| Objective:The purpose of this study was to investigate the optimal water extraction process for Painong Powder and to explain a phenomenon of“guiding action”forPlatycodi Radix while ulcerative colitis rats treated with Painong Powder,so as to provide experimental evidence for further research and develop Painong Powder.Methods:Box-Behnken experimental design combining with response surface methodology（RSM）was employed,taking three characteristic component contents（Naringin,Paeoniflorin,neohesperidin）were detected by HPLC and the paste rate of comprehensive evaluation as the evaluation indexes and the influences on extracting process of the water addition,the soaking and the extraction time were investigated.Pharmacodynamics was investigated by a rat model of ulcerative colitis induced by TNBS to evaluate the index of disease activity and the weight of lung and colon tissues,the degree damage of histology and to investigate the content of cell factor such as TNF-α、IL-1β、IL-6、NF-κB were determined in plasma,colon and lung tissue.Last,HPLC-MS/MS method was established and validated to analyze the pharmacokinetic parameters and tissue distribution of Naringin and Paeoniflorin in PainongPowderorPainongPowderwithoutPlatycodi Radix by oral administration to normal or model rats,so as to provide an explanation of“guiding action”for Platycodi Radix.Results:The optimal extracting process was determined to be 15 times of waters consumption,soaking for 67 min and extracting for 74 min.The microscopic appearance of the damage of both colon and lung tissues in rats of ulcerative colitis two days after the model was established.The high dose of Painong Powder has a significant effect on treating ulcerative colitis induced by TNBS.Compared with the model rats,the weight and the index of lung and weight in rats was decreased significantly（P<0.05）and gross appearance of damage area of the colon tissues was small and partially tissue was healed and colon tissues of edema and hyperemia was reduced after treated with high dose of Painong Powder.The content of TNF-α,IL-1β,IL-6 and NF-κB in plasma,colon and lung tissue and the infiltration of inflammatory cell were decreased in the high dose group of Painong Powder.After oral administration Painong Powder,the pharmacokinetic parameters of Naringin and show that AUC（0-∞）,MRT（0-∞）and Cmaxof normal groups were3023.14±470.25μg/L·h,10.21±0.82 h and 597.57±22.46μg/L,Paeoniflorin show that AUC（0-∞）,MRT（0-∞）and Cmaxof normal groups were 3332.94±255.84μg/L·h,5.15±0.49 h and 816±28.88μg/L.After oral administration Painong Powder without Platycodi Radix,the pharmacokinetic parameters of Naringin and show that AUC（0-∞）,MRT（0-∞）and Cmaxof normal groups were 2034.15±493.25μg/L·h,8.83±0.47 h and477.13±25.67μg/L,Paeoniflorin show that AUC（0-∞）,MRT（0-∞）and Cmaxof normal groups were 1569.75±479.63μg/L·h,13.53±7.33 h and 402.67±58.22μg/L.After oral administration Painong Powder,the pharmacokinetic parameters of Paeoniflorin and show that AUC（0-∞）,CL and Tmaxof model groups were4400.16±518.43μg/L·h,448.31±31.29 L/h/kg and 6.68±0.23 h,Paeoniflorin show that AUC（0-∞）,MRT（0-∞）,Cmaxand Tmaxof model groups were 3873.53±245.81μg/L·h,4.86±0.16 h,766.06±27.38μg/L and 3.41±0.25 h.After oral administration Painong Powder without Platycodi Radix,the pharmacokinetic parameters of Naringin show that AUC（0-∞）,MRT（0-∞）,Cmaxand Tmaxof model groups were 3583.56±250.55μg/L·h,367.78±42.58 L/h/kg,367.78±42.58 L/h/kg and 5.47±0.67 h,Paeoniflorin show that AUC（0-∞）,MRT（0-∞）,Cmaxand Tmaxof model groups were 1917.98±99.88μg/L·h,4.02±0.74 h,435.09±15.97μg/L and 4.02±0.74 h.In normal or model groups,distribution concentration of Naringin in colon and lung tissue show higher in Painong powder than that of Painong powder without Platycodi Radix.Compared with model rats,peak and elimination of time of Naringin and Paeoniflorin were delayed in normal rats.Conclusion:The water extraction process for Painong Powder optimized by Box-Behnken experimental design is feasible and has good predictability.Platycodi Radix has the phenomenon of guiding action by changing the pharmacokinetic parameters of active components and improving the concentration of components in the colon and lung when ulcerative colitis rats treated with Painong Powder. |
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