Fermented Cordyceps Powder alleviates silica-induced inflammation and fibrosis by inhibiting M1 macrophage polarization via the HMGB1-TLR4-NF-κB pathway

Ethnopharmacological relevance: Cordyceps sinensis is a valuable Chinese medicine that has the effects of tonifying the lungs and kidneys, regulating the immune system, etc. Fermented Cordyceps Powder (FCP) is the fermentation product of Cordyceps sinensis mycelium, which has similar composition and effects to natural Cordyceps sinensis. FCP has been used as an adjunctive treatment of silicosis, however, the complete comprehension of these molecular mechanisms remains elusive. Aim of the study: To study the molecular immunological mechanism by which FCP alleviate inflammation and fibrosis in silicosis based on macrophage polarization and High Mobility Group Box protein 1 (HMGB1)-Toll-like receptor 4 (TLR4)-Nuclear factor kappaB (NF-kappa B) pathway through in vivo and in vitro experiments. Materials and methods: A rat model of silicosis and a co-culture cell model (NR8383 and RFL-6) exposed to silica were established and then intervened with different levels of FCP and FCP-containing serum, respectively, to explore the impacts of FCP on silica-induced inflammation and fibrosis and macrophage polarization at different time points. Upon the application of glycyrrhizic acid (GZA) to suppress HMGB1, an extensive analysis was undertaken to elucidate the impact of HMGB1-TLR4-NF-kappa B axis on the macrophages polarization. Results: FCP reduced M1, M2 macrophage polarization, and the HMGB1 expression in the lung of silicosis rats. Suppression of HMGB1 led to a pronounced reduction in the polarization of M1 macrophages, whereas it exerted no significant influence on the polarization of M2 macrophages. FCP-containing serum reduced silica-induced inflammation and fibrosis in the co-culture cell system. FCP-containing serum also reduced M1 macrophage polarization and inhibited stimulation of the HMGB1-TLR4-NF-kappa B signaling axis in NR8383 cells. Conclusions: Reduction of M1, M2 macrophage polarization is an important mechanism by which FCP attenuates inflammation and fibrosis in silicosis, in which reduction of M1 macrophage polarization may be achieved by suppression of the HMGB1-TLR4-NF-kappa B signaling axis.