Saikosaponin-d Attenuates Hashimoto’s Thyroiditis by Regulating Macrophage Polarization

Abstract

Objective. Hashimoto’s thyroiditis (HT) is one of the most common clinical autoimmune diseases. Recent studies have found that HT pathogenesis is associated with macrophage polarization. Saikosaponin-d (SSd) is an active component in the Chinese medicine Bupleurum, which has anti-inflammatory and immunomodulatory effects. The purpose of this study was to verify the therapeutic effect of SSd on HT and to investigate the regulatory effect of SSd on macrophage polarization in HT. Methods. Network pharmacology analysis was used to predict the relevant targets and signaling pathways of SSd for HT treatment. The therapeutic effect of SSd on HT model mice and the effect on macrophage polarization were detected by animal experiment. Results. Network pharmacological analysis showed that SSd can alleviate HT against multiple targets such as IL-6 and IL-10 and can act on macrophage polarization-related signaling pathways such as MAPK and JAK-STAT signaling pathways. Animal experiments showed that SSd intervention attenuated the lymphocytic infiltration in thyroid tissues of HT mice ( P = 0.044 ); SSd intervention reduced serum TPOAb antibody level in HT mice ( P < 0.001 ); SSd adjusted M1/M2 imbalance towards M2-type macrophage polarization in the spleen of HT mice ( P = 0.003 ); SSd inhibited the expressions of Th1-type cytokine IFN-γ and Th17-type cytokine IL-17 systemically and locally in the thyroid of HT mice ( P < 0.05 ). Conclusion. SSd treatment can regulate Th1/Th2 and Th17/Treg imbalances and reduce the severity of HT in mice by promoting the polarization of M2 macrophages.

Effects of iodine intake on gut microbiota and gut metabolites in Hashimoto thyroiditis-diseased humans and mice

“…A study using single-cell RNA sequencing found that immune-dysregulated cells interact and activate relevant immune pathways and further aggravate the immune response in patients 38 . A decrease in Treg cells and an increase in Th17 cells in the peripheral blood of patients with HT have been previously reported 39 , 40 . Evidence shows that an imbalance in the Th17/Treg ratio is a prognostic factor for thyroid gland damage 41 .…”

Effects of iodine intake on gut microbiota community and metabolites: interactions between gut dysbiosis and Hashimoto thyroiditis

“…A study using single-cell RNA sequencing found that immunedysregulated cells interact and activate relevant immune pathways and further aggravate the immune response in patients 37 . A decrease in Treg cells and an increase in Th17 cells in the peripheral blood of patients with HT have been previously reported 38,39 . Evidence shows that an imbalance in the Th17/Treg ratio is a prognostic factor for thyroid gland damage 40 .…”

Paeoniae Radix Alba effectively attenuates Polygonum multiflorum Thunb.-induced idiosyncratic liver injury by modulating M2 macrophage polarization

“…The top five scoring nodes based on degree were ALB, MMP9, TNF, HIF1A, PTGS2, IL1B, STAT3, PPARG, PTEN, BCL2, ICAM1, MAPK1, and RELA (Table 2). A review of previous studies and literature research revealed that the targets are closely related to macrophage polarization [26,27] .…”

“…MMP9, PTGS2, STAT3, and PPARG may also be involved in the regulation of macrophage polarization and inflammation by PRA. For example, overexpression of MMP9 can promote M1 phenotype transformation in LPS-induced murine pulmonary macrophages, whereas inhibition of MMP9 expression can promote M2 phenotype transformation [26,27] . The KEGG pathway enrichment analysis revealed various pathways related to macrophage polarization, including the TNF signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, Toll-like receptor signaling pathway, NF-κB signaling pathway, and phosphoinositide 3-kinase-Akt (PI3K/Akt) signaling pathway.…”