PMID- 34764638
OWN - NLM
STAT- MEDLINE
DCOM- 20220222
LR  - 20220428
IS  - 1177-8881 (Electronic)
IS  - 1177-8881 (Linking)
VI  - 15
DP  - 2021
TI  - Prunella vulgaris L. Attenuates Experimental Autoimmune Thyroiditis by Inhibiting 
      HMGB1/TLR9 Signaling.
PG  - 4559-4574
LID - 10.2147/DDDT.S325814 [doi]
AB  - BACKGROUND: Prunella vulgaris L. (PV) has been used to treat autoimmune 
      thyroiditis (AIT), but the underlying mechanism remains unknown. The present 
      study was designed to evaluate the effect of PV on AIT and explore the role of 
      high-mobility group box-1 (HMGB1) signaling in PV-mediated effects in vivo and in 
      vitro. METHODS: In the present study, bioactive components of PV were identified 
      using UPLC-ESI-MS. The protective effects and potential mechanisms critical for 
      the anti-inflammatory and immunomodulatory effects of PV in AIT were investigated 
      in a rat model of thyroglobulin-induced experimental autoimmune thyroiditis (EAT) 
      and in lipopolysaccharide (LPS)-induced thyroid follicular cells (TFCs). RESULTS: 
      The main bioactive compound identified in PV was rosmarinic acid. The thyroid 
      volume, thyroiditis inflammation score and serum thyroglobulin antibody levels of 
      EAT rats were attenuated by PV treatment (P<0.01). In addition, PV significantly 
      reduced the elevated levels of the proinflammatory cytokines TNF-alpha, IL-6, IL-1beta 
      and monocyte chemoattractant protein-1 (MCP-1) both in vivo (P<0.01) and in vitro 
      (P<0.05). PV downregulated HMGB1 mRNA and protein expression, reduced HMGB1 
      secretion, and inhibited TLR9 signaling pathways (TLR9 and MyD88) in PV-treated 
      EAT rats and TFCs. Moreover, PV reversed the increases in the numbers of splenic 
      Th1, Th2, and Th17 cells. Finally, our results acquired following administration 
      of ethyl pyruvate, an HMGB1 inhibitor, to splenocytes cultured in vitro supported 
      the hypothesis that the HMGB1/TLR9 pathway is involved in the PV-mediated 
      reductions in Th1, Th2 and Th17 cells. CONCLUSION: PV decreased the activity of 
      the TLR9/MyD88 pathway and proinflammatory cytokines through HMGB1. In addition, 
      we are the first to show that PV attenuated the HMGB1-induced increases in Th1, 
      Th2 and Th17 cells in AIT models. These findings provide new evidence for the 
      potential therapeutic value of PV as a treatment for AIT and other autoimmune 
      diseases.
CI  - (c) 2021 Guo et al.
FAU - Guo, Qingling
AU  - Guo Q
AD  - Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong 
      First Medical University, Jinan, 250021, People's Republic of China.
AD  - Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of 
      Medicine,Shandong University, Jinan, 250012, People's Republic of China.
FAU - Qu, Haili
AU  - Qu H
AD  - Department of Nursing, Shandong Provincial Hospital Affiliated to Shandong First 
      Medical University, Jinan, 250021, People's Republic of China.
FAU - Zhang, Hong
AU  - Zhang H
AD  - Department of General Practice, Shandong Provincial Hospital Affiliated to 
      Shandong First Medical University, Jinan, 250021, People's Republic of China.
FAU - Zhong, Xia
AU  - Zhong X
AD  - Department of General Practice, Shandong Provincial Hospital Affiliated to 
      Shandong First Medical University, Jinan, 250021, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20211104
PL  - New Zealand
TA  - Drug Des Devel Ther
JT  - Drug design, development and therapy
JID - 101475745
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cytokines)
RN  - 0 (HMGB1 Protein)
RN  - 0 (Hbp1 protein, rat)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Plant Extracts)
RN  - 0 (Tlr9 protein, rat)
RN  - 0 (Toll-Like Receptor 9)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/isolation & purification/*pharmacology
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - HMGB1 Protein/metabolism
MH  - Lipopolysaccharides
MH  - Plant Extracts/*pharmacology
MH  - Prunella/*chemistry
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Signal Transduction/drug effects
MH  - Th1 Cells/immunology
MH  - Th17 Cells/immunology
MH  - Th2 Cells/immunology
MH  - Thyroiditis, Autoimmune/*drug therapy/immunology
MH  - Toll-Like Receptor 9/metabolism
PMC - PMC8576104
OTO - NOTNLM
OT  - HMGB1
OT  - Prunella vulgaris L.
OT  - TLR9
OT  - autoimmune thyroiditis
COIS- The extracts of PV were prepared by Guiyang Xintian Pharmaceutical Co., Ltd. 
      However, apart from that, no other relationships that might lead to a conflict of 
      interest or artificial bias of the results exist.
EDAT- 2021/11/13 06:00
MHDA- 2022/02/23 06:00
PMCR- 2021/11/04
CRDT- 2021/11/12 06:57
PHST- 2021/06/21 00:00 [received]
PHST- 2021/09/28 00:00 [accepted]
PHST- 2021/11/12 06:57 [entrez]
PHST- 2021/11/13 06:00 [pubmed]
PHST- 2022/02/23 06:00 [medline]
PHST- 2021/11/04 00:00 [pmc-release]
AID - 325814 [pii]
AID - 10.2147/DDDT.S325814 [doi]
PST - epublish
SO  - Drug Des Devel Ther. 2021 Nov 4;15:4559-4574. doi: 10.2147/DDDT.S325814. 
      eCollection 2021.