{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:32:30Z","timestamp":1787239950106,"version":"build-2736575974"},"reference-count":73,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,3,20]],"date-time":"2020-03-20T00:00:00Z","timestamp":1584662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Cuscuta reflexa Roxb. is traditionally used by the indigenous communities of Bangladesh to treat different diseases, such as pain, edema, tumor, jaundice, and skin infections. This study tested neuro-pharmacological, anti-nociceptive, and antidiarrheal activities by in vivo and in silico experiments for the metabolites extracted (methanol) from the leaves of Cuscuta reflexa (MECR). During the anxiolytic evaluation analyzed by elevated plus maze and hole board tests, MECR (200 and 400 mg\/kg) exhibited a significant dose-dependent reduction of anxiety-like behavior in mice. Similarly, mice treated with MECR demonstrated a dose-dependent decrease in the time of immobility in both forced swimming and tail suspension tests. In addition, anti-nociceptive activity was assessed by the chemical-induced (acetic acid and formalin) pain models. In both cases, 400 mg\/kg was found to be most effective and significantly (p &lt; 0.001) inhibited acetic acid stimulated writhing and formalin-induced licking (pain response) in mice. Furthermore, antidiarrheal efficacy determined by the castor-oil induced diarrheal model manifested an evident inhibition of diarrheal stool frequency. In parallel, previously isolated bioactive compounds were documented based on the biological activities and subjected to in silico studies to correlate with the current pharmacological outcomes. The selected isolated compounds (15) displayed favorable binding affinities to potassium channels, human serotonin receptor, COX-1, COX-2, M3 muscarinic acetylcholine receptor, and 5-HT3 receptor proteins. Additionally, the ADME\/T and toxicological properties were justified to unveil their drug-like properties and toxicity level. Overall, Cuscuta reflexa is bioactive and could be a potential source for the development of alternative medicine.<\/jats:p>","DOI":"10.3390\/ph13030050","type":"journal-article","created":{"date-parts":[[2020,3,23]],"date-time":"2020-03-23T04:03:01Z","timestamp":1584936181000},"page":"50","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Unveiling Pharmacological Responses and Potential Targets Insights of Identified Bioactive Constituents of Cuscuta reflexa Roxb. Leaves through In Vivo and In Silico Approaches"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1330-2169","authenticated-orcid":false,"given":"Md.","family":"Adnan","sequence":"first","affiliation":[{"name":"Department of Bio-Health Technology, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2329-0867","authenticated-orcid":false,"given":"Md. Nazim Uddin","family":"Chy","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, International Islamic University Chittagong, Chittagong 4318, Bangladesh"},{"name":"Drug Discovery, GUSTO A Research Group, Chittagong 4000, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.T.M. Mostafa","family":"Kamal","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, International Islamic University Chittagong, Chittagong 4318, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Riad","family":"Chowdhury","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, International Islamic University Chittagong, Chittagong 4318, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Shariful","family":"Islam","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, International Islamic University Chittagong, Chittagong 4318, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Amzad","family":"Hossain","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, International Islamic University Chittagong, Chittagong 4318, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2704-7610","authenticated-orcid":false,"given":"Abu Montakim","family":"Tareq","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, International Islamic University Chittagong, Chittagong 4318, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Imam Hossain","family":"Bhuiyan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, International Islamic University Chittagong, Chittagong 4318, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Nasim","family":"Uddin","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, International Islamic University Chittagong, Chittagong 4318, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afroza","family":"Tahamina","sequence":"additional","affiliation":[{"name":"Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9033-0067","authenticated-orcid":false,"given":"Md Obyedul Kalam","family":"Azad","sequence":"additional","affiliation":[{"name":"Department of Bio-Health Technology, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4167-5824","authenticated-orcid":false,"given":"Young Seok","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Bio-Health Technology, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Ha","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Bio-Health Technology, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"635","DOI":"10.4236\/ijcm.2015.69084","article-title":"The application of medicinal plants in traditional and modern medicine: A review of Thymus vulgaris","volume":"6","author":"Hosseinzadeh","year":"2015","journal-title":"Int. J. Clin. