Phenols from the Roots of Rheum palmatum Attenuate Chemotaxis in Rat Hepatic Stellate Cells

Abstract

In liver injury, hepatic stellate cells (HSCs) acquire an activated phenotype, migrate to the injured region in response to chemotactic factors and produce extracellular matrix (ECM) proteins including α-smooth muscle actin (α-SMA) and collagen in order to repair the damage. HSC-T6, a cell line of rat HSCs, was used in in vitro experiments. TGF-β1 was used as a chemoattractant. The expression of α-SMA was used as a marker of activated hepatic stellate cells and cell migration was assayed with the Transwell method to investigate the active principles of the roots of Rheum palmatum L. (Dahuang), a well-known traditional Chinese herb used for treating liver diseases. Under cell activation and chemotaxis-directed fractionation and purification, four anthraquinones, rhein (1), emodin (2), chrysophanol (3) and physcion (4), and four phenylbutanoids, lindleyin (5), isolindleyin (7), 4-(4′-hydroxyphenyl)-2-butanone 4′-O-β-D-glucopyranoside (8), and 4-(4′-hydroxyphenyl)-2-butanone (9), and a stilbene, 3,5,4′-trihydroxystilbene 4′-O-β-D-glucopyranoside 6′-O-gallate (6) were isolated from the active fractions. Among them, compounds 1 and 2 inhibited α-SMA expression. However, compounds 3, 4, 6 and 8 attenuated chemotactic migration, but not α-SMA expression.

Abbreviations

α-SMA:α-smooth muscle actin

CI:chemotaxis index

ECM:extracellular matrix

HSCs:hepatic stellate cells

Rh:ethanolic extract of the roots of Rheum palmatum

TGF:transforming growth factor

Key words

Rheum palmatum - Polygonaceae - TGF-β1 - chemotaxis - phenylbutanones - stilbene

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