Huangkui capsule alleviates renal tubular epithelial–mesenchymal transition in diabetic nephropathy via inhibiting NLRP3 inflammasome activation and TLR4/NF-κB signaling

Han, Wen-Bei; Ma, Qian; Liu, Yinglu; Wu, Wei; Tu, Ya; Huang, Lu; Long, Yan; Wang, Wenwen; Yee, Hong-Yun; Wan, Zi-Yue; Tang, Renmao; Tang, Haitao; Wan, Yi‐Gang

doi:10.1016/j.phymed.2018.12.021

Cited by 83 publications

(52 citation statements)

References 27 publications

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“…The activation of NLRP3 triggered a cascade process, including ASC and pro-caspase-1 recruitment, caspase-1 activation, and pro-IL-1β being cleavaged into its mature form. Here, the activated NLRP3 inflammasome as an upstream trigger could govern the pathogenesis of tissular inflammatory injuries in psoriasis [51]. Thus, the targeted inhibition of the NLRP3 pathway, and subsequent reducing inflammatory injury might be an effective method of psoriasis treatment.…”

Section: Discussionmentioning

confidence: 99%

Datura Metel L. Ameliorates Imiquimod-Induced Psoriasis-Like Dermatitis and Inhibits Inflammatory Cytokines Production through TLR7/8–MyD88–NF-κB–NLRP3 Inflammasome Pathway

et al. 2019

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Background: Psoriasis is a chronic, immune-mediated inflammatory skin disease, and the inflammatory response plays an important role in its development and progression. Datura metel L. is a traditional Chinese medicine that exhibited a significant therapeutic effect on psoriasis in our previous study due to its remarkable anti-inflammatory effect. Meanwhile, the mechanism underlying its effects on psoriasis is still unclear. Methods: An imiquimod-induced psoriasis-like dermatitis mouse model was constructed to evaluate the protective effect of the effective part of Datura metel L. (EPD), which was verified by evaluations of the Psoriasis Area and Severity Index (PASI) score. Hematoxylin and eosin (H&E) staining, immunohistochemical examination, enzyme-linked immunosorbent assay (ELISA), and Western blot were used to measure the inflammatory cytokines and the protein expression associated with the Toll-like receptor 7– myeloid differentiation primary response gene 88–nuclear Factor-κB–nucleotide-binding oligomerization domain (Nod)-like receptor family pyrin domain-containing 3 (TLR7/8–MyD88–NF-κB–NLRP3) inflammasome pathway. Results: EPD significantly decreased the PASI, reduced epidermal thickness, and decreased the proliferation and differentiation of epidermal cells in psoriasis-like dermatitis C57BL/6 mice induced by imiquimod (IMQ). Furthermore, EPD reduced the infiltration of CD3+ cells to psoriatic lesions, as well as ameliorated the elevations of intercellular adhesion molecule 1 (ICAM-1) and inhibited the production of imiquimod-induced inflammatory cytokines, including IL-1β, IL-2, IL-6, IL-10, IL-12, IL-17, IL-22, IL-23, tumor necrosis factor-α (TNF-α), monocyte chemotactic protein 1 (MCP-1), and interferon-γ (IFN-γ). Besides, EPD decreased the imiquimod-induced expression levels of TLR7, TLR8, TRAF6, MyD88, p-IKKα, p-IKBα, p-NF-κB, NLRP3, apoptosis-associated speck-like protein contained a caspase recruitment domain (ASC), cysteinyl aspartate specific proteinase 1 (caspase-1), and IL-1β. Conclusion: This study demonstrated that EPD exhibited a protective effect on an imiquimod-induced psoriasis mice model by inhibiting the inflammatory response, which might be ascribed to the inhibition of the TLR7/8–MyD88–NF-κb–NLRP3 inflammasome pathway.

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Section: Discussionmentioning

confidence: 99%

Datura Metel L. Ameliorates Imiquimod-Induced Psoriasis-Like Dermatitis and Inhibits Inflammatory Cytokines Production through TLR7/8–MyD88–NF-κB–NLRP3 Inflammasome Pathway

et al. 2019

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“…All procedures involving animals in this study were approved by the Animal Ethics Committee of Nanjing University Medical School (qualified number: SYXK2014-0052). The feeding conditions of rats were previously described (Han et al, 2019). All rats were divided into four groups, according to a random number table, as follows: five, seven, seven, and seven rats in the Normal, Model, TFA, and FEB groups, respectively.…”

Section: Animals and Treatmentsmentioning

confidence: 99%

“…Clinical evidence in China has suggested that HKC (at the safe and effective dose of 7.5 g/kg/day) can reduce urinary albumin in CKD. Our previous studies proved that HKC and its bioactive component hyperoside can alleviate tubular injury in diabetic nephropathy by regulating inflammatory signaling (Han et al, 2019) and in D-galactose-induced aging kidney by adjusting autophagy (Liu et al, 2018). Despite this evidence, important issues remain unresolved in terms of the therapeutic effects of TFA on CRF.…”

Section: Introductionmentioning

confidence: 99%

Total Flavones of Abelmoschus manihot Remodels Gut Microbiota and Inhibits Microinflammation in Chronic Renal Failure Progression by Targeting Autophagy-Mediated Macrophage Polarization

Fang

Sun

et al. 2020

Front. Pharmacol.