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s13596-018-0334-x","article-title":"Evaluation of Bonamia semidigyna (Roxb.) for antioxidant, antibacterial, anthelmintic and cytotoxic properties with the involvement of polyphenols","volume":"19","author":"Adnan","year":"2019","journal-title":"Orient. Pharm. Exp. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Rasool Hassan, B. (2012). Medicinal Plants (Importance and Uses). Pharm. Anal. Acta.","DOI":"10.4172\/2153-2435.1000e139"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Jamshidi-Kia, F., Lorigooini, Z., and Amini-Khoei, H. (2018). Medicinal plants: Past history and future perspective. J. Herbmed Pharmacol., 7.","DOI":"10.15171\/jhp.2018.01"},{"key":"ref_5","unstructured":"Ritchie, H., and Roser, M. (2018). Mental Health, Our World in Data."},{"key":"ref_6","first-page":"1","article-title":"The history and ups and downs of herbal medicines usage","volume":"3","author":"Sewell","year":"2014","journal-title":"J. Herbmed Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1055\/s-0030-1267855","article-title":"Pharmacology of nonsteroidal antiinflammatory drugs and opioids","volume":"Volume 27","author":"Slater","year":"2010","journal-title":"Seminars in Interventional Radiology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1161\/CIRCULATIONAHA.106.181424","article-title":"Use of nonsteroidal antiinflammatory drugs: An update for clinicians: A scientific statement from the American Heart Association","volume":"115","author":"Antman","year":"2007","journal-title":"Circulation"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1078\/0944-7113-00050","article-title":"Plants with central analgesic activity","volume":"8","author":"Almeida","year":"2001","journal-title":"Phytomedicine"},{"key":"ref_10","first-page":"1357","article-title":"A review on antidiarrhoeal activity of herbals","volume":"2","author":"Swati","year":"2011","journal-title":"Int. J. Res. Pharm. Biomed. Sci."},{"key":"ref_11","first-page":"605","article-title":"The magnitude of the global problem of acute diarrhoeal disease: A review of active surveillance data","volume":"60","author":"Snyder","year":"1982","journal-title":"Bull. World Health Organ."},{"key":"ref_12","unstructured":"Wichtl, M. (2004). Herbal Drugs and Phytopharmaceuticals: A Handbook for Practice on a Scientific Basis, Medpharm GmbH Scientific Publishers."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"249","DOI":"10.3736\/jcim20120302","article-title":"An updated review on the parasitic herb of Cuscuta reflexa Roxb","volume":"10","author":"Patel","year":"2012","journal-title":"J. Chin. Integr. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/j.1473-2165.2008.00389.x","article-title":"Effect of Cuscuta reflexa Roxb on androgen-induced alopecia","volume":"7","author":"Pandit","year":"2008","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_15","first-page":"253","article-title":"Ethnobotanical survey of the Tripura tribe of Bangladesh","volume":"3","author":"Hossan","year":"2009","journal-title":"Am. Eurasian J. Sustain. Agric."},{"key":"ref_16","first-page":"323","article-title":"Ethnomedicinal uses of plants among the Satar tribe of Nepal","volume":"24","author":"Siwakoti","year":"2000","journal-title":"J. Econ. Taxon. Bot."},{"key":"ref_17","first-page":"641","article-title":"Anti-steroidogenic activity of methanolic extract of Cuscuta reflexa Roxb. stem and Corchorus olitorius Linn. seed in mouse ovary","volume":"41","author":"Gupta","year":"2003","journal-title":"Indian J. Exp. Biol."},{"key":"ref_18","first-page":"997","article-title":"Cuscuta reflexa Roxb\u2014A wonderful miracle plant in ethnomedicine","volume":"976","author":"Vijikumar","year":"2011","journal-title":"Indian J. Nat. Sci. Int. Bimon."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"109","DOI":"10.4314\/ajtcam.v7i2.50864","article-title":"Effect of Cuscuta reflexa stem and Calotropis procera leaf extracts on glucose tolerance in glucose-induced hyperglycemic rats and mice","volume":"7","author":"Rahmatullah","year":"2010","journal-title":"Afr. J. Tradit. Complement. Altern. