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Huanglian Jiedu plaster (HJP) is a kind of Chinese patent medicine that contains four medicinal plants. It has been clinically proven to be beneficial for the treatment of tumor-associated radiation dermatitis. However, the underlying mechanism of HJP on radiation dermatitis remains unclear. This study aims to investigate the therapeutic effect of HJP on X-ray-induced radiation dermatitis, and how HJP improves the inflammatory response and skin damage of radiation dermatitis. In this study, We selected a case of esophageal cancer as a clinical demonstration of the efficacy of radiation dermatitis. The patient received a total radiation dose of 7000cGY, and treatment by HJP for 14 days.RD mouse models were established through continuous irradiation with X-ray (800cGY) on the right hind limb of mice for 5 days, and the treatment group mice was applied HJP to the irradiated skin for 15 days from modeling. An inflammatory cellular model was induced through irradiation with X-ray (100cGY) in JB6 cells and a co-culture system of JB6 cell and macrophage was established to examine the effect and mechanism of HJP on the inflammatory interaction of these two cells. The activation of HMGB1-TLR4-NF-κB signaling pathway, and the levels of epidermal injury related factors and inflammatory cytokins were subsequently detected. The results showed that HJP can significantly alleviate X-ray-induced skin injury, inhibiting skin inflammation and reducing the expression of inflammatory cytokins (IL-1β, IL-6, TNF-α) and epidermal damage related factors (Integrin β1, CXCL9 and Cytokeratin17), as well as significantly down-regulated the protein level of HMGB1 (a key DAMPs factor) in vivo and in vitro. Cell co-culture experiments demonstrated that HMGB1 released from X-ray-induced JB6 cells can promote inflammatory response of macrophage, which then feedback aggravate epithelial cell damage, notably, HJP can significantly improve radiation skin lesion by inhibiting HMGB1-mediated inflammatory interaction between epithelial cells and macrophages. In summary, these findings indicated the role of HJP in the treatment of RD by inhibiting the inflammatory interaction between macrophage and JB6 cells mediated by HMGB1, which may provide a reliable therapeutic method for RD. Furthermore, HMGB1 may be an effective target for HJP to inhibit inflammation and ameliorate skin damage in RD. [Display omitted] • HJP can alleviate X-ray-induced skin injury, inhibit skin inflammatory reaction. • HMGB1 can promote JB6's damages by mediating the inflammatory interaction with BMDM. • HJP can inhibit HMGB1-mediated inflammatory interaction. [ABSTRACT FROM AUTHOR]

Abstract: Western blot has been used to study the time-course effect of the two most popular parkinsonian neurotoxins, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, i.p.) and 6-hydroxydopamine (6-OHDA, intra-substantia nigra), on the expression of several regulators of G-protein signaling (RGS2, 4 and 9) in striatum in rodents. During the few days after MPTP challenge, there was a decline (as expected) in tyrosine hydroxylase expression in the mouse striatum that was accompanied by a decline in RGS9 protein; the latter was specific and did not extend to RGS2 or RGS4 which were resistant to the MPTP challenge. Much the same pattern was observed in rats after 6-OHDA challenge, again, specific to RGS9, although the effect takes a few weeks, rather than a few days, to develop. These results may be helpful for the understanding of molecular mechanism underlying Parkinson''s disease (PD) and RGS9 might involve in the striatal function associated with PD. [Copyright &y& Elsevier]

Abstract: Garlic oil (GO) has been shown to partially attenuate ethanol-induced fatty liver, but the underlying mechanisms remain unclear. The current study was designed to evaluate the protective effects of GO against ethanol-induced steatosis in vitro and in vivo, and to explore potential mechanisms by investigating the sterol regulatory element binding protein-1c (SREBP-1c), peroxisome proliferators-activated receptor-α (PPAR-α), cytochrome P4502E1 (CYP2E1), and etc. In the in vitro study, human normal cell LO2 was exposed to 100mM ethanol in the presence or absence of GO for 24h. We found that ethanol increased the protein levels of n-SREBP-1c and CYP2E1, but decreased the protein levels of PPAR-α, which was significantly attenuated by GO co-treatment. In the in vivo study, male Kun-Ming mice were pretreated with single dose of GO (50–200mg/kg body weight) at 2h before ethanol (4.8g/kg body weight) exposure. The changes of n-SREBP-1c, PPAR-α and CYP2E1 were paralleled well to those of in vitro study. Furthermore, GO significantly reduced the protein levels of fatty acid synthase (FAS), and suppressed ethanol-induced hepatic mitochondrial dysfunction. These results suggested that GO had the potential to ameliorate alcoholic steatosis which might be related to its modulation on SREBP-1c, PPAR-α, and CYP2E1. [Copyright &y& Elsevier]