Purpose Orbital fibroblasts (OF) are considered the central target cells in the pathogenesis of thyroid-associated orbitopathy (TAO), which comprises orbital inflammation, orbital tissue edema, adipogenesis, fibrosis, oxidative stress and autophagy. Certain active ingredients of traditional Chinese medicine (TCM) demonstrated inhibition of TAO-OF in pre-clinical studies and they could be translated into novel therapeutic strategies. Methods The pertinent and current literature of pre-clinical studies on TAO investigating the effects of active ingredients of TCM was reviewed using the NCBI PubMed database. Results Eleven TCM compounds demonstrated inhibition of TAO-OF in-vitro and three of them (polydatin, curcumin, and gypenosides) resulted in improvement in TAO mouse models. Tanshinone IIA reduced inflammation, oxidative stress and adipogenesis. Both resveratrol and its precursor polydatin displayed anti-oxidative and anti-adipogenic properties. Celastrol inhibited inflammation and triptolide prevented TAO-OF activation, while icariin inhibited autophagy and adipogenesis. Astragaloside IV reduced inflammation via suppressing autophagy and inhibited fat accumulation as well as collagen deposition. Curcumin displayed multiple actions, including anti-inflammatory, anti-oxidative, anti-adipogenic, anti-fibrotic and anti-angiogenic effects via multiple signaling pathways. Gypenosides reduced inflammation, oxidative stress, tissue fibrosis, as well as oxidative stress mediated autophagy and apoptosis. Dihydroartemisinin inhibited OF proliferation, inflammation, hyaluronan (HA) production, and fibrosis. Berberine attenuated inflammation, HA production, adipogenesis, and fibrosis. Conclusions Clinical trials of different phases with adequate power and sound methodology will be warranted to evaluate the appropriate dosage, safety and efficacy of these compounds in the management of TAO.

Promoting the differentiation of neural stem cells (NSCs) into oligodendrocytes is crucial for maintaining myelin integrity in demyelinating diseases, which is regulated by the microglia-mediated inflammatory milieu in the central nervous system (CNS). In this research, we aimed to investigate whether dihydroartemisinin (DHA) could promote the differentiation of C17.2 neural stem cell into oligodendrocytes by regulating microglia, and elucidate the underlying molecular mechanisms. Moreover, DHA trimer self-assembled nanoparticles (DHA3NPs) were prepared to explore the efficacy on attenuating inflammation compared to free DHA. An in vitro microglia-NSCs co-culturing model was established. The level of inflammation and the differentiation of NSCs were accessed via RT-qPCR, ELISA and western blot methods. To inhibit STAT6 activation in microglia, AS1517499 was applied. The results found that DHA effectively rebalanced BV2-mediated inflammation and specifically induced the directed differentiation of NSC cell lines into oligodendrocytes (OLs), as represented by the expression of MBP and PLP. Mechanistically, it was demonstrated that the enhanced expression of Chi3l3 induced by DHA was significantly eliminated by the blockade of STAT6, suggesting that DHA served as a booster for OLs differentiation in a STAT6-depenent manner. In addition, DHA3NPs were more effective than free DHA in attenuating microglia-mediated inflammation stimulated by lipopolysaccharide. In conclusion, DHA attenuated microglia-mediated neuroinflammation and activated the STAT6/Chi3l3 signaling pathway in microglia, inducing C17.2 differentiation into oligodendrocytes. This study reveals the molecular mechanism and the functional impact of DHA in inhibiting inflammation of CNS, and provides preliminary suggestions for the clinical treatment of inflammatory demyelinating diseases.