Lignan derivatives from Krameria lappacea roots inhibit acute inflammation in vivo and pro-inflammatory mediators in vitro.

Abstract

The roots of Krameria lappacea are used traditionally against oropharyngeal inflammation. So far, the astringent and antimicrobial properties of its proanthocyanidin constituents are considered to account for the anti-inflammatory effect. The aim of the present study was to characterize pharmacologically a lipophilic extract of K. lappacea roots and several isolated lignan derivatives (1-11) in terms of their putative anti-inflammatory activity. The dichloromethane extract (ID₅₀ 77 μg/cm²) as well compounds 1-11 (ID₅₀ 0.31-0.60 μmol/cm²) exhibited topical antiedematous properties comparable to those of indomethacin (ID₅₀ 0.29 μmol/cm²) in a mouse ear in vivo model. Two of the most potent compounds, 2-(2-hydroxy-4-methoxyphenyl)-5-(3-hydroxypropyl)benzofuran (5) and (+)-conocarpan (7), were studied regarding their time-dependent edema development and leukocyte infiltration up to 48 h after croton oil-induced dermatitis induction, and they showed activity profiles similar to that of hydrocortisone. In vitro studies of the isolated lignan derivatives demonstrated the inhibition of NF-κB, cyclooxygenase-1 and -2, 5-lipoxygenase, and microsomal prostaglandin E₂ synthase-1 as well as antioxidant properties, as mechanisms possibly contributing to the observed in vivo effects. The present findings not only support the ethnopharmacological use of K. lappacea roots but also reveal that the isolated lignan derivatives contribute strongly to the anti-inflammatory activity of this herbal drug.

• Authors: Lisa Baumgartner, Silvio Sosa, Atanas G Atanasov, Antje Bodensieck, Nanang Fakhrudin, Julia Bauer, Giorgia Del Favero, Cristina Ponti, Elke H Heiss, Stefan Schwaiger, Angela Ladurner, Ute Widowitz, Roberto Della Loggia, Judith M Rollinger, Oliver Werz, Rudolf Bauer, Verena M Dirsch, Aurelia Tubaro, Hermann Stuppner
• Journal: Journal of natural products (J Nat Prod) Vol. 74 Issue 8 Pg. 1779-86 (Aug 26 2011) ISSN: 1520-6025 [Electronic] United States
• PMID: 21800856 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2-(2-hydroxy-4-methoxyphenyl)-5-(3-hydroxypropyl)benzofuran
• Anti-Inflammatory Agents, Non-Steroidal
• Benzofurans
• Lignans
• NF-kappa B
• conocarpan
• Arachidonate 5-Lipoxygenase
• Cyclooxygenase 1
• Intramolecular Oxidoreductases
• Prostaglandin-E Synthases

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (blood, pharmacology, therapeutic use)
• Arachidonate 5-Lipoxygenase (drug effects)
• Austria
• Benzofurans (chemistry, isolation & purification, pharmacology)
• Cyclooxygenase 1 (drug effects)
• Edema (chemically induced, drug therapy)
• Intramolecular Oxidoreductases (antagonists & inhibitors)
• Krameriaceae (chemistry)
• Lignans (blood, chemistry, isolation & purification, pharmacology)
• Male
• Mice
• NF-kappa B (drug effects)
• Plant Roots (chemistry)
• Prostaglandin-E Synthases