Studies On The Quality Control And Pharmacokinetics Of Gastrodia Elata Bl. In Rats

Gastrodia elata Bl.(GE), a notable and valuable traditional Chinese medicine(TCM), is derived from the dried tuber of GE, and has been listed in the ‘Sheng Nong’s herbal classic’ and the Pharmacopoeia of the People’s public of China(2010). GE, the bioactive substances of which were phenols and their glycosides, has been used to treat central nervous system and cardiovascular system disease. Numerous pharmacological effects have attributed to these plant species, e.g. anti-inflammatory, anti-aging, anti-asthmatic, improving intelligence and immunologic function.The therapeutic effects of GE are based on the complex interactions of multiple ingredients, however, unclear concerned pharmacodyamic material basis hampers the development of GE. On the basic of the previous research of serum pharmacological of GE, we make the job of determining the constituents absorbed into blood to control the quality of GE. Meanwhile, analyzing the dynamic changes in animals and timed dose-response relationship of bioactive components in GE. The research aim to provide references of inherent quality in the metabolic, pharmacology and toxicology mechanism, accelerate the research of new medicinal agent and clinical administration. The results are as follows:1. Study on quality standard of GE based on absorbed active components in rat plasmaThe UPLC-ESI-MS/MS method for simultaneous quantification of GAS and PA in rat plasma was developed and validated, and the results show that GAS and PA are the constituents absorbed into blood after oral administration of extract of GE in rat. Combining with HPLC techniques, the RP-HPLC method for determination of GAS and PA was established, and the method had a good precision, stability, linearity, and high recovery(>95%). The determination results of GE from 10 difference areas showed that the content of GAS was stable and PA was such a significant difference. In summary, under the guidance of serum pharmacochemistry of TCM, the quality control of GE are developing in a more effective and comprehensive manner. The method would provide a new strategy to control the quality of TCM.2. Distribution study of GAS and PA after oral administration power and extract of GE in ratThe UPLC-ESI-MS/MS method for simultaneous quantification of GAS and PA in different tissues(including brain, heart, liver, spleen, lung and kidney) was developed and validated. The method had a good sensitivity, accuracy and without the matrix interferences. It was the first time to study the tissue distribution of GAS and PA after oral administration of extract and power of GE in rat. The result indicated that after oral administration of 4 g?kg-1 power GAS and PA distributed in heart, liver, spleen, lung and kidney, the concentration of lung and kidney is higher. It was detected PA in brain, but no GAS. And after oral administration of 600 mg·kg-1 extract(equal to 4 g·kg-1 GE) GAS and PA distributed in heart, liver, spleen, lung and kidney, the concentration of kidney is higher. It was detected PA in brain, but no GAS, too.According to the distribution results, the tissue distribution of GAS and PA after oral administration of extract and power of GE were similar, and the metabolic rate of PA was faster than GAS in rat. Whereas, compared to metabolism of extract, GAS and PA were higher content and longer metabolic time in different tissues.3. Brain pharmacokinetics of GAS and PA after oral administration extract of GE in ratThe results of experiment were that after oral administration of 10.50 g·kg-1 extract GAS and PA were detected in brain with the concentration of 878.66 ng?g-1 and 1289.78 ng?g-1, and with 1052.87 ng and 1540.90 ng in whole brain. The results indicated that after oral administration of high dose extract GAS and PA were detected in brain through blood-brain barrier. In addition, the cumulative effect may be found in kidney and lung.4. Extraction process optimization of GAS in GEBesides, optimization of extraction process of GAS by single-factor experiment combined with response surface methodology was researched. The optimized conditions of the extraction are as follows: reflux extraction, extraction solvent water, solid-liquid ratio 1:12.56(g:m L), extraction time 3.54 h, p H 5.23. Under these conditions, GAS content was 8.29 mg·g-1, the relative error was only 1.2% between true value and predictive value. In this experiment, the extraction process was eco-friendly and high extraction efficiency, so it is available for industrial production.