Medicinal Plant Leaf Extract From Sage and Lemon Verbena Promotes Intestinal Immunity and Barrier Function in Gilthead Seabream ( Sparus aurata)

Front Immunol. 2021 May 14:12:670279. doi: 10.3389/fimmu.2021.670279. eCollection 2021.


The inclusion of a medicinal plant leaf extract (MPLE) from sage (Salvia officinalis) and lemon verbena (Lippia citriodora), rich in verbascoside and triterpenic compounds like ursolic acid, was evaluated in gilthead seabream (Sparus aurata) fed a low fishmeal-based diet (48% crude protein, 17% crude fat, 21.7 MJ kg-1, 7% fishmeal, 15% fish oil) for 92 days. In particular, the study focused on the effect of these phytogenic compounds on the gut condition by analyzing the transcriptomic profiling (microarray analysis) and histological structure of the intestinal mucosa, as well as the histochemical properties of mucins stored in goblet cells. A total number of 506 differentially expressed genes (285 up- and 221 down-regulated) were found when comparing the transcriptomic profiling of the intestine from fish fed the control and MPLE diets. The gut transcripteractome revealed an expression profile that favored biological mechanisms associated to the 1) immune system, particularly involving T cell activation and differentiation, 2) gut integrity (i.e., adherens and tight junctions) and cellular proliferation, and 3) cellular proteolytic pathways. The histological analysis showed that the MPLE dietary supplementation promoted an increase in the number of intestinal goblet cells and modified the composition of mucins' glycoproteins stored in goblet cells, with an increase in the staining intensity of neutral mucins, as well as in mucins rich in carboxylated and weakly sulfated glycoconjugates, particularly those rich in sialic acid residues. The integration of transcriptomic and histological results showed that the evaluated MPLE from sage and lemon verbena is responsible for the maintenance of intestinal health, supporting gut homeostasis and increasing the integrity of the intestinal epithelium, which suggests that this phytogenic may be considered as a promising sustainable functional additive for aquafeeds.

Keywords: GALT; cell proliferation; feed additive; gut health; innate immunity; lectin histochemistry; ursolic acid; verbascoside acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adherens Junctions / drug effects
  • Adherens Junctions / metabolism
  • Animals
  • Cell Differentiation / drug effects
  • Goblet Cells / drug effects
  • Goblet Cells / immunology
  • Goblet Cells / metabolism
  • Immunity, Mucosal / drug effects*
  • Immunologic Factors / isolation & purification
  • Immunologic Factors / pharmacology*
  • Intercellular Junctions / drug effects*
  • Intercellular Junctions / metabolism
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Lymphocyte Activation / drug effects
  • Mucins / metabolism
  • Permeability / drug effects
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Leaves
  • Salvia officinalis* / chemistry
  • Sea Bream* / genetics
  • Sea Bream* / immunology
  • Sea Bream* / metabolism
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Tight Junctions / drug effects
  • Tight Junctions / metabolism
  • Transcriptome
  • Verbenaceae* / chemistry


  • Immunologic Factors
  • Mucins
  • Plant Extracts

Supplementary concepts

  • Aloysia