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Attenuation of CFA-induced arthritis through regulation of inflammatory cytokines and antioxidant mechanisms by Solanum nigrum L. leaves extracts

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Abstract

Solanum nigrum L. is a popular traditional medicine for various inflammatory conditions including rheumatism and joint pain. The current study aimed to evaluate the anti-arthritic mechanism of Solanum nigrum L. Four extracts were prepared using n-hexane, methanol, chloroform, and water. The anti-nociceptive and anti-inflammatory activity was carried out with 100, 200, and 300 mg/kg body wt. PO of each extract by the hot plate and carrageenan-induced paw oedema methods, respectively. The anti-arthritic study was performed with chloroform and aqueous extracts (300 mg/kg) in complete Freund’s adjuvant (CFA)-induced arthritis. Paw size (mm), ankle joint diameter (mm), and latency time (sec) were recorded on day 0 and every 4th day till 28 days. The hematological, inflammatory, and oxidative biomarkers were estimated. Results showed that significant analgesia (p < 0.05) and reduction in paw inflammation were achieved with all extracts. The highest percent inhibition in Carrageenan-induced inflammation was achieved with 300 mg/kg of chloroform (72.19%) and aqueous (71.30%) extracts, respectively. In the CFA model, both extracts showed a significant reduction in paw size and ankle joint diameter (p < 0.05). The RT-qPCR analysis revealed the upregulation of interleukin-4 and interleukin-10, and down-expression of interleukin-1β, interleukin-6, tumor necrosis factor-α, cycloxygenase-2, nuclear factor-κB, prostaglandin E synthase 2, and interferon-γ. A significant increase in superoxide dismutase, catalase, and glutathione levels was observed. Hence, it is concluded that Solanum nigrum L. leaf extracts regulate the expression of inflammatory markers and improve oxidative stress resulting in the attenuation of CFA-induced arthritis.

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Data availability statement

The datasets analyzed during the current study are not publicly available due to the confidentiality of Ph.D. research data but are available from the corresponding author on reasonable request.

Abbreviations

RA:

Rheumatoid arthritis

CFA:

Complete Freund’s adjuvant

IL-1β:

Interleukin- 1Beta

IL-4:

Interleukin-4

IL-6:

Interleukin-6

IL-10:

Interleukin- 10

TNF-α:

Tumor necrosis factor-alpha

COX-2:

Cycloxegenase-2

NF-κB:

Nuclear factor-kappa B

PGES-2:

Prostaglandin E synthase 2

IFN-γ:

Interferon gamma

CRP:

C-reactive protein

PCR:

Polymerase chain reaction

SOD:

Superoxide dismutase

GSH:

Glutathione

ACPA:

Anti-citrullinated protein/peptide antibody

APC:

Antigen-presenting cells

ELISA:

Enzyme-linked immunosorbent assay

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Acknowledgements

The authors express their gratitude to Punjab University College of Pharmacy (PUCP), University of the Punjab Lahore, Pakistan for providing facilities for the conduct of this Ph.D. project of 01-P-PCOL/15a.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

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

    Bazgha Gul, Rukhsana Anwar, Mohammad Saleem, Muhammad Ihsan Ullah & Shahzad Kamran

  2. Institute of Pharmacy, Lahore College for Women University, Lahore, Pakistan

    Bazgha Gul

  3. Gulab Devi Institute of Pharmacy, Gulab Devi Hospital, Lahore, Pakistan

    Mobasher Ahmad

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  1. Bazgha Gul
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Contributions

The study was designed and supervised by RA and MS. Material preparation, data collection, and experiments were performed by BG. HPLC GC–MS data interpreted by SK. The data analysis was done by BG and MA. Manuscript writing was done by BG, MIU, and SK. All the authors read and approved the final manuscript.

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Correspondence to Rukhsana Anwar.

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Gul, B., Anwar, R., Saleem, M. et al. Attenuation of CFA-induced arthritis through regulation of inflammatory cytokines and antioxidant mechanisms by Solanum nigrum L. leaves extracts. Inflammopharmacol 31, 3281–3301 (2023). https://doi.org/10.1007/s10787-023-01357-z

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