Polyphenols are of special relevance for the multiple mechanisms of action of the willow bark extract STW 33-I (Proaktiv®)

O. Kelber; H. Abdel-Aziz; E. F. Elstner; B. L. Fiebich; H. Heinle; R. Jaeggi; M. T. Khayyal; J. Metz; J. Müller; S. N. Okpanyi; D. Weiser

doi:10.1055/s-2006-949982

Polyphenols are of special relevance for the multiple mechanisms of action of the willow bark extract STW 33-I (Proaktiv®)

O Kelber ⁶, H Abdel-Aziz ¹, EF Elstner ², BL Fiebich ³, H Heinle ⁴, R Jaeggi ⁵, MT Khayyal ¹, J Metz ⁷, J Müller ⁶, SN Okpanyi ⁶, D Weiser ⁶

¹Department of Pharmacology, Faculty of Pharmacy, Cairo University, Kasr el-Aini Str, 11562 Cairo, Egypt
²Phytopathology, Laboratory for Applied Biochemistry, TU Munich, Am Hochanger 2, 85350 Freising, Germany
³VivaCell Biotechnology GmbH, Ferdinand-Porsche-Str. 5, 79211 Denzlingen, Germany
⁴Institute for Physiology, University of Tübingen, Gmelinstr. 5, 72076 Tübingen, Germany
⁵Department Bioassays, Vitaplant AG, Benkenstrasse 254, 4108 Witterswil, Switzerland
⁶Scientific Department, Steigerwald Arzneimittelwerk GmbH, Havelstr. 5, 64295 Darmstadt, Germany
⁷Institute of Anatomy and Cell Biology III, University of Heidelberg, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany

Abstract

The pharmacological profile of the willow bark extract STW 33-I (water extract, 16–23:1) and the contribution of its fractions to it were studied in a number of pharmacological models in vitro and in vivo for elucidating its clinical effects.

In Interferon-γ/LPS treated monocytes, STW 33-I reduced expression of iNOS, COX-2, the antiapoptotic protein Bcl2, Il-1β, Il-6 and TNF-α, measured by real time PCR, with IC₅₀ between 10 and 200µg/mL. It inhibited PGE₂, Il-6 and MMP-3 in chondrocytes. Activities of 5-LOX, hyaluronidase, elastase (HLE), COX-1 and -2 and oxidation in AAPH and XOD reactions were inhibited. Five fractions of the extract, obtained by sequential extraction with solvents of increasing polarity and analytically characterized by HPLC, were tested as well, showing that the fractions containing the different groups of polyphenols were responsible for the main part of the effect, while the fraction containing the main part of the salicylates showed only a minor contribution.

In vivo, STW 33-I (50 to 150mg/kg b.w.) was effective in writhing test in mice, Randall-Sellito model, brewers yeast model, paw edema, adjuvant arthritis and air pouch model in rats. In the latter, PGE₂ and LTB₄, Il-1β, Il-6, TNF- α, TxB4, COX-2 and the antioxidative parameters MDH were decreased, GSH increased.

These studies show multiple mechanisms of the willow bark extract, including anti-inflammatory, -oxidative, -pyretic, joint protecting, and analgesic actions. These were mainly not due to salicylates, but to polyphenols, which therefore seem to be the group most relevant for the therapeutic efficacy of STW 33-I (Proaktiv®) in back pain.