Partially Hydrolyzed Guar Gum Attenuates d-Galactose-Induced Oxidative Stress and Restores Gut Microbiota in Rats

Abstract

Partially hydrolyzed guar gum (PHGG) has received considerable attention for its various bioactive functions. The injection of d-galactose can cause aging-related injury which is usually resulted from oxidative stress on tissues and cells. In this study, d-galactose (200 mg/kg/day) was injected into rats, and the protective effects of PHGG (500, 1000, and 1500 mg/kg/day) against oxidative damages, as well as its probiotic functions, were analyzed. The results showed that PHGG treatment at a concentration of 1500 mg/kg/day greatly reduced the levels of lactic acid, nitric oxide, inducible nitric oxide synthase, advanced glycation end products, and increased the telomerase activity, by 7.60%, 9.25%, 12.28%, 14.58%, and 9.01%, respectively. Moreover, PHGG significantly elevated the activities of antioxidant enzymes and decreased the content of malondialdehyde in rat serum and brain. The oxidative damage was also significantly alleviated in the liver and hippocampus and the expressions of brain-derived neurotrophic factor and choline acetyltransferase also increased. Furthermore, PHGG treatment could significantly regulated the expression of sirtuin 1, forkhead box O1, and tumor protein p53 in the hippocampus. It also increased the levels of organic acids and improved the composition of intestinal microbiota. These findings demonstrated that PHGG treatment could effectively alleviate the oxidative damage and dysbacteriosis.

Keywords: aging; d-galactose; dysbacteriosis; oxidative damage; partially hydrolyzed guar gum.

Figure 1

Effects of partially hydrolyzed guar gum (PHGG) on histopathological changes in the liver of rats. (Hematoxylin and eosin staining, 200×). The hepatocytes fit morphological criteria of apoptosis labeled by arrows. NC, normal control (saline); MC, d-gal model control (saline); REV, resveratrol (20 mg/kg/day); L-PHGG, 500 mg/kg/day; M-PHGG, 1000 mg/kg/day; H-PHGG, 1500 mg/kg/day.

Figure 2

Effects of PHGG on the protein expression of brain-derived neurotrophic factor (BDNF) and choline acetyltransferase (ChAT) in the rat hippocampus. Representative images of immunofluorescence staining (600×) of BDNF and ChAT are shown. Cell nuclei are stained in blue, and BDNF/CHAT protein are stained in pink. The percentage of the BDNF-/CHAT-stained area is presented. Statistical significance between the model control group and the other groups was determined by the Kolmogorov–Smirnov test and Levene’s test for hypotheses of normality and variance homogeneity, followed by Student’s t-test or Mann–Whitney’s U non-parametric test. * p < 0.05 compared with the model control group. NC, normal control (saline); MC, d-gal model control (saline); REV, resveratrol (20 mg/kg/day); L-PHGG, 500 mg/kg/day; M-PHGG, 1000 mg/kg/day; H-PHGG, 1500 mg/kg/day.

Figure 3

Effects of PHGG on the levels of sirtuin 1 (SIRT1), Forkhead box O 1 (FOXO1), and tumor protein P53 (P53) protein expression in the rat hippocampus. (A) A representative image of the Western blotting assay. (B) The presented data of the Western blotting assay are expressed as the fold change compared with the NC control, which was arbitrarily set to 1. (C) The mRNA levels of SIRT1, FOXO1 and P53 genes relative to GAPDH and normalized with the control, which was arbitrarily set to 1. Statistical significance between the model control group and the other groups was determined by the Kolmogorov–Smirnov test and Levene’s test for hypotheses of normality and variance homogeneity, followed by Student’s t-test or Mann–Whitney’s U non-parametric test. * p < 0.05 compared with the model control group. NC, normal control (saline); MC, d-gal model control (saline); REV, resveratrol (20 mg/kg/day); L-PHGG, 500 mg/kg/day; M-PHGG, 1000 mg/kg/day; H-PHGG, 1500 mg/kg/day.

Figure 4

The concentration of lactic acid, acetic acid, propionic acid, and butyric acid. Statistical significance between the model control group and the other groups was determined by the Kolmogorov–Smirnov test and Levene’s test for hypotheses of normality and variance homogeneity, followed by Student’s t-test or Mann–Whitney’s U non-parametric test. * p < 0.05 compared with the model control group. NC, normal control (saline); MC, d-gal model control (saline); REV, resveratrol (20 mg/kg/day); L-PHGG, 500 mg/kg/day; M-PHGG, 1000 mg/kg/day; H-PHGG, 1500 mg/kg/day.

Figure 5

Effects of PHGG on the murine gut microbiome based using 16S rDNA sequencing. (A) Microbiota bacterial changes at the phylum level for each treatment groups. (B) Microbiota relative reference (%) are plotted to the genus taxonomy level for each fecal sample. (C) Bacterial population differences among the displayed groups on different taxonomy levels (p, phylum; c, class; o, order; f, family; g, genus). (D) Principle coordinates analysis (PCoA) of the model control and PHGG groups based on the Jaccard distance. Statistical significance between the model control group and the other groups was determined by the Kolmogorov–Smirnov test and Levene’s test for hypotheses of normality and variance homogeneity, followed by Student’s t-test or Mann–Whitney’s U non-parametric test. * p < 0.05 compared with the model control group. NC, normal control (saline); MC, d-gal model control (saline); REV, resveratrol (20 mg/kg/day); L-PHGG, 500 mg/kg/day; M-PHGG, 1000 mg/kg/day; H-PHGG, 1500 mg/kg/day.