Study Of Effect Components For The Yuanhu Painkiller Treat Of Primary Dysmenorrhea

Primary dysmenorrhea（PD）is one of the most common gynecological diseaseswhich occurs in young women with a negative impact on their quality of life. Thehallmark of primary dysmenorrhea s painful menses in the absence of any associatedmacroscopic pathologic process. Painful menses occurs within the first6months ofmenarche. Its prevalence varies between45%and95%. The aetiology of PD has notbeen clearly elucidated. Nonsteroid anti-inflammatory drugs （NSAIDs） and oralcontraceptives are usually applied to treat PD. But NSAIDs and Oral contraceptives havemany side effects on the liver, kidney and digestive function.YuanHu painkillers （YHP）, composed of Corydalis Yanhusuo and Angelicadahurica, were made into traditional Chinese medicine preparations using the scientificmethod. The quality standards of YHP have been recorded in the2010edition of theChinese Pharmacopoeia （volume one）. Literature reports， including those of ourprevious results, have verified that a variety of chemicals constitute YHP, such astetrahydropalmatine（THP）, d-corydaline, imperatorin（IMP）, and isoimperatorin,.YHP and IMP are the two high constituents in YHP, and their standard substances can bepurchase from National Instisutes for Food and Drug Control. YHP’s curative effectshave been confirmed in the treatment of PD, migraines， stomach ache, andhypochondriac pain. However, the effective component of YHP and principle ofcomposition in the treatment of PD are not clearly expounded.In order to find out the effective component and the probably principle of composition ofYHP in the treatment of primary dysmenorrhea, the effects of extracts（yanhusuo andBaizhi） and constituents polypharmacy（THP and IMP as their proportion in YHP） onuterine contraction were investigated in vitro and vivo. Primary dysmenorrhea model wasinduced by oxytocin. H&E staining and histopathological examination of the uteri tissuesamples were performed. We detected superoxide dismutase （SOD） andmalondialdehyde （MDA）, nitric oxide （NO）, as well as inducible nitric oxide synthase（iNOS）, i-κB, nuclear factor-κB （NF-κB）, and cyclooxygenase-2（COX-2） indices.Experiment in vitro detected the effect of THP and IMP on spontaneous contractions, K+depolarization-induced uterine contractions, Drugs（Ach, PGF2α, oxytocin） inducedcontractions or oxytocin-induced Ca²⁺-free uterine contractions.Results:1. THP and IMP could remarkably decrease writhing times of PD model rats andprolong incubation period. The polypharmacy of constituents is better than single use.2.IMP could remarkably low the level of MDA in rat uterus and blood serum, decrease thecontent of NO in rat uterus and enhance the activity of SOD.3. THP could significantlydecrease the content of MDA in rat uterus but had no effect on MDA in blood serum.4.THP and IMP could inhibit the expression of iNOS and COX-2by the inhibition ofactiviton of NF-кB and the enhanced expression of i-κB.5. Our histopathologicalexamination results showed that PD-related inflammation and edema could be alleviatedby THP and IMP.6. IMP had no effect on the isolated uteri of rats. With a contractedstimulated uterus, THP inhibited the frequency or the force of the contraction induced byoxytocin, Ach, or PGF2α in a concentration dependent manner but had no effect onoxytocin induced contraction in Ca²⁺free splution.Conclusion:1. This paper demonstrates that THP and IMP are two effective components of YHP that inhibit uterine contractions in PD model rats and their synergistic effect issignificantly better their solo effect.2. We find out that THP lessens the pain of PD byinhibiting the contraction of uterus through inhibiting the influx of extracellular Ca²⁺.IMP plays a subsidiary role, exerting protective effects on dysmenorrhea by abating lipidperoxidation and preventing the iNOS and COX-2protein expression, thus cooperatingwith THP. Corollary: THP and IMP respectively from Yanhusuo an Baizhi are effectivecomponents of YHP. There are remarkably differences in drug potency, target, pathwayand mechanism between THP and IMP in the treatment of PD.3. YHP’s principle ofcomposition was preliminarily studied. THP as a monarch drug exerts effect of directanalgesia IMP is a ministerial drug exert subsidiary analgesia in constituentspolypharmacy.4. The disadvantages: YHP contains more than ten known constituents.Other constituents polypharmacy may get better effect. The more complex mechanismneeds further research.