The Study On Anti-prrsv Activity Of EGCG Palmitate

The widespread and important biological activities of green tea are often attributed to tea catechins,in particular, epigallocatechin gallate (EGCG). A lot of researched findings revealed that EGCG exhibited many potential pharmacological activities including antioxidant, anticarcinogenic, antibacterial,antivirus and the capacity to scavenge free radicals. However, the further applications of natural EGCG are restricted because its liposoluble is not high, unstability and low bioavailability in vivo. In order to optimize the structure of EGCG and improve its anti-virus activity, we systematically study on the synthesis, purification and activities of palmitoylated EGCG in this paper. The details are as fellows:The synthesis of palmitoylated EGCG (EGCGP) were performed according to the reaction conditions as we known, then got by the two-step method of purifying process including the primary acid, alkaline washing and the further column chromatography, and confirmed the structure by UV、IR、MS:EGCGP appeared a strong UV characteristic absorption peak at280nm, a IR characteristic peak of non-conjugated ester saturated fats at1703cm-1, and mass spectrometry had a molecular ion peak m/z695.4.The stability of EGCGP in simulated gastrointestinal environment of in pigs showed that the stability of the EGCGP was better than EGCG, the stability of the EGCGP and EGCG was increased with pH value of the artificial simulation gastric juices. The initial concentration of EGCG and EGCGP was both5.00mmol/L, in the artificial simulation gastric juices with pH=2.0, the final retention concentration of EGCG and EGCGP was2.01mmol/L、3.42mmol/L after4h, their contents decreased by59.82%、31.60%, respectively; in the artificial simulation gastric juices with pH=3.5, the final retention concentration of EGCG and EGCGP was3.09mmol/L、3.91mmol/L after4h, decreased by38.24%、21.80%, respectively; in artificial simulation intestinal juice, the final retention concentration of EGCG and EGCGP was3.25mmol/L、3.85mmol/L after5h, decreased by33.86%、23.06%.The relative bioavailability of EGCGP in rats showed that the bioavailability of EGCGP was higher than EGCG, the relative bioavailability of EGCGP increased by24.3%compared with EGCG.Anti-PRRSV activity of EGCGP studies showed that in a50%cytotoxic concentration (CC50) of EGCG, EGCGP and ribavirin are2359.71μM,431.42μM and94.06μM, respectively. EGCGP exhibited relatively higher cytotoxicities than EGCG. EGCG, EGCGP and ribavirin blocked, inhibited and killed PRRSV in a dose dependent manner. The blocking activity of EGCGP against PRRSV appears much stronger than its ability to inhibiting and directly kill the virus, the half effective inhibitory concentration (EC50) of blocking activity of EGCG, EGCGP and ribavirin was10TCID50:8.53μM,0.48μM,0.40μM;100TCID50:60.25μM,5.53μM,3.48μM, respectively, and the selectivity index (SI) was10TCID50:276.62,892.29,234.98;100TCID50:39.16,77.96,27.02, respectively.Using EGCG as a lead compound, the preparation of palmitoylated cetylated EGCG derivatives by structural modification, in order to improve the fat-soluble and bioavailability, which can provide technical support for the further development of drugs against PRRSV.