Protective effects of sinomenine against dextran sulfate sodium-induced ulcerative colitis in rats via alteration of HO-1/Nrf2 and inflammatory pathway

Niu, Zhongbao; Li, Xinhong; Yang, Xiuhua; Sun, Zhongwei

doi:10.1007/s10787-024-01455-6

Cited by 4 publications

(1 citation statement)

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“…Moreover, HO-1, a crucial gene regulated by NRF2, demonstrates noteworthy anti-inflammatory and antioxidant characteristics ( Boyanapalli et al, 2014 ). Increased expression of HO-1 helps to reduce the levels of inflammation-associated cytokines, such as TNF-α, IL-6, IL-1β, and IL-18, which in turn attenuates the inflammatory response ( Mills et al, 2018 ; Xu et al, 2020 ; Kang et al, 2022 ; Niu et al, 2024 ). Our results suggest that LHT plays an important role in IBD therapy by increasing SOD levels, decreasing MPO and NO content, and inhibiting the release of inflammatory factors, such as TNF-α, IL-1β, IL-6, and IL-18, and through the NRF2/HO-1 signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Li-Hong Tang alleviates dextran sodium sulfate-induced colitis by regulating NRF2/HO-1 signaling pathway and gut microbiota

Gu,

Tian,

Xia

et al. 2024

Front. Pharmacol.

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IntroductionUlcerative colitis (UC) is marked by recurring inflammation. Existing treatments are ineffective and may have toxic side effects. Thus, new therapeutic agents are urgently needed. We studied the botanical formula “Li-Hong Tang (LHT)", which contains two main ingredients, Salvia plebeia R. Br and Rhodiola crenulata (Hook. f. et Thoms.) H. Ohba. In this study, we aimed to identify the effects of LHT on UC and explore its potential mechanism.MethodsLHT was analyzed using a mass spectrometer (MS). DSS at a dose of 2.5% was utilized to develop UC in mice. The administered groups received low, medium, and high dosages (0.32 g/kg, 0.64 g/kg, and 1.28 g/kg) of LHT and the positive medication, sulfasalazine (0.2 g/kg), respectively. Body weight, disease activity index (DAI) score, colon length, spleen index, serum myeloperoxidase (MPO), nitric oxide (NO), superoxide dismutase (SOD) and inflammatory factor concentrations were monitored. The expression of NRF2 and HO-1 in colonic tissues was evaluated by immunohistochemistry. 16S rDNA sequencing was employed to investigate alterations in the gut microbiota of the mice, aiming to elucidate the extent of LHT’s impact.ResultsLHT may ameliorate DSS-induced colitis in mice by lowering inflammation, reducing oxidative stress, restoring the intestinal barrier, and influencing the NRF2/HO-1 pathway. Moreover, LHT treatment exhibited a regulatory effect on the gut microbiota, characterized by elevated levels of Patescibacteria, Verrucomicrobiota, Candidatus_Saccharimonas, Lactobacillus, and Ligilactobacillus levels while decreasing Oscillibacter and Colidextribacter levels. Further study indicated that MPO, NO, and inflammatory factors were positively correlated with Oscillibacter, Colidextribacter, Escherichia-Shigella, Anaerostines, and negatively with Lactobacillus, Clostridiales_unclassified, Candidatus_Saccharimonas, and Patescibacteria. Furthermore, colony network analysis revealed that Lactobacillus was negatively associated with Oscillibacter and Colidextribacter, whereas Oscillibacter was positively related to Colidextribacter.ConclusionLHT protects against DSS-induced mice by inhibiting the inflammatory response, oxidative stress, and mucosal injury. The protective role may involve regulating the NRF2/HO-1 signaling pathway and gut microbiota.

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Section: Discussionmentioning

confidence: 99%

Li-Hong Tang alleviates dextran sodium sulfate-induced colitis by regulating NRF2/HO-1 signaling pathway and gut microbiota

Gu,

Tian,

Xia

et al. 2024

Front. Pharmacol.

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Recent developments and new directions in the use of natural products for the treatment of inflammatory bowel disease

Feng,

Pan,

et al. 2024

Phytomedicine

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Mechanism of Action and Therapeutic Implications of Nrf2/HO-1 in Inflammatory Bowel Disease

Yuan,

Wang,

et al. 2024

Antioxidants

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Oxidative stress (OS) is a key factor in the generation of various pathophysiological conditions. Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) is a major transcriptional regulator of antioxidant reactions. Heme oxygenase-1 (HO-1), a gene regulated by Nrf2, is one of the most critical cytoprotective molecules. In recent years, Nrf2/HO-1 has received widespread attention as a major regulatory pathway for intracellular defense against oxidative stress. It is considered as a potential target for the treatment of inflammatory bowel disease (IBD). This review highlights the mechanism of action and therapeutic significance of Nrf2/HO-1 in IBD and IBD complications (intestinal fibrosis and colorectal cancer (CRC)), as well as the potential of phytochemicals targeting Nrf2/HO-1 in the treatment of IBD. The results suggest that the therapeutic effects of Nrf2/HO-1 on IBD mainly involve the following aspects: (1) Controlling of oxidative stress to reduce intestinal inflammation and injury; (2) Regulation of intestinal flora to repair the intestinal mucosal barrier; and (3) Prevention of ferroptosis in intestinal epithelial cells. However, due to the complex role of Nrf2/HO-1, a more nuanced understanding of the exact mechanisms involved in Nrf2/HO-1 is the way forward for the treatment of IBD in the future.

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Protective effects of sinomenine against dextran sulfate sodium-induced ulcerative colitis in rats via alteration of HO-1/Nrf2 and inflammatory pathway

Cited by 4 publications

References 43 publications

Li-Hong Tang alleviates dextran sodium sulfate-induced colitis by regulating NRF2/HO-1 signaling pathway and gut microbiota

Li-Hong Tang alleviates dextran sodium sulfate-induced colitis by regulating NRF2/HO-1 signaling pathway and gut microbiota

Recent developments and new directions in the use of natural products for the treatment of inflammatory bowel disease

Mechanism of Action and Therapeutic Implications of Nrf2/HO-1 in Inflammatory Bowel Disease

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