Effects Of Rheum Officinale Baill, Scutellaria Baicalensis Georgi And The Compatibility On Cholinergic Anti-inflammatory Pathway Through PK/PD Method

ObjectiveThe present study, based on detection of pharmacokinetic and pharmacodynamic effects of rhein and baicalin which are respectively indicative constituents of Rheum officinale Baill (RO) and Scutellaria baicalensis Georgi (SB), aims to characterize the effect and dynamic mechanism ofthose Chinese herbs and their combination (RSC) on cholinergic anti-inflammatory pathway in rats with endotoxemia.MethodsThe rat model with endotoxemia was established by tail vein injection with LPS5mg/kg. The rats above were treated with the decoction of RO, SB and RSC by intragastric administration after modeling30min. The rectal temperature (RT) was measured after treated5min,15min,30min,45min,1h,2h,4h,6h,8h,12b,16h,24h. Then, the rats were put to death and the samples such as blood and lung tissues were collected for determination of serum Ach and NO level (sAch and sNO), wet/dry mass ratio of lung tissues (W/D), ChAT and AchE activities in lung tissues (ltChAT and ltAchE). Serum rhein and baicalin concentration were determined through High Performance Liquid Chromatography (HPLC).Results(1) RO, SB and RSC couldn’t remarkably inhibit the increase of W/D in model rats. (2) RO and RSC were capable of significantly inhibiting the increase of RT and sNO in model rats after treated, and what’s more, the effect of RSC is stronger than that of RO. SB didn’t decrease RT and sNO obviously.(3) RO, SB and RSC could markedly increase ltChAT and ltAchE. There was a rising trend but no significant difference in sAch between treatment group and model group. RO showed similar effect intensity to SB but stronger efficacy than RSC. SB showed stronger efficacy than RO and RSC, whereas RO was similar to RSC. The effect on increasing sAch in turn decreased on RO, SB, RSC.(4) Compared to single use of RO and SB, the kinetic parameters Cmax, AUC and Tmax of rhein and baicalin through their combination were obviously increased.Conclusion(1) The antipyretic and anti-inflammatory effect of RO was enhanced via combination with SB, but SB didn’t show that effect significantly in rats with LPS injection(2) Under the combination of RO and SB, SB could obviously quicken the absorption of rhein in RO, and also, RO could quicken the absorption of baicalin in SB.(3) SB can promote the effect of RO on RT and serum NO reduction, which may be involved with improved absorption of rhein driven by SB.(4) RO, SB and RSC make a weak impect on cholinergic anti-inflammatory pathway. The mechanism of RT reduction and anti-inflammation maybe not related to cholinergie anti-inflammatory pathway. Further research will be needed to explain the detailed mechanism.