&amp;lt;i&amp;gt;Sphaeranthus indicus&amp;lt;/i&amp;gt;: Traditional Wisdom to Modern Medicine—An Orally Active, Potent Cytokine Inhibitor for the Management of Inflammatory Disorders

Jacqueline Trivedi,Sapna Parikh,Aurelio Lobo,Ashish Suthar,Mahesh Jadhav,Firuza Kharas,Asha Almeida,Ankita Srivastava,Shruta Dadarkar,Lyle Fonseca,Roda Dalal

doi:10.4236/pp.2016.72014

Abstract

Tumor necrosis factor (TNF-α) is a key regulator of the inflammatory and tissue destruc-tive pathways in rheumatoid arthritis (RA). The clinical success of anti-TNF-α and an-ti-IL-17 biologics has validated the concept that cytokine blockade is beneficial in RA. However, as these drugs are parenterally administered, our efforts are directed at identifying a novel orally active TNF-α inhibitor with a therapeutic profile similar to that of biologics. Since plants are natural immunomodulators, we explored the immunomodulatory potential of Sphaeranthus indicus extract. In our studies, the extract dose-dependently inhibited the release of cytokines in stimulated human peripheral blood mononuclear cells (hPBMCs), and their spontaneous release in synovial cells derived from patients suffering from RA. TNF-α and IFN-γ induced release of p40 subunit of IL-12/ IL-23, and p19 subunit of IL-23 in differentiated THP-1 cells is potently blocked. The expression of endothelial cell adhesion molecules in TNF-α-stimulated HUVECs was also potently inhibited. The oral treatment significantly and dose-dependently reduced LPS-induced TNF-α and IL-1β production in mice. Disease regression was seen in collagen-induced arthritis in DBA/1J mice, which was validated along with radiological and histopathological evaluation. Therefore, the extract of Sphaeranthus indicus could be used in the management of inflammatory conditions.

Highlights

Immune mediated inflammatory disease is a group of unrelated inflammatory conditions that share common inflammatory pathways
Sphira was studied in 12 donors at eight different concentrations (0.3 - 100 μg/ml) in LPS-induced tumor necrosis factor-α (TNF-α), IL-1β, IL-6 and IL-8 release in human peripheral blood mononuclear cells (hPBMCs)
The bright-field images (100×) show that the morphology of HUVECs was maintained, and monocytic cells were shown to be intact in each individual condition (Figure 2(B), lower panel). These results demonstrate that Sphira is effective in blocking adhesion of THP-1 to endothelial cells by inhibiting the TNF-α-induced expression of intercellular adhesion molecule-1 (ICAM-1), VCAM-1 and E-selectin

Summary

Introduction

Immune mediated inflammatory disease is a group of unrelated inflammatory conditions that share common inflammatory pathways. This definition encompasses disorders as diverse as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), psoriatic arthritis (PsA), type 1 diabetes, multiple sclerosis, vasculitis, ankylosing spondylitis (AS), and juvenile chronic arthritis (JCA). Treatment of these conditions incurs substantial costs to patients and society at large. Numerous cytokines have been identified in such diseased tissues across a range of immune mediated inflammatory diseases.

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