{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T09:55:59Z","timestamp":1791453359796,"version":"4.3.3"},"reference-count":41,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T00:00:00Z","timestamp":1623715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Unlike other widely known Aloe species used for treatment of rheumatoid arthritis, this species suffers from a lack of sufficient studies on its biological and chemical characters. This is what drove us to perform this work to evaluate the in vivo anti-arthritic potential of its leaf ethanolic extract. The in vivo anti-arthritic activity of the leaf ethanolic extract at 100 and 200 mg\/kg\/day b.wt. was evaluated alone and in combination with methotrexate (MTX) using complete Freund\u2019s adjuvant. Serum levels of rheumatoid factor, anti-cyclic citrullinated peptide (anti-CCP), cytokines pro-inflammatory marker, inflammatory mediator serum levels, and oxidative stress mediators were analyzed, in addition to liver function. Orientin, isoorientin, \u03b2-sitosterol, its palmitate and its glucoside were isolated. The combined therapy of MTX and the leaf ethanolic extract (especially at 200 mg\/kg b.wt.) group showed better activity compared to MTX alone. Moreover, the combined therapy provided additional benefits in lowering the liver toxicity by comparison to MTX alone. We concluded that a synergetic combination of the leaf ethanolic extract and MTX is beneficial in the management of rheumatoid arthritis with fewer side effects on liver function, as well as the possibility of the leaf extract to stand alone as an effective natural anti-arthritic agent.<\/jats:p>","DOI":"10.3390\/molecules26123660","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T21:24:29Z","timestamp":1623792269000},"page":"3660","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Phytochemical and In-Vivo Anti-Arthritic Significance of Aloe thraskii Baker in Combined Therapy with Methotrexate in Adjuvant-Induced Arthritis in Rats"],"prefix":"10.3390","volume":"26","author":[{"given":"Rania M.","family":"Kamal","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5309-9698","authenticated-orcid":false,"given":"Manal M.","family":"Sabry","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5210-9433","authenticated-orcid":false,"given":"Zeinab Y.","family":"Aly","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, National Organization for Drug Control and Research (NODCAR), Giza 35521, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed S.","family":"Hifnawy","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1016\/S0140-6736(16)30173-8","article-title":"Rheumatoid arthritis","volume":"388","author":"Smolen","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/nrrheum.2014.64","article-title":"Mechanisms, impact and management of pain in rheumatoid arthritis","volume":"10","author":"Walsh","year":"2014","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.3109\/13880209.2015.1125931","article-title":"Protective effects of fenofibrate and resveratrol in an aggressive model of rheumatoid arthritis in rats","volume":"54","author":"Wahba","year":"2016","journal-title":"Pharm. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1093\/rheumatology\/ken395","article-title":"Common inflammatory mediators orchestrate pathophysiological processes in rheumatoid arthritis and atherosclerosis","volume":"48","author":"Montecucco","year":"2009","journal-title":"Rheumatology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.joca.2006.04.008","article-title":"NF-\u03baB as a potential therapeutic target in osteoarthritis and rheumatoid arthritis","volume":"14","author":"Jimenez","year":"2006","journal-title":"Osteoarthr. Cartil."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"El-Shiekh, R.A., El-Mekkawy, S., Mouneir, S.M., Hassan, A., and Abdel-Sattar, E. (2021). Therapeutic potential of russelioside B as anti-arthritic agent in Freund\u2019s adjuvant-induced arthritis in rats. J. Ethnopharmacol., 270.","DOI":"10.1016\/j.jep.2021.113779"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1002\/1097-0142(196604)19:4<600::AID-CNCR2820190420>3.0.CO;2-3","article-title":"Hepatotoxic effects of methotrexate","volume":"19","author":"Hersh","year":"1966","journal-title":"Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1034\/j.1600-079X.2003.00043.x","article-title":"Melatonin prevents methotrexate-induced hepatorenal oxidative injury in rats","volume":"34","author":"Jahovic","year":"2003","journal-title":"J. Pineal Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.jep.2017.11.020","article-title":"Altered TNF-\u03b1 response by Aconibal\u00ae and methotrexate in a lipopolysaccharide-induced setting of inflammatory conditions: Potential on a synergistic combination","volume":"213","author":"Park","year":"2018","journal-title":"J. Ethnopharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1002\/ptr.5108","article-title":"Combination of Mangifera indica L. extract supplementation plus methotrexate in rheumatoid arthritis patients: A pilot study","volume":"28","author":"Garrido","year":"2014","journal-title":"Phyther. