Research Progress on Pharmacological Action and Pharmacokinetics of Hydroxytyrosol / 中国实验方剂学杂志

Hydroxytyrosol as one of natural anti-oxidants，extracted from the fruits and leaves of Olea europaea，is a natural polyphenol compound in the form of esters. Recently，considerable studies showed that hydroxytyrosol demonstrated intrinsic biological activity for metabolic syndromes， cardiovascular- and neurodegenerative-related diseases，and it was revealed to play the roles in the anti-activities of cancerous，inflammatory as well as depressing issues. In addition，hydroxytyrosol is an oleophilic and hydrophilic compound with high bioavailability and low cellular cytotoxicity. It could be absorbed by various tissues and could easily passe through blood brain barrier. Therefore，hydroxytyrosol was introduced as one of the key subjects targeted by innovative drug development. However，it has a short half-life in vivo and non-tissue specific，which lead to its limitation in clinical application， so further in-depth studies are still needed. The authors had a literature review of hydroxytyrosol，and summarized the basic properties of its pharmacokinetic，pharmacological effects and molecular mechanisms. This article mainly focused on it’s pharmacological activity and the mechanism involved in treating damages induced by the oxidative stress，in alleviating cardiovascular diseases and in inhibition of neurodegenerative diseases. In this article， its anti-inflammatory，anti-tumor，anti-depressant effects，other biological activities，and pharmacokinetics were also briefly reviewed. The authors put forward some personal thoughts on its future research direction，hoping to provide ideas and inspirations for the vast number of researchers，and provide references for its further development，research and application.

Coxsackievirus B3 induces viral myocarditis by upregulating toll-like receptor 4 expression.

In the present study, we investigated the potential pathogenesis of coxsackievirus B3 (CVB3)-induced viral myocarditis and the promising protective effect of silencing RNA (small interfering RNA, siRNA). One hundred and twenty mice were included in the study, and 30 mice were intraperitoneally inoculated with CVB3 to establish an acute viral myocarditis model. The survival rate was observed for the CVB3-infected mouse model (MOD), and myocardial injury was examined by HE (hematoxylin and eosin) staining assay. Real-time PCR (RT-PCR) and Western blot assay were selected to detect the toll-like receptor 4 (TLR4) expression in myocardial tissues. The TLR4 gene was silenced for the MOD mice, and the effects of this treatment were observed. The results indicate that the expression of TLR4 mRNA and the protein significantly and persistently increased during the progression of CVB3-induced myocarditis. The activities of cardiac enzymes including CK, LDH, AST, and CK-MB were also enhanced in CVB3-induced myocardial tissues. Interestingly, when the TLR4 gene was silenced, the CVB3-induced TLR4 production was significantly decreased and the severity of myocarditis was significantly lessened. In conclusion, CVB3 may induce viral myocarditis by upregulating toll-like receptor 4 expression. The viral myocarditis can be ameliorated by silencing the TLR4 gene in the CVB3 viral myocarditis model, which may be a feasible therapeutic method for treatment of viral myocarditis.

[Changes of Foxp3(+); regulatory T cells in patients with acute coronary syndrome].

AIM: To investigate the changes of Foxp3(+); (including CD4(+);Foxp3(+); and CD4(+);CD25(+);Foxp3(+);) regulatory T cells (Tregs) in patients with acute coronary syndrome (ACS). METHODS: Forty-four ACS patients, twenty patients with stable angina (SA) and twenty-four control patients were enrolled. The percentages of the peripheral Tregs, Foxp3 mRNA and plasma level of TGF-ß1 were measured by flow cytometry, real-time quantitative PCR and ELISA. RESULTS: The percentages of CD4(+);CD25(+);Foxp3(+); Tregs and CD4(+);Foxp3(+); Tregs, Foxp3 mRNA and plasma level of TGF-ß1 significantly decreased in the ACS group as compared with those in the SA group and the controls (P<0.05), while there was no significant difference in the percentage of CD4(+);CD25(+); Tregs among all three groups. CONCLUSION: There are less Foxp3(+);Tregs, perhaps with impaired function, in ACS patients, which might contribute to plaque destabilization.