Non-Phenolic Linear Diarylheptanoids fromCurcuma xanthorrhiza: A Novel Type of Topical Anti-Inflammatory Agents: Structure-Activity Relationship

Abstract

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.

Inhibitory effect of Curcuma comosa on NO production and cytokine expression in LPS-activated microglia

“…Previous reports have identified the presence of 3 diarylheptanoids from the hexane extract of C. comosa: 1,7-diphenyl-5-hydroxy-(1E)-1-heptane, 5-hydroxy-7-(4-hydroxyphenyl)-1-phenyl-(1E)-1-heptane, and 7-(3,4-dihydroxyphenyl)-5-hydroxy-1-phenyl-(1E)-1-heptane (Suksamrarn et al, 1997). The anti-inflammatory effect of these 3 compounds in C. xanthorrhiza (Jurgens et al, 1994;Suksamrarn et al, 1994) has also been demonstrated in animal models (Claeson et al, 1993(Claeson et al, , 1996.…”

Biological activities of Curcuma longa L.

“…In the literature we can find some authors that associate the anti-inflammatory activity of curcumin and its derivatives to the presence of hydroxyl and phenol groups in the molecule, being essential for the inhibition of prostaglandins (PG synthetase) and leucotrienes (LT) (Kiuchi et al 1982, Iwakami et al 1986). On the other hand, some authors suggested that the anti-inflammatory action is associated to the existence of the β-dicarbonylic system, which has the conjugated double bonds (dienes), being responsible for this activity (Claeson et al 1993(Claeson et al , 1996. This system seems to be responsible not only for anti-inflammatory power, but also to antiparasitic activity (Araújo et al 1998(Araújo et al , 1999.…”

Antibacterial characteristics of Curcuma xanthorrhiza extract on Streptococcus mutans biofilm

“…), which is a medicinal agent in Indonesia. Xanthorrhizol is the main active component of Xan, and has a variety of pharmacological activities, such as anti-metastasis (Choi et al, 2005) and inhibitory effects on nephrotoxicity , as well as anti-cancer and anti-inflammatory effects (Itokawa et al, 1985;Claeson et al, 1993;Claeson et al, 1996). The bactericidal activity of Xan against several oral pathogens has also been reported using planktonic and simple biofilm models Hwang, 2006a, 2006b).…”