{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T23:26:08Z","timestamp":1787959568162,"version":"build-2784847793"},"reference-count":119,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T00:00:00Z","timestamp":1744761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007787","name":"National Research Centre","doi-asserted-by":"publisher","award":["13050203"],"award-info":[{"award-number":["13050203"]}],"id":[{"id":"10.13039\/100007787","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by the inflammation of synovial fluid. The incidence of cardiovascular diseases (CVDs) is increasing in RA patients. This research is the first report to investigate the anti-arthritic effect of avocado peel nutraceutical (APN) and its potential in mitigating the cardiovascular risk associated with RA. The antioxidant activity and phytochemical composition of APN were assessed. The potential interaction of APN\u2019s active compounds with protein tyrosine phosphatase non-receptor type 22 (PTPN22) was studied using molecular docking. The impact of APN on the plasma lipid profile, oxidative and inflammatory markers, and the indices of coronary risk and atherogenicity as CVD markers were evaluated. The gene expression of COX-2, IL-6, IL-1\u03b2, IL-10, and TNF-\u03b1 in liver and spleen tissues were measured. The rat gut microbiota profile was investigated using 16S rRNA amplicon sequencing. APN exhibited high antioxidant activity, low atherogenicity and thrombogenicity indices, and a high ratio of hypocholesterolemic to hypercholesterolemic fatty acids indicating its cardioprotective potential. The administration of APN led to a reduction in oxidative stress markers, inflammatory markers, dyslipidemia, and CVD markers. APN administration downregulated the expression of COX-2, IL-6, IL-1\u03b2, and TNF-\u03b1 genes, while the IL-10 gene was significantly upregulated in the liver and spleen. Treatment with APN was favorable in restoring eubiosis in the gut by modulating RA-associated bacterial taxa linked to impaired immune function and cardiometabolic diseases. In molecular docking, \u03b2-amyrin and ellagic acid showed the highest binding affinity for PTPN22. APN may represent a promising approach to ameliorating the cardiovascular risk of RA. The present results will be offering a foundation for future in-depth research in nutraceuticals from agriculture by-products. Additionally, they will be supporting the public health policies aimed at preventing and controlling rheumatoid arthritis.<\/jats:p>","DOI":"10.3390\/biom15040590","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T06:12:06Z","timestamp":1744783926000},"page":"590","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Persea americana Peel: A Promising Source of Nutraceutical for the Mitigation of Cardiovascular Risk in Arthritic Rats Through the Gut\u2013Joint Axis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0606-9378","authenticated-orcid":false,"given":"Doha A.","family":"Mohamed","sequence":"first","affiliation":[{"name":"Nutrition and Food Science Department, Food Industries and Nutrition Institute, National Research Centre, Cairo 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2626-0006","authenticated-orcid":false,"given":"Asmaa A.","family":"Ramadan","sequence":"additional","affiliation":[{"name":"Nutrition and Food Science Department, Food Industries and Nutrition Institute, National Research Centre, Cairo 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3839-0062","authenticated-orcid":false,"given":"Hoda B.","family":"Mabrok","sequence":"additional","affiliation":[{"name":"Nutrition and Food Science Department, Food Industries and Nutrition Institute, National Research Centre, Cairo 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gamil E.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Chemistry of Aroma and Flavor Department, Food Industries and Nutrition Institute, National Research Centre, Cairo 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3463-8945","authenticated-orcid":false,"given":"Shaimaa E.","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Nutrition and Food Science Department, Food Industries and Nutrition Institute, National Research Centre, Cairo 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103410","DOI":"10.1016\/j.autrev.2023.103410","article-title":"Immune-mediated inflammatory diseases: Common and different pathogenic and clinical features","volume":"22","author":"Monteleone","year":"2023","journal-title":"Autoimmun. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Liang, Y., Liu, M., Cheng, Y., Wang, X., and Wang, W. (2023). Prevention and treatment of rheumatoid arthritis through traditional Chinese medicine: Role of the gut microbiota. