Catalpa Alcohol, Sinistral Shikonin, Regulate Cutin Forming Cells Were Beta Defense Element - 2 Mechanism Research

Psoriasis is a common, chronic, recurring inflammatory disease of the skin, whose typical lesions are red, scaly and indurated plaques. Today, most hypotheses operate from an assumption that the disease is an immune-mediated disorder, in which the excessive proliferation of keratinocytes, new vessel formation, immune cell infiltrated and activated T cells is the consequence of interaction among multigenetic component and environmental factors.Currently, blood-heat is considered the most important pathogenesis for psoriasis,and the removing heat to cool blood is the most common rules of tr eatment. There are many studies about the mechanism of the treatment of psor iasis by heat-removing drugs. With lots of document analysis, we summarized t he regularity that how to use Chinese herbal compound to treat psoriasis and discovered that heat-removing drugs are most frequently used. Rehmannia glu tinosa Libosch,lithospermum and cortex moutan are the get the highest frequ ency in the heat-removing drugs. Catalpol, L-shikonin and paeonol are the On e of the main active ingredient.The human beta-defensin-2(HBD-2) is isolated and purified from psoriatic scale extracts which was found be inducible. It is produced and secreted by keratinocytes, involve in T cell activation, and then promote the production of Thl cytokines.As a result, it invole in the occurrence of psoriasis directly or indirectly. Domestic and international studies have shown that HBD-2was highly expressed in psoriatic skin and serum and strongly correlated with disease activity as assessed by the PASI score and decrease following antipsoriatic treatment. Regulation of HBD-2expression levels may be a new means to treat psoriasis.HBD-2can be strongly induced by IL-1β and TNF-α which secreted by T cells.This process is regulated by many signaling pathways, such as Mitogen-activated protein kinase(MAPK) signaling pathways. C-Jun amino-terminal kinases (JNK) signaling pathway is one of the MAPK signal pathways, which involve in regulating the expression of HBD-2. At earlier experiments, IL-1α and TNF-αcan activate JNK signaling pathway in HacaT cells,to increase the expression of HBD-2. If the heat-removing drugs can restrain activation of JNK signaling pathway, it may restrain the activation of the the keratinocytes-HBD-2-T cells, which maybe a new mechanism for the heat-removing drugs to treat psoriasis.Object:The purpose of this paper is to discuss the influence of catalpol, L-shikonin and paeonol to the HBD-2high-expression and MAPK signaling pathway activation in vitro cytology model, reveal the function of the three monomer of Chinese traditional herbs to HBD-2by JNK signaling pathway and provide the experimental evidence for the clinical application of heat-clearing and blood-cooling Recipe from the target and the target objective.Method:HaCaT cells was stimulated with a mixture of100ng/ml of IL-1β and TNF-α in18h to establish HBD-2high-expression andJNK signaling pathway activa tion in vitro model. Prepare catalpol, L-shikonin and paeonol solution with appropriate concentrationand then add into the cell culture media directly. Use JNK inhibitor for the positive control drugs. Effects of the three monom er of Chinese traditional herb on HBD-2mRNA expression in the cell model w ere detected by real-time PCR. HBD-2expression of the cell culture supernat ant were detected by ELISA in each group. Effects of the three monomer of Ch inese traditional herbs on JNK signaling pathway was detected by Western Blo t. Results:(1) L-shikonin, paeonol and JNK inhibitor can markedly decrease the high expression of HBD-2mRNA in vitro cytology model of psoriasis (P＜0.05). L-shikonin has no significant difference with the JNK inhibitor (P＞0.05), and the effect of paeonol is slightly less than JNK inhibitors (P＜0.05). Catalpol can markedly increase the high expression of HBD-2mRNA in vitro cytology model of psoriasis (P＜0.05).(2) L-shikonin, paeonol and JNK inhibitor can markedly decrease the high expression of HBD-2in the supernatant of vitro cytology model of psoriasis. Catalpol can markedly increase the high expression of of HBD-2in the supernatant of vitro cytology model of psoriasis.(3)Mixture of100ng/ml IL-1β and TNF-α stimulate HaCaT cells18h could make the JNK2MAPK signaling pathway activated; and the intervention of L-shikonin and paeonol can significantly decrease the relative content of P-JNK2protein. Catalpol can significantly increase the relative content of P-JNK2proteinConclusion:Lithospermum and cortex moutan may inhibit JNK2MAPK signaling pathway activation to reduce the expression of HBD-2by IL-1β and TNF-α, and thus play the role of the treatment of psoriasis. The mechanism of Rehmannia glutinosa Libosch for the treatment of psoriasis still need to continue to explore from other aspects.