Trypsin inhibitor LH011 inhibited DSS-induced mice colitis via alleviating inflammation and oxidative stress

Jia, Zhenmao; Wang, Panxia; Xu, Yuanfu; Feng, Guodong; Wang, Quan; He, Xijing; Yan, Shuicheng; Liu, Peiqing; Chen, Jianwen

doi:10.3389/fphar.2022.986510

Cited by 8 publications

(3 citation statements)

References 48 publications

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“…In contrast, another study reported MT’s positive outcomes in TNBS (trinitrobenzene sulfonic acid)—induced colitis in mice are mediated by the inhibition of inflammation through the down-regulation of the TLR4/Myeloid differentiation primary response 88 (MyD88)/NF-κB pathway [ 154 ]. Moreover, TLR4 is overexpressed in IBD, and its activation is linked to intestinal inflammation and ulceration [ 155 ]. Conversely, the inhibition of TLR4 signaling by various compounds was associated with improved histological features, with reduced inflammatory cells infiltration, lymphocyte infiltration of lamina propria, mucosal erosion, congestion, edema, and crypt damage in colonic tissue [ 156 , 157 ].…”

Section: Melatonin Involvement In Dysbiosis-associated Conditions Via...mentioning

confidence: 99%

Melatonin–Microbiome Two-Sided Interaction in Dysbiosis-Associated Conditions

et al. 2022

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Melatonin is a pineal indolamine, allegedly known as a circadian rhythm regulator, and an antioxidative and immunomodulatory molecule. In both experimental and clinical trials, melatonin has been shown to have positive effects in various pathologies, as a modulator of important biochemical pathways including inflammation, oxidative stress, cell injury, apoptosis, and energy metabolism. The gut represents one of melatonin’s most abundant extra pineal sources, with a 400-times-higher concentration than the pineal gland. The importance of the gut microbial community—namely, the gut microbiota, in multiple critical functions of the organism— has been extensively studied throughout time, and its imbalance has been associated with a variety of human pathologies. Recent studies highlight a possible gut microbiota-modulating role of melatonin, with possible implications for the treatment of these pathologies. Consequently, melatonin might prove to be a valuable and versatile therapeutic agent, as it is well known to elicit positive functions on the microbiota in many dysbiosis-associated conditions, such as inflammatory bowel disease, chronodisruption-induced dysbiosis, obesity, and neuropsychiatric disorders. This review intends to lay the basis for a deeper comprehension of melatonin, gut microbiota, and host-health subtle interactions.

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Section: Melatonin Involvement In Dysbiosis-associated Conditions Via...mentioning

confidence: 99%

Melatonin–Microbiome Two-Sided Interaction in Dysbiosis-Associated Conditions

et al. 2022

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“…[19] Numerous studies have revealed that mitochondrial dysfunction plays an important role in UC. [20–23] Consequently, we can further infer that cuproptosis is strongly linked to UC progression. However, there is a lack of knowledge regarding the mechanisms underlying cuproptosis in the progression of UC.…”

Section: Introductionmentioning

confidence: 95%

Identification of 6 cuproptosis-related genes for active ulcerative colitis with both diagnostic and therapeutic values

Zou,

Zhang,

Zhu

et al. 2023

Medicine

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Cuproptosis has been reported to affect a variety of diseases. Therefore, we aimed to examine the role of cuproptosis-related genes in active ulcerative colitis (UC). We acquired 2 datasets of active UC from the Gene Expression Omnibus database and created immune cell infiltrations to research immune cell dysregulation. Based on the cuproptosis gene set and differentially expressed genes (DEGs), we identified the differentially expressed genes of cuproptosis (CuDEGs). We then used 2 machine learning methods to screen hub CuDEGs. Subsequently, we performed validation on additional datasets and investigated the relationship between hub CuDEGs and drug treatments. Thirty-five controls with inactive UC and 90 patients with active UC were obtained from the training sets. A total of 9157 DEGs and 27 CuDEGs were identified, respectively. Immune cell infiltration analysis revealed that patients with active UC exhibited higher levels of activated dendritic cells and neutrophils as well as lower levels of CD8+ T cells, regulatory T cells (Tregs), and macrophage M2. A six-gene cuproptosis signature was identified using machine learning algorithms. We further validated that the 6 hub CuDEGs showed a strong correlation with active UC and acted as cuproptosis-related biomarkers of active UC. Moreover, the expression of ATOX1 was downregulated, and SUMF1, MT1G, ATP7B, FDX1, and LIAS expression was upregulated in the colonic mucosa of active UC patients who responded to golimumab or vedolizumab therapy. With the exception of ATP7B, the expression patterns of hub CuDEGs before and after infliximab treatment of patients with active UC were similar to those of golimumab and vedolizumab. Cuproptosis and active UC have a complex relationship, as illustrated in our study. ATOX1, SUMF1, MT1G, ATP7B, FDX1, and LIAS are cuproptosis-related hub genes of active UC. Our study opens new avenues for investigating UC progression and developing novel therapeutic potential targets for the disease.

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“…The activated M1-type macrophages secrete varieties of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), which can trigger an inflammatory response and attract other inflammatory cells. , It has also been reported that the M1 macrophages interact with TH1/TH17 cells, further aggravating intestinal epithelial damage . Therefore, targeting macrophage inflammation is one of the crucial strategies in the management of IBD. − …”

Section: Introductionmentioning

confidence: 99%

The First Discovery of Marine Polyoxygenated Cembranolides as Potential Agents for the Treatment of Ulcerative Colitis

Cui,

Jin,

Sun

et al. 2024

J. Med. Chem.

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Cembranolides are characteristic metabolites in marine soft corals, with complex structures and widespread biological activities. However, seldom has an intensive pharmacological study been done for these intriguing marine natural products. In this work, systematic chemical investigation was performed on Sinularia pedunculata by HSQC-based small molecule accurate recognition technology (SMART), resulting in the isolation and identification of 31 cembrane-type diterpenoids, including six new ones. In the bioassay, several compounds showed significant anti-inflammatory activities on the inhibition of NO production. The structure−activity relationship (SAR) was comprehensively analyzed, and two most bioactive and less toxic compounds 8 and 9 could inhibit inflammation through suppressing NF-κB and MAPK signaling pathways, and reduce the secretion of inflammatory cytokines. In a mouse model of dextran sodium sulfate (DSS)-induced acute colitis, 8 and 9 exhibited good anti-inflammatory effects and the ability to repair the colon epithelium, giving insight into the application of cembranolides as potential ulcerative colitis (UC) agents.

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Trypsin inhibitor LH011 inhibited DSS-induced mice colitis via alleviating inflammation and oxidative stress

Cited by 8 publications

References 48 publications

Melatonin–Microbiome Two-Sided Interaction in Dysbiosis-Associated Conditions

Melatonin–Microbiome Two-Sided Interaction in Dysbiosis-Associated Conditions

Identification of 6 cuproptosis-related genes for active ulcerative colitis with both diagnostic and therapeutic values

The First Discovery of Marine Polyoxygenated Cembranolides as Potential Agents for the Treatment of Ulcerative Colitis

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