Comparison On The Efficacy Of Lizhong Pills Influenced By Dried Ginger And Its Different Active Components On Digestive And Absorptive Functions And Energy Metabolism On Rats Of Deficiency Of Spleen YANG

Lizhong Pills invented by Zhongzhongjing in Treatise on Cold-Attack is a famous formula used to treat deficiency of spleen YANG,being consist of dried ginger,ginseng,rhizoma atractylodis macrocephalae and radix glycyrrhizae preparata,possessing the function of warming the middle to dispel cold and reinforcing the spleen-qi.As the main herb of Lizhong Pills, dried ginger is the core structure of the compatibility,and plays a key role in treating deficiency of spleen Yang.An experiment was designed to explore a key position of the main herb in a formula.Being selected as a sample, Lizhong Pills and dried ginger was observed in the experiment concerning the regulating efficacy on the models of animals suffering from deficiency of spleen YANG.The different impacts on digestion,assimilates and energy metabolizability of the models were observed in the research,when every kinds of test formulations of Lizhong Pills which contains dried ginger or different components of dried ginger were given to the models respectively.It is indicated that the effects of Lizhong Pills mainly rely on dried ginger, the main herb in the formula,which is the same as the traditional consideration.Just the single change of the main herb concerning about dried ginger or its' different components could transform the efficacy of the whole formula.This paper is mainly comprised of two components:preparation of models of rats suffering from deficiency of spleen Yang;comparison of the pharmacodynamics impacts of different Lizhong Pills formulations made up by dried ginger or its different components in Lizhong Pills to the different groups of the models.1 Establish the model of deficiency of spleen YANG induced by " cypsum fibrosum and anemarrhenae " with complex factors1.1 ObjectivesWith using heat-clearing and fire-purging drug cypsum fibrosum and anemarrhenae,insteading of the common usage of rhubarb and folium sennae,accompanied with irregular diet and overstrained,the model of deficiency of spleen-YANG is to be established,which is much close to the pathopoiesis theory of " frigidity and chilly damaging yang,irregular diet injuring qi,overstrain impairing the spleen" in TCM.1.2 MethodsModel rats is fully fed every other day,given the molding drug of cypsum fibrosum -anemarrhenae(concentration 4:1) with 3 different frequency,and arranged to swim everyday in 25℃water until exhausted(performing as spitting bubble 3 times continuously or sinking unable to float by itself).The influence of each modeling method could be compared through the courses.Method 1:given the modeling drug(dosage 10ml/kg) every other day from 1d to 6d,and everyday from 7d to 12d,accompanied with 15 days' spontaneous recovery.Method 2:given the modeling drug(dosage 10ml/kg) every other day, 20 days continuously,accompanied with 12 days' spontaneous recover.Method 3:given the modeling drug(2ml/each rat) everyday,12 days continuously,accompanied with 9 days' spontaneous recover.Observe the variation of model rats' general preference,detect the change of correlate indexes of digestive and absorptive function and energy metabolism such as body temperature,body weight,food intake and serum D-xylose,GAS and MLT levels and the content of NO in the tissue of jejunum etc. 1.3 ResultsAll methods could induced the changes of general preferences of model rats,appearring diarrhea,lassitude,temperature drop,loss of weight etc.Among the Methods,Method 2 shows the weakest function,with the model rats recovering fast.The modeling effedt of Method 1 and 3 appears stronger than method 2,among which method 3 cause the most distinct and steadiest pathological change.In the aspect of influenced indexes in digestive and absorptive function and energy metabolism,method 3 could decrease the serum levels of D-xylose,GAS,MLT,and lower the content of NO which is the mainly inhibitory neurotransmitter in jejunum,bring down body temperature, degrade food intake and slower body weight grower.There is no significouldt variation between the function of Method 1 and 3 in the indexes of digestive and absorptive function,except the effect on body weight and food intake;as well,model 2 shows no significouldt influence on the indexes besides body weight lose.1.4 ConclusionsContrast the three modeling methods,model 3 is the most obvious and steady method for the establishment of deficiency of spleen YANG.2 comparison on the efficacy of Lizhong Pills influenced by dried ginger and its different components on digestive and absorptive functions and energy