Prevention of supercritical carbon dioxide fluid extract from Chrysanthemum indicum Linnén on cutaneous squamous cell carcinomas progression following UV irradiation in mice.

Chrysanthemum indicum Linnén (C. indicum), a medicinal and food herb with various bioactive components, may be of beneficial use in cosmetics and the treatment of skin-related diseases. However, to date, few studies have been reported on its potential preventive and therapeutic effects on skin cancer. Therefore, the present study aimed to investigate the effect and potential mechanism of action of supercritical carbon dioxide extract from C. indicum (CISCFE) on UV-induced skin cancer in a mouse model. Kunming mice were allocated randomly to five treatment groups: Sham, model, low concentration CISCFE, high concentration CISCFE and positive control nicotinamide groups. The dorsal skin of mice was irradiated with UV light for 31 weeks. Histopathological changes, ELISA assays, immunohistochemical analysis and western blotting were performed to investigate the potential therapeutic effects of CISCFE. The results showed that CISCFE alleviated skin oxidative and inflammatory damage in a UV-induced mouse model of skin cancer. Moreover, CISCFE suppressed abnormal activation of proto-oncogene c-Myc and the overexpression of Ki-67 and VEGF, and increased expression of the anti-oncogene PTEN, thereby reducing abnormal proliferation of the epidermis and blood vessels. Additionally, CISCFE increased the protein expression levels of NAD-dependent protein deacetylase sirtuin-1 (SIRT1), Kelch-like ECH associated protein 1 (Keap1) and inhibited the expression of nuclear factor 2 erythroid 2-related factor 2 (Nrf2), phosphorylated (p)-p62 (Ser 349), p-p65 and acetyl-p65 proteins in a UV-induced skin cancer mouse model. In summary, CISCFE exhibited potent anti-skin cancer activity, which may be attributed its potential effects on the p62/Keap1-Nrf2 and SIRT1/NF-κB pathways.

Asperuloside suppressing oxidative stress and inflammation in DSS-induced chronic colitis and RAW 264.7 macrophages via Nrf2/HO-1 and NF-κB pathways.

BACKGROUND: Inflammatory bowel diseases (IBDs), which mainly include Crohn's disease (CD) and ulcerative colitis (UC), are chronic idiopathic inflammatory disease of the gastrointestinal tract for which effective pharmacological treatments are lacking or options are very limited. PURPOSE: Here, we aim to investigate the therapeutic effects of an iridoid glycoside, asperuloside (ASP) on mice experimental chronic colitis induced by dextran sulfate sodium (DSS) and further explore underlying mechanisms in vitro and in vivo. METHODS: LPS-treated RAW 264.7 cells showed inflammation and were assessed for various physiological, morphological and biochemical parameters in the absence or presence of ASP. Chronic colitis was induced by 2% DSS in mice, which were used as an animal model to explore the pharmacodynamics of ASP. We detected p65 and Nrf2 pathway proteins via Western blot and RT-PCR analysis, assessed the cytokines TNF-α and IL-6 via ELISA, tested p65 and Nrf2 nuclear translocation via fluorescence. In addition, the docking affinity of ASP and p65 or Nrf2 proteins in the MOE 2015 software. RESULTS: We found that ASP attenuated weight loss, disease activity index (DAI) and colonic pathological damage in colitis mice and restored the expressions of inflammatory cytokines in the colon. In addition, ASP restored antioxidant capacity in DSS-induced chronic colitis mice and lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Furthermore, ASP suppressed oxidative stress through increasing Nrf2, HO-1 and NQO-1 proteins expressions, and down-regulated nuclear levels of p65 to inhibit DSS-induced colonic oxidative stress and inflammation. Validation of the molecular docking results also indicated that ASP interacts with Nrf2 or p65 proteins. In summary, ASP improved DSS-induced chronic colitis by alleviating inflammation and oxidative stress, activating Nrf2/HO-1 signaling and limiting NF-κB signaling pathway, which may be an effective candidate for the treatment of IBD.

Chemical Constituents from Sargassum fusiforme (Harv.) Setch.

Phytochemical investigation of Sargassum fusiforme (Harv.) Setch. led to the discovery of fifteen secondary metabolites, including three sterols, three monoterpenes, five nitrogenous compounds, two fatty acids, and two others. Among them, two compounds are new, while the other thirteen compounds were isolated from S. fusiforme for the first time. The structures of the two new compounds were identified by NMR and HR-ESI-MS data analyses, and the absolute configurations were established by comparing the calculated and experimental ECD spectroscopic data.

[Inhibition of sanguinarine on S180 subcutaneously implanted tumors in mice].

OBJECTIVE: To investigate the inhibition of sanguinarine on S180 sarcoma in mice and the effect of angiogenesis. METHODS: S180 subcutaneous implanted tumor model mice were randomly divided into six groups: control group, cyclophosphamide (CTX) group, sanguinarine (10, 20 and 40 mg/kg) groups and combination group. The mice were sacrificed on the 10th day to measure the tumor weight and volumes, and caculate the tumor growth inhibition. Histopathology was performed, while immunohistochemistry was applied for assessment of MVD (microvascular density) and the expression of VEGF (vascular endothelial growth factor). RESULTS: The growth of tumors were significantly inhibited in the treatment groups (CTX group, sanguinarine 20 and 40 mg/kg groups, and combination group). HE staining showed tumor cell atypia and pathologic micosis were lower than that of the control group. Scattered and fusion of the slice necrosis foci were observed in the treatment groups. CTX, sanguinarine (20 and 40 mg/kg) and combination significantly reduced the expression of MVD and VEGF compared with the control group (P < 0.01, P < 0.05). CONCLUSION: Sanguinarine can effectively inhibit the growth of S180 implanted tumors via reducing MVD and the expression of VEGF, which is associated with its anti-angiogenesis.

[Study on absorption mechanism of genistein self-microemulsifying system in rat intestines].

OBJECTIVE: To investigate the absorption mechanism of genistein self-microemulsifying system in rat intestines. METHOD: The concentrations of phenol red and genistein by in situ perfusion in rats were determined by UV and HPLC, respectively. The effects of drug concentrations, pH, various intestinal segments and P-glycoprotein (P-gp) inhibitor verapamil on the absorption had been studied. RESULT: The absorption rate constant (Ka) of genistein had no significant difference at concentrations of 0.05-0.5 mg x mL(-1) and pH of 5.4-7.8 in perfusion. It was Ka of jejunum > ileum > duodenum > colon. The absorption of genistein in jejunum had significant difference (P < 0.05) compared with other parts of intestines. Ka was increased obviously when verapamil was coper-fused with genistein (P < 0. 05). CONCLUSION: The absorption of genistein self-microemulsifying system is a first order process with passive diffusion mechanism related to P-gp efflux. It can be absorbed at all segments of rat intestine, and the jejunum is the best absorption segment, pH had no special effect on the absorption of genistein self-microemulsifying system in rat intestine.