8-Oxypalmatine, a novel oxidative metabolite of palmatine, exhibits superior anti-colitis effect via regulating Nrf2 and NLRP3 inflammasome

Cheng, Juanjuan; Ma, Xingdong; Zhang, Haitao; Wu, Xiaoyan; Li, Minhua; Ai, Gaoxiang; Zhan, Renya; Xie, Jianhui; Su, Ziren; Huang, Xiaoqi

doi:10.1016/j.biopha.2022.113335

Cited by 14 publications

(6 citation statements)

References 60 publications

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“…Although scarce research proved that PAL was associated with NAMPT, TLR2, or CCR1, it was reported to inhibit NLRP3 inflammasome in inflammatory disorders. , The metabolite of PAL, 8-oxypalmatine, also exerted inhibitory effect on NLRP3 inflammasome . The pulmonary edema is attributed to the damage of epithelial–endothelial barrier, which enhances permeability, and the infiltration of inflammatory cell.…”

Section: Discussionmentioning

confidence: 99%

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Palmatine Attenuated Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting M1 Phenotype Macrophage Polarization via NAMPT/TLR2/CCR1 Signaling

Wang,

Han

et al. 2024

J. Agric. Food Chem.

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The present work was conducted to research the potential mechanism of palmatine (PAL) on lipopolysaccharide (LPS)-caused acute lung injury (ALI). Network pharmacology and bioinformatic analyses were carried out. Mice were intragastrically treated with PAL and intratracheally stimulated with LPS. LPS-induced RAW264.7 cells were employed for the in vitro model. The MPO activity, W/D ratio, neutrophils, total cell number in BALF, and histopathological alteration were examined. The levels of TNF-α, IL-1β, IL-6, IL-18, IL-4, and IL-10 in serum, BALF, and supernatant were examined by ELISA. The mRNA expressions of iNOS, CD68, Arg1, Ym1, and CD206 and protein expressions of NAMPT, TLR2, CCR1, and NLRP3 inflammasome were detected by PCR, WB, and immunofluorescence. The NAMPT inhibitor FK866, TLR2 inhibitor C29, CCR1 inhibitor BX471, NAMPT-overexpression (OE) plasmid, and TLR2-OE plasmid were used for mechanism research. As a result, PAL relieved the symptoms of ALI. PAL inhibited M1 phenotype indices and promoted M2 phenotype indices in both LPS-induced mice and RAW264.7 cells. PAL also inhibited the expressions of NAMPT, TLR2, CCR1, and NLRP3 inflammasome. The treatments with FK866, NAMPT-OE plasmid, C29, TLR2-OE plasmid, and BX471 proved that PAL exerted its effect via NAMPT/TLR2/CCR1. Molecular docking suggested that PAL might combine with NAMPT. In conclusion, PAL ameliorated LPS-induced ALI by inhibiting M1 phenotype macrophage polarization via NAMPT/TLR2/CCR1 signaling.

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Section: Discussionmentioning

confidence: 99%

“…14,15 The metabolite of PAL, 8-oxypalmatine, also exerted inhibitory effect on NLRP3 inflammasome. 16 The pulmonary edema is attributed to the damage of epithelial−endothelial barrier, which enhances permeability, and the infiltration of inflammatory cell. The recruitment of immune cells amplifies the inflammatory cascade.…”

Section: Discussionmentioning

confidence: 99%

Palmatine Attenuated Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting M1 Phenotype Macrophage Polarization via NAMPT/TLR2/CCR1 Signaling

Wang,

Han

et al. 2024

J. Agric. Food Chem.

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“…23,24 Palmatine can attenuate colon damage by regulating tryptophan metabolism, intestinal microbes, and NLRP3 inflammasome. [25][26][27] Rutin can induce NrF2-mediated antioxidant response, thereby alleviating DSS-induced colitis. 28 The infiltration of diffuse inflammatory cells in the intestinal laminae propria and elevated TNF-α and IL-6 levels, which promote macrophage and effector T cell infiltration, respectively, are primary inducers of UC.…”

Section: Discussionmentioning

confidence: 99%

Investigating Molecular Mechanisms Underlying the Therapeutic Effects of Zuo Jin Pill in Ulcerative Colitis: A Combined Approach of Network Pharmacology and Experimental Validation

