Anti-diabetic activity of a sulfated galactoarabinan with unique structural characteristics from Cladophora oligoclada (Chlorophyta)

Carbohydr Polym. 2022 Feb 15:278:118933. doi: 10.1016/j.carbpol.2021.118933. Epub 2021 Nov 24.

Abstract

The polysaccharide from green alga Cladophora oligoclada, OHSS2, was a sulfated galactoarabinan which was constituted by a backbone of (1 → 4)-β-l-arabinopyranose units with partial sulfate at C-3 of (1 → 4)-β-l-arabinopyranose units. The side chains containing (1 → 4)-β-l-arabinopyranose, (1 → 4)-β-d-galactopyranose and/or (1 → 4,6)-β-d-galactopyranose units were in C-2/C-3 of (1 → 4)-β-l-arabinopyranose units. OHSS2 had strong anti-diabetic activity in vitro assessed by inhibition of human islet amyloid polypeptide (hIAPP) aggregation. The mechanism analysis of anti-diabetic activity showed that OHSS2 diminished the production of intracellular reactive oxygen species and alleviated hIAPP aggregation-induced oxidative stress in NIT-1 cells. OHSS2 stabilized mitochondrial membrane potential, and enhanced the mitochondrial complex I, II or III activity and ATP level. Thus, OHSS2 effectively protected mitochondria from hIAPP aggregation-induced damage. Furthermore, OHSS2 was co-localized with mitochondria and could have a direct influence on mitochondrial function. These results revealed that OHSS2 had potential as a novel anti-diabetic agent.

Keywords: 1,1,1,3,3,3-Hexafluoro-2-propanol (PubChem CID: 13529); 2′,7′-Dichlorofluorescin diacetate (PubChem CID: 77718); 3′-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (PubChem CID: 22288011); Acetic acid (PubChem CID: 176); Adenosine triphosphate (PubChem CID:5957); Anti-diabetic activity; Cladophora oligoclada; Ethanol (PubChem CID: 702); Hexamethylene diamine (PubChem CID: 16402); Structural characterization; Sulfated polysaccharide; Thioflavine T (PubChem CID: 16953); Uranyl acetate (PubChem CID: 10915); hIAPP; l-Arabinose (PubChem CID: 439195).

MeSH terms

  • Animals
  • Cells, Cultured
  • Chlorophyta / chemistry*
  • Galactans / chemistry
  • Galactans / isolation & purification
  • Galactans / pharmacology*
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / isolation & purification
  • Hypoglycemic Agents / pharmacology*
  • Islet Amyloid Polypeptide / antagonists & inhibitors*
  • Islet Amyloid Polypeptide / metabolism
  • Mice
  • Oxidative Stress / drug effects
  • Protein Aggregates / drug effects
  • Reactive Oxygen Species / metabolism
  • Sulfates / chemistry
  • Sulfates / isolation & purification
  • Sulfates / pharmacology*

Substances

  • Galactans
  • Hypoglycemic Agents
  • Islet Amyloid Polypeptide
  • Protein Aggregates
  • Reactive Oxygen Species
  • Sulfates
  • arabinogalactan