Platycodon grandiflorus polysaccharides combined with hesperidin exerted the synergistic effect of relieving ulcerative colitis in mice by modulating PI3K/AKT and JAK2/STAT3 signaling pathways.
10.1016/S1875-5364(25)60913-7
- Author:
Yang LIU
1
;
Quanwei SUN
1
;
Xuefei XU
2
;
Mengmeng LI
1
;
Wenheng GAO
1
;
Yunlong LI
1
;
Ye YANG
3
;
Dengke YIN
4
Author Information
1. School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.
2. School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
3. School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China; Anhui Provincial Key Laboratory of Pharmaceutical Preparation Technology and Application, Anhui University of Chinese Medicine, Hefei 230021, China. Electronic address: Y.Yang@ahtcm.edu.cn.
4. School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China; Anhui Provincial Key Laboratory of Pharmaceutical Preparation Technology and Application, Anhui University of Chinese Medicine, Hefei 230021, China; Anhui Provincial Key Laboratory of Traditional Chinese Medicine Formula Granule, Anhui Huarun Jinchan Pharmaceutical Co., Ltd., Huaibei 235000, China; Anhui Provincial Key Laboratory of Research & Development of Chinese Medicine, Anhui University of Chinese Medicine, Hefei 230021, China. Electronic address: yindengke@ahtcm.edu.cn.
- Publication Type:Journal Article
- Keywords:
Hesperidin;
JAK2/STAT3;
PI3K/AKT;
Platycodon grandiflorus polysaccharides;
Synergistic effects;
Ulcerative colitis
- MeSH:
Animals;
STAT3 Transcription Factor/genetics*;
Janus Kinase 2/genetics*;
Polysaccharides/administration & dosage*;
Colitis, Ulcerative/chemically induced*;
Mice;
Signal Transduction/drug effects*;
Proto-Oncogene Proteins c-akt/genetics*;
Drug Synergism;
Male;
Hesperidin/administration & dosage*;
Platycodon/chemistry*;
Phosphatidylinositol 3-Kinases/genetics*;
Disease Models, Animal;
RAW 264.7 Cells;
Mice, Inbred C57BL
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(7):848-862
- CountryChina
- Language:English
-
Abstract:
Ulcerative colitis (UC) is a chronic inflammatory disorder with a complex etiology, characterized by intestinal inflammation and barrier dysfunction. Platycodon grandiflorus polysaccharides (PGP), the primary component of Platycodon grandiflorus, and hesperidin (Hesp), a prominent active component in Citrus aurantium L. (CAL), have both demonstrated anti-inflammatory properties. This study aims to elucidate the underlying mechanism of the synergistic effect of PGP combined with Hesp on UC, focusing on the coordinated interaction between the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathways. A mouse model of UC induced by dextran sulfate sodium (DSS) and a cell model using lipopolysaccharide (LPS)-induced RAW264.7/IEC6 cells were employed to investigate the in vitro and in vivo anti-inflammatory effects of PGP combined with Hesp on UC and its potential mechanism of action. The results indicated that compared to the effects of either drug alone, the combination of PGP and Hesp significantly modulated inflammatory factor levels, inhibited oxidative stress, regulated colonic mucosal immunity, suppressed apoptosis, and restored intestinal barrier function in vitro and in vivo. Further in vitro studies revealed that PGP significantly inhibited the PI3K/AKT signaling pathway, while Hesp significantly inhibited the JAK2/STAT3 signaling pathway. The use of inhibitors and activators targeting both pathways validated the synergistic effects of PGP combined with Hesp on the PI3K/AKT and JAK2/STAT3 signaling pathways. These findings suggest that PGP combined with Hesp exhibits a synergistic effect on DSS-induced colitis, potentially mediated through the phosphatase and tensin homolog (PTEN)/PI3K/AKT and interleukin-6 (IL-6)/JAK2/STAT3 signaling pathways.