Xiao,

Wu,

Zhan

et al. 2024

Natural Product Communications

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Objective: The Zuo Jin pill (ZJP), a classic formula for treating gastrointestinal diseases, has demonstrated good efficacy in the treatment of ulcerative colitis (UC). In this study, we aimed to elucidate the mechanism of action of ZJP in UC through network pharmacology and experimental validation. Methods: Bioactive compounds and targets of ZJP, along with UC-related targets, were retrieved from public databases. The intersecting targets of ZJP and UC were visualized using a Venn diagram. Protein–protein interactions and complex target networks were established using Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to enrich the biological functions and pathways of potential targets and to establish a biological process-target-pathway network. Relevant pathways were screened based on literature review and node size, and the interactions between ZJP and UC as well as hub target proteins were verified through animal experiments. Results: The findings suggested that STAT3, AKT1, EGFR, PIK3R1, and various cancer pathways exhibited potential as pivotal targets and biological processes contributing to the therapeutic efficacy of ZJP in UC. These targets were intricately associated with molecular functions, drug response, protein autophosphorylation, and protein kinase binding. Subsequent experimental intervention using ZJP on dextran sulfate sodium-induced UC mice revealed that its mode of action may involve inhibiting the PI3K/AKT/mTOR signaling pathway, mitigating intestinal mucosal inflammation, and modulating apoptosis in intestinal epithelial cells. Conclusions: The findings suggested that STAT3, AKT1, EGFR, PIK3R1, and various cancer pathways exhibited potential as pivotal targets and biological processes contributing to the therapeutic efficacy of ZJP in UC. These targets were associated with drug response, protein autophosphorylation, and protein kinase binding. Further experiments revealed that its mode of action may involve inhibiting the PI3K/AKT/mTOR signaling pathway, mitigating intestinal mucosal inflammation, and modulating apoptosis in intestinal epithelial cells.

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“…Cheng et al [ 57 ], during an in vivo study, comparatively investigated the potential effect and mechanism of 8-oxypalmatine (OPAL) and palmatine (PAL) in a DSS-induced Balb/c mice model of colitis. OPAL is a metabolite derived from PAL, an alkaloid from Fibraureae caulis Pierre.…”

Section: Phytochemicals Targeting Nrf2 Pathwaysmentioning

confidence: 99%

Effects of Medicinal Plants and Phytochemicals in Nrf2 Pathways during Inflammatory Bowel Diseases and Related Colorectal Cancer: A Comprehensive Review

et al. 2023

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Inflammatory bowel diseases (IBDs) are related to nuclear factor erythroid 2-related factor 2 (Nrf2) dysregulation. In vitro and in vivo studies using phytocompounds as modulators of the Nrf2 signaling in IBD have already been published. However, no existing review emphasizes the whole scenario for the potential of plants and phytocompounds as regulators of Nrf2 in IBD models and colitis-associated colorectal carcinogenesis. For these reasons, this study aimed to build a review that could fill this void. The PubMed, EMBASE, COCHRANE, and Google Scholar databases were searched. The literature review showed that medicinal plants and phytochemicals regulated the Nrf2 on IBD and IBD-associated colorectal cancer by amplifying the expression of the Nrf2-mediated phase II detoxifying enzymes and diminishing NF-κB-related inflammation. These effects improve the bowel environment, mucosal barrier, colon, and crypt disruption, reduce ulceration and microbial translocation, and consequently, reduce the disease activity index (DAI). Moreover, the modulation of Nrf2 can regulate various genes involved in cellular redox, protein degradation, DNA repair, xenobiotic metabolism, and apoptosis, contributing to the prevention of colorectal cancer.

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8-Oxypalmatine, a novel oxidative metabolite of palmatine, exhibits superior anti-colitis effect via regulating Nrf2 and NLRP3 inflammasome

Cited by 14 publications

References 60 publications

Palmatine Attenuated Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting M1 Phenotype Macrophage Polarization via NAMPT/TLR2/CCR1 Signaling

Palmatine Attenuated Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting M1 Phenotype Macrophage Polarization via NAMPT/TLR2/CCR1 Signaling

Investigating Molecular Mechanisms Underlying the Therapeutic Effects of Zuo Jin Pill in Ulcerative Colitis: A Combined Approach of Network Pharmacology and Experimental Validation

Effects of Medicinal Plants and Phytochemicals in Nrf2 Pathways during Inflammatory Bowel Diseases and Related Colorectal Cancer: A Comprehensive Review

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