Study On The Absorption And Transport Of Main Chemical Components Of The Compatibility Of Coptis And Magnolia In Caco-2 Cell Model

Oral administration is the most important and preferred route.Duing to the low bioavailability and the resistance of the body,it lead to the absorption of drug is limited.Absorption,distribution,metabolism and excretion of Chinese medicine are basic problems to Chinese medicine modernization.Especially pharmacokinetic study of Chinese herbal formula modernization is a important problem to be solved. Studing the transport mechanism of active components of Chinese medicine in the gastrointestinal tract has a great significance in understanding the scientific connotation of Chinese medicine and the rational formulation.Caco-2 cell line derived from human colon adenocarcinoma,which is widely used to study the transport mechanism of drugs international.The compatibility of Magnolia and Coptis is commonly used in clinical.This paper systematically studied the transport of the main chemical componets in Magnolia and Coptis in Caco-2 model.It is significant for the study of the absorption and transport mechanisms of the main chemical components,and especially for their interactions.At the same time,it provide research experience for pharmacokinetics of Chinese herbal formula.Firstly, this study had investigated the solubility and stability of magnolol and honokiol in HBSS.Secondly,studing the impact with different concentration of magnolol, honokiol and berberine on the activity of Caco-2 cell by MTT.And then,the rapid,reliable and simple model was developed and validated.Caco-2 cell monolayer model was used to research the bi-derection transport.Studing the effects of time,drug concentrations,inhibitor,pH and temperature on the absorption and transport of magnolol,honokiol,bererine. Finally,Comparing the absorption and transport of the monomers with the extractions of magnolia and coptis when administrated individually and simultaneously.Determinating the amounts of transport by using high performance liquid chromatography(HPLC) and calculating the apparent permeability coefficient.The results as follow that the solubility and stability of magnolol and honokiol in HBSS with pH= 7.4 containing 0.1% Tween -80 is good.The stability is good within 24 h at 37℃, and light has no effect on the stability.There are not influence of magnolol,honokiol and berberine with 200μmol/L on the activity of Caco-2 cell in 4 h.In the Caco-2 model's absorption and transport experiment,the amounts of transport of magnolol,honokiol and bererine increasing with time and concentration.The Pratio (BL→AP)/(AP→BL) values of magnolol and honokiol are 0.5-1.Verapamil can significantly improve the amounts of transport in the AP→BL direction.Both in the BL→AP and AP→BL directions,the amounts of transport of magnolol and honokiol decreased by one times at 4℃,And for the AP→BL direction, the amounts of transport of magnolol and honokiol improved a little in HBSS of slightly alkaline,but there are not significant difference.For the absorption and transport of berberine,the amounts of transport in the BL→AP direction is 8-folds greater than it in the AP→BL direction.When the concentration is 50μmol/L,verapamil can significantly decrease the amounts of transport of BL→AP.For the temperature,the amounts of transport in the BL→AP directon decreased by 8-folds compared at 37℃. And the transport was better in HBSS of slightly acidic.Comparing magnolia and honokiol are combined, when magnolol, honokiol and bererine were mixed,the Papp values of magnolol,honokiol and berberine improved a little,especialy when the mix-extractions of Magnolia and Coptis through the Caco-2 cells monolayer,the Papp value of magnolol and honokiol improved significantly. For bererine,the PaPP(AP→BL) value was (12.34±0.45)×10-7cm/s when the mix-extraction of Coptis and Magnolia through the Caco-2 cells monolayer,but the PaPP(AP→BL) value was (5.85±0.48)×10-7cm/s when the extractions administrated individually.And all the PaPP(BL→AP) values decreased when the extraction and monomer were mixed.From the above results, we can conclude that the that magnolol and honokiol transport through the intestinal mucosa via a passive diffusion mechanism primarily, coexisting with a carrier-mediated transport, and they are effluxed by P-gp in the AP side,For the transport of bererine,in the AP→BL direction,it through the intestinal mucosa via a passive diffusion mechanism, but was carrier-mediated transport for the transport of BL→AP,at the same time,verapamil can inhibit the amounts of transport in the BL→AP direction.The transport of monomer differed from that of the corresponding monomer in extraction.When the compounds are combined.Compared the compounds administrated individually in the AP→BL direction,the amounts of transport of magnolia, honokiol and berberine improve,especially when the extractions are combined.At the same time, it can inhibit their efflux each other.Therefore, it suggest that the drug combination can prompt the absorption and transport each other, and also avoid the body's resistance to drugs.At the same time,it show that the pharmacokinetic characteristics of the monomer existed in herbs can't be solely inferred and concluded from the pharmacokinetic conclusion of the monomer.