Constituents from Bupleurum chinense and their effects on PPARα and related nuclear receptors

The peroxisome proliferator-activated receptor α (PPARα) is expressed in liver at high level, and has become an important target for lipid metabolism modulating drugs. Due to the adverse effects of available PPARα modulators it's important to find new agonists with fewer side effects. Medicinal plants used in the traditional Chinese medicine (TCM) are a relevant source for the identification of new pharmaceutical leads. The roots of Bupleurum chinense (Chai Hu) have been used in TCM as a hepatoprotective and antipyretic remedy. Its dichloromethane extract showed strong PPARα agonistic activity. By activity-guided isolation, four polyacetylenes, eight triterpenoid saponins, and one linoleoyl lysolecithin were obtained and examined for PPARα activation and selectivity of action by checking agonism towards PPARγ, PPARβ/δ and LXRβ. Their structures were determined by spectroscopic methods as saikodiyne A (1), 2(E),8(E)- pentadecadiene-4,6-diyne-1,10-diol (2), pentadeca-8(E)-en-4,6-diyne-1,10-diol (3), pentadeca-2(Z), 9(Z)-dien-4,6-diyne-1,8-diol (4), 16-oxo-mullersaponin I (5), saikosaponin B2 (6), saikogenin D (7), 23-deoxy-saikosaponin B2 (8), prosaikogenin D (9), and 1-linoleoylglycerol-3-phosphorylcholine (10) bupleuroside III (11), and bupleuroside IV (12). Compounds 3, 4, and 8 are new chemical entities, and 2, 5 are identified for the first time from a natural source.