New flavon glucuronides, scopoletin glycosides from the roots of Althaea officinalis L. and anti-hyaluronidase-1 activity

Aqueous extracts from the roots of Althea officinalis L. are used for treatment of cough and irritation of the mucosal membranes. Recent investigations indicated specific stimulation of proliferation of epithelial KB cells by aqueous marshmallow extract [1]. Phytochemical investigation of a polysaccharide-depleted methanol-water (1:1) extract (RE) revealed the presence of the flavons Hypolaetin-8-O-β-D-glucuronopyranosyl-1''',4''-β-O-D-glucopyranoside, Hypolaetin-4'-methlyether-8-O-β-D-glucopyranoside-2″-O-sulfate, Hypolaetin-8-O-β-D-glucopyranoside-2″-O-sulfate, Isoscutellarein-4'-methlyether-8-O-β-D-glucuronopyransoide-3″-O-sulfate and Hypolaetin-4'-methylether-8-O-β-D-glucuronopyransoide-3″-O-sulfate, beside the cumarin Scopoletin-O-β-D-glucopyranosyl-L-rhamnoside which are all not described so far. Furthermore the extract was shown to contain 5 different N-phenylpropenoyl-L-amino acid amides, mono- and oligosaccharides, amino acids and glycinbetain.

The effect of RE on human Hyaluronidase-1 (hHyal-1), an enzyme strongly involved in wound healing, inflammation, cell adherence and cell proliferation was investigated by autodisplay technique using Escherichia coli F470 cells expressing hHyal-1 on the cell surface. Glycyrrhicinic acid (1 mM) served as positive control. RE (10 mg/mL) showed about 50% inhibition of hHyal-1. Bioassay-guided fractionation on Sephadex LH20 resulted in 10 subfractions, from which 4 fractions (characterized by the unuasual flavones and cumarin mentioned above) showed strong hHyal-1 inhibition (> 70%) at 70 mg/mL. To investigate the influence of RE on gene expression on hHyal-1 by quantitative real time PCR in epithelial cells, HaCaT keratinocytes, which had been shown by Western blotting to express hHYAL1, were treated with RE (125, 250 µg/mL, 24). Gene expression of hHYAL1 was significantly reduced up to 60% related to the untreated control groups.

Keywords: Althea officinalis, hypolaetin glucuronide, scopoletin glycosides, hyaluronidase.

References:

[1] Deters A, Zippel J, Hellenbrand N, Pappai D, Possemeyer C, Hensel A. Aqueous extracts and polysaccharides from Marshmallow roots (Althea officinalis L.): Cellular internalisation and stimulation of cell physiology of human epithelial cells in vitro. J Ethnopharmacol 2010; 127: 62 – 69