Natural Compounds of Lasia spinosa (L.) Stem Potentiate Antidiabetic Actions by Regulating Diabetes and Diabetes-Related Biochemical and Cellular Indexes

Abstract

Natural biometabolites of plants have been reported to be useful in chronic diseases including diabetes and associated complications. This research is aimed to investigate how the biometabolites of Lasia spinosa methanol stem (MEXLS) extract ameliorative diabetes and diabetes-related complications. MEXLS was examined for in vitro antioxidant and in vivo antidiabetic effects in a streptozotocin-induced diabetes model, and its chemical profiling was done by gas chromatography-mass spectrometry analysis. The results were verified by histopathological examination and in silico ligand-receptor interaction of characterized natural biometabolites with antidiabetic receptor proteins AMPK (PDB ID: 4CFH); PPARγ (PDB ID: 3G9E); and mammalian α-amylase center (PDB ID: 1PPI). The MEXLS was found to show a remarkable α-amylase inhibition (47.45%), strong antioxidant action, and significant (p < 0.05) decrease in blood glucose level, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein (LDL), urea, uric acid, creatinine, total cholesterol, triglyceride (TG), liver glycogen, creatinine kinase (CK-MB), and lactate dehydrogenase (LDH) and increase in serum insulin, glucose tolerance, and high-density lipoprotein (HDL). Rat’s pancreas and kidney tissues were found to be partially recovered in histopathological analyses. Methyl α-d-galactopyranoside displayed the highest binding affinity with AMPK (docking score, −5.764), PPARγ (docking score, −5.218), and 1PPI (docking score, −5.615) receptors. Data suggest that the MEXLS may be an exciting source to potentiate antidiabetic activities affirming a cell-line study.

Keywords: AMPK; Lasia spinosa; Methyl α-d-galactopyranoside; PPARγ; diabetes mellitus; methyl α-d-glucopyranoside.

Figure 1

Gas chromatography-mass spectrometry profile of ME_XLS was obtained from GC-MS with electron impact ionization (EI) method on a gas chromatograph (GC17A, Shimadzu Corporation, Kyoto, Japan) coupled to a mass spectrometer (GC-MS TQ 8040, Shimadzu Corporation, Kyoto, Japan).

Figure 2

Percent of acarbose and ME_XLS’s ability to inhibit α-amylase. A t-test was used to determine the significance of the data after being processed by the analytical program GraphPad Prism, where a significance threshold of p < 0.05 was used. The letters a and b over the bar graph indicate that the values are significant when they are compared to each other.

Figure 3

Changes of BW on intervention of ME_XLS in Albino rats over four weeks (n = 5). Data are expressed as mean ± SEM. Data were analyzed by one way analysis of variance (ANOVA) using the statistical software SPSS followed by a Tukey’s Post Hoc test for significance. p < 0.05 was considered as significant.

Figure 4

(a) Weekly blood glucose level for ME_XLS intervention. (b) A four-week oral glucose tolerance test was conducted on albino rats under specific pressure and temperature conditions (n = 5). Mean ± SEM are used to express data. Data were analyzed by one way analysis of variance (ANOVA) using the statistical software SPSS followed by Tukey’s Post Hoc test. p < 0.05 was consideration as the level of significance. The superscript letter a-e on the lines indicate the significant differences between and among the groups.

Figure 5

Pancreatic tissue from various experimental animals’ groups is shown in a histopathological image (H & E staining × 125) (microscopic resolution: 10 × 40). The pancreatic islet of Langerhans is depicted by an arrow. These pancreatic slices stained with PAS and counterstained with hematoxylin are exhibited under light microscopy.

Figure 6

Image of the kidney tissues from the experimental animal groups as seen through histopathology. The glomerulus of a kidney cell is seen in the image (microscopic resolution: 10 × 40). Hematoxylin and eosin-stained rat kidney micrographs. The images displayed are the glomerulus slices counterstained with hematoxylin and stained with PAS. Arrow signs indicate the point of recovery from necrosis.

Figure 7

Docking study showed that the highest rank poses of methyl α-d-galactopyranoside docked with the active site PPARγ for antidiabetic potential in (A) 2D and (B) 3D molecular interactions.

Figure 8

Docking study displayed that the highest rank poses of methyl α-d-galactopyranoside docked with the active site of AMPK for possible antidiabetic activity in (A) 2D and (B) 3D molecular interactions.

Figure 9

Docking study showed that the highest rank poses of methyl α-d-galactopyranoside docked with the active site 1PPI α-amylase for antidiabetic potential in (A) 2D and (B) 3D molecular interactions.