metabolism2.1 ObjectivesThis research was designed to observed the different influences of Lizhong Pills formula on the models,which contains dried ginger or its main group of components(volatile oil and water solubles).It would be explored from two levels of material base,single herb dried ginger or its different components,to confirm that the whole effects of Lizhong Pills do mainly depend on its main herb dried ginger in the formula just as the traditional acknowledgement in TCM.Further more,the connotative meaning of dried ginger used as the main herb in Lizhong Pills egthe aspect of pharmacology and chemistry would be preliminary revealed.2.2 MethodsEach group of model rats of deficiency of spleen-YANG were to be duplicated by method 3 for 14 days,and be treated by corresponding drug samples for 8 days.The drug samples,respectively,are the liquid of Lizhong Pills(contains original dried ginger,namely LZL),the liquid extract of Sijunzi Decoction(namely SJL),and the liquid extract of Lizhong Pills formulae with the original dried ginger replaced by its water solubles, (namely LZW) or volatile oil from it(namely,LZV).Futhermore,the chemical compositions formula with high dosage volatile oil is named LZVH;with medium dosage volatile oil,the LZVM;and with low dosage volatile oil,the LZVL.And the dosage ratio among high dose,medium dose and low dose groups is 2:1:0.5,and the medium dose formula equals to LZL in component.During the course of the experiment,the body temperature,body weight and food intaking ara to detected everyday.After being treated the following measurement indicators would be detected.The measurement Indicators related to digestive and absorptive function:the gastric evacuation rate and small intestinal propulsion rate; serum contents of D-xylose,GAS and MLT;activity of CHE;H⁺-K⁺-ATPase in stomach tissues;contens of ICC,VIP and NO in the tissue of jejunum; IOD(mean) of AchE and NOS in Myenteric plexus(histochemical method); histopathologic observations on tissue of stomach and jejunum,besides the observation on liver in LZVM and LZVL.The measurement indicators concerning with energy metabolism: fasting blood-glucose;activity of CK and content of LD in serum,activity of ATPase in the mitochondria of gastric,jejunal and skeletal muscle cells; contents of muscle glycogen and 5-HIAA in hypothalamus.2.3 ResultsAll data is organized for three targets. 2.3.1 comparison on the efficacy of LZL and SJL in regulating the digestive and absorptive functions and energy metabolism on model rats of deficiency of spleen YANGOn the aspect of digestive and absorptive functions,SJL could elevate the level of MLT,GAS in serum,and improve the gastric evacuation rate, meanwhile,the effect of LZL is much stronger.SJL could inhibit H⁺-K⁺-ATPase activity of normal stomach,while LZL doesn't work.Both SJL and LZL could reduce the small intestinal propulsion rate, which is closely related to the activity of CHE,rather than NO in the tissue of jejunum being reduced by SJL.and there is no obvious significance among the groups.Although it seems that the SJL could elevate the absorptivity of D-xylose more effeciently than LZL,and improve the appetite of the modeling rats,it fails to increase the body weight of the models as obviously as the above.Evenmore,according to the pathomorphism of the stomach and the enteric of models,the protective action of SJL to the gastric and intestinal mucosa is weaker than LZL's.On the effect of energy metabolism,LZL could lower the serum CK activity and LD level,depress the content of muscle glycogen,reduce 5-HIAA level in hypothalamus and upgrade body temperature inhibited by modeling.LZL could significently inhibited the increasing of blood glycogen and Ca²⁺-Mg²⁺-ATPase activity in the mitochondria of skeletal muscle cells in models.LZL failed to influence the activity of the ATPase detected in mitochondria of gastric and intestinal tissues,while LZL could reduce the the activity of the Na⁺-K⁺-ATPase.The body temperature of models could not be improved effectively by SJL as well as the 5-HIAA level do in hypothalamus.Besides the effect on serum CK activity,the inhibiting effect of SJL on ATPase activity in mitochondria of gastric tissues is stronger than LZL's, while the other influences of SJL is weaker than that of LZL. 2.3.2 comparison on the efficacy of LZV and LZW in regulating the digestive and absorptive functions and energy metabolism on model rats of deficiency of spleen YANGOn the aspect of digestive absorption,both LZW and LZV could elevate the MLT,GAS in serum of models.The effect of LZV is more stronger than that of LZW,as well as that of LZL.But there is no differenece in effects observed between LZW and LZV in gastric