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.biopha.2018.07.001","article-title":"Evaluation of the effect of andrographolide and methotrexate combined therapy in complete Freund\u02bcs adjuvant induced arthritis with reduced hepatotoxicity","volume":"106","author":"Li","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1016\/j.sajb.2011.07.002","article-title":"Current perspectives on the economic botany of the genus Aloe L. (Xanthorrhoeaceae)","volume":"77","author":"Grace","year":"2011","journal-title":"S. Afr. J. Bot."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Bodede, O., and Prinsloo, G. (2020). Ethnobotany, phytochemistry and pharmacological significance of the genus Bulbine (Asphodelaceae). J. Ethnopharmacol., 112986.","DOI":"10.1016\/j.jep.2020.112986"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"201","DOI":"10.11646\/phytotaxa.261.3.1","article-title":"The number of known plants species in the world and its annual increase","volume":"261","author":"Christenhusz","year":"2016","journal-title":"Phytotaxa"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.jff.2015.12.026","article-title":"Isolation and identification of chromone and pyrone constituents from Aloe and their anti-inflammatory activities","volume":"21","author":"Sun","year":"2016","journal-title":"J. Funct. Foods"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez, M., Gonz\u00e1lez-Burgos, E., Iglesias, I., and G\u00f3mez-Serranillos, M.P. (2020). Pharmacological update properties of aloe vera and its major active constituents. Molecules, 25.","DOI":"10.3390\/molecules25061324"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Salehi, B., Albayrak, S., Antolak, H., Kr\u0119giel, D., Pawlikowska, E., Sharifi-Rad, M., Uprety, Y., Fokou, P.V.T., Yousef, Z., and Zakaria, Z.A. (2018). Aloe genus plants: From farm to food applications and phytopharmacotherapy. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092843"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.bjp.2016.01.009","article-title":"In vivo diabetic wound healing effect and HPLC\u2013DAD\u2013ESI\u2013MS\/MS profiling of the methanol extracts of eight Aloe species","volume":"26","author":"Ezzat","year":"2016","journal-title":"Braz. J. Pharmacogn."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1159\/000180569","article-title":"The antidiabetic activity of aloes: Preliminary clinical and experimental observations","volume":"24","author":"Ghannam","year":"1986","journal-title":"Horm. Res. Paediatr."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Rainsford, K.D., Powanda, M.C., and Whitehouse, M.W. (2015). Preface. Novel Natural Products: Therapeutic Effects in Pain Arthritis and Gastro-Intestinal Diseases. Prog. Drug Res., 70.","DOI":"10.1007\/978-3-0348-0927-6"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.sajb.2019.02.012","article-title":"Zulu medicinal ethnobotany: New records from the Amandawe area of KwaZulu-Natal, South Africa","volume":"122","author":"Mhlongo","year":"2019","journal-title":"S. Afr. J. Bot."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/0305-1978(94)00095-X","article-title":"Chemotaxonomic survey of anthraquinones and pre-anthraquinones in roots of Aloe species","volume":"23","author":"Yenesew","year":"1995","journal-title":"Biochem. Syst. Ecol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/S0254-6299(15)30302-1","article-title":"Screening of Aloe species for antioxidant activity","volume":"69","author":"Lindsey","year":"2003","journal-title":"S. Afr. J. Bot."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.jep.2008.07.002","article-title":"Van Therapeutic uses of Aloe L. (Asphodelaceae) in southern Africa","volume":"119","author":"Grace","year":"2008","journal-title":"J. Ethnopharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.sajb.2020.10.012","article-title":"Ethnobotanical review of plants used for the management and treatment of childhood diseases and well-being in South Africa","volume":"137","author":"Ndhlovu","year":"2021","journal-title":"S. Afr. J. Bot."