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1233994"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1146\/annurev-med-060513-093205","article-title":"The gut microbial endocrine organ: Bacterially derived signals driving cardiometabolic diseases","volume":"66","author":"Brown","year":"2015","journal-title":"Annu. Rev. Med."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Yang, Y., Hong, Q., Zhang, X., and Liu, Z. (2024). Rheumatoid arthritis and the intestinal microbiome: Probiotics as a potential therapy. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1331486"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Attur, M., Scher, J.U., Abramson, S.B., and Attur, M. (2022). Role of Intestinal Dysbiosis and Nutrition in Rheumatoid Arthritis. Cells, 11.","DOI":"10.3390\/cells11152436"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Sun, X., Qian, Y., Cheng, W., Ye, D., Liu, B., Zhou, D., Wen, C., Andreassen, O.A., and Mao, Y. (2024). Characterizing the polygenic overlap and shared loci between rheumatoid arthritis and cardiovascular diseases. BMC Med., 22.","DOI":"10.1186\/s12916-024-03376-1"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"102776","DOI":"10.1016\/j.autrev.2021.102776","article-title":"Rheumatoid arthritis: Extra-articular manifestations and comorbidities","volume":"20","author":"Figus","year":"2021","journal-title":"Autoimmun. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1038\/s41423-021-00661-4","article-title":"Gut microbiota-derived metabolites in the regulation of host immune responses and immune-related inflammatory diseases","volume":"18","author":"Yang","year":"2021","journal-title":"Cell Mol. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"103001","DOI":"10.1016\/j.jaut.2023.103001","article-title":"Gut microbiota in pre-clinical rheumatoid arthritis: From pathogenesis to preventing progression","volume":"141","author":"Lin","year":"2023","journal-title":"J. Autoimmun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1002\/art.42616","article-title":"Alteration of gut microbiota in individuals at high-Risk for rheumatoid arthritis associated with disturbed metabolome and the initiation of arthritis through the triggering of mucosal immunity imbalance","volume":"75","author":"Luo","year":"2023","journal-title":"Arthritis Rheumatol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Wang, Q., Zhang, S.-X., Chang, M.-J., Qiao, J., Wang, C.-H., Li, X.-F., Yu, Q., and He, P.-F. (2022). Characteristics of the gut microbiome and its relationship with peripheral cd4+ T cell subpopulations and cytokines in rheumatoid arthritis. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.799602"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Gomez, A., Luckey, D., Yeoman, C.J., Marietta, E.V., Berg Miller, M.E., Murray, J.A., White, B.A., and Taneja, V. (2012). Loss of sex and age driven differences in the gut microbiome characterize arthritis-susceptible 0401 mice but not arthritis-resistant 0402 mice. PLoS ONE., 7.","DOI":"10.1371\/journal.pone.0036095"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/ar4360","article-title":"Periodontal disease, Porphyromonas gingivalis, and rheumatoid arthritis: What triggers autoimmunity and clinical disease?","volume":"15","author":"Scher","year":"2013","journal-title":"Arthritis Res. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Xu, X., Wang, M., Wang, Z., Chen, Q., Chen, X., Xu, Y., Dai, M., Wu, B., and Li, Y. (2022). The bridge of the gut-joint axis: Gut microbial metabolites in rheumatoid arthritis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1007610"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Yu, D., Du, J., Pu, X., Zheng, L., Chen, S., Wang, N., Li, J., Chen, S., Pan, S., and Shen, B. (2021). The gut microbiome and metabolites are altered and interrelated in patients with rheumatoid arthritis. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.763507"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"eabm1511","DOI":"10.1126\/sciadv.abm1511","article-title":"Intestinal butyrate-metabolizing species contribute to autoantibody production and bone erosion in rheumatoid arthritis","volume":"8","author":"He","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Sayago-Ayerdi, S., Garc\u00eda-Mart\u00ednez, D.L., Ram\u00edrez-Castillo, A.C., Ram\u00edrez-Concepci\u00f3n, H.R., and Viuda-Martos, M. (2021). Tropical Fruits and Their Co-Products as Bioactive Compounds and Their Health Effects: A Review. Foods, 10.","DOI":"10.3390\/foods10081952"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Izu, G.O., Mfotie Njoya, E., Tabakam, G.T., Nambooze, J., Otukile, K.P., Tsoeu, S.E., Fasiku, V.O., Adegoke, A.M., Erukainure, O.L., and Mashele, S.S. (2024). Unravelling the Influence of Chlorogenic Acid on the Antioxidant Phytochemistry of Avocado (Persea americana Mill.) Fruit Peel. Antioxidants, 