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A molecular insight of inflammatory cascades in rheumatoid arthritis and anti-arthritic potential of phytoconstituents

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Abstract

Rheumatoid arthritis (RA) is an auto-immune inflammatory disorder of the synovial lining of joints marked by immune cells infiltration and hyperplasia of synovial fibroblasts which results in articular cartilage destruction and bone erosion. The current review will provide comprehensive information and results obtained from the recent research on the phytochemicals which were found to have potential anti-arthritic activity along with the molecular pathway that were targeted to control RA progression. In this review, we have summarized the scientific data from various animal studies about molecular mechanisms, possible side effects, associations with conventional therapies, and the role of complementary and alternative medicines (CAM) for RA such as ayurvedic medicines in arthritis. In the case of RA, phytochemicals have been shown to act through different pathways such as regulation of inflammatory signaling pathways, T cell differentiation, inhibition of angiogenic factors, induction of the apoptosis of fibroblast-like synoviocytes (FLS), inhibition of autophagic pathway by inhibiting High-mobility group box 1 protein (HMGB-1), Akt/ mTOR pathway and HIF-1α mediated Vascular endothelial growth (VEGF) expression. Also, osteoclasts differentiation is inhibited by down-regulating the VEGF expression by decreasing the accumulation of the ARNT (Aryl Hydrocarbon Receptor Nuclear Translocator)-HIF-1α complex Although phytochemicals have shown to exert potential anti-arthritic activity in many animal models and further clinical data is needed to confirm their safety, efficacy, and interactions in humans.

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Abbreviations

bFGF:

Basic fibroblast growth factor

CAM:

Complementary and alternative medicine

CXCR4:

CXC chemokine receptor 4

DNMT:

DNA methyltransferase

ERK:

Extracellular-signal-regulated kinase

FLS:

Fibroblast-like synoviocytes

FOXP3:

Forkhead box P3

GSK3B:

Glycogen synthase kinase 3B

HMGB-1:

High-mobility group box 1 protein

MALAT1:

Metastasis associated lung adenocarcinoma transcript 1

MAPK:

Mitogen activated protein kinase

MHC:

Major histocompatibility complex

OPG:

Osteoprotegerin

RAGE:

Receptor for advanced glycation end products

RANKL:

Receptor activator of nuclear factor-κB ligand

ROR:

Retinoic orphan receptor

STAT3:

Signal transducer and activator of transcription 3

UAA:

Ursolic acid-3-acetate

VEGF:

Vascular endothelial growth factor

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Acknowledgements

The authors would like to acknowledge the Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Government of India for their financial support.

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  1. Department of Biological Science, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India

    Vaibhav Patidar, Shruti Shah, Rahul Kumar, Shashi Bala Singh & Dharmendra Kumar Khatri

  2. Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India

    Pankaj Kumar Singh

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Patidar, V., Shah, S., Kumar, R. et al. A molecular insight of inflammatory cascades in rheumatoid arthritis and anti-arthritic potential of phytoconstituents. Mol Biol Rep 49, 2375–2391 (2022). https://doi.org/10.1007/s11033-021-06986-7

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