Früher|Nächster

Efficacy and Mechanism of Shuanghua Drink in Treating Primary Dysmenorrhea Based on COX-2/NF-κB Signaling Pathway

  • role： First author第一作者
  • Affiliation：

    School of Life Sciences， Beijing University of Chinese Medicine， Beijing 100029， China

  • Email：mayuncheng8467@163.com
  • Introduction：马筠程，在读硕士，从事中药药理、中医妇科研究，E-mail：mayuncheng8467@163.com
MA Yuncheng1,  
  • Affiliation：

    School of Life Sciences， Beijing University of Chinese Medicine， Beijing 100029， China

SHI Yuanyuan1,  
  • Affiliation：

    School of Chinese Materia Medica， Beijing University of Chinese Medicine， Beijing 100029， China

LIU Zhen2,  
  • Affiliation：

    School of Life Sciences， Beijing University of Chinese Medicine， Beijing 100029， China

WANG Yuxi1,  
  • Affiliation：

    School of Chinese Materia Medica， Beijing University of Chinese Medicine， Beijing 100029， China

TIAN Yuan2,  
  • Affiliation：

    School of Chinese Materia Medica， Beijing University of Chinese Medicine， Beijing 100029， China

LI Qian2,  
  • Affiliation：

    School of Chinese Materia Medica， Beijing University of Chinese Medicine， Beijing 100029， China

WANG Xiaozhu2,  
  • Affiliation：

    Beijing Research Institute of Traditional Medicine， Beijing University of Chinese Medicine， Beijing 100029， China

HE Cheng3,  
  • Affiliation：

    Beijing Research Institute of Traditional Medicine， Beijing University of Chinese Medicine， Beijing 100029， China

XU Wenhui3,  
  • Affiliation：

    Beijing Research Institute of Traditional Medicine， Beijing University of Chinese Medicine， Beijing 100029， China

WANG Weiling3,  
  • role： Corresponding author通信作者
  • Affiliation：

    Beijing Research Institute of Traditional Medicine， Beijing University of Chinese Medicine， Beijing 100029， China

  • Email：gaojian_5643@163.com
  • Introduction：高健，助理研究员，从事新药研发研究和中药药效物质基础研究，E-mail：gaojian_5643@163.com；
GAO Jian3*,  
  • role： Corresponding author通信作者
  • Affiliation：

    School of Chinese Materia Medica， Beijing University of Chinese Medicine， Beijing 100029， China

    Beijing Research Institute of Traditional Medicine， Beijing University of Chinese Medicine， Beijing 100029， China

  • Email：wangting1973@sina.com
  • Introduction：王停，教授，博士生导师，从事新药研发研究和名老中医传承研究，E-mail：wangting1973@sina.com
WANG Ting23*