13.","DOI":"10.3390\/antiox13040456"},{"key":"ref_19","first-page":"S51","article-title":"Determination of the Chemical Composition of Avocado (Persea americana) Seed","volume":"2","author":"Ejiofor","year":"2018","journal-title":"Adv. Food Technol. Nutr. Sci. SE"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Guti\u00e9rrez, E. (2023). Study of Influence of Extraction Method on the Recovery Bioactive Compounds from Peel Avocado. Molecules, 28.","DOI":"10.3390\/molecules28062557"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"100253","DOI":"10.1016\/j.crgsc.2021.100253","article-title":"Beneficiation of avocado processing industry by-product: A review on future prospect","volume":"5","author":"Tesfaye","year":"2022","journal-title":"Curr. Res. Green Sustain. Chem."},{"key":"ref_22","first-page":"37","article-title":"Activity-guided identification of acetogenins as novel lipophilic antioxidants present in avocado pulp (Persea americana)","volume":"942","author":"Rojo","year":"2013","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Donoso, C., Raluca, M.A., Ch\u00e1vez-Jinez, S., and Vera, E. (2024). Hass Avocado (Persea americana Mill.) Peel Extract Reveals Antimicrobial and Antioxidant Properties against Verticillium theobromae, Colletotrichum musae, and Aspergillus niger Pathogens Affecting Musa acuminata Colla Species, in Ecuador. Microorganisms, 12.","DOI":"10.3390\/microorganisms12091929"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Bhuyan, D.J., Alsherbiny, M.A., Perera, S., Low, M., Bas, A., Devi, O.A., Barooah, M.S., Li, C.G., and Papoutsis, K. (2019). The Odyssey of bioactive compounds in avocado (Persea americana) and their health benefits. Antioxidant, 8.","DOI":"10.3390\/antiox8100426"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Olas, B. (2024). The Pulp, Peel, Seed, and Food Products of Persea americana as Sources of Bioactive Phytochemicals with Cardioprotective Properties: A Review. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252413622"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Rojas-Garc\u00eda, A., Fuentes, E., C\u00e1diz-Gurrea, M.L., Rodriguez, L., Villegas-Aguilar, M.D.C., Palomo, I., Arr\u00e1ez-Rom\u00e1n, D., and Segura-Carretero, A. (2022). Biological Evaluation of Avocado Residues as a Potential Source of Bioactive Compounds. Antioxidants, 11.","DOI":"10.3390\/antiox11061049"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4113","DOI":"10.1021\/jf9801973","article-title":"Antioxidant activity and total phenolics in selected fruits, vegetables and grain products","volume":"46","author":"Velioglu","year":"1998","journal-title":"J. Agri Food Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/S0308-8146(98)00102-2","article-title":"The determination of flavonoid contents in mulberry and their scavenging effect on superoxide radicals","volume":"64","author":"Zhishen","year":"1999","journal-title":"Food Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"12033","DOI":"10.1039\/D4FO03567D","article-title":"Alkaline Diets Potential Role in Prevention of Kidney Stone Formation: In-vivo and Molecular Docking Studies","volume":"15","author":"Mohamed","year":"2024","journal-title":"Food Funct."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"14736","DOI":"10.33263\/BRIAC116.1473614750","article-title":"Spirulina-Enriched Pasta as Functional Food Rich in Protein and Antioxidant","volume":"11","author":"Hussein","year":"2021","journal-title":"Biointerface Res. Appl. Chem."},{"key":"ref_31","unstructured":"Adams, R. (2007). Identification of Essential Oil Components by Gas Chromatography\/Mass Spectrometry, Allured Publishing Corporation. [4th ed.]."},{"key":"ref_32","unstructured":"AOAC (2023). Official Methods of Analysis of the Association of Official Analytical Chemists, AOAC. [22nd ed.]."},{"key":"ref_33","first-page":"2037","article-title":"Utilization of grape and apricot fruits by-products as cheap source for biologically active compounds for health promotion","volume":"64","author":"Mohamed","year":"2021","journal-title":"Egypt. J. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/BF02533555","article-title":"Analysis of Oleate, Linoleate and Linolenate Hydroperoxides in Oxidized Ester Mixtures","volume":"15","author":"Fatemi","year":"1980","journal-title":"Lipids"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/0140-6736(91)91846-M","article-title":"Coronary Heart Disease: Seven Dietary Factors","volume":"338","author":"Ulbricht","year":"1991","journal-title":"Lancet"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0023-6438(95)80008-5","article-title":"Use of a free redical method to evaluate antioxidant activity","volume":"28","author":"Cuvelier","year":"1995","journal-title":"LWT\u2014Food Sci. Technol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/S0891-5849(98)00315-3","article-title":"Antioxidant activity applying an improved ABTS radical cation decolorization assay","volume":"26","author":"Re","year":"1999","journal-title":"Free Radic. Biol. Med."