evacuation rate.LZW could strongly depress the serum CHE activity,while elevate the NO level and reduce the quantity of ICC in the jejunum.But there is no change to the VIP level in the jejunum.The inhibition of LZV to serum CHE activity is weaker than that of LZW, but LZV could not increase the release of NO in the jejunum.Moreover,it could not change the quantity of the VIP in the jejunum,while the number of ICC in the jejunum could be reduced obviously.But there is no obvious difference among the groups of LZV,LZW and LZL.In addition,the effect of LZV in increasing the D-xylose absorption rate and promoting the body weight is better than LZW's and LZL's.As to protecting morphology of stomach intestine tissue,LZV has the advantage over the others.On the impact of energy metabolism,LZV could reduce 5-HIAA level in hypothalamus and upgrade the body temperature.At the same time,the serum CK activity and LD level could be depressed effectively by LZV.The skeletal muscle ATPase activity and the fasting blood-glucose increase in blood induced by modeling could be decreased to normal level by LZV.On the contrary,the 5-HIAA level in hypothalamus could be increased by LZW, while there is no obvious influence on the decreased body temperature. Except the stronger inhibition of skeletal muscle ATPase,the effect of LZW on the other Indicators is weaker than LZV's.2.3.3 Influence on digestive and absorptive functions and energy metabolism of the model of deficiency of spleen-YANG in different dosage of volatile oil in dried gingerLZVM could significantly raise the serum GAS and MLT level exceeding the normal value,and then could elevate the gastric evacuation rate.LZVH and LZVL effect similarly,but weaker than LZVM.Compatibility with the dried ginger volatile oil could restrain the enterokinesia in way of influencing cholinergic neuron(nerve) function and the quantity of ICC.LZVM has the strongest effect in decreasing the number of ICC,at the same time,LZVH plays an important role in lowing serum CHE activity.Comparing the contribution on enhancing NO levels in the jejunum,it is indicated that LZVL increases its level,while LZVM and LZVH decrease it.But LZVM could raise the IOD of nitrergic neuron(nerve) in myenteric nerve plexus.On the improving of total length and propulsion rate of small intestinal, three formulae with the dried ginger volatile oil appear no differences.But LZVM effects significantly in protecting morphology of stomach intestine tissue.On the effect of energy metabolism,LZVM and LZVH both could reduce the 5-HIAA levels in hypothalamus,and upgrade the body temperature to the normal level.Although LZVL also could reduce the 5-HIAA levels in hypothalamus either,but it has no significance in improving the decreased body temperature of modeling rats.All the three formulae could depress the serum CK activity,LD level and muscle glycogen content,in which LZVM and LZVH are more effiency.With the compensated increase of blood glycogen and Ca²⁺-Mg²⁺--ATPase activity in the mitochondria of skeletal muscle cells,all the three groups could influent them,and while LZVM processes the most efficent function in depressing blood glycogen,LZVL does the same in influencing ATPase.In the experiment,it is found that LZVH could increase the serum GOT activity.At the same time,we could find the slight neorobiosis of liver tissue. Contrarily,there is no evidence indicating the damage in liver concerning with LZVL and LZVM.2.4 ConclusionsIn the treatment of deficiency of spleen-YANG,LZL which represented the method of warming YANG and invigorate the spleen,aims directly at the basic method to deficiency of spleen-YANG.As the main herb of LZL,dried ginger plays a key role in warming the middle-jiao to dispelling cold.Comparing the volatile oil and water-soluble contained in the dried ginger,the volatile oil contributes to the most prominent efficacy of LZL,and decisively adjusts the digestive and absorptive functions and energy metabolism on the model.Along with the dosage increasing of dried ginger volatile oil,the potency of LZL enhances correspondingly.But high dosage compatibility of volatile oil tends to lead to slight harm to the liver of model rats.Therefore, according to the results of this research,middle-dosage volatile oil compatibility wins the best potency without no obvious insecurity.It is proved in the research that dried ginger,the major herb of LZL,has the core position and decisive function.This is not only the theory of TCM, but also the modern pharmacological facts.Come to the conclusion that It is vital to reveal material base of effecacy in the formula of Chinese medicine in order to thoroughly understand and master the main principle theory of Fangji.