Parishin From Gastrodia Elata Ameliorates Aging Phenotype in Mice in a Gut Microbiota-Related Manner

Abstract

The physiological and pathological processes that accompany aging can seriously affect the quality of life of the elderly population. Therefore, delaying aging and developing antiaging products have become popular areas of inquiry. Gut microbiota plays an important role in age-related phenotypes. The present study aimed to investigate the antiaging effects and underlying mechanism of parishin, a phenolic glucoside isolated from traditional Chinese medicine Gastrodia elata. Samples from adult (12 weeks), low-dose (10 mg/kg/d) or high-dose (20 mg/kg/d) parishin-treated and untreated aged (19 months) mice were collected to determine blood indicators, gut microbiota and metabolome, and cardiopulmonary histopathological features. The results showed that parishin treatment ameliorates aging-induced cardiopulmonary fibrosis and increase in serum p16 ^Ink4a , GDF15, and IL-6 levels. Furthermore, parishin treatment alleviated dysbiosis in gut microbiota, including altered microbial diversity and the aberrant abundance of opportunistic pathogenic bacteria such as Turicibacter and Erysipelatoclostridium. Gene function prediction and gut metabolome analysis results indicated that the parishin treatment-altered gut microbiota played important roles in sugar, lipid, amino acid and nucleic acid metabolism, and improved gut metabolic disorders in aged mice. In conclusion, the present study provides an experimental basis of potential applications of parishin against aging.

Keywords: antiaging; gut microbiota; metabolome; natural products; traditional Chinese medicine.

FIGURE 1

Parishin treatment alleviates aging-induced abnormal blood indicator levels and cardiopulmonary injury. (A) Serum p16^Ink4a, GDF15, and IL-6 levels. (B) Representative images of lung and heart samples stained by H&E and Masson’s trichrome. (C) Fibrosis degree of lung and heart samples. *P < 0.05; **P < 0.01; ***P < 0.001.

FIGURE 2

Parishin treatment alleviates aging-induced dysbiosis of the gut microbiota. (A) Box plot of community biodiversity and richness estimated based on the Shannon indexes and Chao1 indexes. (B) Two-dimensional PCoA and NMDS plot based on the Bray–Curtis dissimilarity. (C) Alterations in the relative abundance of bacterial taxa in the AC, LPar, HPar and YC groups. *P < 0.05; **P < 0.01.

FIGURE 3

Pathway enrichment of differential gut microbial genes between the YC, AC, LPar and HPar groups based on function prediction using Picrust 2 (P < 0.05).

FIGURE 4

Pathways of gut microbial genes altered by aging (A) and whose alterations were alleviated by high-dose parshin treatment (B) and low-dose parshin treatment (C). *P < 0.05; **P < 0.01; ***P < 0.001.

FIGURE 5

Parishin alleviates aging-induced gut metabolic disorder. (A) OPLS-DA plot illustrating clear separation of gut metabolic profiles of the AC, LPar and YC groups, and the AC, HPar and YC groups. (B) VIP values of 4 metabolites with the highest contribution to the separation of the AC, LPar and YC groups in the OPLS-DA model. (C) VIP values of 8 metabolites with the highest contribution to the separation of the AC, HPar and YC groups in the OPLS-DA model. (D) Levels of five differentially distributed metabolites in the four groups. *P < 0.05; **P < 0.01; ***P < 0.001.

FIGURE 6

Associations among gut bacteria, metabolites, and aging-related indicators influenced by parishin (P < 0.05). (A) Correlation of parishin-influenced gut microbes with gut metabolites. (B) Correlation of parishin-influenced microbes and metabolites with serum biomarkers and cardiopulmonary fibrosis degrees.