Antinociceptive Diterpenoids from the Leaves and Twigs of Rhododendron decorum

Abstract

Three new leucothane-type (1-3), two new micrathane-type (4, 5), eight new grayanane-type diterpenoids (6-13), and four known compounds were obtained from the ethanol extract of the leaves and twigs of Rhododendron decorum. The structures were determined based on NMR spectra, quantum chemical calculations, and X-ray crystallography. The antinociceptive activities of compounds 1, 3, 4, 6, 8, 10-13, and 15-17 were evaluated via the acetic acid-induced writhing test. Compounds 1, 8, 11-13, and 15 exhibited significant antinociceptive activities. In particular, 12 and 15 were found to be effective at doses of 0.8 and 0.08 mg/kg, respectively.

Micranthanosides I and II, two novel 1,10-secograyanane diterpenoids and their antinociceptive analogues from the leaves and twigs of Rhododendron micranthum

“…The NMR spectroscopic data of 4 were comparable to those of pierisformoside C. 16 The only difference was the location of the double bond. The HMBC correlations from H 3 -20/H 2 -11 to C-9 (d C 142.6)/C-10 (d C 124.3) located the double bond at D 9,10 instead of D 10,20 . The glucose unit was placed at C-3 based on the HMBC correlation from H-1 0 to C-3.…”

“…Further HSQC and HMBC experiments allowed full assignment of the 1 H and 13 C NMR spectra of 6. The location of the two double bonds (D 5,6 , D 10,20 ) was determined via HMBC correlations from H-1 to C-5/C-10, from H 2 -20 to C-1/C-9/C-10, and from H 2 -7 to C-5/C-6. The glucose unit was placed at C-16, which was supported by the HMBC correlation from H-1 0 to C-16.…”

“…8,13,30 Some kauranes and leucothanes also showed signicant antinociceptive activity at relatively high doses, but no toxic reaction was observed. 10,14 This fact suggests that they may have different mechanisms of action.…”

“…The preliminary analysis of the structures (present and reported) and their bioactivities revealed that the presence of sugar unit at C-3, C-6, or C-16 decreases the activity as well as the toxicity (as in 11/17, 10/19, 15/rhododecorumin I, rhodomicranoside E/rhodomicranone E). 10,14 Compound 2 is more active than 1, which suggested that sugar unit at C-3 is likely to hinder activity to a lesser degree. Traditionally, "zhaoshanbai" was extracted by water decoction.…”

“…Among them, rhodojaponin III and VI, craiobiotoxin IX, and pieristoxin N and P were found to be highly potent in several antinociceptive models. [9][10][11][12] In addition, micranthanoside A, grayanotoxins I, and III in R. micranthum were reported to have signicant antinociceptive activity at a dose of 0.2 mg kg À1 in the acetic acid-induced writhing test. 13,14 In order to provide chemical evidence for rational application of "zhaoshanbai" and discover structurally interesting lead compounds, leaves and twigs of R. micranthum (107.5 kg) were collected from Shandong Province.…”