Planta Med 2012; 78(08): 779-786
DOI: 10.1055/s-0031-1298458
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Flavonoids Eupatorin and Sinensetin Present in Orthosiphon stamineus Leaves Inhibit Inflammatory Gene Expression and STAT1 Activation

Mirka Laavola
1  The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland
,
Riina Nieminen
1  The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland
,
Mun Fei Yam
2  School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia
3  Department of Human Anatomy, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
,
Amirin Sadikun
2  School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia
,
Mohd Zaini Asmawi
2  School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia
,
Rusliza Basir
3  Department of Human Anatomy, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
,
Jukka Welling
1  The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland
,
Heikki Vapaatalo
4  Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland
,
Riku Korhonen
1  The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland
,
Eeva Moilanen
1  The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland
› Author Affiliations
Further Information

Publication History

received 14 November 2011
revised 20 March 2012

accepted 24 March 2012

Publication Date:
19 April 2012 (eFirst)

Abstract

Cytokines and other inflammatory mediators, such as prostaglandin E2 (PGE2) and nitric oxide (NO) produced by cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), respectively, activate and drive inflammation and therefore serve as targets for anti-inflammatory drug development. Orthosiphon stamineus is an indigenous medicinal plant of Southeast Asia that has been traditionally used in the treatment of rheumatoid arthritis, gout, and other inflammatory disorders. The present study investigated the anti-inflammatory properties of Orthosiphon stamineus leaf chloroform extract (CE), its flavonoid-containing CE fraction 2 (CF2), and the flavonoids eupatorin, eupatorin-5-methyl ether (TMF), and sinensetin, identified from the CF2. It was found that CE (20 and 50 µg/mL) and CF2 (20 and 50 µg/mL) inhibited iNOS expression and NO production, as well as PGE2 production. Eupatorin and sinensetin inhibited iNOS and COX-2 expression and the production of NO (IC50 5.2 µM and 9.2 µM for eupatorin and sinensetin, respectively) and PGE2 (IC50 5.0 µM and 2.7 µM for eupatorin and sinensetin, respectively) in a dose-dependent manner. The extracts and the compounds also inhibited tumor necrosis factor α (TNF-α) production (IC50 5.0 µM and 2.7 µM for eupatorin and sinensetin, respectively). Eupatorin and sinensetin inhibited lipopolysaccharide (LPS)-induced activation of transcription factor signal transducers and activators of transcription 1α (STAT1α). Furthermore, eupatorin (50 mg/kg i. p.) and sinensetin (50 mg/kg i. p.) inhibited carrageenan-induced paw inflammation in mice. The results suggest that CE and CF2, as well as the known constituents of CF2, i.e., eupatorin and sinensetin, have meaningful anti-inflammatory properties which may be utilized in the development of novel anti-inflammatory treatments.