Antifatigue Effects of Deer‐Hide Gelatin on Mice by Regulating Nrf2/Keap1 and AMPK/PGC1α Signaling Pathways and Intestinal Flora

Abstract

Objective: This study investigated the antifatigue effects of deer‐hide gelatin (DHG) and its mechanism in mice through a weight‐loaded swimming experiment.Methods: The subjects were assigned to the blank group (BC), positive group (PC), model group (MC), and high, medium, and low doses of DHG groups (HP, MP, and LP). After 4 weeks of treatment, the subjects were sacrificed to detect fatigue‐related biochemical indicators and the protein and mRNA expressions of Nrf2/Keap1 and AMPK/PGC1α pathways. The morphological changes of skeletal muscle were detected. High‐throughput sequencing technology was used to detect the changes in the relative abundance of intestinal flora and the content of short‐chain fatty acids (SCFAs) in tired subjects.Results: Compared with MC, DHG could prolong the exhaustion time of weight‐loaded swimming mice; reduce the CK, BUN, lactic acid, MDA, 5‐HT, and GABA levels; and increase the LDH, SOD, CAT, Glycogen, MG, BG, ACH, and Glu levels. Moreover, DHG increased the protein and mRNA expression of Nrf2, HO‐1, AMPK, PGC1α, and P‐AMPK and reduced the protein and mRNA expression of Keap1. The 16S rDNA sequencing analysis also showed that DHG regulated the abundance of intestinal microbiota and the content of SCFAs and increased the growth of beneficial bacteria.Conclusions: DHG exhibited antifatigue effects on mice by activating Nrf2/Keap1 and AMPK/PGC1α pathways, reducing oxidative stress damage, and enhancing mitochondrial energy supply. The study’s findings confirmed the considerable antioxidant and antifatigue activities of DHG, providing a preliminary foundation and practical theory for the further development of DHG as a nutritional supplement.