Rubia tinctorum root extracts: chemical profile and management of type II diabetes mellitus

Abstract

The chemical and biological profiling of the root extracts of Rubia tinctorum was performed. The activities of different extracts were determined considering the antidiabetic effect against type II diabetes mellitus together with anti-obesity and hepatoprotective effects and lipid profile. The methanolic extract of Rubia tinctorum exhibited significant results in decreasing body weight, improving lipid profile, normalizing hyperglycaemia, insulin resistance, hyperinsulinemia. Additionally, it showed enhancement of liver tissue structure and function. The methanolic extract, being the most significant one, was subjected to LC-HRMS analysis to determine its chemical constituents. Finally, the chemical constituents were evaluated by molecular docking study that was carried out to identify the interaction of a panel of 45 compounds in silico and to correlate the structures to their anti-diabetic activity. Among the tested compounds, 1-hydroxy-2-hydroxymethyl anthra-quinone and naringenin-7-O-glucoside showed the most potent activity as α-amylase inhibitors.

Fig. 1. Histopathological picture for hepatic specimens stained with hematoxylin and eosin with magnification power 40×. (A) Histopathology images for liver sections from normal group uniform hepatocytes arranged in plates radiating from central vein (black arrows) (H&E, 40×). (B) Diabetic group in which hepatocytes show evidence of injury; hydropic degeneration (black arrows) and steatosis (red arrows) (H&E, 40×). (C) Diabetic + pioglitazone (10 mg kg⁻¹) shows mild histopathological changes (H&E, 40×). (D) Diabetic + RM (200 mg kg⁻¹) group which shows mild hitopathological changes. (E) Diabetic + RH (200 mg kg⁻¹) group which shows mild hydropic degeneration of hepatocytes (black arrows) and many hepatocytes show uniform morphology (red arrows) (H&E, 40×). (F) Diabetic + RC (200 mg kg⁻¹) which shows moderate degeneration in hepatocytes (black arrows) (H&E, 40×). (G) Diabetic + RE (200 mg kg⁻¹) which shows moderate hydropic degeneration of hepatocytes (black arrows). Congested sinusoids are seen (red arrows) (H&E, 40×). (H) Effect of different extracts of Rubia tinctorum and pioglitazone (10 mg kg⁻¹) on percent of liver steotosis. (A) Normal group. (B) Diabetic group. (C) Diabetic + pioglitazone (10 mg kg⁻¹). (D) Diabetic + RM (200 mg kg⁻¹). (E) Diabetic + RH (200 mg kg⁻¹). (F) Diabetic + RC (200 mg kg⁻¹). (G) Diabetic + RE (200 mg kg⁻¹). Results are expressed as mean ± S. E. M. and analyzed using one-way ANOVA followed by Bonferroni's test for multiple comparisons. ^aP ≤ 0.05 versus normal group. ^bP ≤ 0.05 versus diabetic group. n = 5.

Fig. 2. Chromatogram of methanolic root extract of Rubia tinctorum in positive mode ion.

Fig. 3. Binding disposition and ligand–receptor interactions of (A) co-crystallized ligand (AC1), and the two high affinity. Docked compounds; (B) 1-hydroxy-2-hydroxymethyl AQ, and (C) naringenin-7-O-glucoside inside the 1HX0 binding site as alpha-amylase inhibitor. Co-crystallized ligand (orange), and docked compounds (green).