A comprehensive review on celastrol, triptolide and triptonide: Insights on their pharmacological activity, toxicity, combination therapy, new dosage form and novel drug delivery routes

Song, Jian; He, Guannan; Dai, Long

doi:10.1016/j.biopha.2023.114705

Cited by 38 publications

(7 citation statements)

References 141 publications

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“…In addition, there was no significant change in body weight (Figure 1A), food intake (Figure 1B), and urine indicators (Table 1) between HBHGE and vehicle groups. However, the brain organ coefficients of male rats in the HBHGE group were significantly higher than those in the vehicle group ( p < 0.05), which might be related to some components of HBHGE like as triptolide and celastrol according to the previous study (Cui et al, 2022;Li & Hao, 2019;Song et al, 2023).…”

Section: Discussionmentioning

confidence: 77%

Subchronic toxicity evaluation of Huobahuagen extract and plasma metabolic profiling analysis combined with conventional pathology methods

Long,

He,

et al. 2023

J of Applied Toxicology

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Huobahua, namely, Tripterygium hypoglaucum (Levl.) Hutch, known as a traditional Chinese herbal medicine, especially its underground parts, has been widely developed into several Tripterygium agents for the treatment of rheumatoid arthritis and other autoimmune diseases. It has sparked wide public concern about its safety, such as multi‐organ toxicity. However, the toxic characteristics and damage mechanism of Huobahuagen extract (HBHGE) remain unclear. In the present study, subchronic oral toxicity study of HBHGE (10.0 g crude drug/kg/day for 12 weeks) was performed in male rats. Hematological, serum biochemical, and histopathological parameters, urinalysis, and plasma metabolic profiling were assessed. The single‐dose subchronic toxicity results related to HBHGE exhibited obvious toxicity to the testis and epididymis of male rats. Furthermore, plasma metabolomics analysis suggested that a series of metabolic disorders were induced by oral administration of HBHGE, mainly focusing on amino acid (glutamate, phenylalanine, and tryptophan) metabolisms, pyrimidine metabolism, glutathione metabolism, and steroid hormone biosynthesis. Moreover, it appeared that serum testosterone in male rats treated with HBHGE for 12 weeks, decreased significantly, and was susceptible to the toxic effects of HBHGE. Taken together, conventional pathology and plasma metabolomics for preliminarily exploring subchronic toxicity and underlying mechanism can provide useful information about the reduction of toxic risks from HBHGE and new insights into the development of detoxification preparations.

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Section: Discussionmentioning

confidence: 77%

Subchronic toxicity evaluation of Huobahuagen extract and plasma metabolic profiling analysis combined with conventional pathology methods

Long,

He,

et al. 2023

J of Applied Toxicology

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“…In the core potential toxic compounds, Triptonide was the unique compounds in TwHF caused KI. Triptonide, a diterpenoid whose structure was similar to Triptolide, had been confirmed to have nephrotoxicity [56,57] and Ge et al found Triptonide might cause toxic effects through binding to PIK3CA [58] that was correlation with KEGG pathways analysis results. Other core potential toxic compounds such as kaempferol, Isoxanthohumol, N-benzoylphenylalanylphenylalinol acetate with isolariciresinol existed not only in TwHF but also in other TCM.…”

Section: Discussionmentioning

confidence: 99%

Tripterygium wilfordii Hook.f induced kidney injury through mediating inflammation via PI3K-Akt/HIF-1/TNF signaling pathway: A study of network toxicology and molecular docking

