Prolactinoma was the most common functional pituitary neuroendocrine tumor tissue type, which was caused by excessive proliferation of pituitary prolactin (PRL) cells. Drug therapy of dopamine receptor agonists was generally considered as the prior treatment for prolactinoma patients. However, there were still prolactinoma patients who were resistant to dopamine agonists. Studies have been reported that paeoniflorin can inhibit the secretion of PRL in prolactinoma cells lacking dopamine D2 receptor (D2R) expression, and paeoniflorin can be metabolized into albiflorin by intestinal flora in rats. The effect of albiflorin on prolactinoma has not been reported yet. In this study, network pharmacology was used to analyze the mechanism of paeoniflorin and its metabolite albiflorin as multi-target therapy for prolactinoma, and the experimental verification was carried out. In order to clarify the complex relationship among paeoniflorin, albiflorin and prolactinoma, we constructed a component-target-disease network, and further constructed interaction network, MMP9, EGFR, FGF2, FGFR1 and LGALS3 were screened as the core targets. Kyoto encyclopedia of genes and genomes (KEGG) analysis showed that paeoniflorin and albiflorin may be involved in various pathways in the treatment of prolactinoma, included relaxin signaling pathway and PI3K-Akt signaling pathway. Molecular docking analysis showed that paeoniflorin and albiflorin had good binding activity with MMP9. Western blotting results showed that paeoniflorin and albiflorin could significantly reduce the expression of MMP9, and ELISA results showed that paeoniflorin and albiflorin could significantly reduce the concentration of PRL in GH3 cells, and the reduce degree of albiflorin was stronger than paeoniflorin at 50 mu M, which indicated that albiflorin might be a potential drug to treat prolactinoma, which can regulate prolactinoma through MMP9 and reduce the concentration of PRL. Our study provided a new therapeutic strategy for prolactinoma.Graphical abstractNetwork pharmacology and experimental verification revealed the anti-prolactinoma mechanism of paeoniflorin and albiflorin.
机构:
Wuhan Univ, Hosp Wuhan 3, Tongren Hosp, Dept Pharm, Wuhan, Hubei, Peoples R ChinaWuhan Univ, Hosp Wuhan 3, Tongren Hosp, Dept Pharm, Wuhan, Hubei, Peoples R China
Meng, Jun-Hua
Ni, Ping
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Hubei Univ Tradit Chinese Med, Sch Pharm, Wuhan, Hubei, Peoples R ChinaWuhan Univ, Hosp Wuhan 3, Tongren Hosp, Dept Pharm, Wuhan, Hubei, Peoples R China
Ni, Ping
Cao, Yu-Ling
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Wuhan ASIA Gen Hosp, Dept Pharm, Wuhan, Hubei, Peoples R ChinaWuhan Univ, Hosp Wuhan 3, Tongren Hosp, Dept Pharm, Wuhan, Hubei, Peoples R China
Cao, Yu-Ling
Zhang, Yu
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First Peoples Hosp Jiangxia Dist, Dept Pharm, Wuhan, Hubei, Peoples R ChinaWuhan Univ, Hosp Wuhan 3, Tongren Hosp, Dept Pharm, Wuhan, Hubei, Peoples R China
Zhang, Yu
Wang, Xiong
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Wuhan Univ, Hosp Wuhan 3, Tongren Hosp, Dept Pharm, Wuhan, Hubei, Peoples R ChinaWuhan Univ, Hosp Wuhan 3, Tongren Hosp, Dept Pharm, Wuhan, Hubei, Peoples R China
Wang, Xiong
Zhang, Hong
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Wuhan ASIA Gen Hosp, Dept Pharm, Wuhan, Hubei, Peoples R China
First Peoples Hosp Jiangxia Dist, Dept Pharm, Wuhan, Hubei, Peoples R ChinaWuhan Univ, Hosp Wuhan 3, Tongren Hosp, Dept Pharm, Wuhan, Hubei, Peoples R China
Zhang, Hong
Chen, Yong-Gang
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Wuhan Univ, Hosp Wuhan 3, Tongren Hosp, Dept Pharm, Wuhan, Hubei, Peoples R China
Wuhan Univ, Hosp Wuhan 3, Tongren Hosp, Dept Pharm, Wuhan 430600, Hubei, Peoples R ChinaWuhan Univ, Hosp Wuhan 3, Tongren Hosp, Dept Pharm, Wuhan, Hubei, Peoples R China
机构:
