[Protective effects and mechanisms of Sanguisorbae Radix Carbonisata nano-components against ulcerative colitis]

This study aims to isolate and extract Sanguisorbae Radix Carbonisata nano-components(SRC-NCs) from Sanguisorbae Radix Carbonisata(SRC) and investigate their protective effects against ulcerative colitis(UC) and the underlying mechanisms. The SRC-NCs were systematically characterized by nanomaterial characterization techniques to analyze their morphological structure, optical properties, and characteristics of functional groups on the surface. Meanwhile, a dextran sulfate sodium(DSS)-induced UC mouse model was established to evaluate the general condition, disease activity index(DAI) score, and pathological damage degree of the colon tissue of mice after SRC-NCs intervention. The level or activity of inflammatory factors(interleukin(IL)-17A, IL-6, IL-10, IL-2, tumor necrosis factor alpha(TNF-α), and IL-1β) and oxidative stress markers(myeloperoxidase(MPO), malondialdehyde(MDA), superoxide dismutase(SOD), glutathione(GSH), and nitric oxide(NO)) in the colon tissue was detected. The expression level of key proteins, such as Toll-like receptor 4(TLR4), myeloid differentiation primary response protein 88(MYD88), and nuclear factor-kappa B p65(NF-κB p65), in the colon tissue was detected by Western blot to provide key molecular evidence for revealing the intervention mechanism of SRC-NCs. The results showed that SRC-NCs were nearly spherical under transmission electron microscope(TEM), with a uniform particle size distribution(0.8-2.6 nm), a lattice spacing of 0.17 nm, and multiple active genes such as hydroxyl, amino, and carboxyl groups on the surface. In the UC model, SRC-NCs could slow down the weight loss and increase in DAI score of mice, and alleviate the shortening of the colon and the degree of tissue damage. SRC-NCs could down-regulate the levels of pro-inflammatory factors such as IL-17A, IL-6, IL-2, TNF-α, and IL-1β in the colon tissue, up-regulate the level of anti-inflammatory factor IL-10, reduce the activity of MPO and the content of MDA and NO, increase the activity of SOD and the level of GSH, and inhibit the expression of TLR4/MYD88/NF-κB p65 proteins. In conclusion, the study for the first time demonstrates that SRC-NCs are the key active components of SRC in exerting protective effects against UC, and the mechanism may be related to the inhibition of inflammatory responses of the TLR4/MYD88/NF-κB pathway and the reduction of oxidative stress.