of Ca2+ in the Inhibition by Crocetin of Platelet Activity and Thrombosis Formation","volume":"56","author":"Yang","year":"2008","journal-title":"J. Agric. Food Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1016\/j.phymed.2008.06.003","article-title":"Safety evaluation of saffron (Crocus sativus) tablets in healthy volunteers","volume":"15","author":"Modaghegh","year":"2008","journal-title":"Phytomedicine"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1002\/ptr.5021","article-title":"Effect of Crocus sativus L.(saffron) on coagulation and anticoagulation systems in healthy volunteers","volume":"28","author":"Ayatollahi","year":"2014","journal-title":"Phytother. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.socscimed.2016.12.030","article-title":"How is depression experienced around the world? A systematic review of qualitative literature","volume":"183","author":"Haroz","year":"2017","journal-title":"Soc. Sci. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"351","DOI":"10.3949\/ccjm.73.4.351","article-title":"Side effects of antidepressants: an overview","volume":"73","author":"Khawam","year":"2006","journal-title":"Cleve. Clin. J. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1007\/s11418-009-0360-6","article-title":"Antidepressant properties of bioactive fractions from the extract of Crocus sativus L.","volume":"64","author":"Wang","year":"2009","journal-title":"J. Nat. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"377","DOI":"10.3736\/jintegrmed2013056","article-title":"Saffron (Crocus sativus L.) and major depressive disorder: a meta-analysis of randomized clinical trials","volume":"11","author":"Hausenblas","year":"2013","journal-title":"J. Integr. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s00213-004-2048-7","article-title":"Forced swimming test in mice: a review of antidepressant activity","volume":"177","author":"Chenu","year":"2005","journal-title":"Psychopharmacology"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Kayani, W.K., Dilshad, E., Ahmed, T., Ismail, H., and Mirza, B. (2016). Evaluation of Ajuga bracteosa for antioxidant, anti-inflammatory, analgesic, antidepressant and anticoagulant activities. BMC Complement. Altern. Med., 16.","DOI":"10.1186\/s12906-016-1363-y"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Ismail, H., and Mirza, B. (2015). Evaluation of analgesic, anti-inflammatory, anti-depressant and anti-coagulant properties of Lactuca sativa (CV. Grand Rapids) plant tissues and cell suspension in rats. BMC Complement. Altern. Med., 15.","DOI":"10.1186\/s12906-015-0742-0"},{"key":"ref_85","first-page":"367","article-title":"Antidepressant effect of kaempferol, a constituent of saffron (Crocus sativus) petal, in mice and rats","volume":"2","author":"Hosseinzadeh","year":"2007","journal-title":"Pharmacologyonline"},{"key":"ref_86","first-page":"385","article-title":"Synthetic analgesics. II. Dithienylbutenyl- and dithienylbutylamines","volume":"107","author":"Eddy","year":"1953","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"544","DOI":"10.3181\/00379727-111-27849","article-title":"Carrageenin-induced edema in hind paw of the rat as an assay for antiinflammatory drugs","volume":"111","author":"Winter","year":"1962","journal-title":"Exp. Biol. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/0014-2999(79)90366-2","article-title":"Immobility induced by forced swimming in rats: Effects of agents which modify central catecholamine and serotonin activity","volume":"57","author":"Porsolt","year":"1979","journal-title":"Eur. J. Pharmacol."}],"container-title":["Plants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2223-7747\/9\/11\/1414\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:26:24Z","timestamp":1760178384000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2223-7747\/9\/11\/1414"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,22]]},"references-count":88,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["plants9111414"],"URL":"https:\/\/doi.org\/10.3390\/plants9111414","relation":{},"ISSN":["2223-7747"],"issn-type":[{"value":"2223-7747","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,22]]}}}