RESUMO
The essential oil of the rhizome of Zingiber cassumunar was found to exhibit a topical antiinflammatory effect, when tested using the model of carrageenan-induced hind paw edema in rats (ID(50) = 22 mg oil/paw). Individual assessment of topical antiinflammatory activity of the five major components of the oil demonstrated that (E)-1-(3,4-dimethoxyphenyl)butadiene (DMPBD), terpinen-4-ol and α-terpinene significantly inhibited edema formation, whereas sabinene and γ-terpinene were inactive up to 6 mg/paw. The most active compound, DMPBD, was found to be an antiinflammatory agent twice as potent as the reference drug diclofenac (ID(50) = 3 vs 6 mg/paw, respectively).
RESUMO
A hexane extract of the rhizome of Zingiber cassumunar was found to exhibit topical antiinflammatory activity, when tested in the model of 12-O-tetradecanoylphorbol-13-acetate-induced ear edema in rats (ID(50) = 854 µg/ear). Bioassay-guided fractionation (by MPLC on silica gel) of the hexane extract led to the isolation and identification of (E)-4-(3',4'-dimethoxyphenyl)but-3-enyl acetate (1), cis-3-(3',4'-dimethoxyphenyl)-4-[(E)-3,â´,4â´- dimethoxystyryl]cyclohex-l-ene (2), cis-3-(3',4'-dimethoxyphenyl)-4-[(E)-2â´,4â´,5â´- trimethoxystyryl]cyclohex-1-ene (3), cis-3-(2',4',5'-trimethoxyphenyl)-4-[(E)-2â´,4â´,5â´- trimethoxystyryl]cyclohex-l-ene (4) and (E)-4-(3'-4'-dime-thoxyphenyl)but-3-en-l-ol (5). Compounds 1-5 exerted potent topical antiinflammatory activities with ID(50)-values of 62, 21, 20, 2 and 47µg/ear, respectively. The ID(50) of the reference drug diclofenac was determined to be 61 µg/ear.
RESUMO
The topical anti-inflammatory activity of three non-phenolic linear 1,7-diarylheptanoids, previously isolated from a Thai medicinal plant, Curcuma xanthorrhiza (Zingiberaceae) and four new semi-synthetic derivatives of the naturally occurring compounds were assessed in the murine model of ethyl phenylpropiolate-induced ear edema. The naturally occurring compound 1E,3E,1,7-diphenylheptadien-5-one (6) exerted the most potent anti-inflammatory activity, with an ID50 value of similar magnitude to that of the reference drug oxyphenbutazone (67 vs. 46 micrograms/ear, respectively). None of the semi-synthetic diarylheptanoids was more active than 6. The chemical structures and pharmacological data of the natural and semi-synthetic derivatives identified a distinct structure-activity relationship. The degree of unsaturation in positions 1 and 3, and the nature of the oxygenated functional group in position 5 of the C7-chain were found to play significant roles in determining the observed in vivo activity. Based on these findings, the non-phenolic linear 1,7-diarylheptanoids-are proposed to represent a novel class of topical anti-inflammatory agents.