Jilin Agr Univ, Coll Tradit Chinese Med Mat, Changchun 130118, Peoples R ChinaJilin Agr Univ, Coll Tradit Chinese Med Mat, Changchun 130118, Peoples R China
Su, Lili
Wang, Zixian
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Jilin Agr Univ, Coll Tradit Chinese Med Mat, Changchun 130118, Peoples R ChinaJilin Agr Univ, Coll Tradit Chinese Med Mat, Changchun 130118, Peoples R China
Wang, Zixian
Guo, Pengli
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Jilin Agr Univ, Coll Tradit Chinese Med Mat, Changchun 130118, Peoples R ChinaJilin Agr Univ, Coll Tradit Chinese Med Mat, Changchun 130118, Peoples R China
Guo, Pengli
He, Zhongmei
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Jilin Agr Univ, Coll Tradit Chinese Med Mat, Changchun 130118, Peoples R ChinaJilin Agr Univ, Coll Tradit Chinese Med Mat, Changchun 130118, Peoples R China
He, Zhongmei
Li, Jianming
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Jilin Agr Univ, Coll Tradit Chinese Med Mat, Changchun 130118, Peoples R ChinaJilin Agr Univ, Coll Tradit Chinese Med Mat, Changchun 130118, Peoples R China
Li, Jianming
Zhao, Yan
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Jilin Agr Univ, Coll Tradit Chinese Med Mat, Changchun 130118, Peoples R ChinaJilin Agr Univ, Coll Tradit Chinese Med Mat, Changchun 130118, Peoples R China
Zhao, Yan
Zong, Ying
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Jilin Agr Univ, Coll Tradit Chinese Med Mat, Changchun 130118, Peoples R ChinaJilin Agr Univ, Coll Tradit Chinese Med Mat, Changchun 130118, Peoples R China
Zong, Ying
Chen, Weijia
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Jilin Agr Univ, Coll Tradit Chinese Med Mat, Changchun 130118, Peoples R ChinaJilin Agr Univ, Coll Tradit Chinese Med Mat, Changchun 130118, Peoples R China
Chen, Weijia
Du, Rui
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Jilin Agr Univ, Coll Tradit Chinese Med Mat, Changchun 130118, Peoples R China
Jilin Prov Engn Res Ctr Efficient Breeding & Prod, Changchun 130118, Peoples R China
Minist Natl Educ, Minist Educ, Key Lab Anim Prod & Prod Qual & Secur, Changchun 130118, Peoples R ChinaJilin Agr Univ, Coll Tradit Chinese Med Mat, Changchun 130118, Peoples R China
机构:
Chongqing Med Univ, Affiliate Hosp 1, Dept Integrated Tradit Chinese & Western Med, Chongqing, Peoples R ChinaChongqing Med Univ, Affiliate Hosp 1, Dept Integrated Tradit Chinese & Western Med, Chongqing, Peoples R China
Cao, Chunhao
Zhao, Wenting
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Hubei Univ Chinese Med, Wuhan, Peoples R ChinaChongqing Med Univ, Affiliate Hosp 1, Dept Integrated Tradit Chinese & Western Med, Chongqing, Peoples R China
Zhao, Wenting
Chen, Xianglin
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Hubei Univ Chinese Med, Wuhan, Peoples R ChinaChongqing Med Univ, Affiliate Hosp 1, Dept Integrated Tradit Chinese & Western Med, Chongqing, Peoples R China
Chen, Xianglin
Shen, Bin
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Chongqing Med Univ, Chongqing, Peoples R ChinaChongqing Med Univ, Affiliate Hosp 1, Dept Integrated Tradit Chinese & Western Med, Chongqing, Peoples R China
Shen, Bin
Wang, Teng
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Chongqing Med Univ, Chongqing, Peoples R ChinaChongqing Med Univ, Affiliate Hosp 1, Dept Integrated Tradit Chinese & Western Med, Chongqing, Peoples R China
Wang, Teng
Wu, Chaoxu
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Chongqing Med Univ, Affiliate Hosp 1, Dept Integrated Tradit Chinese & Western Med, Chongqing, Peoples R ChinaChongqing Med Univ, Affiliate Hosp 1, Dept Integrated Tradit Chinese & Western Med, Chongqing, Peoples R China
Wu, Chaoxu
Rong, Xiaofeng
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Chongqing Med Univ, Affiliate Hosp 1, Dept Integrated Tradit Chinese & Western Med, Chongqing, Peoples R ChinaChongqing Med Univ, Affiliate Hosp 1, Dept Integrated Tradit Chinese & Western Med, Chongqing, Peoples R China