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1590\/S0103-50532002000500021","article-title":"Fatty acid esters of triterpenes from Erythroxylum passerinum","volume":"13","author":"Barreiros","year":"2002","journal-title":"J. Braz. Chem. Soc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.phytol.2012.07.012","article-title":"Phytochemistry Letters Phytochemistry and antiglycation activity of Aloe sinkatana Reynolds","volume":"5","author":"Elhassan","year":"2012","journal-title":"Phytochem. Lett."},{"key":"ref_28","first-page":"41","article-title":"Tryptophan and sterols from Salvia limbata","volume":"10","author":"Saeidnia","year":"2011","journal-title":"J. Med. Plants"},{"key":"ref_29","unstructured":"Organisation for Economic Cooperation and Development (OECD) (2001). Test No. 423: Acute Oral toxicity\u2014Acute Toxic Class Method. OECD Guidelines for the Testing of Chemicals, OECD."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1111\/jphp.12156","article-title":"Curcumin potentiates the anti-arthritic effect of prednisolone in Freund\u2019s complete adjuvant-induced arthritic rats","volume":"66","author":"Kuncha","year":"2014","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"104867","DOI":"10.1016\/j.phrs.2020.104867","article-title":"Isoorientin: A dietary flavone with the potential to ameliorate diverse metabolic complications","volume":"158","author":"Ziqubu","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.imlet.2018.11.009","article-title":"Anti-rheumatoid arthritis effects in adjuvant-induced arthritis in rats and molecular docking studies of Polygonum orientale L. extracts","volume":"201","author":"Gou","year":"2018","journal-title":"Immunol. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1007\/s43440-019-00048-3","article-title":"Inhibitory effects of orientin in mast cell-mediated allergic inflammation","volume":"72","author":"Dhakal","year":"2020","journal-title":"Pharmacol. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1080\/13880209.2019.1577461","article-title":"\u03b2-Sitosterol modulates macrophage polarization and attenuates rheumatoid inflammation in mice","volume":"57","author":"Liu","year":"2019","journal-title":"Pharm. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"(2013). World Medical Association declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA, 310, 2191\u20132194.","DOI":"10.1001\/jama.2013.281053"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.ejphar.2011.06.006","article-title":"Synergistic activity of curcumin with methotrexate in ameliorating Freund\u2019s Complete Adjuvant induced arthritis with reduced hepatotoxicity in experimental animals","volume":"668","author":"Banji","year":"2011","journal-title":"Eur. J. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S0009-9120(99)00004-1","article-title":"Determination of tumor necrosis factor-\u03b1 (TNF-\u03b1) in serum by a highly sensitive enzyme amplified lanthanide luminescence immunoassay","volume":"32","author":"Petrovas","year":"1999","journal-title":"Clin. Biochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"112052","DOI":"10.1016\/j.jep.2019.112052","article-title":"Anti-inflammatory and phytochemical evaluation of Combretum aculeatum Vent growing in Sudan","volume":"242","author":"Hamad","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1136\/jcp.54.5.356","article-title":"Method for the measurement of antioxidant activity in human fluids","volume":"54","author":"Koracevic","year":"2001","journal-title":"J. Clin. Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"103151","DOI":"10.1016\/j.arabjc.2021.103151","article-title":"Identification of phenolic compounds in Australian grown dragon fruits by LC-ESI-QTOF-MS\/MS and determination of their antioxidant potential","volume":"14","author":"Chen","year":"2021","journal-title":"Arab. J. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"139","DOI":"10.4236\/abb.2015.63014","article-title":"Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) Activities in Selected Tissues of Rats Fed on Processed Atlantic Horse Mackerel (Trachurus trachurus)","volume":"6","author":"Adeyemi","year":"2015","journal-title":"Adv. Biosci. Biotechnol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/12\/3660\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:16:34Z","timestamp":1760163394000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/12\/3660"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,15]]},"references-count":41,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["molecules26123660"],"URL":"https:\/\/doi.org\/10.3390\/molecules26123660","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,15]]}}}