Picrorhizae Rhizoma as a hepatoprotective herb, has been applied for thousands of years, and picroside was proved to be its active constituent. In this study, twelve derivatives of picroside were synthesized and the hepatoprotective activity of the derivatives was evaluated on SMMC-7721 cells. Six out of the derivatives had shown a better protective effect on H 2 O 2 -induced SMMC-7221 cells than picroside, and the activity of two derivatives (2 and 4) was stronger than that of the reference compound, silybin. Compound 2 shown the strongest protective effect (EC 50 =6.064 ± 1.295 μM).
Picrorhiza kurroa has a long medicinal history as a traditional medicinal plant in China and India that is widely used in clinical treatments. It is a common treatment for liver diseases, fever, diarrhoea, indigestion, and some other diseases. Modern pharmacological studies proved that P. kurroa rhizomes have high levels of picroside I and II, which were identified as main constituents with anti‐inflammatory and hepatoprotective activities. In our study, we used picroside I and II as the lead compounds to generate derivatives by reactions with Boc‐valine or Boc‐proline, which underwent dehydration and condensation with the hydroxyl groups in the lead compounds in the presence of coupling reagent N,N′‐dicyclohexylcarbodiimide. We synthesized 11 derivatives and examined their hepatoprotective effects in vitro by assessing the proliferation rates of H2O2‐exposed HepG2 cells using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. We found that some derivatives promoted higher proliferation rates in HepG2 cells than the natural compounds before derivatization, suggesting that those derivatives possessed an improved hepatoprotective capacity. The novel derivatization strategy for picrosides had the additional benefit that the esterification of their hydroxyl groups created derivatives not only with increased stability but also with improved pharmacokinetic properties and potentially prolonged half‐life.
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