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Diospyros malabarica (Desr.) Kostel fruits extract attenuated acute and chronic inflammation through modulation of the expression of pro- and anti-inflammatory biomarkers in rat models

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Abstract

Rheumatoid arthritis is a chronic inflammatory disorder of polyarticular tissues, characterised by progressive synovitis. Its prolonged treatment imparts a huge burden on the healthcare system and results in toxicity, which necessitates the search for safe, efficacious and cost-effective therapies. Diospyros malabarica (Desr.) Kostel is traditionally used for anti-inflammatory purposes; however, to the best of our knowledge, there is no detailed study reporting the in vivo anti-inflammatory potential of this plant. Therefore, in the current study, the methanol extract of D. malabarica (Desr.) Kostel fruit (mDMF) was evaluated for its antioxidant, anti-inflammatory and anti-arthritic potentials, along with its underlying mechanisms. The antioxidant activity was evaluated by DPPH assay. Total phenolic and flavonoid contents were estimated via colorimetric and high-performance liquid chromatography (HPLC) methods. Different doses (250, 500 and 750 mg/kg) of mDMF were used to evaluate the anti-inflammatory and anti-arthritis actions in acute inflammatory (carrageenan and histamine-induced paw oedema) and Freund’s complete adjuvant (FCA)-induced arthritis rat models. Levels of various pro- and anti-inflammatory biomarkers were estimated using ELISA and RT-PCR techniques. Paw samples were used for different histopathological and radiographic studies. Qualitative phytochemical and HPLC analyses indicated the presence of various polyphenolic compounds in mDMF, which exhibited marked antioxidant activity in the DPPH assay. mDMF showed time-dependent anti-inflammatory and anti-arthritic effects in in vivo models. ELISA assay data showed significant (p < 0.05) reduction in the serum levels of C-reactive protein and rheumatoid factor in the mDMF treatment groups. RT-PCR data showed significant (p < 0.05) down-regulation of various pro-inflammatory markers (TNF-α, NF-κB, COX-2, IL-1β and IL-6) and up-regulation of anti-inflammatory markers (IκB, IL-4 and IL-10) in serum samples of rats treated with mDMF. The histopathology of the ankle joints showed reduced pannus formation, joint swelling and synovial hyperplasia in mDMF-treated animals when compared with the untreated disease control group. Overall, it may be concluded that the antioxidant, anti-inflammatory and anti-arthritis properties of mDMF are due to its flavonoid and phenolic constituents. Further studies using a stable oral dosage form of D. malabarica (Desr.) Kostel fruits extract are warranted to explore its effects in other inflammatory disorders, including irritable bowel syndrome, appendicitis and hepatitis.

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Data availability

All the raw data of the study are available to reviewers on reasonable request.

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Acknowledgements

We would like to thank the University College of Pharmacy, University of the Punjab, Lahore, Pakistan for providing the research facilities to carry out this project.

Funding

This project was funded by the Punjab University College of Pharmacy, University of the Punjab, Lahore, Pakistan internal research funds.

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Authors and Affiliations

  1. Punjab University College of Pharmacy, University of the Punjab, Lahore, Pakistan

    Saba Zia, Mohammad Saleem & Khalid Hussain

  2. Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Punjab, Pakistan

    Muhammad Asif

  3. School of Science, Monash University, Subang Jaya, Selangor, Malaysia

    Beenish Zia Butt

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  1. Saba Zia
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  2. Mohammad Saleem
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  3. Muhammad Asif
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  4. Khalid Hussain
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  5. Beenish Zia Butt
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Contributions

All authors contributed equally in the current work. This research work was performed by Saba Zia as a part of her PhD thesis under the supervision of Prof. Dr. Mohammad Saleem and Prof. Dr. Khalid Hussain.

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Correspondence to Saba Zia or Mohammad Saleem.

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The study complied with ethical considerations vide No. D/344/IIM.

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Zia, S., Saleem, M., Asif, M. et al. Diospyros malabarica (Desr.) Kostel fruits extract attenuated acute and chronic inflammation through modulation of the expression of pro- and anti-inflammatory biomarkers in rat models. Inflammopharmacol 30, 2211–2227 (2022). https://doi.org/10.1007/s10787-022-01048-1

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