},{"key":"ref_38","first-page":"539","article-title":"Antioxidant, anti-cancer and anti-arthritic activities of acetogenin-rich extract of avocado pulp","volume":"65","author":"Hassan","year":"2022","journal-title":"Egypt. J. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/0009-8981(78)90081-5","article-title":"Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method","volume":"90","author":"Satoh","year":"1978","journal-title":"Clin. Chim. Acta"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0076-6879(84)05016-3","article-title":"Catalase in vitro","volume":"105","author":"Aebi","year":"1984","journal-title":"Methods Enzym."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394Ct method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1984238","DOI":"10.1155\/2016\/1984238","article-title":"Anti-inflammatory and anti-osteoarthritis effects of Saposhnikovia divaricata ethanol extract: In vitro and in vivo studies","volume":"2016","author":"Chun","year":"2016","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5851","DOI":"10.4238\/2013.November.22.12","article-title":"Transient increase in IL-1\u03b2, IL-6 and TNF-\u03b1 gene expression in rat liver exposed to gold nanoparticles","volume":"12","author":"Khan","year":"2013","journal-title":"Genet. Mol. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1038\/nmeth.2604","article-title":"UPARSE: Highly accurate OTU sequences from microbial amplicon reads","volume":"10","year":"2013","journal-title":"Nat. Methods"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nmeth.2276","article-title":"Quality-filtering vastly improves diversity estimates from Illumina amplicon sequencing","volume":"10","author":"Bokulich","year":"2013","journal-title":"Nat. Methods"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Kebede, B., Ting, V., Eyres, G., and Oey, I. (2020). Volatile changes during storage of shelf stable Apple juice: Integrating GC-MS fingerprinting and chemometrics. Foods, 9.","DOI":"10.3390\/foods9020165"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1016\/j.foodchem.2005.10.070","article-title":"Effect of ascorbic acid on the odours of cloudy apple juice","volume":"100","author":"Komthong","year":"2007","journal-title":"Food Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"365","DOI":"10.3989\/gya.125010","article-title":"Evaluation of the Anti-inflammatory and Anti-arthritic Effects of Some Plants Extracts","volume":"62","author":"Mohamed","year":"2011","journal-title":"Grasas y Aceites"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e180","DOI":"10.3989\/gya.0796161","article-title":"Anti-inflammatory activity of two varieties of pumpkin seed oil in an adjuvant arthritis model in rats","volume":"68","author":"Mohamed","year":"2017","journal-title":"Grasas y Aceites"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"317","DOI":"10.3923\/jbs.2018.317.328","article-title":"Evaluation of Antioxidant, Anti-inflammatory and Anti-arthritic Activities of Yarrow (Achillea millefolium)","volume":"18","author":"Mohamed","year":"2018","journal-title":"J. Biol. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1186\/s12967-024-05228-1","article-title":"Resveratrol attenuates inflammation and fibrosis in rheumatoid arthritis-associated interstitial lung disease via the AKT\/TMEM175 pathway","volume":"22","author":"Liu","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1186\/s13063-024-07977-2","article-title":"The effects of intermittent fasting diet on quality of life, clinical symptoms, inflammation, and oxidative stress in overweight and obese postmenopausal women with rheumatoid arthritis: Study protocol of a randomized controlled trial","volume":"25","author":"Ranjbar","year":"2024","journal-title":"Trials"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/978-94-024-0921-5_5","article-title":"Regulation of Interleukin-10 Expression","volume":"941","author":"Rutz","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Laragione, T., Harris, C., Azizgolshani, N., Beeton, C., Bongers, G., and Gulko, P.S. (2023). Magnesium increases numbers of Foxp3+ Treg cells and reduces arthritis severity and joint damage in an IL-10-dependent manner mediated by the intestinal microbiome. EBioMedicine, 92.","DOI":"10.1016\/j.ebiom.2023.104603"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Pandolfi, F., Franza, L., Carusi, V., Altamura, S., Andriollo, G., and Nucera, E. (2020). Interleukin-6 in Rheumatoid Arthritis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155238"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"100","DOI":"10.4103\/ijabmr.IJABMR_248_18","article-title":"Effect of Boswellia Serrata extract on acute inflammatory parameters and tumor necrosis factor-\u03b1 in complete Freund\u2019s adjuvant-induced animal model of rheumatoid arthritis","volume":"9","author":"Kumar","year":"2019","journal-title":"Int. J. Appl. Basic Med. Res."