Chemical Composition of Pterospermum heterophyllum Root and its Anti-Arthritis Effect on Adjuvant-Induced Arthritis in Rats via Modulation of Inflammatory Responses.

Li Yang,Ronghua Liu,Yong Zhang,Jingjing Zhao,Aiguo Fan,Junwei He

doi:10.3389/fphar.2020.584849

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease without effective and beneficial drugs. Many traditional folk medicines have been proven to be effective in treating RA. Among these, the root of Pterospermum heterophyllum Hance has been widely used as a traditional remedy against RA in China, but there is no scientific basis yet. The aim of this study was to investigate for the first time the chemical compositions and therapeutic effect of P. heterophyllum on adjuvant-induced arthritis (AIA) model in rats. 73 compounds were identified from P. heterophyllum based on ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-qTOF-MS/MS), and flavonoids may be partly responsible for the major anti-arthritic effect. In parallel, the P. heterophyllum extract at 160, 320, and 640 mg/kg/day were orally administered to rats for 22 days after post-administration adjuvant. The results showed that P. heterophyllum remarkably ameliorated histological lesions of the knee joint, increased body weight growth, decreased arthritis score, reduced thymus and spleen indices in model rats. Moreover, P. heterophyllum treatment persuasively downregulated the levels of rheumatoid factor (RF), C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-6, IL-17, cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) and matrix metalloproteinase-2 (MMP-2), and observably upregulated IL-4 and IL-10 levels in model rats. These findings suggest that P. heterophyllum has a prominent anti-RA effect on AIA rats by modulating the inflammatory responses, and supports the traditional folk use of this plant.

Highlights

Rheumatoid arthritis (RA) is a chronic, systematic and autoimmune inflammatory disease that results in progressive synovitis, joint swelling and damage, synovial hyperplasia, and bone and cartilage erosion (Yousefi et al, 2014; Saleem et al, 2020; Zhu et al, 2020)
Flavonoids may be responsible for the major active constituents in the roots of P. heterophyllum against RA as traditional folk medicine in China for centuries; further studies are needed to isolate and identify the bioconstituents directly related to anti-RA activity and its probable mechanism in vivo and in vitro of this plant
Our results indicate that treatment of P. heterophyllum obviously reduces the levels of TNF-α, IL-1β, IL-6 and IL-17, and increases the expression of IL-4 and IL-10, implying that the anti-RA effect of P. heterophyllum is achieved to a certain extent via the inhibition of pro-inflammatory cytokines and the elevation of anti-inflammatory cytokines in adjuvant-induced arthritis (AIA) model rats

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic, systematic and autoimmune inflammatory disease that results in progressive synovitis, joint swelling and damage, synovial hyperplasia, and bone and cartilage erosion (Yousefi et al, 2014; Saleem et al, 2020; Zhu et al, 2020). The etiology of RA is intricate and vague, inflammatory factors, including pro-inflammatory cytokines, anti-inflammatory cytokines and inflammatory mediators, are responsible for bone and cartilage erosions, and play a crucial role in this disease (Wang et al, 2017a; Rui et al, 2019; Saleem et al, 2020). The root of P. heterophyllum is a vital TCM and has been used for centuries as an empiric treatment for RA and other inflammation-related diseases (Editorial Committee of Traditional Chinese Medicine 1999; Yang et al, 2016; Yang et al, 2019a). Despite good clinical practice and good clinical effects, the phytochemical profiling and anti-RA efficacy of P. heterophyllum are still unknown, leading to numerous obstacles in the clinical application and reasonable development of this plant

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