Anti-anaphylactic potential of benzoylpaeoniflorin through inhibiting HDC and MAPKs from Paeonia lactiflora.
10.1016/S1875-5364(21)60086-9
- Author:
Wan-Chao ZHONG
1
;
En-Can LI
2
;
Rui-Rui HAO
2
;
Jing-Fang ZHANG
1
;
Hong-Tao JIN
3
,
4
;
Sheng LIN
5
,
6
Author Information
1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
2. New Drug Safety Evaluation Center, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
3. New Drug Safety Evaluation Center, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
4. Beijing Union-Genius Pharmaceutical Technology Co., Ltd., Beijing 100176, China. Electronic address: jinhongtao@imm.ac.cn.
5. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
6. Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China. Electronic address: lsznn@126.com.
- Publication Type:Journal Article
- Keywords:
Anti-anaphylactic action;
HDC;
MAPKs;
Paeonia lactiflora;
RBL-2H3
- MeSH:
Animals;
Glucosides;
Mice;
Mice, Inbred BALB C;
Molecular Docking Simulation;
Monoterpenes;
Paeonia;
Plant Roots
- From:
Chinese Journal of Natural Medicines (English Ed.)
2021;19(11):825-835
- CountryChina
- Language:English
-
Abstract:
Guided by cell-based anti-anaphylactic assay, eighteen cage-like monoterpenoid glycosides (1-18) were obtained from the bioactive fraction of P. lactiflora extract. Among these, compounds 1, 5, 6, 11, 12, 15, and 17 significantly reduced the release rate of β-HEX and HIS without or with less cytotoxicity. Furthermore, the most potent inhibitor benzoylpaeoniflorin (5) was selected as the prioritized compound for the study of action of mechanism, and its anti-anaphylactic activity was medicated by dual-inhibiting HDC and MAPK signal pathway. Moreover, molecular docking simulation explained that benzoylpaeoniflorin (5) blocked the conversion of L-histidine to HIS by occupying the HDC active site. Finally, in vivo on PCA using BALB/c mice, benzoylpaeoniflorin (5) suppressed the IgE-mediated PCA reaction in antigen-challenged mice. These findings indicated that cage-like monoterpenoid glycosides, especially benzoylpaeoniflorin (5), mainly contribute to the anti-anaphylactic activity of P. lactiflora by dual-inhibiting HDC and MAPK signal pathway. Therefore, benzoylpaeoniflorin (5) may be considered as a novel drug candidate for the treatment of anaphylactic diseases.