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Jang, D.I., Lee, A.H., Shin, H.Y., Song, H.R., Park, J.H., Kang, T.B., Lee, S.R., and Yang, S.H. (2021). The Role of Tumor necrosis factor alpha (TNF-\u03b1) in autoimmune disease and current TNF-\u03b1 inhibitors in therapeutics. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052719"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Al-Roub, A., Al Madhoun, A., Akhter, N., Thomas, R., Miranda, L., Jacob, T., Al-Ozairi, E., Al-Mulla, F., Sindhu, S., and Ahmad, R. (2021). IL-1\u03b2 and TNF\u03b1 Cooperativity in Regulating IL-6 Expression in Adipocytes Depends on CREB Binding and H3K14 Acetylation. Cells, 10.","DOI":"10.3390\/cells10113228"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/s41586-024-07098-5","article-title":"IL-10 constrains sphingolipid metabolism to limit inflammation","volume":"627","author":"York","year":"2024","journal-title":"Nature"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.immuni.2019.03.020","article-title":"IL-10 Family Cytokines IL-10 and IL-22: From Basic Science to Clinical Translation","volume":"50","author":"Ouyang","year":"2019","journal-title":"Immunity"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1615\/JEnvironPatholToxicolOncol.2018027078","article-title":"Antiarthritic activity of diallyl disulfide against Freund\u2019s adjuvant-induced arthritic rat model","volume":"37","author":"Chen","year":"2018","journal-title":"J. Environ. Pathol. Toxicol. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"453","DOI":"10.4196\/kjpp.2020.24.6.453","article-title":"Anti-arthritic activity of D-carvone against complete Freund\u2019s adjuvant-induced arthritis in rats through modulation of inflammatory cytokines","volume":"24","author":"Chen","year":"2020","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1097\/CRD.0000000000000486","article-title":"Cardiovascular Manifestations in Rheumatoid Arthritis","volume":"32","author":"Sanghavi","year":"2024","journal-title":"Cardiol. Rev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1254753","DOI":"10.3389\/fimmu.2023.1254753","article-title":"Dyslipidemia in rheumatoid arthritis: The possible mechanisms","volume":"14","author":"Yan","year":"2023","journal-title":"Front Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Popescu, D., Rezus, E., Badescu, M.C., Dima, N., Seritean Isac, P.N., Dragoi, I.T., and Rezus, C. (2023). Cardiovascular Risk Assessment in Rheumatoid Arthritis: Accelerated Atherosclerosis, New Biomarkers, and the Effects of Biological Therapy. Life, 13.","DOI":"10.3390\/life13020319"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1007\/s00204-023-03562-9","article-title":"Reactive oxygen species, toxicity, oxidative stress, and antioxidants: Chronic diseases and aging","volume":"97","author":"Jomova","year":"2023","journal-title":"Arch. Toxicol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.lwt.2015.07.048","article-title":"Optimization of the antioxidant and antimicrobial response of the combined effect of nisin and avocado byproducts","volume":"65","year":"2016","journal-title":"LWT Food Sci. Technol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.lwt.2016.06.049","article-title":"HPLC-DAD-ESI QTOF-MSandHPLC-FLD-MSasvaluable tools for the determination of phenolic and other polar compounds in the edible part and by-products of avocado","volume":"73","author":"Pasini","year":"2016","journal-title":"LWT"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.biopha.2017.10.064","article-title":"Chlorogenic acid (CGA): A pharmaco logical review and call for further research","volume":"97","author":"Naveed","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Tremocoldi, M.A., Rosalen, P.L., Franchin, M., Massarioli, A.P., Denny, C., Daiuto, \u00c9.R., Paschoal, J.A.R., Melo, P.S., and Alencar, S.M. (2018). Exploration of avocado by-products as natural sources of bioactive compounds. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0192577"},{"key":"ref_71","first-page":"66","article-title":"Studying the anti-inflammatory and biochemical effects of wheat germ oil","volume":"101","author":"Mohamed","year":"2005","journal-title":"Dtsch. Leb. Rundsch."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1093\/advances\/nmaa029","article-title":"Fish consumption and the risk of chronic disease: An umbrella review of meta-analyses of prospective cohort studies","volume":"11","author":"Jayedi","year":"2020","journal-title":"Adv. Nutr."