Yang,

Wang,

et al. 2024

Medicine

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We intend to explore potential mechanisms of Tripterygium wilfordii Hook.f (TwHF) induced kidney injury (KI) using the methods of network toxicology and molecular docking. We determined TwHF potential compounds with its targets and KI targets, obtained the TwHF induced KI targets after intersecting targets of TwHF and KI. Then we conducted protein-protein interaction (PPI) network, gene expression analysis, gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis to explore the mechanism of TwHF-induced KI. Finally we conducted molecular docking to verify the core toxic compounds and the targets. We obtained 12 TwHF toxic compounds and 62 TwHF-induced KI targets. PPI network, gene expression analysis and GO function enrichment analysis unveiled the key biological process and suggested the mechanism of TwHF-induced KI might be associated with inflammation, immune response, hypoxia as well as oxidative stress. KEGG pathway enrichment analysis indicated PI3K-Akt signaling pathway, HIF-1 signaling pathway and TNF signaling pathway were key signaling pathways of TwHF induced KI. Molecular docking showed that the binding energy of core targets and toxic compounds was all less than −6.5 kcal/mol that verified the screening ability of network pharmacology and provided evidence for modifying TwHF toxic compounds structure. Through the study, we unveiled the mechanism of TwHF induce KI that TwHF might activate PI3K-Akt signaling pathway as well as TNF signaling pathway to progress renal inflammation, mediate hypoxia via HIF-1 signaling pathway to accelerate inflammatory processes, and also provided a theoretical basis for modifying TwHF toxic compounds structure as well as supported the follow-up research.

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“…Disulfiram, a therapeutic agent targeting GSDMD, has rare side effects, including papular acne, pruritus, exfoliative dermatitis, myopathy, and cardiomyopathy [ 162 , 163 , 164 ]. Celastrol, an inhibitor of the ROS-NF-κB-NLRP3 inflammasome axis, may induce hepatotoxicity, ototoxicity, or cardiotoxicity [ 165 ]. The rare side effects of sulforaphane include dyspepsia and gastric upset [ 166 ].…”

Section: Therapeutic Potential By Targeting the Nlrp3 Inflammasomementioning

confidence: 99%

The NLRP3 Inflammasome as a Pathogenic Player Showing Therapeutic Potential in Rheumatoid Arthritis and Its Comorbidities: A Narrative Review

Chen,

Tang,

Chen

2024

IJMS

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Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by chronic synovitis and the progressive destruction of cartilage and bone. RA is commonly accompanied by extra-articular comorbidities. The pathogenesis of RA and its comorbidities is complex and not completely elucidated. The assembly of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activates caspase-1, which induces the maturation of interleukin (IL)-1β and IL-18 and leads to the cleavage of gasdermin D with promoting pyroptosis. Accumulative evidence indicates the pathogenic role of NLRP3 inflammasome signaling in RA and its comorbidities, including atherosclerotic cardiovascular disease, osteoporosis, and interstitial lung diseases. Although the available therapeutic agents are effective for RA treatment, their high cost and increased infection rate are causes for concern. Recent evidence revealed the components of the NLRP3 inflammasome as potential therapeutic targets in RA and its comorbidities. In this review, we searched the MEDLINE database using the PubMed interface and reviewed English-language literature on the NLRP3 inflammasome in RA and its comorbidities from 2000 to 2023. The current evidence reveals that the NLRP3 inflammasome contributes to the pathogenesis of RA and its comorbidities. Consequently, the components of the NLRP3 inflammasome signaling pathway represent promising therapeutic targets, and ongoing research might lead to the development of new, effective treatments for RA and its comorbidities.

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A comprehensive review on celastrol, triptolide and triptonide: Insights on their pharmacological activity, toxicity, combination therapy, new dosage form and novel drug delivery routes

Cited by 38 publications

References 141 publications

Subchronic toxicity evaluation of Huobahuagen extract and plasma metabolic profiling analysis combined with conventional pathology methods

Subchronic toxicity evaluation of Huobahuagen extract and plasma metabolic profiling analysis combined with conventional pathology methods

Tripterygium wilfordii Hook.f induced kidney injury through mediating inflammation via PI3K-Akt/HIF-1/TNF signaling pathway: A study of network toxicology and molecular docking

The NLRP3 Inflammasome as a Pathogenic Player Showing Therapeutic Potential in Rheumatoid Arthritis and Its Comorbidities: A Narrative Review

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