| Houttuynia cordata Thunb.(H. Cordata) is a member of Saururaceae and has a wide value of academic research both as an edible vegetable and a kind of traditional Chinese medicine. Among chemical components of H. Cordata, volatile constituents has the highest medicinal value, which were mainly consisted of aliphatic components such as Decanoyl acetaldehyde,2-Undecanone (methyl nonyl ketone) and terpenoids such as alpha pinene, beta myrcene, etc. Combined with the local characteristics resources, nasal drops made by steam distillation liquid from H. Cordata has been used in the treatment of acute and chronic rhinitis, sinusitis for nearly40years in Tongji hospital. Then, researches on nasal spray of H. Cordata were conducted by our team. The recent phase Ⅱ clinical trials demonstrated that, Yuxingcao nasal spray showed a significantly better effect on acute and chronic rhinitis than the saline placebo group.Traditional Chinese medicine and its preparations with complex compositions play their overall effects through multi-level and multi-target on the organism in some specific aspects of biological networks. In order to truly reflect the intrinsic and overall quality, and guarantee the clinical effectiveness and safety of traditional Chinese medicine and its preparations, establishment of quality evaluation model based on biological activity will be the trend in quality study of them. To explore a quality evaluation model based on the common components with anti-inflammatory activity, four compounds as a-pinene, β-myrcene,1-decanol and2-Undecanone were selected as analytes based on literatures and previous experimental results of our team. The dose-effect relationships of the common compounds were evaluated with the result that they provided inhibitory effect on xylene-induced ear edema formation in a dose-dependent manner. Then an analytical method for simutaneous determination of the four volatile components was established. And they were also found by GC/MS in mouse serum after oral administration of volatile oil and water distillate liquid of H. Cordata. Samples with higher contents of the four components have stronger anti-inflammatory activity than those with lower contents inExcept the four compounds above, Sodium Houttuyfonate, the additional compound of Decanoyl acetaldehyde and sodium bisulfite, is also an important active component from H. Cordata. Preparations with Sodium Houttuyfonate as material have been used in clinic for many years. But Houttuyfonate will be converted into2-Undecanone in the progress of stem distillation. It is possible that Sodium Houttuyfonate may be converted into2-Undecanone. For ensuring the stability of Sodium Houttuyfonate in process of pharmaceutics technology and exploring its material basis of anti-inflammatory efficacy, inflammation models of RAW264.7cell induced by LPS and xylene-induced ear edema in mice were used for anti-inflammatory activity comparison of Sodium Houttuyfonate and2-Undecanone. Sodium Houttuyfonate was found to have better anti-inflammatory bioactivity than2-Undecanone at the same dosage both in vitro and in vivo. Then some conditions were studied to find that the main influence factors on transformation from Sodium Houttuyfonate to2-Undecanone were solvent, temperature and pH value. Ingredients analysis in vivo showed that Sodium Houttuyfonate quickly entered the blood circulation and tissues without transformation to2-Undecanone.Because Sodium Houttuyfonate which has the same pharmaceutical efficacy as Decanoyl acetaldehyde showed better anti-inflammatory effect than2-Undecanone, previous study only with2-Undecanone as indicator cannot really reflect the quality of H. Cordata and its preparations. Ingredients in ethyl acetate extract of different plant parts of H. cordata from different seasons and drying methods were analyzed by GC and GC-MS combined with cluster analysis and discriminant analysis. Eight common ingredients of higher contents including Decanoyl acetaldehyde were selected as comprehensive indicators to evaluate the quality of H. cordata. Different parts of fresh herbs have their corresponding better harvest season. At the same drying degree, freeze-drying method could retain relatively more Decanoyl acetaldehyde than air-drying and sun-dring method. Through researches above, it was wished to provide some useful information for ensuring the quality uniformity and clinical effectiveness of H. cordata related preparations, and benefit for the rational use of its resources.To explore the differences on the anti-inflammatory mechanism between volatile oil, Sodium Houttuyfonate and2-Undecanone, so as to provide theoretical basis for their different anti-inflammatory efficacy in vivo, TLR4/MD2blocker was used to close the site, then expression level of TLR4and JNK MAPK in cells after being intervented by volatile oil, Sodium Houttuyfonate and2-Undecanone were analyzed using western blot. Elisa method was used to detect the secretion of the inflammatory cytokines such as TNF-a, IL-1β and IL-10. Comparison analysis was then performed between the results of cell experiments in vitro and anti-inflammatory efficacy in vivo. The results showed that volatile oil and2-Undecanone may play their anti-inflammatory effects by partly inhibiting LPS-TLR4/MD-2-MAPK-TNF-a signaling pathway, TLR4/MD-2may be one of their anti-inflammatory targets. But Sodium Houttuyfonate possibly play its anti-inflammatory effect through other ways except TLR4/MD-2, so as to demonstrate the differences on anti-inflammatory activity in vivo as well as in vitro compared with volatile oil and2-Undecanone.Through all above study, a quality evaluation model of H. Cordata and its preparations based on the common components with anti-inflammatory effect was established in this paper. The material basis of anti-inflammatory effect and their action mechanism were also explored. It was wished to provide some new ideas for the quality assessment and control of H. cordata and its preparations, and provide some information resources for further research and development of new anti-inflammatory drugs with H. cordata as raw materials and benefit for the rational use of its resources. |
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