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"83","DOI":"10.34172\/jhp.2022.09","article-title":"Chia seeds oil enriched with phytosterols and mucilage as a cardioprotective dietary supplement towards inflammation, oxidative stress, and dyslipidemia","volume":"11","author":"Mohamed","year":"2022","journal-title":"J. Herbmed. Pharmacol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"109774","DOI":"10.1016\/j.foodres.2020.109774","article-title":"Avocado fruit and by-products as potential sources of bioactive compounds","volume":"138","author":"Yahia","year":"2020","journal-title":"Food Res. Int."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1016\/j.jksus.2018.10.010","article-title":"Antioxidant, anti-inflammatory and anti-cancer activities of avocado (Persea americana) fruit and seed extract","volume":"31","author":"Alkhalaf","year":"2019","journal-title":"J. King Saud Univ. Sci."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Rosero, J.C., Cruz, S., Osorio, C., and Hurtado, N. (2019). Analysis of Phenolic Composition of Byproducts (Seeds and Peels) of Avocado (Persea americana Mill.) Cultivated in Colombia. Molecules, 24.","DOI":"10.3390\/molecules24173209"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s11745-015-4113-x","article-title":"Current Evidence Supporting the Link between Dietary Fatty Acids and Cardiovascular Disease","volume":"51","author":"Hammad","year":"2016","journal-title":"Lipids"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"4120","DOI":"10.1111\/1541-4337.12784","article-title":"Avocado oil: Production and market demand, bioactive components, implications in health, and tendencies and potential uses","volume":"20","author":"Yahia","year":"2021","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Marovi\u0107, R., Badanjak Sabolovi\u0107, M., Brn\u010di\u0107, M., Nin\u010devi\u0107 Grassino, A., Kljak, K., Vo\u0107a, S., Karlovi\u0107, S., and Rimac Brn\u010di\u0107, S. (2024). The Nutritional Potential of Avocado By-Products: A Focus on Fatty Acid Content and Drying Processes. Foods, 13.","DOI":"10.3390\/foods13132003"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Khalili Tilami, S., and Kou\u0159imsk\u00e1, L. (2022). Assessment of the Nutritional Quality of Plant Lipids Using Atherogenicity and Thrombogenicity Indices. Nutrients, 14.","DOI":"10.3390\/nu14183795"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Rabiej-Kozio\u0142, D., Momot-Ruppert, M., Stawicka, B., and Szyd\u0142owska-Czerniak, A. (2023). Health Benefits, Antioxidant Activity, and Sensory Attributes of Selected Cold-Pressed Oils. Molecules, 28.","DOI":"10.3390\/molecules28145484"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Kinashi, Y., and Hase, K. (2021). Partners in Leaky Gut Syndrome: Intestinal Dysbiosis and Autoimmunity. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.673708"},{"key":"ref_83","first-page":"4835189","article-title":"Intestinal Dysbiosis and Rheumatoid Arthritis: A Link between Gut Microbiota and the Pathogenesis of Rheumatoid Arthritis","volume":"2017","year":"2017","journal-title":"J. Immunol. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1136\/gutjnl-2021-325209","article-title":"Hidden link in gut\u2013joint axis: Gut microbes promote rheumatoid arthritis at early stage by enhancing ascorbate degradation","volume":"71","author":"Zhao","year":"2022","journal-title":"Gut"},{"key":"ref_85","first-page":"187","article-title":"Vitamin C alleviates rheumatoid arthritis by modulating gut microbiota balance","volume":"18","author":"Zhang","year":"2024","journal-title":"Biol. Sci. Trends"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s13073-016-0299-7","article-title":"An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis","volume":"8","author":"Chen","year":"2016","journal-title":"Genome Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1182\/blood.2022015554","article-title":"Protein tyrosine phosphatase PTPN22 negatively modulates platelet function and thrombus formation","volume":"140","author":"Wang","year":"2022","journal-title":"Blood"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Lee, J.Y., Mannaa, M., Kim, Y., Kim, J., Kim, G.T., and Seo, Y.S. (2019). Comparative Analysis of Fecal Microbiota Composition Between Rheumatoid Arthritis and Osteoarthritis Patients. Genes, 10.","DOI":"10.3390\/genes10100748"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1210\/er.2009-0030","article-title":"Gut microbiota, lipopolysaccharides, and innate immunity in the pathogenesis of obesity and cardiovascular risk","volume":"31","author":"Manco","year":"2010","journal-title":"Endocr. Rev."