Bioguidage search of active compounds from Waltheria indica L. (Malvaceae) used for asthma and inflammation treatment in Burkina Faso

Waltheria indica is used in traditional pharmacopeia in Burkina Faso for the treatment of asthma and conditions of inflammation. To evaluate its pharmacological properties and isolate the active compounds, a study through a bioguided phytochemical approach was conducted. This search was guided by a two-level investigation. First, we evaluated the impact of various fractions on the activity of enzymes involved in smooth muscle contraction (PDE4A1 alpha) and inflammatory processes (PLA(2), 5-LOX). Second, we investigated the inhibitory effect of fractions on isolated rat trachea. The initial hydroalcoholic extract from roots of W.indica (HA), n-hexane fraction (F-1), dichloromethane fraction (F-2), ethyl acetate fraction (F-3), residuary fraction (F-4) reduced enzyme activity of PDE4A1 alpha (inhibition of 22-42% at 50 mu g/mL), 5-LOX (60-80% at 10 mu g/mL), and PLA(2) (42-94% at 100 mu g/mL). On isolated rat trachea, only HA, F-3, and fractions obtained from F-3 by chromatography on silica gel column, using dichloromethane/methanol, dose dependently inhibited contraction induced by acetylcholine. IC50 was 1051 mu g/mL for HA and comprised between 181 and 477 mu g/mL for F-3 and its fractions. The most active fractions were purified and led to the identification of (-)-epicatechin. (-)-epicatechin from W.indica dose dependently inhibited PLA(2) (IC50=154.7 mu m) and 5-LOX (IC50=15.8 mu m). In conclusion, both inhibition of PDE4A1 alpha, 5-LOX, and PLA(2) activities and rat trachea relaxation by W.indica validate its use in traditional management of asthma and other conditions of inflammation. These effects should be, at least in part, attributed to the presence of (-)-epicatechin in roots of W.indica.