Resümee

ObjectiveTo evaluate the efficacy of Shuanghua drink in treating primary dysmenorrhea in the rat model and explore its mechanism of action.MethodsAn oxytocin-induced writhing mouse model was established to evaluate the analgesic effect of Shuanghua drink. Forty-eight non-pregnant female institute of cancer research （ICR） mice were randomly divided into six groups， including a blank group， a model group， an ibuprofen group （85.00 mg·kg-1）， a low-dose group of Shuanghua drink （7.14 mL·kg-1）， a medium-dose group of Shuanghua drink （14.28 mL·kg-1）， and a high-dose group of Shuanghua drink （28.57 mL·kg-1）. Each group consisted of eight mice. All treatment groups received daily intragastric administration at corresponding doses for 10 consecutive days. One hour after the final administration， 2 U of oxytocin was intraperitoneally injected per mouse. The writhing latency and number of writhing within 20 minutes were recorded. A primary dysmenorrhea rat model was established by using estradiol benzoate and oxytocin to evaluate the inhibitory effect of Shuanghua drink on the contraction of uterine smooth muscle. Forty-eight non-pregnant female Sprague-Dawley （SD） rats were divided into six groups， including a blank group， a model group， an ibuprofen group （51.00 mg·kg-1）， a low-dose group of Shuanghua drink （4.28 mL·kg-1）， a medium-dose group of Shuanghua drink （8.57 mL·kg-1）， and a high-dose group of Shuanghua drink （17.10 mL·kg-1）. Each group consisted of eight rats. Rats received subcutaneous injections of estradiol benzoate for 10 consecutive days to enhance uterine sensitivity. On the eleventh day， oxytocin （2 U/rat） was intraperitoneally administered to induce abnormal uterine contractions for establishing the primary dysmenorrhea model. All treatment groups received daily intragastric administration from the second day of modeling for 10 days. The effects of Shuanghua drink were evaluated by using parameters including uterine motility and the variation rate of uterine motility. The mechanism of action was investigated in rats with primary dysmenorrhea. The content of prostaglandin F2α （PGF2α）， prostaglandin E2 （PGE2）， thromboxane B2 （TXB2）， prostacyclin metabolite （6-keto-PGF1α）， and β-endorphin （β-EP） in uterine tissue of rats was detected by using enzyme-linked immunosorbent assay （ELISA）. The changes in the content of nitric oxide （NO） and inducible nitric oxide synthase （iNOS） were analyzed via colorimetric assay. Western blot was performed to determine the content of phosphorylated inhibitor of kappa B kinase beta （p-IKKβ）/IKKβ， phosphorylated inhibitor of kappa B alpha （p-IκBα）， IκBα， phosphorylated p65 （p-p65）， p65， and cyclooxygenase-2 （COX-2） proteins in uterine tissue of rats.ResultsIn the oxytocin-induced writhing mouse model， the model group exhibited significantly shortened writhing latency and increased writhing frequency compared to the control group （P<0.01）. Both the ibuprofen group and the high-dose group of Shuanghua drink displayed prolonged writhing latency （P<0.05）， while the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink exhibited reduced writhing frequency （P<0.01）. In the primary dysmenorrhea rat model， the uterine motility and its variation rate in the model group were significantly higher than those in the blank group （P<0.01）. These parameters were markedly suppressed by ibuprofen and Shuanghua drink at all tested doses （P<0.01）. For the mechanism of action， the model group showed significantly increased PGF2α/PGE2， TXB2/6-keto-PGF1α， NO， and iNOS in uterine tissue （P<0.05， P<0.01） and significantly decreased β-EP （P<0.01）. These parameters were significantly attenuated in the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink. The PGF2α/PGE2 （P<0.01）， TXB2/6-keto-PGF1α （P<0.01）， NO （medium-dose group P<0.05）， and iNOS （P<0.01） were reduced， and the β-EP （medium-dose group P<0.05） was up-regulated. Compared to the model group， the ibuprofen group and medium-dose group of Shuanghua drink showed significantly increased content of β-EP in the serum of rats （P<0.05）. Compared to the blank group， the model group showed significantly elevated expressions of COX-2， p-IKKβ/IKKβ， p-IκBα/IκBα， and p-p65/p65 proteins （P<0.01） and significantly reduced anti-inflammatory protein IκBα （P<0.05）. Compared to the model group， the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink showed significantly reduced expressions of COX-2 （P<0.01）， p-IKKβ/IKKβ （P<0.01）， p-IκBα/IκBα （P<0.05， P<0.01）， and p-p65/p65（P<0.01） and up-regulated expression of IκBα protein （P<0.05， P<0.01）.ConclusionShuanghua drink effectively alleviates primary dysmenorrhea through analgesia and suppression of abnormal contractions of uterine smooth muscle. Its mechanism may be mediated by reduced levels of PGF2α/PGE2， TXB2/6-keto-PGF1α， iNOS， and NO， elevated β-EP level， and inhibited COX-2/NF-κB signaling pathway.

Schlüsselwort

Shuanghua drink;primary dysmenorrhea;cyclooxygenase-2 / nuclear factor-κB （COX-2 / NF-κB） signaling pathway;prostaglandin;inducible nitric oxide synthase （ iNOS ）