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Han, S.K., Shin, Y.J., Lee, D.Y., Kim, K.M., Yang, S.J., Kim, D.S., Choi, J.W., Lee, S., and Kim, D.H. (2021). Lactobacillus rhamnosus HDB1258 modulates gut microbiota-mediated immune response in mice with or without lipopolysaccharide-induced systemic inflammation. BMC Microbiol., 21.","DOI":"10.1186\/s12866-021-02192-4"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1007\/s00284-013-0338-1","article-title":"Analysis of Fecal Lactobacillus Community Structure in Patients with Early Rheumatoid Arthritis","volume":"67","author":"Liu","year":"2013","journal-title":"Curr. Microbiol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s12986-024-00869-x","article-title":"High-fat diet stimulated butyric acid metabolism dysbiosis, altered microbiota, and aggravated inflammatory response in collagen-induced arthritis rats","volume":"21","author":"Liu","year":"2024","journal-title":"Nutr. Metab."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"G\u00e1mez-Mac\u00edas, P.E., F\u00e9lix-Soriano, E., Samblas, M., S\u00e1inz, N., Moreno-Aliaga, M.J., and Gonz\u00e1lez-Muniesa, P. (2024). Intestinal Permeability, Gut Inflammation, and Gut Immune System Response Are Linked to Aging-Related Changes in Gut Microbiota Composition: A Study in Female Mice. J. Gerontol. A Biol. Sci. Med. Sci., 79.","DOI":"10.1093\/gerona\/glae045"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Hamada, K., Isobe, J., Hattori, K., Hosonuma, M., Baba, Y., Murayama, M., Narikawa, Y., Toyoda, H., Funayama, E., and Tajima, K. (2023). Turicibacter and Acidaminococcuspredict immune-related adverse events and efficacy of immune checkpoint inhibitor. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1164724"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3669","DOI":"10.1038\/s41467-023-39403-7","article-title":"Gut microbiota Turicibacter strains differentially modify bile acids and host lipids","volume":"14","author":"Lynch","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e034230","DOI":"10.1161\/JAHA.123.034230","article-title":"Disordered gut microbiome and alterations in metabolic patterns are associated with hypertensive left ventricular hypertrophy","volume":"13","author":"Cao","year":"2024","journal-title":"J. Am. Heart Assoc."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Li, M., Yang, L., Zhao, L., Bai, F., and Liu, X. (2022). Comparison of intestinal microbes in noninfectious anterior scleritis patients with and without rheumatoid arthritis. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.925929"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Yang, K., Zhang, L., Liao, P., Xiao, Z., Zhang, F., Sindaye, D., Xin, Z., Tan, C., Deng, J., and Yin, Y. (2020). Impact of gallic acid on gut health: Focus on the gut microbiome, immune response, and mechanisms of action. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.580208"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Kasprzak-Drozd, K., Oniszczuk, T., Stasiak, M., and Oniszczuk, A. (2021). Beneficial effects of phenolic compounds on gut microbiota and metabolic syndrome. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073715"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Matsumura, Y., Kitabatake, M., Kayano, S.I., and Ito, T. (2023). Dietary phenolic compounds: Their health benefits and association with the gut microbiota. Antioxidants, 12.","DOI":"10.3390\/antiox12040880"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Nesci, A., Carnuccio, C., Ruggieri, V., D\u2019Alessandro, A., Di Giorgio, A., Santoro, L., Gasbarrini, A., Santoliquido, A., and Ponziani, F.R. (2023). Gut Microbiota and Cardiovascular Disease: Evidence on the Metabolic and Inflammatory Background of a Complex Relationship. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24109087"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e035693","DOI":"10.1161\/JAHA.124.035693","article-title":"Metagenomic Study of the MESA: Detection of Gemella Morbillorumand association with coronary heart disease","volume":"13","author":"Taylor","year":"2024","journal-title":"J. Am. Heart Assoc."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.phrs.2018.01.009","article-title":"Metabolic syndrome, autoimmunity and rheumatic diseases","volume":"133","author":"Medina","year":"2018","journal-title":"Pharmacol. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1080\/03009742.2018.1464205","article-title":"Helicobacter pylori infection is not associated with rheumatoid arthritis","volume":"48","author":"Bartels","year":"2019","journal-title":"Scand. J. Rheumatol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"5273","DOI":"10.2147\/IJN.S462374","article-title":"2-Monoacylglycerol Mimetic Liposomes to Promote Intestinal Lymphatic Transport for Improving Oral Bioavailability of Dihydroartemisinin","volume":"19","author":"Zheng","year":"2024","journal-title":"Int. J. Nanomed."