Incredible affinity of Kattosh with PPAR-γ receptors attenuates STZ-induced pancreas and kidney lesions evidenced in chemicobiological interactions

Abstract

Since ancient times, plants have been used as green bioresources to ensure a healthier life by recovering from different diseases. Kattosh (Lasia spinosa L. Thwaites) is a local plant with various traditional uses, especially for arthritis, constipation and coughs. This research investigated the effect of Kattosh stem extract (LSES) on streptozotocin-induced damage to the pancreas, kidney, and liver using in vitro, in vivo and in silico methods. In vitro phytochemical, antioxidative and anti-inflammatory effects of LSES were accomplished by established methods followed by antidiabetic actions in in vivo randomized controlled intervention in STZ-induced animal models for four weeks. In an in silico study, LSES phytocompounds interacted with antidiabetic receptors of peroxisome proliferator-activated receptor-gamma (PPAR, PDB ID: 3G9E), AMP-activated protein kinase (AMPK, PDB ID: 4CFH) and α-amylase enzyme (PDB ID: 1PPI) to verify the in vivo results. In addition, LSES showed promising in vitro antioxidative and anti-inflammatory effects. In contrast, it showed a decrease in weekly blood glucose level, normalized lipid profile, ameliorated liver and cardiac markers, managed serum AST and ALT levels, and increased glucose tolerance ability in the animal model study. Restoration of pancreatic and kidney damage was reflected by improving histopathological images. In ligand-receptor interaction, ethyl α-d-glucopyranoside of Kattosh showed the highest affinity for the α-amylase enzyme, PPAR, and AMPK receptors. Results demonstrate that the affinity of Kattosh phytocompounds potentially attenuates pancreatic and kidney lesions and could be approached as an alternative antidiabetic source with further clarification.

Keywords: Lasia spinosa; diabetes mellitus; ethyl alpha-D-glucopyranoside; histopathological examination; phytochemical screening; α-amylase.

FIGURE 1

Percentage of α‐amylase inhibition of standard (Acarbose), LSES. All data were analysed using the statistical software SPSS (Statistical Package for the Social Sciences, Version 22.0; IBM Corporation, NY), followed by Tukey’s post hoc test for significance. p < 0.05 was considered as significant. The alphabetical notation with a‐c (p < 0.001 = a; p < 0.01 = b; and p < 0.05 = c) on the bar graph represents the values are significant compared with each other for the intervention period

FIGURE 2

(A) Body weight changes; (B) weekly blood glucose concentration for the intervention of LSES; and (C) oral glucose tolerance test in Albino rats over four weeks at certain temperature and pressure (n = 6). Data are expressed as mean ± SEM. All data were analysed by the statistical software SPSS (Statistical Package for the Social Sciences, Version 22.0; IBM Corporation, NY) followed by Tukey’s post hoc test for significance. p < 0.05 was considered as significant

FIGURE 3

Histopathological image (H & E staining × 125) of pancreatic tissue of the experimental animals from different groups. The arrow shows the pancreatic islet of Langerhans (microscopic resolution: 10 × 40). Micrographs of haematoxylin and eosin staining of rat pancreas. Light microscopies of pancreatic sections stained with PAS and counterstained with haematoxylin are shown

FIGURE 4

Histopathological image of kidney tissue of the experimental animals from different groups. The arrow shows the glomerulus of kidney cells (microscopic resolution: 10 × 40). Micrographs of haematoxylin and eosin staining of rat kidney. Light microscopies of glomerulus sections stained with PAS and counterstained with haematoxylin are shown

FIGURE 5

Best rank poses of (A) 2D and (B) 3D molecular interactions of ethyl alpha‐d‐glucopyranoside docked with the active‐site PPAR‐γ for antidiabetic potential

FIGURE 6

Best rank poses of (A) 2D and (B) 3D molecular interactions of ethyl alpha‐d‐glucopyranoside docked with the active‐site AMPK for antidiabetic potential

FIGURE 7

Best rank poses of (A) 2D and (B) 3D molecular interactions of ethyl alpha‐d‐glucopyranoside docked with the active‐site 1PPI α‐amylase for antidiabetic potential