Flaxseed extract reduces tissue accumulation and enhances urinary excretion of chondroitin sulphate in the rat: a possible new path in substrate reduction therapy for mucopolysaccharidosis

Pharm Biol. 2022 Dec;60(1):879-888. doi: 10.1080/13880209.2022.2068618.

Abstract

Context: Chondroitin 6 sulphate (C6S) is a glycosaminoglycan (GAG) whose accumulation is notable in mucopolysaccharidosis type IVA and VII. Flaxseed, Linum usitatissimum L. (Linaceae) (FS), is reported to have comparable properties to those of soybean, a source of genistein, a potential new treatment for MPSs.

Objective: We assess the effect of total ethanol flaxseed extract (EFSE) in an animal model of C6S accumulation.

Materials and methods: The study was performed in adult male Wistar rats (n = 24) for 15 successive days. The animals were divided into four groups: (1) control injected with physiological saline buffer, (2) intoxicated rats injected intraperitoneally with C6S, (3) intoxicated with C6S and treated with EFSE, and (4) treated with EFSE. All groups were subjected to histopathological and biochemical studies. The antioxidant and phytochemical properties of EFSE were examined.

Results: Dry EFSE contains total phenols (6.28 mg EAG/g), condensed tannins (2.98 mg ECAT/g) and flavonoids (0.44 mg ECAT/g) with high antioxidant potential [RPE (IC50 = 8.37 ± 0.176), DPPH (IC50 = 12.79 ± 0.273)]. The LD50 is higher than 5000 mg/kg. The histopathological examination showed an accumulation of C6S in the C6S intoxicated group, which disappeared in the C6S-EFSE treated group. GAGs assays showed an increased excretion in the C6S intoxicated group and increased excretion of 14% in the C6S-EFSE group compared to the C6S group.

Discussion and conclusions: EFSE showed significant potential for chelation. Its use for the treatment of GAG accumulation could be suggested and generalized to a larger study population.

Keywords: Antioxidant activity; chelating effect; chondroitin 6-sulphate; genistein; lignans; quercetin.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Chondroitin Sulfates / chemistry
  • Flax*
  • Glycosaminoglycans
  • Humans
  • Male
  • Mucopolysaccharidoses*
  • Plant Extracts / pharmacology
  • Rats
  • Rats, Wistar

Substances

  • Antioxidants
  • Glycosaminoglycans
  • Plant Extracts
  • Chondroitin Sulfates