53Abstract Chronic/acute synovitis, an early phase of RA, can be experimentally
induced in mice by autoantigen/bacterial antigen challenging and live bacterial
feeding. While a donor of NO replicates the modeling of synovitis, an inhibitor of
NOS blocks the progression of synovitis, suggesting inflammation-triggered NO
burst represents an etiological cause of synovitis. ART, via inhibiting iNOS, can
ameliorate the synovial inflammation by mitigating NO-driven hypoxia, angiogen-
esis, and hyperplasia.
Keywords ART · Antigen · Bacteria · NO · Synovitis
5.1 An Overview on Synovitis and Antisynovitis
RA is a chronic and progressive inflammatory disease that mainly destroys
cartilage and bone (Toes and Huizinga 2009 ). RA is recognized initially by
synovial inflammation (synovitis) in multiple joints, and eventually leading to
the localized destruction of articulates (arthritis). RA also affects lungs, pleura,
pericardium, sclera and subcutaneous tissue, so patients with RA have a raised
risk developing cardiovascular diseases, such as arteriosclerosis and myocardial
infarction (van Zonneveld et al. 2010 ). In a histopathological view, RA is char-
acterized by a pronounced synovial hyperplasia, or called the pannus, a thick-
ened membrane-like covering of the inflammatory granulation tissue over the
articular cartilage. Like a malignant tumor, the pannus can invade and destroy
cartilage and bone by secreting matrix proteases such as metalloproteinases and
aggrecanases (Laragione and Gulko 2010 ). The synovitis-associated synovial
hyperplasia and pannus formation can also promote the excretion of proinflam-
matory cytokines (Smith 2011 ).
Although the etiological cue initiating RA remains undefined, several kinds
of disease-modifying antirheumatic drugs have been applied to the clinical
treatment of RA for over 60 years. There was a significant explosion of such
Chapter 5
ART for Anti-inflammation
© The Author(s) 2015
Q.-P. Zeng, Artemisinin and Nitric Oxide, SpringerBriefs in Molecular Science,
DOI 10.1007/978-3-662-47688-8_5