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.ejps.2010.05.002","article-title":"Intestinal permeability enhancement of levothyroxine sodium by straight chain fatty acids studied in MDCK epithelial cell line","volume":"40","author":"Dimple","year":"2010","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.tifs.2021.02.016","article-title":"Yogurts supplemented with lipid emulsions rich in omega-3 fatty acids: New insights into the fortification, microencapsulation, quality properties, and health-promoting effects","volume":"110","author":"Gumus","year":"2021","journal-title":"Trends Food Sci. Technol."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Machado, M., Sousa, S.C., Rodr\u00edguez-Alcal\u00e1, L.M., Pintado, M., and Gomes, A.M. (2023). Bigels as Delivery Systems of Bioactive Fatty Acids Present in Functional Edible Oils: Coconut, Avocado, and Pomegranate. Gels, 9.","DOI":"10.3390\/gels9040349"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Deng, H., Jiang, J., Zhang, S., Wu, L., Zhang, Q., and Sun, W. (2023). Network pharmacology and experimental validation to identify the potential mechanism of Hedyotis diffusa Willd against rheumatoid arthritis. Sci. Rep., 13.","DOI":"10.1038\/s41598-022-25579-3"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Radu, A.-F., Negru, P.A., Radu, A., Tarce, A.G., Bungau, S.G., Bogdan, M.A., Tit, D.M., and Uivaraseanu, B. (2023). Simulation-Based Research on Phytoconstituents of Embelia ribes Targeting Proteins with Pathophysiological Implications in Rheumatoid Arthritis. Life, 13.","DOI":"10.3390\/life13071467"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Gong, N., Wang, L., An, L., and Xu, Y. (2023). Exploring the active ingredients and potential mechanisms of action of sinomenium acutum in the treatment of rheumatoid arthritis based on systems biology and network pharmacology. Front. Mol. Biosci., 10.","DOI":"10.3389\/fmolb.2023.1065171"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Remuzgo-Mart\u00ednez, S., Genre, F., Casta\u00f1eda, S., Corrales, A., Moreno-Fresneda, P., Ubilla, B., Mijares, V., Portilla, V., Gonz\u00e1lez-Vela, J., and Pina, T. (2017). Protein tyrosine phosphatase non-receptor 22 and C-Src tyrosine kinase genes are down-regulated in patients with rheumatoid arthritis. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-10915-9"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Sharp, R.C., Beg, S.A., and Naser, S.A. (2018). Polymorphisms in Protein Tyrosine Phosphatase Non-receptor Type 2 and 22 (PTPN2\/22) Are Linked to Hyper-Proliferative T-Cells and Susceptibility to Mycobacteria in Rheumatoid Arthritis. Front. Cell. Infect. Microbiol., 8.","DOI":"10.3389\/fcimb.2018.00011"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"e22710","DOI":"10.1002\/jcla.22710","article-title":"PTPN22 1858C>T polymorphism is associated with increased CD154 expression and higher CD4+ T cells percentage in rheumatoid arthritis patients","volume":"33","year":"2019","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1080\/15548627.2017.1341453","article-title":"PTPN22 regulates NLRP3-mediated IL1B secretion in an autophagy-dependent manner","volume":"13","author":"Spalinger","year":"2017","journal-title":"Autophagy"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1007\/s00281-019-00753-4","article-title":"Omnipresence of Inflammasome Activities in Inflammatory Bone Diseases","volume":"41","author":"Alippe","year":"2019","journal-title":"Semin. Immunopathol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1111\/j.1365-2249.2006.03278.x","article-title":"Autoimmunity and atherosclerosis: Functional polymorphism of PTPN22 is associated with phenotypes related to the risk of atherosclerosis. The Cardiovascular Risk in Young Finns Study","volume":"147","author":"Pertovaara","year":"2007","journal-title":"Clin. Exp. Immunol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1159\/000329919","article-title":"Atherosclerosis and PTPN22: A study in coronary artery disease","volume":"119","author":"Saccucci","year":"2011","journal-title":"Cardiology"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Li, S., Luo, Z., Su, S., Wen, L., Xian, G., Zhao, J., Xu, X., Xu, D., and Zeng, Q. (2023). Targeted inhibition of PTPN22 is a novel approach to alleviate osteogenic responses in aortic valve interstitial cells and aortic valve lesions in mice. BMC Med., 21.","DOI":"10.1186\/s12916-023-02888-6"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/4\/590\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:15:29Z","timestamp":1760030129000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/4\/590"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,16]]},"references-count":119,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["biom15040590"],"URL":"https:\/\/doi.org\/10.3390\/biom15040590","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,16]]}}}