Nuciferine Regulates Immune Function and Gut Microbiota in DSS-Induced Ulcerative Colitis

Abstract

Nuciferine, a major aporphine alkaloid obtained from the leaves of Nelumbo nucifera, exhibits anti-cancer and anti-inflammatory properties; however, its protective effects against inflammatory bowel diseases (IBD) has never been explored. In this study, an ulcerative colitis (UC) model was established in BALb/c mice by the continuous administration of 5% dextran sulfate sodium (DSS) in drinking water for 1 week. From day 8 to day 14, the DSS-treated mice were divided into a high-dose and a low-dose nuciferine treatment group and were intraperitoneally injected with the corresponding dose of the drug. Body weight loss, disease activity index (DAI), and colon length were measured. Histological changes were observed using hematoxylin and eosin staining. T lymphocyte proliferation was assessed by MTT assay. The ratio of CD3+, CD4+, CD8+, Th1, Th2, Th17, and Treg cells were estimated by flow cytometry. Finally, 16S rRNA sequencing was performed to compare the composition and relative abundance of the gut microbiota among the different treatment groups. The results showed that nuciferine treatment led to a significant improvement in symptoms, such as histological injury and colon shortening in mice with DSS-induced UC. Nuciferine treatment improved the Th1/Th2 and Treg/Th17 balance in the DSS-induced IBD model, as well as the composition of the intestinal microflora. At the phylum level, compared with the control group, the abundance of Firmicutes and Actinobacteriota was decreased in the model group, whereas that of Bacteroidetes increased. Meanwhile, at the genus level, compared with the control group, the numbers of the genera Lachnospiraceae_Clostridium, Bilophila and Halomonas reduced in the model group, while those of Bacteroides, Parabacteroides, and Paraprevotella increased. Notably, nuciferine administration reversed this DSS-induced gut dysbiosis. These results indicated that nuciferine modulates gut microbiota homeostasis and immune function in mice with DSS-induced UC.

Lotus leaf extract can attenuate salpingitis in laying hens by inhibiting apoptosis

“…Meanwhile, upregulation of anti-inflammatory cytokine IL-10 and IL-4 might inhibit the induced inflammation. Our previous studies had found that Nuciferine , a major bioactive component of lotus leaves, could improve intestinal inflammation induced by DSS ( Zhu et al, 2022 ). Thus, it was concluded that LLE-injected could inhibit the expression of inflammation-related genes through the TLR4/NF-κB signaling pathway, thereby alleviating oviduct inflammation in mixed bacteria-challenged laying hens.…”

“…Like other traditional Chinese medicine, lotus leaves are also characterized by multiple components, targets, and pathways for treating diseases. Although there is evidence that lotus leaves may provide an anti-inflammatory and immunoenhancement effect on the chicken, the effect and specific mechanism (active components, specific targets, and pathways) on salpingitis of laying hens is still unclear ( Cheng et al, 2021 ; Zhu et al, 2022 ). With the development of technology, different hyphenated chromatography techniques are more and more applied to the analysis of components, especially liquid chromatography-mass spectrometry (UPLC-Q-TOF-MS) ( Abdullah AlFaris et al, 2020 ; Feng et al, 2021 ).…”

Potential efficacy and mechanism of eight mild-natured and bitter-flavored TCMs based on gut microbiota: A review

“…Except for improving metabolic activity, nuciferine can also regulate the immune response and alleviate inflammation. For example, intraperitoneal injection of nuciferine could promote the growth of Lachnospiraceae, _Clostridium , Bilophila and Halomonas , whereas inhibit the proliferation of Bacteroides , Parabacteroides , and Paraprevotella , further improve the Th1/Th2 and Treg/Th17 balance, and attenuate inflammatory cell infiltration in ulcerative colitis mice ( Zhu et al, 2022 ). Similarly, supplementation with Nelumbinis Folium extract enhanced thymus index, spleen index, and bursa index, along with increased serum interleukin 2 (IL-2), total immunoglobulin G (IgG) and secretory immunoglobulin A (sIgA) concentrations, which correlated with the remodeling of gut microbiota ( Cheng et al, 2021 ).…”

Treatment Effects of Natural Products on Inflammatory Bowel Disease In Vivo and Their Mechanisms: Based on Animal Experiments

“…Numerous studies have also demonstrated the ability of NPs to improve IBD symptoms by modulating immune metabolic processes in experimental IBD models. For example, nuciferine, an alkaloid, can improve DSS-induced UC in mice by regulating the differentiation of T cells and IgA+ B220+ B cells and restoring the balance of Th17/Treg and CD4+/CD8+ [ 215 ]. Similarly, celastrol improves Treg/Th1 and Treg/Th17 homeostasis in UC mice to maintain immune homeostasis in the gut [ 155 ].…”