The basis of analgesic activity of four Chinese herbs.
This study investigate the effects of four Chinese herbs for their potential therapeutic
use as analgesics. It involved screening for inhibitors of enkephalin-hydrolysing
enzymes, especially selective NEP inhibitors, mixed NEP/APN inhibitors and mixed
NEP/ACE inhibitors. NEP was the key enzyme in the screening systems.
Four Chinese herbs Yan (Corydalis yanhusuo 7: Wang); Gou (Nauclea siý7ensis
Oliv. ); Qiang (Notopterygium incisum Ting ex H. T (7hang); and Chuan (Ligusticum
chuanxiong Hort. ) were tested for their inhibitory effects on NEP activity measured
in a rat kidney extract. Aqueous extracts of Gou and Qiang showed the significant
inhibitory activity on NEP but results with organic extracts were not significant. Gou
showed the strongest inhibitory activity on NEP. It was found that Gou also showed
an inhibitory activity on the other two enkephalin-hydrolysing enzymes, APN and
ACE in the microsomal mixture.
A rat-brain opiate-receptor preparation (section 5.2.1) was used in ligand binding
experiments with competition for the receptor sites between the aqueous Gou extract
and tritium-labelled naloxone. For very small quantities of Gou there was a lowering
of naloxone binding showing the antagonistical action of Gou. At higher
concentrations (> 4 mg/ml of Gou) there was a tendency for naloxone binding to
increase demonstrating potential agonistic activity.
To test whether one compound in Gou had inhibitory activity on the three enzymes,
or several compounds acting together, the aqueous extract of Gou was separated by
HPLC. The HPLC-eluted fractions were pooled into seven parts and collected. The
seven eluates were assayed for their effects on NEP proteolysis of 3H(leu)-
enkephalin. Only six eluates showed inhibitory activity on NEP. The three single
compounds already fractionated by others (rhynchophylline, mitraphylline and
poteropodine) were shown to correspond in the Pool 7. An unexpectedly large
number of active fractions suggest that many active compounds are present in Gou.
It can be concluded that of the four herbs tested Gou (Nauclea sinensis Oliv) offers
considerable potential as a novel analgesic agent.The work described in this dissertation was carried out in the School of Biomolecular
Science, Liverpool John Moores University from October 1994 to May 1999. Unless
otherwise stated it is the original work of the author. This dissertation has not been
submitted, in whole or in part, for any other degree at this or any other university.