Ursolic acid regulates gut microbiota and corrects the imbalance of Th17/Treg cells in T1DM rats.

Ursolic acid (UA), a natural pentacyclic triterpenoid obtained from fruit and several traditional Chinese medicinal plants, exhibits anti-inflammatory and hypoglycemic properties. However, its protective effects against type 1 diabetes mellitus (T1DM) have not been explored. In this study, streptozo...

Full description

Bibliographic Details
Main Authors: Weiwei Chen, Yingying Yu, Yang Liu, ChaoJie Song, HuanHuan Chen, Cong Tang, Yu Song, Xiaoli Zhang
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0277061
_version_ 1798015509691629568
author Weiwei Chen
Yingying Yu
Yang Liu
ChaoJie Song
HuanHuan Chen
Cong Tang
Yu Song
Xiaoli Zhang
author_facet Weiwei Chen
Yingying Yu
Yang Liu
ChaoJie Song
HuanHuan Chen
Cong Tang
Yu Song
Xiaoli Zhang
author_sort Weiwei Chen
collection DOAJ
description Ursolic acid (UA), a natural pentacyclic triterpenoid obtained from fruit and several traditional Chinese medicinal plants, exhibits anti-inflammatory and hypoglycemic properties. However, its protective effects against type 1 diabetes mellitus (T1DM) have not been explored. In this study, streptozotocin-induced T1DM rat models were established and treated with UA for six weeks. T1DM rats treated with UA were used to observe the effects of UA on body weight and fasting blood glucose (FBG) levels. Pathological changes in the pancreas were observed using immunohistochemical staining. The gut microbiota distribution was measured using 16S rDNA high-throughput sequencing. The proportions of Th17 and Treg cells were examined using flow cytometry. Protein and mRNA expression of molecules involved in Th17/Treg cell differentiation were assessed by quantitative real-time PCR and western blotting. The correlation between gut microbiota and Th17/Treg cell differentiation in T1DM was analyzed using redundancy analysis (RDA) analysis. Compared with the model group, FBG levels declined, and the progressive destruction of pancreatic β cells was alleviated. The diversity and uniformity of gut microbiota in T1DM rats treated with UA increased significantly. Interestingly, the Th17/Treg cell differentiation imbalance was corrected and positively correlated with the expression of Foxp3 and IL-10, and negatively correlated with the expression of RORγt, IL-17A, and TNF-α. These findings suggest that UA can lower FBG levels in T1DM rats, delay the progressive destruction of pancreatic β-cells, and modulate gut microbiota homeostasis and immune function in streptozotocin-induced T1DM rats.
first_indexed 2024-04-11T15:34:34Z
format Article
id doaj.art-623f6958ff894eabb1165e4304240731
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-04-11T15:34:34Z
publishDate 2022-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-623f6958ff894eabb1165e43042407312022-12-22T04:16:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-011711e027706110.1371/journal.pone.0277061Ursolic acid regulates gut microbiota and corrects the imbalance of Th17/Treg cells in T1DM rats.Weiwei ChenYingying YuYang LiuChaoJie SongHuanHuan ChenCong TangYu SongXiaoli ZhangUrsolic acid (UA), a natural pentacyclic triterpenoid obtained from fruit and several traditional Chinese medicinal plants, exhibits anti-inflammatory and hypoglycemic properties. However, its protective effects against type 1 diabetes mellitus (T1DM) have not been explored. In this study, streptozotocin-induced T1DM rat models were established and treated with UA for six weeks. T1DM rats treated with UA were used to observe the effects of UA on body weight and fasting blood glucose (FBG) levels. Pathological changes in the pancreas were observed using immunohistochemical staining. The gut microbiota distribution was measured using 16S rDNA high-throughput sequencing. The proportions of Th17 and Treg cells were examined using flow cytometry. Protein and mRNA expression of molecules involved in Th17/Treg cell differentiation were assessed by quantitative real-time PCR and western blotting. The correlation between gut microbiota and Th17/Treg cell differentiation in T1DM was analyzed using redundancy analysis (RDA) analysis. Compared with the model group, FBG levels declined, and the progressive destruction of pancreatic β cells was alleviated. The diversity and uniformity of gut microbiota in T1DM rats treated with UA increased significantly. Interestingly, the Th17/Treg cell differentiation imbalance was corrected and positively correlated with the expression of Foxp3 and IL-10, and negatively correlated with the expression of RORγt, IL-17A, and TNF-α. These findings suggest that UA can lower FBG levels in T1DM rats, delay the progressive destruction of pancreatic β-cells, and modulate gut microbiota homeostasis and immune function in streptozotocin-induced T1DM rats.https://doi.org/10.1371/journal.pone.0277061
spellingShingle Weiwei Chen
Yingying Yu
Yang Liu
ChaoJie Song
HuanHuan Chen
Cong Tang
Yu Song
Xiaoli Zhang
Ursolic acid regulates gut microbiota and corrects the imbalance of Th17/Treg cells in T1DM rats.
PLoS ONE
title Ursolic acid regulates gut microbiota and corrects the imbalance of Th17/Treg cells in T1DM rats.
title_full Ursolic acid regulates gut microbiota and corrects the imbalance of Th17/Treg cells in T1DM rats.
title_fullStr Ursolic acid regulates gut microbiota and corrects the imbalance of Th17/Treg cells in T1DM rats.
title_full_unstemmed Ursolic acid regulates gut microbiota and corrects the imbalance of Th17/Treg cells in T1DM rats.
title_short Ursolic acid regulates gut microbiota and corrects the imbalance of Th17/Treg cells in T1DM rats.
title_sort ursolic acid regulates gut microbiota and corrects the imbalance of th17 treg cells in t1dm rats
url https://doi.org/10.1371/journal.pone.0277061
work_keys_str_mv AT weiweichen ursolicacidregulatesgutmicrobiotaandcorrectstheimbalanceofth17tregcellsint1dmrats
AT yingyingyu ursolicacidregulatesgutmicrobiotaandcorrectstheimbalanceofth17tregcellsint1dmrats
AT yangliu ursolicacidregulatesgutmicrobiotaandcorrectstheimbalanceofth17tregcellsint1dmrats
AT chaojiesong ursolicacidregulatesgutmicrobiotaandcorrectstheimbalanceofth17tregcellsint1dmrats
AT huanhuanchen ursolicacidregulatesgutmicrobiotaandcorrectstheimbalanceofth17tregcellsint1dmrats
AT congtang ursolicacidregulatesgutmicrobiotaandcorrectstheimbalanceofth17tregcellsint1dmrats
AT yusong ursolicacidregulatesgutmicrobiotaandcorrectstheimbalanceofth17tregcellsint1dmrats
AT xiaolizhang ursolicacidregulatesgutmicrobiotaandcorrectstheimbalanceofth17tregcellsint1dmrats