Paeoniflorin alleviates inflammatory response in IBS-D mouse model via downregulation of the NLRP3 inflammasome pathway with involvement of miR-29a

Wei Ke; Yongfu Wang; Siyu Huang; Shan Liu; He Zhu; Xiangyu Xie; Huifei Yang; Qin Lu; Jianfeng Gan; Guodong He; Fei Che; Xin Wan; Hongmei Tang

doi:10.1016/j.heliyon.2022.e12312

Paeoniflorin alleviates inflammatory response in IBS-D mouse model via downregulation of the NLRP3 inflammasome pathway with involvement of miR-29a

Heliyon. 2022 Dec 15;8(12):e12312. doi: 10.1016/j.heliyon.2022.e12312. eCollection 2022 Dec.

Authors

Wei Ke^{1

2

3}, Yongfu Wang⁴, Siyu Huang^{1

2

5}, Shan Liu^{1

2

3}, He Zhu^{1

2}, Xiangyu Xie^{1

2

3}, Huifei Yang^{1

2

3}, Qin Lu^{1

2

3}, Jianfeng Gan^{1

2

3}, Guodong He^{1

2

3}, Fei Che^{1

6}, Xin Wan^{1

2

3}, Hongmei Tang²

Affiliations

¹ The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
² The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
³ Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
⁴ Department of Traditional Chinese Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
⁵ Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems and Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong, China.
⁶ Guangzhou Liwan District Hospital of Traditional Chinese Medicine, Guangzhou 510160, Guangdong, China.

Abstract

Paeoniflorin has been traditionally used to treat pain and immunologic derangement in China. However, its detailed mechanism remains to be illuminated. We investigated the mechanism by which paeoniflorin alleviates the inflammatory response in a mouse model of irritable bowel syndrome with predominant diarrhea (IBS-D). C57BL/6 wild type (WT) and miR-29a knockout (KO) mice were randomly divided into control, model, rifaximin, and paeoniflorin groups (n = 7). IBS-D model was induced by single intracolonic instillation of 0.1 mL trinitro-benzene-sulfonic acid (TNBS, 50 mg/mL) combined with restraint stress for seven consecutive days. The treatment groups received rifaximin (100 mg/kg) and paeoniflorin (50 mg/kg) via intragastric administration for seven days, respectively. The results showed that the fecal water content, fecal pellet output, visceral sensitivity, and histopathological score after paeoniflorin treatment were lower than those of the model group in both WT and miR-29a KO mice (P < 0.05). In both lineage mice, damage was observed in the colon tissues of model group, while paeoniflorin treatment partially ameliorated the tissue damage. Serum levels of DAO, DLA, IL-1β, IL-18, TNF-α, and MPO were decreased after paeoniflorin treatment (P < 0.05), with miR-29a KO mice in a lower level compared with that of WT mice. RT-PCR showed that the relative expression of miR-29a, NF-κB (p65), NLRP3, ASC, caspase-1, IL-1β, and TNF-α was downregulated while NKRF was upregulated after paeoniflorin treatment (P < 0.05). Immunohistochemistry showed that intestinal epithelial protein levels of NLRP3, ASC, and caspase-1 decreased while those of Claudin-1 and ZO-1 increased in the paeoniflorin treatment group (P < 0.05). In general, compared with WT mice, NLRP3 inflammasome pathway targets was in much lower expression level than miR-29a KO mice. In conclusion, paeoniflorin could inhibit abnormal activation of the NLRP3 inflammasome pathway by inhibiting miR-29a in IBS-D, thereby relieving the inflammatory response of the intestinal mucosa and reconstructing the intestinal epithelial barrier.

Keywords: NLRP3 inflammasome; Paeoniflorin; irritable bowel syndrome; miR-29a.