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Curcuminoids-enriched extract and its cyclodextrin inclusion complexes ameliorates arthritis in complete Freund’s adjuvant-induced arthritic mice via modulation of inflammatory biomarkers and suppression of oxidative stress markers

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Abstract

Curcuma longa extract and its marker curcuminoids have potential use in inflammatory conditions. However, curcuminoids solubility and bioavailability are major hindrances to their bioactivity. The current study investigated green extraction-based curcuminoids-enriched extract (CRE) prepared from C. longa and its cyclodextrin inclusion complexes, i.e., binary inclusion complexes (BC) and ternary inclusion complexes (TC), in complete Freund’s adjuvant (CFA)-induced mice for their comparative anti-arthritic efficacy. CRE, BC, and TC (2.5 and 5 mg/kg) with the standard drug diclofenac sodium (13.5 mg/kg) were orally administered to mice for 4 weeks. Variations in body weight, hematological and biochemical parameters, along with gene expression analysis of arthritis biomarkers, were studied in animals. The histopathological analysis and radiographic examination of joints were also performed. CRE, BC and TC treatment significantly restored the arthritic index, histopathology and body weight changes. The concentration of C-reactive protein, rheumatoid factor and other liver function parameters were significantly recovered by curcuminoids formulations. The pro-inflammatory cytokines (NF-κB, COX-2, IL-6, IL-1β, and TNF-α) gene expression was considerably (p < 0.001) downregulated, while on the other side, the anti-inflammatory genes IL-4 and IL-10 were upregulated by the use of CRE and its complexes. The concentration of antioxidant enzymes was considerably (P < 0.001) recovered by CRE, BC and TC with marked decrease in lipid peroxidation, erosion of bone, inflammation of joints and pannus formation in comparison to arthritic control animals. Therefore, it is concluded that green CRE and its cyclodextrin formulations with enhanced solubility could be considered as an applicable therapeutic choice to treat chronic polyarthritis.

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Acknowledgements

This research was financially supported by Prince of Songkla University and the Ministry of Higher Education, Science, Research and Innovation under the Reinventing University Project (Grant Number REV65026).

Funding

This research was financially supported by Prince of Songkla University and Ministry of Higher Education, Science, Research and Innovation under the Reinventing University Project (Grant Number REV65026).

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, Pakistan

    Uzma Saleem, Zunera Chauhdary, Zunaira Bakhtawar & Maryam Farrukh

  2. Department of Pharmacognosy, College of Pharmacy, Kingdom of Saudi Arabia, King Saud University, P.O. Box 22452, 11495, Riyadh, Saudi Arabia

    Jawaher Alqahtani

  3. Department of Biology, Jamoum University College, Umm Al-Qura University, 21955, Makkah, Saudi Arabia

    Ifat Alsharif

  4. Department of Medical Emergency Services, College of Health Sciences-AlQunfudah, Umm Al-Qura University, Makkah, Saudi Arabia

    Tourki A. S. Baokbah

  5. Department of Pharmacy, Hazara University, Mansehra, Pakistan

    Muhammad Ajmal Shah

  6. Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida, MSD2080, Malta

    Renald Blundell

  7. Centre for Molecular Medicine and Biobanking, University of Malta, Msida, MSD2080, Malta

    Renald Blundell

  8. Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai, 90112, Thailand

    Muhammad Ajmal Shah & Pharkphoom Panichayupakaranant

  9. Phytomedicine and Pharmaceutical Biotechnology Excellence Centre, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai, 90112, Thailand

    Pharkphoom Panichayupakaranant

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  1. Uzma Saleem
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Saleem, U., Chauhdary, Z., Bakhtawar, Z. et al. Curcuminoids-enriched extract and its cyclodextrin inclusion complexes ameliorates arthritis in complete Freund’s adjuvant-induced arthritic mice via modulation of inflammatory biomarkers and suppression of oxidative stress markers. Inflammopharmacol 31, 3047–3062 (2023). https://doi.org/10.1007/s10787-023-01370-2

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