Study Of Active Ingredients And Mechanisms For The Yuanhu Analgesia Tablet As Traditional Chinese Medicine Treatment Of Gastric Ulcer

Purpose：Study of active ingredients and mechanisms for the yuanhu analgesia tablet astraditional Chinese medicine treatment of gastric ulcer.Methods:In vitro and in vivo, combination use of MTT, pathological examination, colorimetricmethod, enzyme-linked immunosorbent assay, computer-aided drug design, RT-PCR anddopamine D2receptor antagonist domperidone for the study of active ingredients andmechanisms for the yuanhu analgesia tablet as traditional Chinese medicine treatment ofgastric ulcer.Results:â‘ Yuanhu analgesia tablet （YAT） and ingredients component （IC） promoted theproliferation of gastric mucosa cell. pathological examination demonstrated that YAT and IC-I promoted proliferation of gastric mucosa cell in rats with gastric ulcer induced byacetic acid. in vitro, compared to the normal control group,3μg/ml tetrahydropalmatine（THP） promoted GES-1proliferation14.7%（P<0.05）.2.4×10^-1μg/ml imperatorin （IMP）promoted GES-1proliferation12.4%（P<0.05）.100μg/ml YAT promoted GES-1proliferation52.1%（P<0.05）. Compared to the control group damaged by8%ethanol for1h,3μg/ml THP promoted GES-1proliferation26.5%（P<0.05）.2.4μg/ml promoted GES-1proliferation26.9%（P<0.05）.100μg/ml YAT promoted GES-1proliferation27.1%（P<0.05）. In vivo, compared to the control group （gastric ulcer in rats induced by aceticacid）, PCNA were up regulated in following groups:50mg/kg THP+40mg/kg IMP（T50+I40）（151.2%, P<0.05）,50mg/kg THP+20mg/kg IMP （T50+I20）（144.6%,P<0.05）,YAT（141.9%, P<0.05）. Compared to50mg/kg THP （T50） or40mg/kg IMP （I40）, T50+I40up regulated PCNA447.8%（P<0.05） or298.7%（P<0.05）, respectively.â‘¡YAT and IC up regulated manydefense factors to protect gastric mucosa.Compared to the gastric ulcer induced by acetic acid control group in rats, SP were upregulated in the following groups: T50+I40（58.6%, P<0.01）, T50+I20（40.4%,P<0.01）,YAT （41.8%, P<0.01）. bFGF were up regulated in the following groups: T50+I40（146.6%, P<0.01）, T50+I20（59.0%, P<0.05） and YAT （182.8%, P<0.01）.Compared toT50or I40or I20or T50+I20, T50+I40significantly （P<0.05） up regulated bFGF,respectively. This was in line with the results of pathological examination and inhibitinggastric acid. YAT and IC protected the gastric mucosa from the damage caused by absoluteethyl alcohol in rats. Compared to the control group, TSOD were up regulated in thefollowing groups: YAT （125%, P<0.001）, T50+I40（127.6%, P<0.001）, T50+I20（97.0%,P<0.001）. Individually using THP or IMP did not achieve the same effect, respectively.And compared to T50or I20, T50+I40up regulated TSOD60.6%（P<0.05） or70.3%（P<0.05）. Compared to the control group, MDA were down regulated in the followinggroups: YAT （46.7%, P<0.05）, T50+I40（51.6%, P<0.05）. The other treatments did notdown regulated MDA significantly. Compared to the control group, Na+K+-ATPaseactivities were up regulated in the following groups: YAT （43.2%, P<0.05）, T50+I40（52.1%, P<0.05）. The other treatments did not up regulated Na+K+-ATPase activity significantly. And compared to T50, T50+I40up regulated Na+K+-ATPase activity38.1%（P<0.05）. Compared to the control group, Ca²⁺Mg²⁺-ATPase activities were up regulatedin the following groups: YAT （47.8%, P<0.05）, T50+I40（58.0%, P<0.0001）. Comparedto T50, T50+I40up regulated Ca²⁺Mg²⁺-ATPase activity37.5%（P<0.05）. The othertreatments did not up regulated Ca²⁺Mg²⁺-ATPase activity significantly. Compared to thecontrol group, TNOS was up regulated