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已发表论文
异荭草素通过 P-糖蛋白/内源性大麻素系统降低肠通透性，调节肠道微生物及其代谢产物，缓解 Caco-2 细胞单层炎症
Authors Wang Z, Jiang Y , Duan B, Zhang H, Li A, Yang J, Lv M, Yang J
Received 26 March 2025
Accepted for publication 9 September 2025
Published 16 October 2025 Volume 2025:18 Pages 14365—14379
DOI https://doi.org/10.2147/JIR.S530562
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Nadia Andrea Andreani
Zhenzhen Wang,1 Yuang Jiang,2 Bensong Duan,3 Haibin Zhang,3 Aoxiang Li,1 Jin Yang,1 Mengke Lv,1 Jingya Yang1,4
1College of Food Science and Technology, Shanghai Ocean University, Shanghai, 201306, People’s Republic of China; 2College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, 201306, People’s Republic of China; 3Department of Gastroenterology Shanghai East Hospital, School of Medicine, Endoscopy Center, Tongji University, Shanghai, People’s Republic of China; 4Marine Biomedical Science and Technology Innovation Platform of Lin-Gang Special Area, Shanghai, 201306, People’s Republic of China
Correspondence: Jingya Yang, College of Food Science and Technology, Shanghai Ocean University, No. 999 Hu-Cheng Huan Road, Shanghai, 201306, People’s Republic of China, Email jyyang@shou.edu.cn
Introduction: Isoorientin (ISO) is a naturally occurring flavonoid that studies have shown to have strong experimental antioxidant, anti-inflammatory, anti-diabetic and anti-obesity properties. It has been shown that ISO alleviates Dextran sodium sulfate (DSS) induced colitis in mice by modulating gut microbes and their metabolites. The aim of this study was to modulate gut microbes and their metabolism by ISO to investigate its anti-inflammatory effects and its specific molecular mechanisms in a lipopolysaccharide (LPS)-induced monolayer inflammation model in Caco-2 cells.
Methods: Feces from ISO-treated DSS colitis mice were collected and gut flora culture supernatants were prepared. Detection of the effect of intestinal flora supernatants on the monolayer barrier of Caco-2 cells by inoculation of Caco-2 cells into the Transwell transmembrane culture system to simulate the intestinal mucosal barrier.
Results: The results revealed that ISO-conditioned intestinal flora supernatant significantly increased TEER values, decreased intestinal epithelial FITC-dextran flux permeability, and restored LPS-induced occludin, ZO-1 protein expression in Caco-2 cells. Meanwhile, intestinal flora supernatant significantly ameliorated the LPS-induced inflammatory response. In addition, ISO further enhanced its protective effect on intestinal permeability by regulating the expression of P-glycoprotein (P-gp) and endogenous cannabinoid system (eCB)-related proteins, which may attenuate the inflammatory response by activating the P-gp/eCB signaling pathway.
Conclusion: The present study offers fresh perspectives into the application of ISO-conditioned intestinal flora supernatant as a potential anti-inflammatory agent and intestinal barrier protector in vitro. The unique regulation of the P-gp/eCBs pathway by ISO-conditioned intestinal flora supernatant was the novel mechanistic insights provided in this study.
Keywords: isoorientin, Caco-2 cell, intestinal mucosal barrier, ZO-1, occludin, P-glycoprotein
1College of Food Science and Technology, Shanghai Ocean University, Shanghai, 201306, People’s Republic of China; 2College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, 201306, People’s Republic of China; 3Department of Gastroenterology Shanghai East Hospital, School of Medicine, Endoscopy Center, Tongji University, Shanghai, People’s Republic of China; 4Marine Biomedical Science and Technology Innovation Platform of Lin-Gang Special Area, Shanghai, 201306, People’s Republic of China
Correspondence: Jingya Yang, College of Food Science and Technology, Shanghai Ocean University, No. 999 Hu-Cheng Huan Road, Shanghai, 201306, People’s Republic of China, Email jyyang@shou.edu.cn
Introduction: Isoorientin (ISO) is a naturally occurring flavonoid that studies have shown to have strong experimental antioxidant, anti-inflammatory, anti-diabetic and anti-obesity properties. It has been shown that ISO alleviates Dextran sodium sulfate (DSS) induced colitis in mice by modulating gut microbes and their metabolites. The aim of this study was to modulate gut microbes and their metabolism by ISO to investigate its anti-inflammatory effects and its specific molecular mechanisms in a lipopolysaccharide (LPS)-induced monolayer inflammation model in Caco-2 cells.
Methods: Feces from ISO-treated DSS colitis mice were collected and gut flora culture supernatants were prepared. Detection of the effect of intestinal flora supernatants on the monolayer barrier of Caco-2 cells by inoculation of Caco-2 cells into the Transwell transmembrane culture system to simulate the intestinal mucosal barrier.
Results: The results revealed that ISO-conditioned intestinal flora supernatant significantly increased TEER values, decreased intestinal epithelial FITC-dextran flux permeability, and restored LPS-induced occludin, ZO-1 protein expression in Caco-2 cells. Meanwhile, intestinal flora supernatant significantly ameliorated the LPS-induced inflammatory response. In addition, ISO further enhanced its protective effect on intestinal permeability by regulating the expression of P-glycoprotein (P-gp) and endogenous cannabinoid system (eCB)-related proteins, which may attenuate the inflammatory response by activating the P-gp/eCB signaling pathway.
Conclusion: The present study offers fresh perspectives into the application of ISO-conditioned intestinal flora supernatant as a potential anti-inflammatory agent and intestinal barrier protector in vitro. The unique regulation of the P-gp/eCBs pathway by ISO-conditioned intestinal flora supernatant was the novel mechanistic insights provided in this study.
Keywords: isoorientin, Caco-2 cell, intestinal mucosal barrier, ZO-1, occludin, P-glycoprotein