Novel lipid-peroxidation- and cyclooxygenase-inhibitory tannins from Picrorhiza kurroa seeds

From the AcOEt extract of the seed of Picrorhiza kurroa were isolated picrorhiza acid (1), picrorhizoside A (2), picrorhizoside B (3), picrorhizoside C (4), (-)-shikimic acid (5), gallic acid (6), ellagic acid (7), isocorilagin (8), 1-O-galloyl-beta-D-glucose (9), 1-O,3-O,6-O-trigalloyl-beta-D-glucose (10), and 1-O,2-O,3-O,4-O,6-O-pentagalloyl-beta-D-glucose (11), and their structures were established by extensive NMR and chemical studies. Constituents 1 - 4 are novel compounds, and the known compounds 5 - 11 have been isolated for the first time from the seeds of P. kurroa. Compounds 2 and 3 were hydrolyzed and yielded 12, isochebulic acid. Compounds 1-12 showed 89.6, 77.3, 56.1, 50.5, 11.0, 86.4, 50.5, 29.2, 70.9, 50.5, 56.5, and 86.1% inhibition of lipid peroxidation at 5 mug/ml, respectively. The commercial antioxidants BHA (1.8 mug/ml), BHT (2.2 mug/ml), and TBHQ (1.66 mug/ml) inhibited lipid peroxidation at 85.6, 87.1, and 81.1%, respectively. The inhibition of cyclooxygenase-1 (COX-1) by 2-5,7,8, and 10-12 at 100 mug/ml was 41.9,28.4,32.9,9.3,70.7,34.7,16.0,89.6, and 53.4%, respectively. Similarly, compounds 1-8 and 11 and 112, at 100 mug/ml, inhibited COX-2 by 12.6,15.3,25.1, 5.3, 13.2, 21.7, 2.0, 42.4, 43.4, and 36.9%, respectively.