Unveiling the chemical profiling and remarkable modulation of carbohydrate metabolism by costus root, Dolomiaea costus (Falc.) in streptozotocin (STZ)-induced diabetic rats

J Ethnopharmacol. 2024 May 23:326:117911. doi: 10.1016/j.jep.2024.117911. Epub 2024 Feb 12.

Abstract

Ethnopharmacological relevance: Dolomiaea costus (Falc.), formerly Saussurea costus (Falc.) Lipsch., an ayurvedic medicinal plant, has long been recognized and utilized in diverse indigenous systems of medicine for its multifaceted therapeutic properties, including anti-inflammatory, carminative, expectorant, antiarthritic, antiseptic, aphrodisiac, anodyne, and antidiabetic effects.

Aim of the study: The potential and underlying mechanisms of D. costus root as an antidiabetic agent were investigated in this study. Additionally, the quantification of phenolic and flavonoid compounds, which dominate the extracts, was of particular interest in order to elucidate their contribution to the observed effects.

Materials and methods: High-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was employed to analyze the chemical constituents in D. costus root aqueous extract (DCA) and D. costus root ethanolic extract (DCE). Furthermore, the inhibitory potentials of DCE and its respective fractions as well as DCA against α-amylase, α-glucosidase, and lipase enzymes were assessed. Subsequently, the efficacy of DCA and DCE extracts was evaluated using an established streptozotocin (STZ)-induced diabetic animal model; this involved administering the extracts at doses of 200 and 400 mg/kg bwt. and comparing them with a positive control (glibenclamide (Glib.) at 0.6 mg/kg bwt.). After induction of diabetes (except for negative control), all animals received the treatments orally for 21 days consecutively, followed by the collection of rat serum to assess various parameters including, glycemic and lipid profiles, liver and kidney functions, antioxidant activity, glycolysis, and gluconeogenesis pathways.

Results: The results of HPLC-ESI-MS/MS revealed that isochlorogenic acid A (8393.64 μg/g) and chlorogenic acid (6532.65 μg/g) were the predominant compounds in DCE and DCA, respectively. Both extracts exhibited notable antidiabetic properties, as evidenced by their ability to regulate blood glycemic and lipid profiles (glucose, insulin, HBA1C; HDL, TC, TGs), liver enzymes (ALT, ALP, AST), kidney function (urea, creatinine, uric acid), oxidative stress biomarkers (MDA), antioxidant enzymes (CAT, GSH, SOD), as well as glycolysis (glucokinase) and gluconeogenesis (G-6-P, FBP1) pathways.

Conclusions: Furthermore, the administration of D. costus extracts significantly mitigated STZ-induced diabetic hyperglycemia. These results can be attributed, at least partially, to the presence of several polyphenolic compounds with potent antioxidant and anti-inflammatory activities.

Keywords: Dolomiaea costus (Falc.) Lipsc. roots; HPLC-ESI-MS/MS; In vitro enzyme inhibition assays; STZ-induced diabetes mellitus.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Blood Glucose
  • Carbohydrate Metabolism
  • Costus* / chemistry
  • Diabetes Mellitus, Experimental* / chemically induced
  • Diabetes Mellitus, Experimental* / drug therapy
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Lipids / therapeutic use
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Rats
  • Streptozocin
  • Tandem Mass Spectrometry

Substances

  • Antioxidants
  • Streptozocin
  • Plant Extracts
  • Hypoglycemic Agents
  • Anti-Inflammatory Agents
  • Lipids
  • Blood Glucose