References

  1. 1.
    LE J. Obstetrics and gynecology［M］. 7th ed. Beijing： People's Med Publ House， 2008： 318-319.
  2. 2.
    National Cooperative Group on Menstrual Physiological Constants of Women， ZHANG Q B， SUN X C， et al. Investigation and analysis of menstrual physiological constants in Chinese women ［J］. Chin J Obstet Gynecol， 1980，15（4）：219-223.
  3. 3.
    DU Q， YE M F， GUAN Y M， et al. Research progress on essential oils from traditional Chinese medicine in the treatment of dysmenorrhea ［J］. Chin J Exp Tradit Med Form， 2022，28（6）：254-261.
  4. 4.
    IACOVIDES S， AVIDAN I， BAKER F C. What we know about primary dysmenorrhea today： A critical review ［J］. Hum Reprod Update， 2015， 21（5）： 762-778.
  5. 5.
    WANG L， LI T， CAO W X， et al. Acupoint sticking therapy regulates immune function in primary dysmenorrhea rats via TLR4/MyD88/NF-κB pathway ［J］. Acupunct Res， 2024， 49（1）： 1-10.
  6. 6.
    BINDU S， MAZUMDER S， BANDYOPADHYAY U. Non-steroidal anti-inflammatory drugs （NSAIDs） and organ damage： A current perspective ［J］. Biochem Pharmacol， 2020，180：114147.
  7. 7.
    LIN G H， WANG X L. Modified GeXia ZhuYu decoction in treating primary dysmenorrhea of Qi stagnation and blood stasis type： Efficacy and effects on VAS score and TCM syndrome score ［J］. Clin Reason Drug Use， 2025， 18（1）： 113-115，125.
  8. 8.
    TANG B， LIU D， CHEN L， et al. NLRP3 inflammasome inhibitor MCC950 attenuates primary dysmenorrhea in mice via the NF-κB/COX-2/PG pathway ［J］. J Inflamm （Lond），2020，17：22.
  9. 9.
    FERRIES-ROWE E， COREY E， ARCHER J S. Primary dysmenorrhea： Diagnosis and therapy ［J］. Obstet Gynecol， 2020， 136（5）： 1047-1058.
  10. 10.
    SALVEMINI D， MISKO T P， MASFERRER J L， et al. Nitric oxide activates cyclooxygenase enzymes ［J］. Proc Natl Acad Sci U S A， 1993， 90（15）： 7240-7244.
  11. 11.
    MA G Y， LI C J， LI D L， et al. Topical application of ginger volatile oil and gingerols in a mouse model of primary dysmenorrhea： A preliminary study ［J］. Chin Med Mod Distance Educ China， 2020， 18（9）： 112-114.
  12. 12.
    XUE X， LIU Y， HUANG Y， et al. Electroacupuncture regulates A20/NF-κB/NLRP3/GSDMD signaling pathway in primary dysmenorrhea rats ［J/OL］. Acupunct Res， 2025：1-11. ［2025-03-22］. .
  13. 13.
    HONG F， HE G， ZHANG M， YU B， CHAI C. The establishment of a mouse model of recurrent primary dysmenorrhea ［J］. Int J Mol Sci， 2022， 23（11）： 6128.
  14. 14.
    XIANG M， LIN F. Pharmacology experimental tutorial ［M］. Beijing： Chemical Industry Press， 2024： 214.
  15. 15.
    HU J， WANG Z S， BAO W D， et al. Analgesic effect of sparrow-pecking moxibustion on primary dysmenorrhea model rats ［J/OL］. Acta Chin Med， 2025， 1-9. ［2025-03-22］. .
  16. 16.
    JI Y Q， LI L M， CHEN Y， et al. Mechanism of Danggui Shaoyao San in protecting against uterine ischemia-reperfusion injury in rats ［J］. J Hubei Univ Med， 2022， 41（1）： 28-33.
  17. 17.
    LI Y L， SONG Y P， ZHAO G. Effects of Siwu Yimu decoction on isolated uterine motility in normal and oxytocin-treated rats ［J］. Mod Tradit Chin Med， 2006 （2）： 48-51.
  18. 18.
    LI P， HU Y F， QIN J， et al. Experimental study on Jingtongting in the treatment of primary dysmenorrhea ［J］.Chin J Exp Tradit Med Form，2008，14（12）： 71-74.
  19. 19.
    FAN Z Y， HU F R， HE Q S. Research progress on the protective effects and mechanisms of flavonoids in traditional Chinese medicine against cerebral ischemia injury ［J］. J Guiyang Univ Chin Med， 2019，41（4）：91-95.
  20. 20.
    SUN Y Y， JI H Y， CHEN B， et al. Research progress on the pathogenesis and traditional Chinese medicine treatment of primary dysmenorrhea ［J］. China Pharmacist， 2017， 20： 144-147.
  21. 21.
    WANG R， SUN Y， JIAO B Y， et al. Effects and mechanisms of Carthamus tinctorius aqueous extract and hydroxysafflor yellow A on primary dysmenorrhea with cold coagulation and blood stasis syndrome in rats ［J］. J Beijing Univ Tradit Chin Med， 2024， 47（10）： 1397-1407.
  22. 22.
    LONG J T， ZHENG W L. Research progress on pathogenesis and treatment of primary dysmenorrhea from perspectives of traditional Chinese and Western medicine ［J］. Matern Child Health Care China， 2024， 39（21）： 4359-4362.
  23. 23.
    TANG MJ， LIAO Z. Introduction to animal models of dysmenorrhea ［J］. Chin J Clin Pharmacol，2024， 40（7）： 1072-1075.
  24. 24.
    FU Q， YANG J， JIANG H， et al. Pulsed red photobiomodulation boosts the inhibition of oxytocin-induced primary dysmenorrhea in mice by suppressing oxidative stress and inflammation ［J］. J Biophotonics， 2024： e202400398.
  25. 25.
    SHAO J， LIU X， LIAN M， et al. Citronellol prevents 6-OHDA-induced oxidative stress， mitochondrial dysfunction， and apoptosis in Parkinson disease model of SH-SY5Y cells via modulating ROS-NO， MAPK/ERK， and PI3K/Akt signaling pathways ［J］. Neurotox Res， 2022， 40（6）： 2221-2237.
  26. 26.
    DING M P， FENG F， HU H T. Effect of puerarin on the expression of nuclear factor kappa B （NF-κB） after cerebral ischemia-reperfusion ［J］. Chin J Chin Mater Med，2007， 32（23）： 2515-2518.
  27. 27.
    MA T， LIU P， WEI J， et al. Imperatorin alleviated endometriosis by inhibiting the activation of PI3K/Akt/NF-κB pathway in rats ［J］. Life Sci， 2021， 274： 119291.
  28. 28.
    LEE W， YANG S， LEE C， et al. Aloin reduces inflammatory gene iNOS via inhibition activity and p-STAT-1 and NF-κB ［J］. Food Chem Toxicol， 2019， 126： 67-71.

Lesen Sie die ganze Passage

The above content is generated by Large Model Translation. The translated content is for reference only. We do not assume any commercial or legal responsibilty for any consequences arising from the use of our website