Recent advances in the pharmacological applications and liver toxicity of triptolide

Cui, Dai; Xu, Ding‐Qiao; Yue, Shi‐Jun; Yan, Chao-Qun; Liu, Wenjuan; Fu, Ruonong; Ma, Wenfu; Tang, Yuping

doi:10.1016/j.cbi.2023.110651

Cited by 11 publications

(3 citation statements)

References 101 publications

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“…Currently, there are conflicting reports on the toxicity and therapeutic effects of TP on the kidney [10,27,28]. TP showed renoprotection effects against metronidazole-induced injury in zebrafish, puromycin-induced nephropathy, PM 2.5-induced podocyte injury, and deoxycorticosterone acetate-salt hypertension-induced renal injury in mice subjected to uninephrectomy [13,29,30].…”

Section: Experimental Biology and Medicinementioning

confidence: 99%

Triptolide decreases podocytes permeability by regulating TET2-mediated hydroxymethylation of ZO-1

Tang,

Jiang,

Cao

et al. 2024

Exp. Biol. Med.

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Podocyte injury or dysfunction can lead to proteinuria and glomerulosclerosis. Zonula occludens 1 (ZO-1) is a tight junction protein which connects slit diaphragm (SD) proteins to the actin cytoskeleton. Previous studies have shown that the expression of ZO-1 is decreased in chronic kidney disease (CKD). Thus, elucidation of the regulation mechanism of ZO-1 has considerable clinical importance. Triptolide (TP) has been reported to exert a strong antiproteinuric effect by inhibiting podocyte epithelial mesenchymal transition (EMT) and inflammatory response. However, the underlying mechanisms are still unclear. We found that TP upregulates ZO-1 expression and increases the fluorescence intensity of ZO-1 in a puromycin aminonucleoside (PAN)-induced podocyte injury model. Permeablity assay showed TP decreases podocyte permeability in PAN-treated podocyte. TP also upregulates the DNA demethylase TET2. Our results showed that treatment with the DNA methyltransferase inhibitors 5-azacytidine (5-AzaC) and RG108 significantly increased ZO-1 expression in PAN-treated podocytes. Methylated DNA immunoprecipitation (MeDIP) and hydroxymethylated DNA immunoprecipitation (hMeDIP) results showed that TP regulates the methylation status of the ZO-1 promoter. Knockdown of TET2 decreased ZO-1 expression and increased methylation of its promoter, resulting in the increase of podocyte permeability. Altogether, these results indicate that TP upregulates the expression of ZO-1 and decreases podocyte permeability through TET2-mediated 5 mC demethylation. These findings suggest that TP may alleviate podocyte permeability through TET2-mediated hydroxymethylation of ZO-1.

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Section: Experimental Biology and Medicinementioning

confidence: 99%

Triptolide decreases podocytes permeability by regulating TET2-mediated hydroxymethylation of ZO-1

Tang,

Jiang,

Cao

et al. 2024

Exp. Biol. Med.

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“…For instance, TP is a pharmacologically active ingredient of Tripterygium wilfordii, but its clinical application is limited due to a restricted therapy window and multi-organ toxicity. Triptolide can disrupt a number of cellular structures and functions, including membrane injury, mitochondrial disruption, metabolic malfunction (Xi et al, 2017;Cui et al, 2023). Therefore, reducing the toxicity of terpenoids and increasing their bioavailability through structural modification are very important for further application of terpenoids.…”

Section: Terpenoidsmentioning

confidence: 99%

The protective effect of natural medicines in rheumatoid arthritis via inhibit angiogenesis

Gao,

Song,

Chen

et al. 2024

Front. Pharmacol.

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Rheumatoid arthritis is a chronic immunological disease leading to the progressive bone and joint destruction. Angiogenesis, accompanied by synovial hyperplasia and inflammation underlies joint destruction. Delaying or even blocking synovial angiogenesis has emerged as an important target of RA treatment. Natural medicines has a long history of treating RA, and numerous reports have suggested that natural medicines have a strong inhibitory activity on synovial angiogenesis, thereby improving the progression of RA. Natural medicines could regulate the following signaling pathways: HIF/VEGF/ANG, PI3K/Akt pathway, MAPKs pathway, NF-κB pathway, PPARγ pathway, JAK2/STAT3 pathway, etc., thereby inhibiting angiogenesis. Tripterygium wilfordii Hook. f. (TwHF), sinomenine, and total glucoside of Paeonia lactiflora Pall. Are currently the most representative of all natural products worthy of development and utilization. In this paper, the main factors affecting angiogenesis were discussed and different types of natural medicines that inhibit angiogenesis were systematically summarized. Their specific anti-angiogenesis mechanisms are also reviewed which aiming to provide new perspective and options for the management of RA by targeting angiogenesis.

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“…RA is a chronic inflammatory disease characterized by joint inflammation, hyperplasia and swelling, the production of autoantibodies, and bone destruction [58]. Studies have shown that the severity of RA is associated with a large number of CD4 + CD28 − T cells [43,48,59].…”

Section: Ramentioning

confidence: 99%

The Role of NKG2D and Its Ligands in Autoimmune Diseases: New Targets for Immunotherapy

Wei,

Xiang,

Zou

2023

IJMS

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Natural killer (NK) cells and CD8+ T cells can clear infected and transformed cells and generate tolerance to themselves, which also prevents autoimmune diseases. Natural killer group 2 member D (NKG2D) is an important activating immune receptor that is expressed on NK cells, CD8+ T cells, γδ T cells, and a very small percentage of CD4+ T cells. In contrast, the NKG2D ligand (NKG2D-L) is generally not expressed on normal cells but is overexpressed under stress. Thus, the inappropriate expression of NKG2D-L leads to the activation of self-reactive effector cells, which can trigger or exacerbate autoimmunity. In this review, we discuss the role of NKG2D and NKG2D-L in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), type I diabetes (T1DM), inflammatory bowel disease (IBD), and celiac disease (CeD). The data suggest that NKG2D and NKG2D-L play a pathogenic role in some autoimmune diseases. Therefore, the development of strategies to block the interaction of NKG2D and NKG2D-L may have therapeutic effects in some autoimmune diseases.

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Recent advances in the pharmacological applications and liver toxicity of triptolide

Cited by 11 publications

References 101 publications

Triptolide decreases podocytes permeability by regulating TET2-mediated hydroxymethylation of ZO-1

Triptolide decreases podocytes permeability by regulating TET2-mediated hydroxymethylation of ZO-1

The protective effect of natural medicines in rheumatoid arthritis via inhibit angiogenesis

The Role of NKG2D and Its Ligands in Autoimmune Diseases: New Targets for Immunotherapy

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