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Innate Immune-Modulatory Activity of Prunella vulgaris in Thyrocytes Functions as a Potential Mechanism for Treating Hashimoto's Thyroiditis.

ABSTRACT: Prunella vulgaris (PV), a perennial herb, has been used to treat thyroid diseases in China for over 2,000 years. In particular, its therapeutic effect has been described for Hashimoto's thyroiditis, including reducing titers autoantibodies against thyroid peroxidase and thyroglobulin of and T helper 17 (Th17) cells. However, the underlying mechanism for how PV exerts such effects has not been investigated. We examined the effects of PV on innate immune activation, which is thought to be one of the triggers for the development of autoimmune diseases, including Hashimoto's thyroiditis. In cultured thyrocytes, PV reduced mRNA levels of inflammatory cytokines that were originally induced as a result of innate immune activation initiated by transfection of double-stranded DNA (dsDNA) or dsRNA. PV suppressed activation of nuclear factor ?B (NF-?B) and interferon regulatory factor 3 (IRF3), and suppressed corresponding promoter activation, which were initially activated by dsDNA or dsRNA. PV also suppressed the mRNA levels of molecules responsible for antigen processing and presentation, and PV protected thyrocytes from apoptosis induced by dsDNA and dsRNA. Additionally, PV suppressed the expression of genes involved in iodide uptake and oxidation. Taken together, these results suggest that PV exerts its protective effect on thyrocytes by suppressing both innate and adaptive immune responses and cell death. PV may also protect cells from iodide-associated oxidative injury. This report is among the first to identify the mechanisms to explain PV's beneficial effects in Hashimoto's thyroiditis.

SUBMITTER: Chen F

PROVIDER: S-EPMC7701117 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Innate Immune-Modulatory Activity of <i>Prunella vulgaris</i> in Thyrocytes Functions as a Potential Mechanism for Treating Hashimoto's Thyroiditis.

Chen Fei F Kawashima Akira A Luo Yuqian Y Kiriya Mitsuo M Suzuki Koichi K

Frontiers in endocrinology 20201116

<i>Prunella vulgaris</i> (PV), a perennial herb, has been used to treat thyroid diseases in China for over 2,000 years. In particular, its therapeutic effect has been described for Hashimoto's thyroiditis, including reducing titers autoantibodies against thyroid peroxidase and thyroglobulin of and T helper 17 (Th17) cells. However, the underlying mechanism for how PV exerts such effects has not been investigated. We examined the effects of PV on innate immune activation, which is thought to be o ...[more]

PMID: 33304319

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Project description:BackgroundThe study created mice model of Hashimoto's thyroiditis (HT) and induced thyroid inflammatory cell lines, exploring the mechanism of Xiaoying Daotan decoction on HT.MethodsDivided HT mice models into model group (0.2 mL saline), Western medicine group (0.2 mL levothyroxine sodium tablets), traditional Chinese medicine group (0.2 mL Xiaoyin Daotan prescription), and Notch protein inhibition group (0.2 mL Xiaoyin Daotan prescription). After treatment, serum Notch protein expression and T cell (Treg)/T helper cell 17 (Th17) cytokines levels were detected through Enzyme linked immunosorbent assay (ELISA). Use real-time qualitative polymerase chain reaction detected Notch protein expression. Thyroid inflammatory cell lines were induced and divided into 5 groups: blank group, iNotch group (knocking down the Notch protein gene of thyroid inflammatory cells), NC group (Notch protein carrier negative control group), iNotch + DS group and DS group (knocking down the Notch protein gene of thyroid inflammatory cells). The cells were treated with serum containing Xiaoying Daotan decoction. After culture, detected Notch protein expression level and Treg/Th17 cytokine level in each group.ResultsFor the animal experiment, the serum Notch protein expression, the serum levels of key activating proteins Signal Transducer and Activator of Transcription 3 (STAT3), RAR-related orphan receptor gamma T (RORγt), and interleukin (IL)-22 of Th17 cells of mice in the model group was significantly higher than that of the other groups. Compared with the model group and Western medicine group, the serum transforming growth factor-β (TGF-β) level of the mice in the traditional Chinese medicine group and the Notch protein inhibition group was significantly higher. All the differences were statistically significant (P<0.05). For the cell experiment, the β-actin value of Notch protein in thyroid inflammatory cell genes was significantly downregulated and the key activation protein of Treg was significantly upregulated in iNotch + DS group and DS group compared with the other 3 groups. Levels of Th17 key activating proteins STAT3, IL-17, and IL-22 in the iNotch group, iNotch + DS group, and DS group were lower than those of the blank group and NC group, both with statistically significant difference (P<0.001).ConclusionsThe mechanism of Xiaoying Daotan decoction on HT could be related to the immune inflammatory response of the Treg/Th17 cell axis mediated by the Notch protein pathway.

Project description:BackgroundPrunella vulgaris L. is effective in the treatment of breast cancer (BRCA); however, the underlying mechanism is still unclear. The aim of this study was to elucidate the mechanism of treatment of BRCA by P. vulgaris using network pharmacology and molecular docking technology, and to verify the experimental results using human BRCA MDA-MB-231 cells.MethodsActive components and action targets of P. vulgaris were determined using the TCMSP™, SwissTarget Prediction™, and TargetNet™ databases. GeneCards™ and OMIM™ provided BRCA targets. After obtaining common targets, a protein-protein interaction (PPI) network was constructed using the STRING™ database, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted using the Xiantao™ academic database. Cytoscape™ was used to construct "single drug-disease-component-target" and "single drug-disease-component-target-pathway" networks. The Human Protein Atlas™ was used to determine protein expression levels in BRCA cell lines. AutoDock tools™ were used to carry out molecular docking for the first 10 targets of quercetin and the PPI network. Finally, the abovementioned results were verified using cell experiments.ResultsWe obtained 11 active components, 198 targets, and 179 common targets, including DUOX2, MET, TOP2A, and ERBB3. The results of KEGG pathway analysis screened 188 related signaling pathways and indicated the potential key role of PI3K-Akt and MAPK signaling pathways in the antibreast cancer process of P. vulgaris. The results of molecular docking showed that the first 10 targets of quercetin interacted well with the protein network. Cell experiments showed that quercetin effectively inhibited the proliferation of MDA-MB-231 cells by regulating apoptosis and cell cycle, which may be partly related to the MAPK signaling pathway.ConclusionSynergistic effects of multiple components, targets, and pathways on the anti-BRCA activity of P. vulgaris could provide a theoretical basis for further study on its complex anti-BRCA mechanism.

Dataset Information

Innate Immune-Modulatory Activity of Prunella vulgaris in Thyrocytes Functions as a Potential Mechanism for Treating Hashimoto's Thyroiditis.

Publications

Innate Immune-Modulatory Activity of <i>Prunella vulgaris</i> in Thyrocytes Functions as a Potential Mechanism for Treating Hashimoto's Thyroiditis.

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