机构:
Hebei North Univ, Dept Pharm, Zhangjiakou, Peoples R China
Chinese Peoples Liberat Army Gen Hosp, Dept Pharm, Med Ctr 5, Beijing, Peoples R ChinaHebei North Univ, Dept Pharm, Zhangjiakou, Peoples R China
Chen, Lisheng
Zhao, Xu
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Chinese Peoples Liberat Army Gen Hosp, Hepotol Dept, Med Ctr 5, Beijing, Peoples R ChinaHebei North Univ, Dept Pharm, Zhangjiakou, Peoples R China
Zhao, Xu
Wei, Shizhang
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Chinese Peoples Liberat Army Gen Hosp, Dept Pharm, Med Ctr 5, Beijing, Peoples R ChinaHebei North Univ, Dept Pharm, Zhangjiakou, Peoples R China
Wei, Shizhang
Ma, Xiao
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Chengdu Univ Tradit Chinese Med, Coll Pharm, Chengdu, Peoples R ChinaHebei North Univ, Dept Pharm, Zhangjiakou, Peoples R China
Ma, Xiao
Liu, Honghong
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Chinese Peoples Liberat Army Gen Hosp, Integrated TCM & Western Med Dept, Med Ctr 5, Beijing, Peoples R ChinaHebei North Univ, Dept Pharm, Zhangjiakou, Peoples R China
Liu, Honghong
Li, Jianyu
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Chinese Peoples Liberat Army Gen Hosp, Integrated TCM & Western Med Dept, Med Ctr 5, Beijing, Peoples R ChinaHebei North Univ, Dept Pharm, Zhangjiakou, Peoples R China
Li, Jianyu
Jing, Manyi
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Chinese Peoples Liberat Army Gen Hosp, Dept Pharm, Med Ctr 5, Beijing, Peoples R ChinaHebei North Univ, Dept Pharm, Zhangjiakou, Peoples R China
Jing, Manyi
Wang, Min
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Chinese Peoples Liberat Army Gen Hosp, Dept Pharm, Med Ctr 5, Beijing, Peoples R ChinaHebei North Univ, Dept Pharm, Zhangjiakou, Peoples R China
Wang, Min
Zhao, Yanling
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Hebei North Univ, Dept Pharm, Zhangjiakou, Peoples R China
Chinese Peoples Liberat Army Gen Hosp, Dept Pharm, Med Ctr 5, Beijing, Peoples R ChinaHebei North Univ, Dept Pharm, Zhangjiakou, Peoples R China
机构:
Hebei Med Univ, Sch Pharm, Dept Pharmaceut Anal, Shijiazhuang 050017, Hebei, Peoples R ChinaHebei Med Univ, Sch Pharm, Dept Pharmaceut Anal, Shijiazhuang 050017, Hebei, Peoples R China
Tian, Xi
Wei, Jinhuan
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Hebei Med Univ, Sch Pharm, Dept Pharmaceut Anal, Shijiazhuang 050017, Hebei, Peoples R ChinaHebei Med Univ, Sch Pharm, Dept Pharmaceut Anal, Shijiazhuang 050017, Hebei, Peoples R China
Wei, Jinhuan
Yang, Mengxin
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Hebei Med Univ, Sch Pharm, Dept Pharmaceut Anal, Shijiazhuang 050017, Hebei, Peoples R ChinaHebei Med Univ, Sch Pharm, Dept Pharmaceut Anal, Shijiazhuang 050017, Hebei, Peoples R China
Yang, Mengxin
Niu, Yukun
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Hebei Med Univ, Sch Pharm, Dept Pharmaceut Anal, Shijiazhuang 050017, Hebei, Peoples R ChinaHebei Med Univ, Sch Pharm, Dept Pharmaceut Anal, Shijiazhuang 050017, Hebei, Peoples R China
Niu, Yukun
Liu, Minyan
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Shijiazhuang Univ, Chem Engn Inst, Shijiazhuang, Hebei, Peoples R ChinaHebei Med Univ, Sch Pharm, Dept Pharmaceut Anal, Shijiazhuang 050017, Hebei, Peoples R China
Liu, Minyan
Du, Yingfeng
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Hebei Med Univ, Sch Pharm, Dept Pharmaceut Anal, Shijiazhuang 050017, Hebei, Peoples R ChinaHebei Med Univ, Sch Pharm, Dept Pharmaceut Anal, Shijiazhuang 050017, Hebei, Peoples R China
Du, Yingfeng
Jin, Yiran
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Hebei Med Univ, Second Hosp, Dept Pharm, Shijiazhuang, Hebei, Peoples R ChinaHebei Med Univ, Sch Pharm, Dept Pharmaceut Anal, Shijiazhuang 050017, Hebei, Peoples R China