Bioactivity-guided fractionation resulted in the isolation of two new ent-labdane diterpenoids (1-2), along with eighteen known congeners (3-20) from the aerial parts of Andrographis paniculata. Except andrographolide (3) and isoandrographolide (4), eighteen diterpenoids (1-2, 5-20) exhibited potent anticomplement activity with the CH50 and AP50 values of 23.1-638.3 μg/mL and 54.2-603.9 μg/mL, respectively. The structure-activity relationships of the isolates showed that 14-dehydroxylation, glycosidation and the opening of lactone were essential for anticomplement activity. Although inactive, andrographolide (3) was successfully transformed to anticomplement compounds (5 and 10) in vitro by human fecal bacteria, indicating that this major ent-labdane diterpenoid of A. paniculata might also exhibit anticomplement activity in vivo through their potential active metabolites. The targets of several bioactive ent-labdane diterpenoids in complement activation cascade were identified as well.
Keywords: Andrographis paniculata; Anticomplement activity; Ent-labdane diterpenoids.
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