Combined Analysis of Gut Microbiota and Plasma Metabolites Reveals the Effect of Red-Fleshed Apple Anthocyanin Extract on Dysfunction of Mice Reproductive System Induced by Busulfan.

Bin Wang,Shenhui Jiang,Yugang Zhang,Yanbo Wang,Jihua Xu,Jun Zhu

doi:10.3389/fnut.2021.802352

Abstract

Busulfan is currently an indispensable anti-cancer drug, but the side effects on male reproductive system are so serious. Meanwhile, red-fleshed apples are natural products with high anthocyanin content. In this research, we analyzed the effect of red-fleshed apple anthocyanin extract (RAAE) on busulfan-treated mice. Compared with the busulfan group, main plasma biochemical indicators were significantly improved after RAAE treatment. Compared with BA0 (busulfan without RAAE) group, total antioxidant capacity(T-AOC) and the activity of superoxide dismutase (SOD) and glutathione catalase (GSH-Px) in RAAE treatment groups were obviously increased, while the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly decreased. Malondialdehyde (MDA) was significantly decreased in the RAAE groups. In addition, we found RAAE alleviated busulfan-disrupted spermatogenesis through improving genes expression which are important for spermatogenesis, such as DDX4, PGK2, and TP1. Furthermore, we found that RAAE increased beneficial bacteria Akkermansia and Lactobacillaceae, and significantly depleted harmful bacteria Erysipelotrichia. The correlation studies indicated that RAAE ameliorated busulfan-induced rise in LysoPC levels through regulating gut microbial community and their associated metabolites. In conclusion, this study extends our understanding of the alleviated effect of RAAE on busulfan-induced male reproductive dysfunction through regulating the relationships between gut microbiota and metabolites.

Highlights

Red-fleshed apple is a type of valuable and special variety of fruit and has always been attractive to consumers due to the red flesh color
We found that anthocyanin could reduce the oxidative damage caused by busulfan in mice by reducing the content of reactive oxygen species (ROS), and the restoration of the mice reproductive system was mainly achieved through the regulation of genes related to the spermatogenesis pathway
It has been reported that the organ damage induced by busulfan is caused by a large increase in the content of reactive oxygen species (ROS) including free radicals, causing oxidative damage in the cell [16]

Summary

Introduction

Red-fleshed apple is a type of valuable and special variety of fruit and has always been attractive to consumers due to the red flesh color. Red-fleshed apple is rich in polysaccharides, anthocyanins and other flavonoids, and its flavonoids content is several times more than ordinary white apple [1]. Anthocyanins can effectively inhibit oxygen free radicals and maintain the balance of the Anthocyanin Relieves Reproductive Damage radicals [2]. It exerts antioxidant effects in the body, having significant therapeutic effects on many chronic diseases [2]. Study found the anthocyanin extracts of red-fleshed apple “Bekran” are effective in scavenging reactive oxygen species such as peroxides and superoxide anions [3]. Red-fleshed apple is a natural antioxidant with significant antioxidative activities and liver protective effects. Study found that among the four species studied, “Roberts Crab” had the highest content of total phenols, flavonoids and anthocyanins, and the strongest scavenging ability on DPPH, ABTS, and FRAP [5]

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Results

Conclusion