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.fitote.2006.06.015","article-title":"Antibacterial activity of Cuscuta reflexa stem and Corchorus olitorius seed","volume":"77","author":"Pal","year":"2006","journal-title":"Fitoterapia"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1248\/cpb.50.112","article-title":"\u03b1-glucosidase inhibitory constituents from Cuscuta reflexa","volume":"50","author":"Anis","year":"2002","journal-title":"Chem. Pharm. Bull."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/0091-3057(86)90552-6","article-title":"Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: A novel test of anxiety in the rat","volume":"24","author":"Pellow","year":"1986","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0091-3057(01)00660-8","article-title":"Anxiogenic activity of Myristica fragrans seeds","volume":"71","author":"Sonavane","year":"2002","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_24","first-page":"327","article-title":"Behavioral despair in mice: A primary screening test for antidepressants","volume":"229","author":"Porsolt","year":"1977","journal-title":"Arch. Int. Pharmacodyn. Th\u00e9rapie"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/BF00428203","article-title":"The tail suspension test: A new method for screening antidepressants in mice","volume":"85","author":"Steru","year":"1985","journal-title":"Psychopharmacology"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Adnan, M., Nazim Uddin Chy, M., Mostafa Kamal, A.T.M., Barlow, J.W., Faruque, M.O., Yang, X., and Uddin, S.B. (2019). Evaluation of anti-nociceptive and anti-inflammatory activities of the methanol extract of Holigarna caustica (Dennst.) Oken leaves. J. Ethnopharmacol., 236.","DOI":"10.1016\/j.jep.2019.01.025"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Adnan, M., Chy, N.U., Mostafa Kamal, A.T.M., Azad, M.O.K., Paul, A., Uddin, S.B., Barlow, J.W., Faruque, M.O., Park, C.H., and Cho, D.H. (2019). Investigation of the Biological Activities and Characterization of Bioactive Constituents of Ophiorrhiza rugosa var. prostrata (D. Don) & Mondal Leaves through In Vivo, In Vitro, and In Silico Approaches. Molecules, 24.","DOI":"10.3390\/molecules24071367"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1107\/S0907444902003451","article-title":"The protein data bank","volume":"58","author":"Berman","year":"2002","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5365","DOI":"10.1021\/bi500525s","article-title":"Structures of KcsA in complex with symmetrical quaternary ammonium compounds reveal a hydrophobic binding site","volume":"53","author":"Lenaeus","year":"2014","journal-title":"Biochemistry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/nature17629","article-title":"X-ray structures and mechanism of the human serotonin transporter","volume":"532","author":"Coleman","year":"2016","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"28096","DOI":"10.1074\/jbc.M701335200","article-title":"Structural basis of enantioselective inhibition of cyclooxygenase-1 by S-\u03b1-substituted indomethacin ethanolamides","volume":"282","author":"Harman","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"22152","DOI":"10.1074\/jbc.M110.119867","article-title":"Structural basis of fatty acid substrate binding to cyclooxygenase-2","volume":"285","author":"Vecchio","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1016\/j.str.2014.08.022","article-title":"Modified T4 lysozyme fusion proteins facilitate G protein-coupled receptor crystallogenesis","volume":"22","author":"Thorsen","year":"2014","journal-title":"Structure"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1021\/cn500369h","article-title":"Varenicline interactions at the 5-HT3 receptor ligand binding site are revealed by 5-HTBP","volume":"6","author":"Price","year":"2015","journal-title":"ACS Chem. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1007\/s00406-016-0684-7","article-title":"The relevance of \u2018mixed anxiety and depression\u2019as a diagnostic category in clinical practice","volume":"266","author":"Bandelow","year":"2016","journal-title":"Eur. Arch. Psychiatry Clin. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S0165-1781(00)00131-1","article-title":"Mixed anxiety\u2013depressive disorder and major depressive disorder: Comparison of the severity of illness and biological variables","volume":"94","author":"Kara","year":"2000","journal-title":"Psychiatry Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/nrn1846","article-title":"New approaches to antidepressant drug discovery: Beyond monoamines","volume":"7","author":"Berton","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4306\/pi.2015.12.1.1","article-title":"Pain and depression: A neurobiological perspective of their relationship","volume":"12","author":"Han","year":"2015","journal-title":"Psychiatry Investig."