PMID- 36555745
OWN - NLM
STAT- MEDLINE
DCOM- 20221226
LR  - 20221226
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 24
DP  - 2022 Dec 17
TI  - Regulating Th17/Treg Balance Contributes to the Therapeutic Effect of 
      Ziyuglycoside I on Collagen-Induced Arthritis.
LID - 10.3390/ijms232416105 [doi]
LID - 16105
AB  - To investigate the therapeutic effect and primary pharmacological mechanism of 
      Ziyuglycoside I (Ziyu I) on collagen-induced arthritis (CIA) mice. CIA mice were 
      treated with 5, 10, or 20 mg/kg of Ziyu I or 2 mg/kg of methotrexate (MTX), and 
      clinical manifestations, as well as pathological changes, were observed. T cell 
      viability and subset type were determined, and serum levels of transforming 
      growth factor-beta (TGF-beta) and interleukin-17 (IL-17) were detected. The mRNA 
      expression of retinoid-related orphan receptor-gammat (RORgammat) and transcription 
      factor forkhead box protein 3 (Foxp3) in mouse spleen lymphocytes was ascertained 
      by the real-time reverse transcriptase-polymerase chain reaction (RT-qPCR). 
      Molecular docking was used to detect whether there was a molecular interaction 
      between Ziyu I and protein kinase B (Akt). The activation of mechanistic target 
      of rapamycin (mTOR) in T cells was verified by Western blotting or 
      immunofluorescence. Ziyu I treatment effectively alleviated arthritis symptoms of 
      CIA mice, including body weight, global score, arthritis index, and a number of 
      swollen joints. Similarly, pathological changes of joints and spleens in 
      arthritic mice were improved. The thymic index, T cell activity, and RORgammat 
      production of Ziyu I-treated mice were significantly reduced. Notably, through 
      molecular docking, western blotting, and immunofluorescence data analysis, it was 
      found that Ziyu I could interact directly with Akt to reduce downstream mTOR 
      activation and inhibit helper T cell 17 (Th17) differentiation, thereby 
      regulating Th17/regulatory T cell (Treg) balance and improving arthritis 
      symptoms. Ziyu I effectively improves arthritic symptoms in CIA mice by 
      inhibiting mTOR activation, thereby affecting Th17 differentiation and regulating 
      Th17/Treg balance.
FAU - Wang, Manman
AU  - Wang M
AD  - Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of 
      Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative 
      Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei 230032, China.
FAU - Su, Tiantian
AU  - Su T
AD  - Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of 
      Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative 
      Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei 230032, China.
FAU - Sun, Hanfei
AU  - Sun H
AD  - Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of 
      Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative 
      Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei 230032, China.
FAU - Cheng, Huijuan
AU  - Cheng H
AD  - Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of 
      Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative 
      Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei 230032, China.
FAU - Jiang, Chunru
AU  - Jiang C
AD  - Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of 
      Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative 
      Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei 230032, China.
FAU - Guo, Paipai
AU  - Guo P
AD  - Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of 
      Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative 
      Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei 230032, China.
FAU - Zhu, Zhenduo
AU  - Zhu Z
AD  - Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of 
      Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative 
      Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei 230032, China.
FAU - Fang, Ruhong
AU  - Fang R
AD  - Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of 
      Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative 
      Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei 230032, China.
FAU - He, Feng
AU  - He F
AD  - Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of 
      Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative 
      Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei 230032, China.
FAU - Ge, Mingli
AU  - Ge M
AD  - Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of 
      Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative 
      Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei 230032, China.
FAU - Guan, Qiuyun
AU  - Guan Q
AD  - Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of 
      Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative 
      Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei 230032, China.
FAU - Wei, Wei
AU  - Wei W
AD  - Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of 
      Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative 
      Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei 230032, China.
FAU - Wang, Qingtong
AU  - Wang Q
AD  - Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of 
      Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative 
      Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei 230032, China.
LA  - eng
GR  - 81973314/National Natural Science Foundation of China/
GR  - 81202541/National Natural Science Foundation of China/
GR  - 81973332/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20221217
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - 0 (ziyuglycoside I)
RN  - 0 (Nuclear Receptor Subfamily 1, Group F, Member 3)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Arthritis, Experimental/metabolism
MH  - T-Lymphocytes, Regulatory/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Nuclear Receptor Subfamily 1, Group F, Member 3/genetics/metabolism
MH  - Molecular Docking Simulation
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Th17 Cells/metabolism
PMC - PMC9786935
OTO - NOTNLM
OT  - Foxp3
OT  - RORgammat
OT  - Th17/Treg
OT  - Ziyuglycoside I
OT  - mTOR
OT  - rheumatoid arthritis
COIS- The authors declare that they have no known competing financial interest or 
      personal relationships that could have appeared to influence the work reported in 
      this paper.
EDAT- 2022/12/24 06:00
MHDA- 2022/12/27 06:00
PMCR- 2022/12/17
CRDT- 2022/12/23 01:36
PHST- 2022/11/14 00:00 [received]
PHST- 2022/12/11 00:00 [revised]
PHST- 2022/12/14 00:00 [accepted]
PHST- 2022/12/23 01:36 [entrez]
PHST- 2022/12/24 06:00 [pubmed]
PHST- 2022/12/27 06:00 [medline]
PHST- 2022/12/17 00:00 [pmc-release]
AID - ijms232416105 [pii]
AID - ijms-23-16105 [pii]
AID - 10.3390/ijms232416105 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Dec 17;23(24):16105. doi: 10.3390/ijms232416105.