Modern Experimental Study On The "Guide Action" Of Platycodon Grandiflorum

Triditional Chinese Medicine medicinal guide theory was a controversial theory of Chinese Medicine theory,which thought that the guide action could change other drug's direction or location,otherwise made them concentrated in special direction or location. Those drug was called guide medicine. Different doctor in different dynasties had different or even completely opposite view on it, which cause the theory have been still on the theoretical stadge and its experimental verification have been still a blank. The study was depended on the characteristic that chemical drugs have identificated structure so that they can be detected quantitative. Choosed Levofloxacin, florfenicol, diofloxacin were given with classic guide drug glatycodon grandiflorum orally, used research methods of pharmacokinetics and organizations pharmacokinetics, and studyed on the glatycodon grandiflorum to three drug's influences on the perperity of pharmacokinetics and distribution in vivo. Perified experimently that latycodon grandiflorum's "guide drugs up" existed objectively. And also explored the mechanism of latycodon grandiflorum's guide action by the method of immunohistochemistry. The study is divide into six part as follows:1. 72 healthy chickens were allocated into two groups at random, group1: The chickens were orally given with single dose of Levofloxacin at 10mg/kg·b·w ,group2:the chickens were given with glatycodon grandiflorum at 2g/kg. b. w simultaneously. The concentrations of Levofloxacin in plasma and tissues were determined by high performance liquid chromatography with a limit of detection of 0.001mg /L in plasma and 0.001μg/g in tissues, respectively. The pharmacokinetic variables were calculated by 3P97 pharmacokinetic program.the results shows:1) Platycodon grandiflorum's guide actiong could influence the pharmacokinetic variables of Levofloxacin in healthy chickens significantly:①decreased the speed of absorption, but enhanced the degree of absorption.②accelerated the distribution from blood to tissues.③decreased the speed of elimination, increased the time of drug action.2) Platycodon grandiflorum's guide actiong could also influence the distribution of Levofloxacin in healthy chickens:①changed the distribution amoung tissues.②increase the concentration in lung notably.2. 40 newsland white rabbits were allocated into two groups at random. groupA:the rabbite were orally given with single dosage of florfenicol at 30 mg/kg·b·w, group B: the abbite were orally given with florfenicol and Platycodon grandiflorum with single dosage of 30 mg/kg·b·w and 2g/kg·b·w respectively. The concentrations of florfenicol in plasma and tissues were determined by high performance liquid chromatography with a limit of detection of 0.001mg /L in plasma and 0.001μg/g in tissues, respectively. The pharmacokinetic variables were calculated by 3P97 pharmacokinetic program.the results shows:1). Platycodon grandifiorum's guide actiong could influence the pharmacokinetic variables of florfenicol in healthy chickens significantly: decreased the speed of absorption, but didn't influence the degree of absorption; accelerated the distribution from blood to tissues,and made it distribution much broad in vivo;decreased the the speed of elimination.2). Platycodon grandifiorum's guide actiong enhance florfenicol's transmission from blood to tissues. Secondly,changed the distribution among different tissues,and increased the concentration in heart, lung, live, significantly, while reduced the concentration in kidney.3. 195 healthy chickens were allocated into five groups at random. GroupⅠ: diofloxacin[10mg/(kg·b·w)] was administrated orally alone. GroupⅡ: in combination with Platycodon grandiflorum total saponin[20mg/(kg·b·w)]. GroupⅢ: in combination with Platycodon grandiflorum total saponin[40mg/(kg·b·w)]. GroupⅣ: in combination with Platycodon grandiflorum total saponin[60mg/(kg·b·w)]. GroupⅤ: diofloxacin[10mg/(kg·b·w)] was administrated by intravenous. The concentrations of diofloxacin in plasma and lung were determined by RP-high performance liquid chromatography with a limit of detection of 0.05mg /L in plasma and 0.05μg/g in lung, respectively. The pharmacokinetic variables were calculated by 3P97 pharmacokinetic program and SPSS 9(11.0) Statistical software. the results shows:1)the Platycodon grandiflorum total saponin decreased the speede of absorption in healthy chicken, but increased the degree;accelerated the transmission to tissues; and made the action time longer in vivo.2) increased the bioavailability of Difloxacin.3) increased the concentration in lung notably in chicken.4. study on the influence on p-glycoprotein's expression in mouse's lung and intestine after orally given hydrochloride difloxacin, Platycodon grandiflorum total saponin expectively, and difloxacin in conjunction with Platycodon grandiflorum total saponin stimutaneously by the mean of immunohistochemistry. The results showed: the p-glycoprotein's expression in mouse's lung and intestine could be influenced by drug which was given orally;among them, hydrochloride difloxacin induced the p-glycoprotein's expression in lung and intestine, and have the property of time-dependent(P<0.01) ; Platycodon grandiflorum total saponin inhabit its activity and expression,and the effect isextremely notable (P<0.01) . Therefore, Platycodon grandiflorum total saponin and hydrochloridedifloxacin were applicated at the same time can improved the the bioavailability of Difloxacin by oraland increased the concentration in lung.This study shows that: the guide action in Triditional Chinese Medicine theory is exists objectivly. Platycodon grandiflorum total saponin could inhabit the p-glycoprotein's activity and the intensity of expression, which was the mechanism of "guide action".