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"331","DOI":"10.2174\/157015909790031201","article-title":"Serotonin-norepinephrine reuptake inhibitors for pain control: Premise and promise","volume":"7","author":"Marks","year":"2009","journal-title":"Curr. Neuropharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"K\u00fcpeli Akkol, E., G\u00fcra\u011fa\u00e7 Dereli, F.T., and Ilhan, M. (2019). Assessment of Antidepressant Effect of the Aerial Parts of Micromeria myrtifolia Boiss. & Hohen on Mice. Molecules, 24.","DOI":"10.3390\/molecules24101869"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1177\/2045125312445469","article-title":"The drugs don\u2019t work? Antidepressants and the current and future pharmacological management of depression","volume":"2","author":"Penn","year":"2012","journal-title":"Ther. Adv. Psychopharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.lfs.2005.09.012","article-title":"Drug discovery from medicinal plants","volume":"78","author":"Balunas","year":"2005","journal-title":"Life Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1007\/BF00177912","article-title":"The use of a plus-maze to measure anxiety in the mouse","volume":"92","author":"Lister","year":"1987","journal-title":"Psychopharmacology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1177\/0269881109103091","article-title":"Long-term anxiolytic and antidepressant-like behavioural effects of tiagabine, a selective GABA transporter-1 (GAT-1) inhibitor, coincide with a decrease in HPA system activity in C57BL\/6 mice","volume":"24","author":"Thoeringer","year":"2010","journal-title":"J. Psychopharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1590\/S0100-879X1997000300002","article-title":"Animal models of anxiety: An ethological perspective","volume":"30","author":"Rodgers","year":"1997","journal-title":"Brazilian J. Med. Biol. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1007\/s00213-008-1232-6","article-title":"Profiling of behavioral changes and hippocampal gene expression in mice chronically treated with the SSRI paroxetine","volume":"200","author":"Sillaber","year":"2008","journal-title":"Psychopharmacology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1055\/s-0030-1250290","article-title":"Re-introduction of kava (Piper methysticum) to the EU: Is there a way forward?","volume":"77","author":"Sarris","year":"2011","journal-title":"Planta Med."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Mennini, T., Caccia, S., and Garattini, S. (1987). Mechanism of action of anxiolytic drugs. Progress in Drug Research\/Fortschritte der Arzneimittelforschung\/Progr\u00e8s des Recherches Pharmaceutiques, Springer.","DOI":"10.1007\/978-3-0348-9289-6_10"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.euroneuro.2011.04.002","article-title":"Herbal medicine for depression, anxiety and insomnia: A review of psychopharmacology and clinical evidence","volume":"21","author":"Sarris","year":"2011","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.pbb.2013.10.007","article-title":"Antidepressant-like activity of resveratrol treatment in the forced swim test and tail suspension test in mice: The HPA axis, BDNF expression and phosphorylation of ERK","volume":"112","author":"Wang","year":"2013","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0896-6273(02)00653-0","article-title":"Neurobiology of depression","volume":"34","author":"Nestler","year":"2002","journal-title":"Neuron"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1677\/joe.0.1600001","article-title":"The role of corticotropin-releasing factor in depression and anxiety disorders","volume":"160","author":"Arborelius","year":"1999","journal-title":"J. Endocrinol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Sheng, J., Liu, S., Wang, Y., Cui, R., and Zhang, X. (2017). The link between depression and chronic pain: Neural mechanisms in the brain. Neural Plast., 2017.","DOI":"10.1155\/2017\/9724371"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Chy, M.N.U., Adnan, M., Rauniyar, A.K., Amin, M.M., Majumder, M., Islam, M.S., Afrin, S., Farhana, K., Nesa, F., and Sany, M.A. (2019). Evaluation of anti-nociceptive and anti-inflammatory activities of Piper sylvaticum (Roxb.) stem by experimental and computational approaches. Orient. Pharm. Exp. Med., 1\u201315.","DOI":"10.1007\/s13596-019-00395-9"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Shoibe, M., Chy, M.N.U., Alam, M., Adnan, M., Islam, M.Z., Nihar, S.W., Rahman, N., and Suez, E. (2017). In vitro and in vivo biological activities of Cissus adnata (Roxb.). Biomedicines, 5.","DOI":"10.3390\/biomedicines5040063"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"170","DOI":"10.5455\/jcmr.20190805024523","article-title":"Assessment of anti-nociceptive and anthelmintic activities of Vitex Peduncularis Wall. leaves and in silico molecular docking, ADME\/T, and PASS prediction studies of its isolated compounds","volume":"10","author":"Auniq","year":"2019","journal-title":"J. Complement. Med. