Multi-Target Pharmacological Evaluation of Embelin and Piperine against Rheumatoid Arthritis: A Network Pharmacology and Molecular Docking Study
DOI:
https://doi.org/10.56511/JIPBS.2026.13106Abstract
Rheumatoid arthritis is a chronic autoimmune inflammatory illness that causes synovial inflammation, cartilage degradation, joint deterioration, and increasing disability. Conventional medicinal techniques are frequently linked with side effects and poor long-term success, prompting the search for safer multitarget phytotherapeutics. The present study used an integrated network pharmacology and molecular docking technique to examine Embelin and Piperine's antiarthritic potential. SwissTargetPrediction and PubChem were used to identify potential Embelin and Piperine targets, while the GeneCards database was used to find rheumatoid arthritis-associated targets. To discover critical hub genes, common targets were studied using protein-protein interaction (PPI) networks. GO and KEGG pathway enrichment analysis revealed a considerable involvement of inflammatory and immune-regulatory pathways, notably the PI3K-Akt signaling pathway. The Key hub genes discovered were HSP90AA1, SRC, PIK3CA, JAK2, PTK2, and MET. Piperine binds strongly to HSP90AA1 (-7.2 kcal/mol) and JAK2 (-7.5 kcal/mol), similar to the standard treatment Tofacitinib (-7.5 kcal/mol), according to a molecular docking investigation. Embelin had a positive affinity with HSP90AA1 (-6.1 kcal/mol) and JAK2 (-5.8 kcal/mol). These data indicate that Embelin and Piperine may have antiarthritic properties through multitarget regulation of inflammatory and immunological pathways.
Keywords:
Network Pharmacology, Molecular Docking, Inflammation, JAK2, Rheumatoid Arthritis, Autoimmune DiseaseDownloads
References
Firestein GS, McInnes IB. Immunopathogenesis of rheumatoid arthritis. Immunity. 2017 Feb 21;46(2):183 - 96.
O’Sullivan O. Osteoarthritis: pathophysiology and classification of a common disabling condition. In The Palgrave Encyclopedia of Disability 2024 Aug 25 (pp. 1 - 11). Cham: Springer Nature Switzerland.
Abramson SB, Attur M. Developments in the scientific understanding of osteoarthritis. Arthritis research & therapy. 2009 May 19;11(3):227.
Choy E. Understanding the dynamics: pathways involved in the pathogenesis of rheumatoid arthritis. Rheumatology. 2012 Jul 1;51(suppl_5):v3 - 11.
Aletaha D, Smolen JS. Diagnosis and management of rheumatoid arthritis: a review. Jama. 2018 Oct 2;320(13):1360 - 72.
Ma W, Chen H, Yuan Q, Chen X, Li H. Global, regional, and national epidemiology of osteoarthritis in working - age individuals: insights from the global burden of disease study 1990 – 2021. Scientific Reports. 2025 Mar 6;15(1):7907.
Deseatnicova E, Frunze V, Usatii R, Groppa L. Rheumatoid arthritis worldwide: inequalities in epidemiology and care. Revista de Ş tiin ţ e ale S ă n ă t ăţ ii din Moldova. 2026 Mar 10(1):120 - 7.
Gladman DD, Antoni C, Mease P, Clegg DO, Nash P. Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Annals of the rheumatic diseases. 2005 Mar 1;64:ii14 - 7.
Safiri S, Kolahi AA, Smith E, Hill C, Bettampadi D, Mansournia MA, Hoy D, Ashrafi - Asgarabad A, Sepidarkish M, Almasi - Hashiani A, Collins G. Global, regional and national burden of osteoarthritis 1990 - 2017: a systematic analysis of the Global Burden of Disease Study 2017. Annals of the rheumatic diseases. 2020 Jun 1;79(6):819 - 28.
Almutairi K, Nossent J, Preen D, Keen H, Inderjeeth C. The global prevalence of rheumatoid arthritis: a meta - analysis based on a systematic review. Rheumatology international. 2021 May;41(5):863 - 77.
