Increasing studies have shown that walnut green husk (WGH) has obvious effects on reducing lipid, resisting oxidation, and protecting the liver. However, the mechanism by which WGH can prevent high-fat diet (HFD)-induced non-alcoholic steatohepatitis (NASH) remains unclear. This study is aimed at investigating the effects of WGH ethanol extract (WGHE) on NLRP3-related biochemical indicators and the diversity and metabolism of gut microbiota in HFD-induced NASH rats. WGHE was administered to HFD-induced NASH rats for 6 weeks. The results showed that WGHE could decrease the levels of blood and liver TC, TG, LDL-C, AST, and ALT and the levels of liver indices, including IL-1β, IL-6, TNF-α, TGF-β, FFA, VLDL, caspase-1, ASC, and NLRP3, while it could increase the levels of HDL-C. The pathological damage to liver tissues was significantly reduced. Moreover, WGHE could reduce the Firmicutes/Bacteroidetes (F/B) ratio and the relative abundances of potentially harmful bacteria, such as Lachnospiraceae and Christensenellaceae, and increase that of potentially beneficial bacteria, such as norank_f__Muribaculaceae. These bacteria were associated with NASH and most of them were significantly associated. A total of 23 gut bacteria and 31 metabolites were significantly altered by HFD, which was reversed by WGHE. The common functional pathways, including lipid metabolism and steroid biosynthesis, were identified through the analysis of KEGG metabolic pathways. In addition, the changes in gut microbiota, such as unclassified_f__Lachnospiraceae, unclassified_g__Blautia, and unclassified_g__Desulfovibrio, were associated with the changes in key intestinal metabolites, such as arachidonoyl amine, xanthine, and 25,26-epoxy-1α-hydroxyvitamin D3. In conclusion, WGHE could mitigate HFD-induced NASH in rats by interfering with the NLRP3-related gut microbiota and their metabolites.

Daphne koreana Nakai is a cherished medicinal plant in the Changbai Mountain region of China. It can be incorporated into medicinal meals and used for various skin diseases by infiltrating liquor. Daphnetin (7,8-dihydroxycoumarin, Dap.) is a main constituent of D. koreana Nakai, which has been used to treat inflammatory conditions and immune disorders due to its numerous pharmacological activities, including anti-oxidant, anti-inflammatory, analgesic, etc. Atopic dermatitis (AD) and allergic asthma are typical diseases of type 2-immune responses. In the present study, the therapeutic potential of Dap. against AD and allergic asthma was investigated using animal and cell experiments. AD-like lesions were induced by repeated application of 1-chloro-2,4-dinitrobenzene (DNCB) to the shaved dorsal skin of BALB/c mice. Ovalbumin (OVA) induction was utilized to establish a mouse asthma model. A passive cutaneous anaphylaxis (PCA) mouse ear model and immunoglobulin E (IgE)/bovine serum albumin (BSA)-stimulated RBL-2H3 cells were used for in vitro assays. The skin lesions and serum and tissue homogenates of the mice were analyzed using histological analysis, immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA), respectively, in order to investigate the anti-AD effects of Dap. Histological analysis was performed on the allergic asthma model to observe inflammatory cell infiltration in the lung tissues. Total IgE and OVA-specific IgE in the serum were measured by ELISA. The levels of inflammatory cytokines in BALF were detected by ELISA. In addition, ELISA and western blotting were performed for the in vitro analysis of RBL-2H3 cells. The results showed that Dap. inhibited the development of DNCB-induced AD-like lesions in the BALB/c mice by reducing the severity of the lesions, epidermal thickness and mast cell infiltration; this was accompanied by reduced levels of IgE and inflammatory cytokines [interleukin (IL)-4, IL-5, IL-9, IL-13, IL-33 and thymic stromal lymphopoietin (TSLP)]. In the allergic asthma model, Dap. reduced the number of infiltrated inflammatory cells in the lung tissues. Moreover, the levels of total serum IgE and OVA-specific IgE were reduced in the high daphnetin dose groups (Dap., −100 mg kg⁻¹). Dap. administered at a dose of −100 mg kg⁻¹ decreased the levels of inflammatory cytokines (IL-4, IL-5, IL-9, IL-13, IL-33 and TSLP in BALF). Furthermore, Dap. administered to IgE-sensitized mice effectively attenuated the IgE-triggered PCA reaction. In vitro, Dap. decreased the expression levels of histamine, IL-4, IL-6, IL-13, MIP-1α and INF-α, and reduced the protein expression levels of phosphorylated MAPKs, P-Lyn and P-syk in the RBL-2H3 cells. Therefore, Dap. can be represented as a potential therapeutic strategy for the treatment of allergic inflammatory conditions via immunoregulation.

