Chemical Constituents Against Drug-resistant Staphylococcus Aureus From Sophora Moorcroftiana And Rheum Officinale

Staphylococcus aureus is threating human health, especially the drug-resistance S. aureus is getting increasingly serious-currently the S. aureus is resistant to many antibiotics including vancomycin. The development of antibiotics hits big obstacles. Therefore, many researchers turn to explore antibacterial compounds from plants. The ’heat clearing and detoxifying’Chinese traditional medicines have the indication which is similar to symptoms of microorganism infection, they has been mostly studied. According to researches, most of the ’heat clearing and detoxifying’ Chinese traditional medicines have been found antibacterially active, especially against Gram-positive bacteria. In this project, according to our antibacterial assay on 40 ’heat clearing and detoxifying’ Chinese herbs, we selected two Chinese herbs, Sophora moorcroftiana and Rheum officinale for further study. Our aim is to explore the foundation of antibacterial and search for anti-bacteria compounds in these two herbs.Sophora moorcroftiana is a Tibetan herb possessing the property of’heat clearing and detoxifying’, which is used in the treatment of damp-heat jaundice, diphtheria, dysentery, digest disorder and echinococcosis. Sophora moorcroftiana grows in limited distribution, it is therefore seldom researched. In our antibacterial assay, the crude extract of Sophora moorcroftiana showed antibacterial activity against six Staphylococcus aureus strains, namely SA1199B, XU212, ATCC25923, RN4220, EMRSA-15, EMRSA-16, and the MIC is 8 mg/L for all the tested strains, which indicated a strong antibacterial activity. The crude extract is separated and purified by means of column chromatography and seven compounds were obtained, of which five were flavonoids and two were matrines.The flavonoid compounds, except compound 5 (tiny amount), were tested for antimicrobial activity against the six strains. Pratensein (2) and alpinumisoflavone (3) have weak antibacterial activity against strains SA1199B, RN4220 and EMRSA-15 (all of their MICs> 32 mg/L). The rest four compounds were tested for their synergistic activity in combination with antibiotics against the mentioned strains, and genistein (1) were found to reduce the MIC value of norfloxacin against strain SA1199B and it showed efflux pump inhibit activity in the efflux pump inhibition assay. Though diosemtin (4) showed no inhibition to efflux pump, it exhibited strong synergistic activity against strain SA1199B, RN4220 and EMRSA-15, reducing the MIC values of the relative antibiotics by 4,8 and 32 fold respectively.Rhubarb is an important ’heat clearing and detoxifying’Chinese traditional medicines. It is the dry roots of plants from Polygonaceae family Rheum palmatum L., Rheum tanguticum Maxim, ex Balf. and Rheum officinale Baill. Of all Chinese medicine in clinical use,105 have the ingredient rhubarb. Over 200 compounds have been isolated from rhubarb, mainly including six chemical skeleton types:anthraquinone, anthrone, stilbenoids, flavonoids, acylglucoside, and pyrone, of which anthraquinones are the symbolic ingredients. Pharmaceutical study indicates that rhubarb exhibited comprehensive biological activites in vitro such as cathartic, anticancer, antibacterial, anti-inflammatory et al.In this study, ten compounds were isolated from Rheum officinale, including five anthraquinones:chrysophanol (8), emodin (9), aloe-emodin (10), physicion (11), desoxyerythrolaccin (12), three flavonoids, namely 2,5-dimethyl-7-hydroxyl chromone (15), (s)-naringenin,16), (-)-catechin (17) and two compounds of other chemical skeletons. The compounds were tested for their antimicrobial activity against the S. aureus metioned above and two of them, emodin and desoxyerylaccin, exhibited strong activity. Their MIC values of emodin is 16 mg/L for all the tested strains and desoxyetylaccin showed a MIC in the rang of 2 to 8 mg/L, differing according to the strains.This thesis contains three parts. Part 1 is preface, in which the backgrounds of this study is introduced, including the present research situation of drug-resistant S. aureus, the distribution of herbs S. moorcroftiana and Chinese tradicinal medicin rhubarb, phytochemical and pharmaceutical study of the two medical plants. In part 2, the identification of the isolated compounds, the results of antibacterial assay and the analysis of the synergy test are presented in detail. The related experimental material and methods as well as the physical and chemical data of the compounds were described in part 3.