Devanshu, Raj A, Singh RP, Gulia M, Arora S, Dutt R, Jhawat V. Nanoparticle embedded dot matrix transdermal patches: a novel approach for targeted and controlled drug delivery in rheumatoid arthritis. Inflammopharmacology. 2026 Mar 27:1 - 20.
Burmester GR, Pope JE. Novel treatment strategies in rheumatoid arthritis. The Lancet. 2017 Jun 10;389(10086):2338 - 48.
Kunnumakkara AB, Sailo BL, Banik K, Harsha C, Prasad S, Gupta SC, Bharti AC, Aggarwal BB. Chronic diseases, inflammation, and spices: how are they linked?. Journal of translational medicine. 2018 Jan 25;16(1):14.
Bhandari U, Jain N, Pillai KK. Further studies on antioxidant potential and protection of pancreatic β‐ cells by Embelia ribes in experimental diabetes. Journal of Diabetes Research. 2007;2007(1):015803.
Chitra M, Sukumar E, Suja V, Devi S. Antitumor, anti - inflammatory and analgesic property of embelin, a plant product. Chemotherapy. 1994 Sep 11;40(2):109 - 13.
Nikolovska - Coleska Z, Xu L, Hu Z, Tomita Y, Li P, Roller PP, Wang R, Fang X, Guo R, Zhang M, Lippman ME. Discovery of embelin as a cell - permeable, small - molecular weight inhibitor of XIAP through structure - based computational screening of a traditional herbal medicine three - dimensional structure database. Journal of medicinal chemistry. 2004 May 6;47(10):2430 - 40.
Poojari R. Embelin – a drug of antiquity: shifting the paradigm towards modern medicine. Expert opinion on investigational drugs. 2014 Mar 1;23(3):427 - 44.
Srinivasan K. Black pepper and its pungent principle - piperine: a review of diverse physiological effects. Critical reviews in food science and nutrition. 2007 Oct 25;47(8):735 - 48.
Meghwal M, Goswami TK. Piper nigrum and piperine: an update. Phytotherapy Research. 2013 Aug;27(8):1121 - 30.
Atal CK, Dubey RK, Singh J. Biochemical basis of enhanced drug bioavailability by piperine: evidence that piperine is a potent inhibitor of drug metabolism. The Journal of pharmacology and experimental therapeutics. 1985 Jan 1;232(1):258 - 62.
Bang JS, Oh DH, Choi HM, Sur BJ, Lim SJ, Kim JY, Yang HI, Yoo MC, Hahm DH, Kim KS. Anti - inflammatory and antiarthritic effects of piperine in human interleukin 1 β - stimulated fibroblast - like synoviocytes and in rat arthritis models. Arthritis research & therapy. 2009 Mar 30;11(2):R49.
Umar S, Sarwar AH, Umar K, Ahmad N, Sajad M, Ahmad S, Katiyar CK, Khan HA. Piperine ameliorates oxidative stress, inflammation and histological outcome in collagen induced arthritis. Cellular Immunology. 2013 Jul 1;284(1 - 2):51 - 9.
Ahmad AV, Khan SW, Ali SA, Yasar Q. Integrated network pharmacology analysis and experimental validation to investigate the mechanism of Flavan - 3 - ols and aromatic resins in depression. Metabolic Brain Disease. 2024 Jun;39(5):763 - 82.
Vikhar Danish Ahmad A, Khan SW, Ali SA, Yasar Q. Network pharmacology combined with molecular docking and experimental verification to elucidate the effect of flavan - 3 - ols and aromatic resin on anxiety. Scientific Reports. 2024 Apr 29;14(1):9799.
Ahmad AV, Yasar Q, Ali SA, Khan SW, Khan MM. Harnessing the synergistic potential of EGCG and camptothecin against skin melanoma: a computational and experimental approach. Mol Divers. 2026;30(1):1553 - 1568.
Published
How to Cite
Issue
Section
Copyright (c) 2026 Sulaiman Ahmad, Shaikh Mahmad kaif, Shaikh Mehmood Dawood
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Journal of Innovations in Pharmaceutical and Biological Sciences is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Based on a work at