Psoriasis is a common chronic immune-mediated inflammatory skin disorder. Sophora flavescens Alt. (S. flavescens) has been widely acknowledged in the prevention and treatment of psoriasis. Kushenol F (KSCF) is a natural isopentenyl flavonoid extracted from the root of S. flavescens. We aimed to investigate the effect and mechanism of KSCF on imiquimod (IMQ)-induced psoriasis-like skin lesions in mice. A mouse model of psoriasis was induced with 5% IMQ for 5 days, and the mice were given KSCF dermally for 5 days. Changes in skin morphology, the psoriasis area, the severity index (PASI), and inflammatory factors of psoriasis-like skin lesions were evaluated. Metabolites in the psoriasis-like skin lesions were analyzed with ultra-high-performance liquid chromatography/mass spectrometry followed by a multivariate statistical analysis to identify the differential metabolites and metabolic pathway. The results of the present study confirmed that KSCF significantly reduced PASI scores, epidermal thickening, and epidermal cell proliferation and differentiation. KSCF also reduced the levels of interleukin (IL)-1β, IL-6, IL-8, IL-17A, IL-22, IL-23, and tumor necrosis factor (TNF)-α in the injured skin tissues while increasing IL-10 content. KSCF significantly regulated metabolites in the skin samples, and a total of 161 significant metabolites were identified. These differential metabolites involved sphingolipid and linoleic acid metabolism and steroid hormone biosynthesis. Collectively, KSCF inhibited the inflammatory response to prevent IMQ-induced psoriasis-like skin lesions in mice by call-backing the levels of 161 endogenous metabolites and affecting their related metabolic pathways. KSCF has the potential to be developed as a topical drug for treating psoriasis symptoms.

Seseli mairei Wolff extracts (SMWE) are widely used to treat psoriasis as a Chinese medicine, but their effect and mechanism are unclear. This study verified the effect of SMWE on psoriasis by regulating Th17 cells. HaCaT cells were treated with IL-17A in vitro to evaluate the effect of SMWE on psoriasis. In vivo, the mice psoriasis model was established using imiquimod (IMQ, 62.5 mg/d), and intragastrically treated with the different drugs for six days. The severity of skin inflammation was evaluated with Psoriasis Area and Severity Index (PASI) scores and pathology. The levels of inflammation cytokines were assessed with immunofluorescence, immunochemistry, ELISA, and real-time PCR. The number of Th17 cells was determined with flows. SMWE inhibited the proliferation of HaCaT cells and reduced the IL-17A-induced IL-6 production in vitro. In vivo, SMWE deduced the levels of IL-1β, IL-6, IL-8, IL-17A, IL-17F, IL-22, IL-23, and TNF-α, while increasing the level of IL-10 compared to the model group. SMWE also inhibited the levels of NF-κB, JAK2, and STAT3 proteins, while declining the expressions of Gr-1, and MPO. Interestingly, SMWE significantly decreased the number of Th17 cells. SMWE inhibited the proliferation of HaCaT cells and attenuated the development of psoriasis lesions by inhibiting Th17 cells to regulate the levels of inflammation cytokines.