Analgesic diterpenoids from the twigs of Pieris formosa

Abstract

Eight new grayanane-type diterpenoids, pieristoxin L-S (1–8), and seven known diterpenoids, grayanoside D (9), rhodomolin I (10), pieristoxin H (11), grayanotoxin II (12), pierisformoside B (13), grayanoside C (14) and bis-deacetylkalmitoxin-VI (15), were isolated from the twigs of Pieris formosa. The structures of these compounds were elucidated using extensive spectroscopic analyses, including electronic circular dichroism (ECD). Pieristoxin L (1) is the first example of a 1,7-epoxy-grayanane-type diterpenoid. The analgesic activities of compounds 2–6, 8, and 10–15 were evaluated using an acetic acid-induced writhing test in mice. Compounds 3–6, 8, 10, 12, and 15 exhibited significant analgesic activity at 5 mg/kg (ip) compared to vehicle-injected mice (P<0.01). The writhe inhibition rates of compounds 3, 5, and 6 at 0.08 mg/kg (ip) were 37.6%, 56.8% and 49.8%, respectively. The control drug morphine achieved comparable writhe inhibition at a 10-fold dose.