Quinic acid derivatives from Artemisia annua L. leaves; biological activities and seasonal variation

Abstract

Genus Artemisia is widely known to have various therapeutic applications and chemical constituents. A. annua L. (commonly known as sweet wormwood or Qinghao) is an annual herb native to China, traditionally used for treating fever and malaria, and as a source of artemisinin. In the present study, a bio-guided fractionation of the 70% ethanolic extract of the leaves of A. annua cultivated in Egypt produced a bioactive polar fraction. Daily doses of this fraction (100 mg/kg b.wt) for 4 weeks substantially reduced the level of the CCl4-mediated increase in the liver enzymes; AST, ALT and ALP. Similarly, daily doses of the polar fraction (100 mg/kg) significantly reduced the blood glucose level in alloxan-induced diabetic by 32.1% in the second week and 46.9% in the fourth week, relative to that demonstrated by metformin (66.2%), and significantly (p < 0.01) restored to normal the blood glutathione level (35.2 ± 1.3 mg/dL), almost identical to that shown by vitamin E. Further purification of the bioactive fraction led to the isolation of 5 quinic acid derivatives; 3-feruloylquinic acid, 3,5-dicaffoeylquinic acid, 4,5-dicaffoeylquinic acid, 3,4-dicaffoeylquinic acid, and 3,4-dicaffoeylquinic acid methyl ester. The isolated compounds are reported here for the first time in A. annua, leaves cultivated in Egypt and suggested to be responsible, at least in part, to the biological activities of the polar fraction. Seasonal variation in the content of quinic acid derivatives in the leaves of A. annua L. was investigated during four harvest seasons (March, May, July "pre-flowering stage" and August-September "flowering stage") using RP-HPLC. The content of 3-feruloylquinic acid varied greatly throughout the year. It was found to be the lowest (0.036% w/w) in March "leaf stage" but increased through the warmer months from May to June (0.61% w/w), and reached the highest (1.34% w/w) in leaves harvested in July "early summer". Then-after, gradual decline in the content of quinic acid derivatives was evident in leaves collected during flowering stage in late summer "August-September" (0.84% w/w).