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Liu, B
Languages: English
Types: Doctoral thesis
Subjects: RV

Classified by OpenAIRE into

mesheuropmc: fungi
his 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 siĆ½7ensis 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.
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