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Isolated Compound
from Chinese Herb Proven to Work in Collagen-Induced Arthritis
What problem was studied?
There has been a great demand for new antirheumatic agents that are able to
act on chemical mediators of inflammation, but have fewer toxic effects and cost
less than the current treatments that block the actions of tumor necrosis factor
α and interleukin-1. Practitioners of traditional Chinese medicine have been
using the medicinal plant Tylophora atrofolliculata to treat rheumatism
for a thousand years; the herb is not readily available in the United States,
however. Researchers from Yale University and University of Tennessee,
Knoxville, have isolated an active compound from the Tylophora plant and have
been studying its effects on collagen-induced arthritis, a well-studied animal
model of rheumatoid arthritis (RA).
What was done in the study?
Several extracts have been isolated and synthesized from the Tylophora
plant. One such analog, DCB 3503, was previously shown to inhibit the actions of
a chemical known to be involved in tumor growth and inflammation. This analog
was therefore chosen to be used in this experiment.
Arthritis Foundation-funded
researcher Zhinan Yin, MD, and colleagues injected mice with bovine
collagen. In this particular strain of mice, such an injection is known to
induce inflammatory arthritis that mimics RA. After 21 days, the mice were given
a booster injection of bovine collagen. Thereafter, mice were monitored daily
for signs of arthritis. Arthritis severity was graded on a scale of 0-3.
The injection of
lipopolysaccharide (LPS) is known to accelerate the development of
collagen-induced arthritis. On day 28 after the initial collagen immunization,
some of the mice were injected with LPS.
To test the effects of DCB 3503
on collagen-induced arthritis, mice were treated with either the analog or a
control chemical at different time points after collagen immunization. Mice were
treated either before the onset of inflammation or after the onset of
inflammation. To test the effects of DCB 3503 on the LPS-enhanced arthritis
model, a portion of the collagen-injected mice were treated with the DCB 3503
either before or after the injection of LPS.
What were the study results?
Mice treated with DCB 3503 before the onset of inflammation showed decreased
severity and delayed onset of arthritis. Only 1 of 8 mice in the active
treatment group developed mild arthritis, but 9 of 10 mice in the control group
developed arthritis. Once DCB 3503 therapy was discontinued, the incidence and
severity of arthritis increased in the treatment group.
Mice treated with DCB 3503
after the onset of inflammation showed no progression or even a reduced severity
of arthritis. The control mice, however, continued to develop severe arthritis.
Some of the mice were injected
with LPS to accelerate the development of arthritis. Mice treated with DCB 3503
before the LPS injection remained free of arthritis. However, the control group
(which received LPS but not DCB 3503) developed severe arthritis. Likewise,
progression of arthritis in mice treated with DCB 3503 after the LPS injection
was halted.
Microscopic views of the
affected joints further showed that the degree of joint destruction was reduced
in treated animals. Additional laboratory tests showed that DCB 3503 had little
effect on the initiation of inflammatory joint disease, but rather worked on
events in the chemical cascade that are important for the continuation and
dissemination of inflammatory joint disease.
What’s the relevance to
people with arthritis?
This study demonstrates that DCB 3503, a tylophorine analog derived from the
Tylophora plant, effectively inhibits the development and progression of
collagen-induced arthritis in mice. It has been shown to do this by suppressing
the production of proinflammatory chemicals and mediators of inflammation. These
results suggest that DCB 3503 has potential as a therapeutic agent for
inflammatory arthritis in humans.
The next step toward the
development of such a therapeutic agent is a clinical trial. Researchers at Yale
are now seeking the funding to begin such a trial.
Source: Arthritis &
Rheumatism, Vol. 54, No. 3
http://www3.interscience.wiley.com/cgi-bin/abstract/112468467/ABSTRACT
 
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