in the following groups: YAT （105.5%, P<0.05）,T50+I40（149.2%, P<0.05）, T50+I20（94.5%, P<0.05）. Individually using THP or IMP didnot achieve the same effect,respectively. Compared to the control group, iNOS was upregulated in the following groups: YAT （115.6%, P<0.01）, T50+I40（120.9%, P<0.01）,T50+I20（63.4%, P<0.05）. Individually using THP or IMP did not achieve the same effect,respectively. Compared to the control group, EGF was up regulated in the followinggroups: YAT （13.7%, P<0.05）, T50+I40（19.8%, P<0.01）. The other treatments did not upregulated EGF significantly. Compared to the control group, TNF-α was up regulated inthe following groups: YAT （39.6%, P<0.001）, T50+I40（44.9%, P<0.01）, T50+I20（85.3%,P<0.001）, T50（30.6%, P<0.05）, I20（36.3%, P<0.05）. Compared to T50+I40, T50+I20upregulated TNF-α27.9%（P<0.05）.â‘¢IC promoted the healing of gastric ulcer was due to up regulating AHCE, downregulating ACH, inhibiting H⁺-K⁺ATPase activity and antiacid. In vivo, compared to thecontrol group （gastric ulcer in rats induced by acetic acid）, T50+I40increased pH27.0%（P<0.05）, decreased H⁺-K⁺ATPase activity47.9%（P<0.01）, up regulated ACHE90.4%（P<0.01） and down regulated ACH37.2%（P<0.05）. The other treatments did not achievethe same effect as T50+I40did.â‘£The protection of IC to gastric mucosa was blocked by domperidone. Compared tothe control group （induced by absolute ethyl alcohol in rats）,0.2ml/ratdomperidone+T50+I40did not change TSOD, MDA, Na+K+-ATPase activity andCa²⁺Mg²⁺-ATPase activity. However0.2ml/rat domperidone did not block the effect ofT50+I40to TNOS, iNOS, EGF and TNF-α.0.2ml/rat domineering did not block theeffect of YAT to these mechanisms. Compared to control group, PGE2was downregulated in the following groups:0.2ml/rat domineering （45.4%, P<0.001）, YAT （28.4%, P<0.05）,0.2ml/rat domineering+T50+I40（53.2%, P<0.001）.Conclusions:â‘ we found that IC promoted the healing of gastric ulcer induced by acetic acid inrats and protected gastric mucosa from the damage caused by absolute ethyl alcohol. Thiswas in line with YAT. However individually using THP or IMP did not achieve the sameeffect as IC did.â‘¡First time discovery that THP and IMP are probably active ingredients of YAT astraditional Chinese medicine treatment of gastric ulcer. There are two reasons:1. THP isfrom rhizoma corydalis and IMP is from radix angelicae. Combination of THP and IMP asIC got a mutual reinforcement of compounds.2. IC achieved the same effect as YAT didto gastric ulcer according to the assays （pathological examination, gastric mucosa cellproliferation, antiacid, scavenging free radical, up regulating ATPase, many defencefactors for gastric mucosa, and dopamine D2receptor antagonist domperidone）.â‘¢Mechanisms of YATas traditional Chinese medicine treatment of gastric ulcerprobably via THP and IMP were promoting the healing of gastric ulcer due to upregulating ACHE, down regulating ACH, decreasing H⁺-K⁺ATPase and antiacid.â‘£The pharmacologicalmechanisms and actions of IC provided a new thinking andexperiment data for new drug discovery based on YAT.⑤It was first observed that dopamine D2receptor blocked effect and mechanisms ofIC as treatment of gastric ulcer but did not block YAT. Thus dopamine D2receptor was thetarget of IC. There were many compounds in YAT playing more performance via multipletargets. Above all, there are at least dozens of compounds in YAT. Therefore maybe morecompounds involved in IC achieve better effect, and the pharmacological mechanisms andactions respected to further research..