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oxidase, serine racemase, D-serine, and L-serine; inhibited microinflammation, including interleukin 1b (IL1b), tumor necrosis factor-a, and nuclear factor-kB; and modulated macrophage polarization, including markers of M1/M2 macrophages. More importantly, TFA and FEB reversed the expression of beclin1 (BECN1) and phosphorylation of p62 protein and light chain 3 (LC3) conversion in the kidneys by activating the adenosine monophosphate-activated protein kinase-sirtuin 1 (AMPK-SIRT1) signaling. Further, TFA and FEB have similar effects on macrophage polarization and autophagy and its related signaling in vitro. Conclusion: In this study, we demonstrated that TFA, similar to FEB, exerts its renoprotective effects partially by therapeutically remodeling gut microbiota dysbiosis and inhibiting intestinal metabolite-derived microinflammation. This is achieved by adjusting autophagy-mediated macrophage polarization through AMPK-SIRT1 signaling. These findings provide more accurate information on the role of TFA in delaying CRF progression.

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“…In addition, NLRP3 was also reported to participate in the regulation of EMT in BLM-induced pulmonary fibrosis 18 . Besides, Huangkui capsule was reported to alleviate renal tubular EMT in diabetic nephropathy via inhibiting NLRP3 inflammasome activation 19 . LFG-500 suppressed EMT in human lung adenocarcinoma cells by inhibiting NLRP3 in inflammatory microenvironment 20 .…”

Section: Introductionmentioning

confidence: 99%

Scutellarin ameliorates pulmonary fibrosis through inhibiting NF-κB/NLRP3-mediated epithelial–mesenchymal transition and inflammation

et al. 2020

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Idiopathic pulmonary fibrosis (IPF) is featured with inflammation and extensive lung remodeling caused by overloaded deposition of extracellular matrix. Scutellarin is the major effective ingredient of breviscapine and its anti-inflammation efficacy has been reported before. Nevertheless, the impact of scutellarin on IPF and the downstream molecular mechanism remain unclear. In this study, scutellarin suppressed BLM-induced inflammation via NF-κB/NLRP3 pathway both in vivo and in vitro. BLM significantly elevated p-p65/p65 ratio, IκBα degradation, and levels of NLRP3, caspase-1, caspase-11, ASC, GSDMDNterm, IL-1β, and IL-18, while scutellarin reversed the above alterations except for that of caspase-11. Scutellarin inhibited BLM-induced epithelial–mesenchymal transition (EMT) process in vivo and in vitro. The expression levels of EMT-related markers, including fibronectin, vimentin, N-cadherin, matrix metalloproteinase 2 (MMP-2) and MMP-9, were increased in BLM group, and suppressed by scutellarin. The expression level of E-cadherin showed the opposite changes. However, overexpression of NLRP3 eliminated the anti-inflammation and anti-EMT functions of scutellarin in vitro. In conclusion, scutellarin suppressed inflammation and EMT in BLM-induced pulmonary fibrosis through NF-κB/NLRP3 signaling.

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Huangkui capsule alleviates renal tubular epithelial–mesenchymal transition in diabetic nephropathy via inhibiting NLRP3 inflammasome activation and TLR4/NF-κB signaling

Cited by 83 publications

References 27 publications

Datura Metel L. Ameliorates Imiquimod-Induced Psoriasis-Like Dermatitis and Inhibits Inflammatory Cytokines Production through TLR7/8–MyD88–NF-κB–NLRP3 Inflammasome Pathway

Datura Metel L. Ameliorates Imiquimod-Induced Psoriasis-Like Dermatitis and Inhibits Inflammatory Cytokines Production through TLR7/8–MyD88–NF-κB–NLRP3 Inflammasome Pathway

Total Flavones of Abelmoschus manihot Remodels Gut Microbiota and Inhibits Microinflammation in Chronic Renal Failure Progression by Targeting Autophagy-Mediated Macrophage Polarization

Scutellarin ameliorates pulmonary fibrosis through inhibiting NF-κB/NLRP3-mediated epithelial–mesenchymal transition and inflammation

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