Topical antiinflammatory activity of the major lipophilic constituents of the rhizome of Zingiber cassumunar. Part I: The essential oil.

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).

Topical antiinflammatory activity of the major lipophilic constituents of the rhizome of Zingiber cassumunar. Part II: Hexane extractives.

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,‴,4‴- dimethoxystyryl]cyclohex-l-ene (2), cis-3-(3',4'-dimethoxyphenyl)-4-[(E)-2‴,4‴,5‴- trimethoxystyryl]cyclohex-1-ene (3), cis-3-(2',4',5'-trimethoxyphenyl)-4-[(E)-2‴,4‴,5‴- 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.

Non-phenolic linear diarylheptanoids from Curcuma xanthorrhiza: a novel type of topical anti-inflammatory agents: structure-activity relationship.

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.

Antispasmodic activity of beta-damascenone and E-phytol isolated from Ipomoea pes-caprae.

The crude extract (IPA) of the plant Ipomoea pes-caprae (L.) R. Br. has previously been shown to antagonize smooth muscle contractions induced by several agonists via a non-specific mechanism. Bioassay-guided fractionation of IPA resulted in isolation of the antispasmodically acting isoprenoids beta-damascenone and E-phytol. Their antispasmodic potencies were found to be in the same range as that of papaverine, a general spasmolytic agent. This effect was suggested to play a role in the previously observed anti-inflammatory activity of IPA by interfering with the contraction of endothelial cells. Severe vascular contraction has been shown to be involved in the dermatitis caused by toxic jellyfishes. It is possible that beta-damascenone and E-phytol, by interfering with the contraction of vascular smooth muscle cells, are partly responsible for the previously reported effectiveness of IPA in the treatment of such dermatitis.

Compounds inhibiting prostaglandin synthesis isolated from Ipomoea pes-caprae.

The crude extract (IPA) of the plant Ipomoea pes-caprae (L.) R. Br. showed an inhibitory effect on prostaglandin synthesis in vitro. Bioassay-guided separation of the extract led to the isolation of four active compounds: 2-hydroxy-4,4,7-trimethyl-1(4H)-naphthalenone (1), (-)-mellein (2), eugenol (3), and 4-vinyl-guaiacol (4). Among the isolated compounds, 3 and 4 were the most active with IC50 values of 9.2 and 18 microM, respectively. For 1 and 2 the IC50 values were 230 and 340 microM, respectively. The influence of 1, 2, 3, and 4 on the formation of prostaglandins may partly explain a previously observed anti-inflammatory effect of the extract IPA.

Neutralization of toxic effects of different crude jellyfish venoms by an extract of Ipomoea pes-caprae (L.) R. Br.

An extract (IPA) of the plant Ipomoea pes-caprae (L.) R. Br., previously shown to be clinically effective toward dermatitis caused by venomous jellyfishes, was studied as to its ability to neutralize toxic activities of jellyfish venoms. Different venoms exhibited different degrees of activity. When IPA was incubated with active venoms, it inhibited the actions of all jellyfish venoms tested, with IC50 values in the range of 0.3-0.8 mgIPA/mg venom for proteolytic action, and with about 10 times lower IC50 values for the neutralization of haemolytic action. These activities of IPA support the previously reported effectiveness in the treatment of dermatitis caused by jellyfish sting.

Inhibitory effect of extract of Ipomoea pes-caprae on guinea-pig ileal smooth muscle.

An extract of the plant Ipomoea pes-caprae, used in Thailand as a folk remedy for treating dermatitis caused by jellyfish and Portuguese man-of-war, has been tested for antagonistic activity against histamine, acetylcholine, bradykinin and barium chloride on the isolated guinea-pig ileum. The extract reversibly inhibited the contraction induced by all the spasmogens in a concentration-dependent manner and decreased both the slope and the maximal response of the concentration response curves. It is not likely that the extract specifically interferes at the receptor level. It may be due to the direct action of the extract on the ileal smooth muscle.