Nerolidol: a potential approach in rheumatoid arthritis through reduction of TNF-α, IL-1β, IL-6, NF-kB, COX-2 and antioxidant effect in CFA-induced arthritic model.

Shanila Akhter,Muhammad Shahzad,Shah Jahan,Muhammad Bilal Latif,Alamgeer Alamgeer,Hafiz Muhammad Irfan

doi:10.1007/s10787-022-00930-2

Abstract

Rheumatoid arthritis is primarily associated with inflammation and increased level of proinflammatory cytokines which are released by immune cells, macrophages or activation of arachidonic acid metabolism. The expression of these cytokines, oxidative free radicals and the activation of COX-2 enzymes are crucial targets for chronic inflammation. On the basis of established anti-inflammatory efficacy of nerolidol, the primary study was further appraised to determine its approach against Freund's complete adjuvant (CFA) rheumatoid model. Arthritis was induced by inoculation of 0.1mL CFA injection into the left hind footpad of rats. Anti-arthritic potential of nerolidol (at 200, 400 and 800mg/kg doses) was assessed by measuring the paw volume, body weight, serum analysis, histopathological and radiographs of ankle joints. Expressions of cytokine's panels such as IL-10, IL-4, COX-2, NF-kB, TNF-α, IL-6, PGE-2 and IL-1β were determined by real-time qPCR. Antioxidant enzyme analyses were conducted by measuring the SOD, POD and catalase activity from serum and equated with arthritic control group. Nerolidol prevented body weight loss, stabilized biochemical and haematological homeostasis and significantly reduced the paw volume. Furthermore, X-ray and histopathological assessment of ankle joints showed an improvement in the joint structure of rats treated with nerolidol. Besides that, overexpression of gene pointers like TNF-α, IL-1β, IL-6, NF-kB, PGE-2 and COX-2 in CFA-treated control rats were also reversed with nerolidol. This anti-arthritic mechanism was further supported by the increased level of IL-10, IL-4 and serum antioxidant activity. The present findings demonstrate that nerolidol reduced adjuvant arthritis by downregulating the proinflammatory cytokines and upregulating the aforementioned anti-inflammatory cytokines and may be used as a therapeutic substance for the management of human rheumatoid arthritis.

Highlights

Cytokines are involved in many biological processes including activation, differentiation and growth of cells, as well as inflammation (Feldmann et al, 1996)
Expressions of cytokine’s panels like IL-10, IL-4, COX-2, NF-Kβ, TNF-α, IL-6, PGE-2 and IL-1β were determined by real time qPCR
The present findings demonstrate that nerolidol reduce the adjuvant arthritis by down-regulating the proinflammatory cytokines and up-regulating the aforementioned anti-inflammatory cytokines and may be used as a therapeutic substance for the management of human rheumatoid arthritis

Summary

Introduction

Cytokines are involved in many biological processes including activation, differentiation and growth of cells, as well as inflammation (Feldmann et al, 1996). Apart from augmented level of proinflammatory cytokines, increased level of oxidative strain is an important factor that damages the joints during pathogenesis of RA. These factors increase the production of inflammatory cells especially neutrophils and macrophages, accelerates the release of reactive oxygen sorts in synovial fluid, and cause further tissue destruction (Uttra et al, 2018). Antioxidants defend the cells against oxidative stress on deoxyribonucleic acid, lipids and protein that has been associated with diseases like RA, diabetes, cancer and Alzheimer, and involve in the improvement of treatment (De Carvalho et al, 2018). Glutathione peroxidase, catalase and superoxide dismutase are the enzymes that catalysis the hydrogen peroxides and hydro peroxides into harmless molecules including metal ion binding proteins such as caeruloplasmin and transferrin ( that chelates, sesquter iron) and prevent the production of free radicals (Ighodaro and Akinloye, 2018)

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