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1172\/JCI108975","article-title":"Ricinoleic acid effect on the electrical activity of the small intestine in rabbits","volume":"61","author":"Mathias","year":"1978","journal-title":"J. Clin. Investig."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"9179","DOI":"10.1073\/pnas.1201627109","article-title":"Castor oil induces laxation and uterus contraction via ricinoleic acid activating prostaglandin EP3 receptors","volume":"109","author":"Tunaru","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1172\/JCI109358","article-title":"Ricinoleic acid stimulation of active anion secretion in colonic mucosa of the rat","volume":"63","author":"Racusen","year":"1979","journal-title":"J. Clin. Investig."},{"key":"ref_60","doi-asserted-by":"crossref","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":"ref_61","doi-asserted-by":"crossref","first-page":"298","DOI":"10.2174\/138955711795305335","article-title":"A review on the dietary flavonoid kaempferol","volume":"11","year":"2011","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.4314\/tjpr.v13i9.26","article-title":"Pharmacological applications of quercetin and its derivatives: A short review","volume":"13","author":"Maalik","year":"2014","journal-title":"Trop. J. Pharm. Res."},{"key":"ref_63","first-page":"672","article-title":"Pharmacological applications of isorhamnetin: A short review","volume":"1","author":"Kandakumar","year":"2017","journal-title":"Int. J. Trend Sci. Res. Dev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"177","DOI":"10.3389\/fphar.2013.00177","article-title":"The growing use of herbal medicines: Issues relating to adverse reactions and challenges in monitoring safety","volume":"4","author":"Ekor","year":"2014","journal-title":"Front. Pharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4236","DOI":"10.2174\/092986709789578187","article-title":"The structure and pharmacological functions of coumarins and their derivatives","volume":"16","author":"Wu","year":"2009","journal-title":"Curr. Med. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/S0367-326X(99)00030-1","article-title":"Membrane stabilizing activity\u2014A possible mechanism of action for the anti-inflammatory activity of Cedrus deodara wood oil","volume":"70","author":"Shinde","year":"1999","journal-title":"Fitoterapia"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.3390\/nu6051931","article-title":"Antinociceptive and anti-inflammatory activities of the sesame oil and sesamin","volume":"6","author":"Monteiro","year":"2014","journal-title":"Nutrients"},{"key":"ref_68","first-page":"978","article-title":"Role of oleic acid in immune system; mechanism of action; a review","volume":"27","author":"Camarero","year":"2012","journal-title":"Nutr. Hosp."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0378-8741(00)00379-2","article-title":"Study of antidiarrhoeal activity of four medicinal plants in castor-oil induced diarrhoea","volume":"76","author":"Shoba","year":"2001","journal-title":"J. Ethnopharmacol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"13997","DOI":"10.1038\/ncomms13997","article-title":"Saturated palmitic acid induces myocardial inflammatory injuries through direct binding to TLR4 accessory protein MD2","volume":"8","author":"Wang","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.jep.2018.05.019","article-title":"Anti-inflammatory effects of luteolin: A review of in vitro, in vivo, and in silico studies","volume":"225","author":"Aziz","year":"2018","journal-title":"J. Ethnopharmacol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(96)00423-1","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings","volume":"23","author":"Lipinski","year":"1997","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Duffy, F.J., Devocelle, M., and Shields, D.C. (2015). Computational approaches to developing short cyclic peptide modulators of protein\u2013protein interactions. Computational Peptidology, Springer.","DOI":"10.1007\/978-1-4939-2285-7_11"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/13\/3\/50\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:10:17Z","timestamp":1760173817000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/13\/3\/50"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,20]]},"references-count":73,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["ph13030050"],"URL":"https:\/\/doi.org\/10.3390\/ph13030050","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,20]]}}}