Chinese herb proven in arthritis therapy

A root extract of a traditional Chinese medicine called Lei Gong Teng (Tripterygium Wilfordii Hook) has been shown to safely and effectively reduce pain and inflammation in a randomised, double-blind, placebo-controlled trial of a small group of people with treatment-resistant rheumatoid arthritis (RA). In the 20-week clinical trial, 21 RA patients were randomly assigned to one of three treatment groups: placebo, low-dose extract, or high-dose extract. After four weeks, 80% of patients in the high-dose group and 40% in the low-dose group showed rapid improvement in symptoms compared with no improvement in the placebo group. Side effects were minor for all three treatment groups. According to the researchers Lei Gong Teng is unique, because it slows down the overactive immune system, reduces inflammation by turning off inflammatory genes such as tumour necrosis factor alpha, and reduces the activity of B and T cells. It has the potential to treat other immune diseases such as lupus, and further studies are planned. (Arthritis & Rheumatism 2002;46(7):1735-43).

DALLAS, TEXAS. A team of researchers from the University of Texas and the National Institutes of Health reports that an extract of the Chinese herbal remedy Tripterygium wilfordii Hook F (TWHF) has proven effective in the treatment of severe rheumatoid arthritis. TWHF has been used for centuries in China to treat rheumatoid arthritis, ankylosing spondylitis, psoriasis, and IgA nephropathy. Preliminary studies in animals have shown that TWHF extracts have anti- inflammatory and immunosuppressive effects comparable to those of prednisone.

Thirteen patients with long standing rheumatoid arthritis participated in the trial. The initial dosage was 30 mg/day; this was gradually increased to 570 mg/day over a 12-18 month period. Nine of the patients went through the whole program. The patients all experienced marked improvement and one went into complete remission on a dose of 390 mg/day. Morning stiffness was the first symptom to improve. At baseline it lasted an average of 265 minutes. On a dose of 390 mg/day it reduced to 10 minutes. ESR (erythrocyte sedimentation rate) went from 55 mm/hour to 22 mm/hour on a dose of 480 mg/day. Sixty per cent of the patients experienced significant (more than 20 per cent) improvement on a dose of 180 mg/day. A dose of 300-480 mg/day was required for maximum benefit. This is comparable to the dosages used in China and was found to be entirely safe. The researchers are currently conducting a much larger, double- blind, controlled study to confirm the benefits of TWHF extracts.

Tao, Xuelian, et al. A phase I study of ethyl acetate extract of the Chinese antirheumatic herb Tripterygium wilfordii Hook F in rheumatoid arthritis. Journal of Rheumatology, Vol. 28, October 2001, pp. 2160-67

Discovery of molecular mechanism reveals other benefits of Tripterygium wilfordii Hook F (Lei gong teng - Thunder God Vine)

Researchers at the Johns Hopkins School of Medicine have discovered that a
natural product isolated from a traditional Chinese medicinal plant commonly
known as thunder god vine, or lei gong teng, and used for hundreds of years
to treat many conditions including rheumatoid arthritis works by blocking
gene control machinery in the cell. The report, published as a cover story
of the March issue of Nature Chemical Biology, suggests that the natural
product could be a starting point for developing new anticancer drugs.

"Extracts of this medicinal plant have been used to treat a whole host of
conditions and have been highly lauded for anti-inflammatory,
immunosuppressive, contraceptive and antitumor activities," says Jun O. Liu,
Ph.D., a professor of pharmacology and molecular sciences at Johns Hopkins.
"We've known about the active compound, triptolide, and that it stops cell
growth, since 1972, but only now have we figured out what it does."

Triptolide, the active ingredient purified from the plant Tripterygium
wilfordii Hook F, has been shown in animal models to be effective against
cancer, arthritis and skin graft rejection. In fact, says Liu, triptolide
has been shown to block the growth of all 60 U.S. National Cancer Institute
cell lines at very low doses, and even causes some of those cell lines to
die. Other experiments have suggested that triptolide interferes with
proteins known to activate genes, which gives Liu and colleagues an entry
point into their research.

The team systematically tested triptolide's effect on different proteins
involved with gene control by looking at how much new DNA, RNA and protein
is made in cells. They treated HeLa cells with triptolide for one hour,
compared treated to untreated cells and found that triptolide took much
longer to have an effect on the levels of newly made proteins and DNA, yet
almost immediately blocked manufacture of new RNA. The researchers then
looked more closely at the three groups of enzymes that make RNA and found
that low doses of triptolide blocked only one, RNAPII.

But the RNAPII enzyme complex actually requires the assistance of several
smaller clusters of proteins, according to Liu, which required more
investigative narrowing down. Using a small gene fragment in a test tube,
the researchers mixed in RNAPII components and in some tubes included
triptolide and some not to see which combinations resulted in manufacture of
new RNA. Every combination of proteins that included a cluster called TFIIH
stopped working in the presence of triptolide.

But again, TFIIH is made of 10 individual proteins, many of which, according
to Liu, have distinct and testable activities. Using information already
known about these proteins and testing the rest to see if triptolide would
alter their behaviors, the research team finally found that triptolide
directly binds to and blocks the enzymatic activity of one of the 10, the
XPB protein.

"We were fairly certain it was XPB because other researchers had found
triptolide to bind to an unknown protein of the same size, but they weren't
able to identify it," says Liu. "

To convince themselves that the interaction between triplotide and XPB is
what stops cells from growing, the researchers made 12 chemicals related to
triplotide with a wide range of activity and treated HeLa cells with each of
the 12 chemicals at several different doses. By both counting cells and
testing XPB activity levels, the team found that the two correlate;
chemicals that were better at decreasing XPB activity were also better at
stopping cell growth and vice versa.

"Triptolide's general ability to stop RNAPII activity explains its
anti-inflammatory and anticancer effects," says Liu. "And its behavior has
important additional implications for circumventing the resistance that some
cancer cells develop to certain anticancer drugs. We're eager to study it
further to see what it can do for future cancer therapy."

This research was supported in part by discretionary funds from the Johns
Hopkins Department of Pharmacology and the Sidney Kimmel Comprehensive
Cancer Center at Johns Hopkins.

Authors on the paper include Denis Titov, Qing-Li He, Shridhar Bhat,
Woon-Kai Low, Yongjun Dang, Michael Smeaton and Jun O. Liu of Johns Hopkins;
Benjamin Gilman, Jennifer Kugel and James Goodrich of the University of
Colorado, Boulder; and Arnold Demain of Drew University, Madison, N.J.

: Herbal Medicine