Piperhancins A and B, Two Pairs of Antineuroinflammatory Cycloneolignane Enantiomers from Piper hancei

Two pairs of cycloneolignane enantiomers, piperhancins A and B ( 1 and 2, respectively), along with two enantiomeric pairs of biosynthetic related neolignanes, hancinone C ( 3 ) and piperhancin C ( 4 ), were isolated from the stems of Piper hancei . Compound 1 is an unprecedented 1′,2:1,2′-dicyclo-8,3′-neolignane. Their structures and absolute configurations were elucidated by spectroscopic analyses, X-ray diffraction, and electronic circular dichroism calculations. Among all of the isolates, compounds (+)- 1, (−)- 1, (+)- 2, (−)- 2, and (+)- 3 could significantly inhibit the production of nitric oxide secreted by lipopolysaccharide (LPS)-induced neuroinflammation in BV-2 microglial cells, with IC 50 values of 1.1–26.3 μM. In addition, compound (−)- 1 could decrease the mRNA levels of iNOS, IL-6, and TNF-α induced by LPS in BV-2 microglial cells.