Transformation of bioactive diterpene lactone andrographolides from Andrographis paniculata Nees by superoxide radical in vitro: Structure of reaction products and antioxidant mechanism of andrographolides.

摘要

The medicinal plant Andrographis paniculata Nees plant is found in many Asian countries. It is used in traditional medicine against several ailments including cold, fever, snakebite, diarrhea, liver diseases, diabetes, cancer, inflammation and malaria. Pharmacological studies have demonstrated that the major compounds of the plant, diterpene lactone andrographolides, protected rats' liver against carbon tetrachloride and tert-butyl hydroperoxide toxicity by protecting liver from oxidative damage induced by the two liver toxins. Authors suggested that the ability of andrographolides to inhibit carbon tetrachloride-induced liver damage revealed that they might function as free radical scavengers. However, no chemical study was done to substantiate the free scavenging mechanism of andrographolides.; In the present study, we formulated the hypothesis that diterpene lactone andrographolides might scavenge free radicals by donating the allylic hydrogen of the unsaturated lactone ring. The main objective of the study was to demonstrate the formulated hypothesis by means of kinetic studies and structure elucidation of the reaction products of andrographolides with free radicals.; We found that andrographolides were effective in scavenging DPPH., ABTS +, and superoxide radicals. Steric factors and solubility affected their reactivity with free radicals. The reaction of andrographolides with superoxide yielded two new diacids, neoandrographic and didehydroandrographic diacids. The initial attack of superoxide radical on andrographolides consisted of deprotonation of carbon C-11 or C-15 depending on the isomer. The antioxidant mechanism of neoandrographolide, 14-deoxy-11,12-didehydroandrographolide, and andrographolide was proposed. A key feature of the proposed mechanism was that andrographolide hydroperoxides were formed as reaction transients, but spontaneously dehydrated into cyclic anhydrides that in turn hydrolyzed into water-soluble diacids. One minor dimer was isolated from the reaction of superoxide with andrographolide and was found to be termination product of transient radicals that had their lone electrons on carbon C-11 or C-15. The new dimer was named bisandrographolide K. The isolation of bisandrographolide K provided the most tangible and unambiguous validation of the proposed reaction mechanism.; We concluded that this study provided a scientific basis for the use of andrographolides in antioxidant therapy and offered an interesting model that could be used in the design of a new class of nutritional antioxidants.