Magnolia Officinalis Alcohol Extract Alleviates the Intestinal Injury Induced by Polygala Tenuifolia Through Regulating the PI3K/AKT/NF-κB Signaling Pathway and Intestinal Flora

Abstract

Purpose

Polygala tenuifolia Willd. (PT), a traditional Chinese medicinal plant extensively employed in managing Alzheimer’s disease, exhibits notable gastrointestinal side effects as highlighted by prior investigations. In contrast, Magnolia officinalis Rehd. et Wils (MO), a traditional remedy for gastrointestinal ailments, shows promising potential for ameliorating this adverse effect of PT. The objective of this study is to examine the underlying mechanism of MO in alleviating the side effects of PT.

Methods

Hematoxylin-eosin (H&E) staining was used to observe the structural damage of zebrafish intestine, and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors and oxidative stress. The integrity of the intestinal tight junctions was examined using transmission electron microscope (TEM). Moreover, the expression of intestinal barrier genes and PI3K/AKT/NF-κB signaling pathway-related genes was determined through quantitative real-time PCR. The changes in intestinal microbial composition were analyzed using 16S rRNA and metagenomic techniques.

Results

MO effectively ameliorated intestinal pathological damage and barrier gene expression, and significantly alleviated intestinal injury by reducing the expression of inflammatory cytokines IL-1β, IL-6, TNF-α, and inhibiting the activation of PI3K/AKT/NF-κB pathway. Furthermore, MO could significantly increase the relative abundance of beneficial microorganisms (Lactobacillus, Blautia and Saccharomyces cerevisiae), and reduce the relative abundance of pathogenic bacteria (Plesiomonas and Aeromonas).

Conclusion

MO alleviated PT-induced intestinal injury, and its mechanism may be related to the inhibition of PI3K/AKT/NF-κB pathway activation and regulation of intestinal flora.

Keywords:

• polygala tenuifolia
• PI3K/AKT/NF-κB
• gut microbiota
• inflammation
• intestinal injury

Abbreviations

ANOVA, analysis of variance; CAT catalase; DMSO, dimethyl sulfoxide; ELISA, enzyme-linked immunosorbent assay; Epox, Epoxy embedding medium; ESI, electrospray ionization; GSH-Px, glutathione peroxidase; H&E, hematoxylin and eosin; IL-1β, interleukin-1β; IL-6, interleukin-6; LEFSE, linear discriminant analysis effect size; MDA, malondialdehyde; NF-κB, nuclear factor kappa B; OTU operational taxonomic unit; PCoA, principal co-ordinates analysis; PhC, pharmacopoeia of the people’s republic of China; PI3K/AKT, phosphoinositide 3‑kinase/protein kinase B; qRT-PCR, quantitative real time polymerase chain reaction; SOD, superoxide dismutase; TCM, traditional Chinese medicine; TJP, tight junction protein; TNF-α, tumor necrosis factor-α; UPLC-MS/MS, ultra-high performance liquid chromatography-tandem triple quadrupole mass Spectrometry.

Data Sharing Statement

The datasets PRJNA1054352 and PRJNA1054761 for this study can be found in the National Center for Biotechnology Information (NCBI). https://www.ncbi.nlm.nih.gov/sra/PRJNA1054352 and https://www.ncbi.nlm.nih.gov/sra/PRJNA1054761.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This research was funded by the National Natural Science Foundation of China (Grant Nos. 82003965 and 82022072), improvement plan of “Xinglin scholar” scientific research talent, Chengdu University of Traditional Chinese Medicine (Grant Nos. XKTD2023002 and QJRC2022033) and the State Administration of Traditional Chinese Medicine of the People’s Republic of China.