The Synergistic Effects of Polysaccharides and Ginsenosides From American Ginseng (Panax quinquefolius L.) Ameliorating Cyclophosphamide-Induced Intestinal Immune Disorders and Gut Barrier Dysfunctions Based on Microbiome-Metabolomics Analysis.

Rongrong Zhou,Dan He,Jing Xie,Hongliang Zeng,Luqi Huang,Qingyijun Zhou,Hongmei Li

doi:10.3389/fimmu.2021.665901

Abstract

Cyclophosphamide (CTX), used in cancer chemotherapy, a high dose of which would cause immunosuppressive effect and intestinal mucosa damage. American ginseng (Panax quinquefolius L.) has a long history of functional food use for immunological disorder, colitis, cancer, and so on. This study aimed to illustrate the underlying mechanism of American ginseng’s immunomodulatory effect in CTX-induced mice. In this study, all groups of American ginseng (American ginseng polysaccharide [AGP], American ginseng ginsenoside [AGG], co-treated with American ginseng polysaccharide and ginsenoside [AGP_AGG]) have relieve the immune disorder by reversing the lymphocyte subsets ratio in spleen and peripheral blood, as well as stimulating CD4+T cells and IgA-secreting cells in small intestine. These three treatment groups, especially AGP_AGG co-treated group recovered the intestine morphology that up-regulated villus height (VH)/crypt depth (CD) ratio, areas of mucins expression, quantity of goblet cells, and expression of tight junction proteins (ZO-1, occludin). Importantly, the microbiome-metabolomics analysis was applied in this study to illustrate the possible immuno-modulating mechanism. The synergistic effect of polysaccharides and ginsenosides (AGP_AGG group) restored the gut microbiota composition and increased various beneficial mucosa-associated bacterial taxa Clostridiales, Bifidobacterium, and Lachnospiraceae, while decreased harmful bacteria Escherichia-Shigella and Peptococcaceae. Also, AGP_AGG group altered various fecal metabolites such as uric acid, xanthurenic acid, acylcarnitine, 9,10-DHOME, 13-HDoHE, LysoPE15:0, LysoPC 16:0, LysoPI 18:0, and so on, that associated with immunometabolism or protective effect of gut barrier. These results suggest AG, particularly co-treated of polysaccharide and ginsenoside may be used as immunostimulants targeting microbiome-metabolomics axis to prevent CTX-induced side effects in cancer patients.

Highlights

Panax quinquefolius L. (AG, American ginseng) as one of the Panax species, is native to Canada and eastern America and largely exported to China [1]
High dose of CTX treatment can lead to immunosuppressive effects, damage of intestinal epithelium, and dysfunction of gut microbiota [37, 38]
Our study showed the combination use of AG polysaccharide and ginsenoside has a better effect in modulation of mucosal immunity and protection of gut barrier

Summary

Introduction

Panax quinquefolius L. (AG, American ginseng) as one of the Panax species, is native to Canada and eastern America and largely exported to China [1]. (AG, American ginseng) as one of the Panax species, is native to Canada and eastern America and largely exported to China [1]. Both in vitro and in vivo studies have suggested that American ginseng can be applied as dietary supplement in modulating immune system and used against cancer, viral, and bacterial infection [2]. CVT-E002, an aqueous extract from American ginseng (Panax quinquefolius L.), which mainly contains polysaccharides, stimulated proliferation of normal mouse spleen cells, and macrophage cytokine production in vitro, as well as activated immunoglobulin G production in vivo [7]. The combination therapy of AG berry and Scutellaria baicalensis could ameliorate side effects of cisplatin-induced vomiting and nausea [14]

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