Triptolide and its expanding multiple pharmacological functions

Liu, Qiuyan

doi:10.1016/j.intimp.2011.01.012

Cited by 303 publications

(212 citation statements)

References 75 publications

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“…However, the toxicity and water-insolubility of triptolide reduce the clinical feasibility of this drug. Triptolide derivates have been designed and currently are being tested for cancer treatments (reviewed in [157]). …”

Section: Therapeutic Potential Of Hspmentioning

confidence: 99%

Heat Shock Protein 70: Roles in Multiple Sclerosis

Mansilla

Montalbán

Espejo

2012

Mol Med

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Heat shock proteins (HSP) have long been considered intracellular chaperones that possess housekeeping and cytoprotective functions. Consequently, HSP overexpression was proposed as a potential therapy for neurodegenerative diseases characterized by the accumulation or aggregation of abnormal proteins. Recently, the discovery that cells release HSP with the capacity to trigger proinflammatory as well as immunoregulatory responses has focused attention on investigating the role of HSP in chronic inflammatory autoimmune diseases such as multiple sclerosis (MS). To date, the most relevant HSP is the inducible Hsp70, which exhibits both cytoprotectant and immunoregulatory functions. Several studies have presented contradictory evidence concerning the involvement of Hsp70 in MS or experimental autoimmune encephalomyelitis (EAE), the MS animal model. In this review, we dissect the functions of Hsp70 and discuss the controversial data concerning the role of Hsp70 in MS and EAE.

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Section: Therapeutic Potential Of Hspmentioning

confidence: 99%

Heat Shock Protein 70: Roles in Multiple Sclerosis

Mansilla

Montalbán

Espejo

2012

Mol Med

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“…using Ad5-I kappa B alpha Delta N; MG132 [28]) will need to be performed in the future. This will be important as in tumor cells, TPL could in contrast block TNF-ainduced activation of NF-jB, resulting in enhanced apoptosis induced by TNF-a [29].…”

Section: Discussionmentioning

confidence: 99%

Triptolide exhibits anti-inflammatory, anti-catabolic as well as anabolic effects and suppresses TLR expression and MAPK activity in IL-1β treated human intervertebral disc cells

et al. 2011

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Introduction Increased levels of proinflammatory cytokines seem to play a pivotal role in the development of back pain in a subpopulation of patients with degenerative intervertebral disc (IVD) disease. As current treatment options are mostly limited to surgical interventions or conservative treatment, anti-inflammatory substances might offer a novel, more target-orientated therapeutic approach. Triptolide (TPL), a natural substance found in the Chinese medicinal herb Tripterygium wilfordii Hook, has been demonstrated to possess anti-inflammatory effects in various cells, but no studies exist so far for the IVD. Therefore, the aim of this study was to determine the effects of TPL on human IVD cells by analyzing changes in gene expression and underlying molecular mechanisms. Materials and methods In order to investigate the antiinflammatory, anabolic and anti-catabolic effect of TPL, dose-dependency experiments (n = 5) and time course experiments (n = 5) were performed on IL-1b prestimulated human IVD cells and changes in gene expression of IL-6/-8, TNF-a, PGE2S, MMP1/2/3/13, aggrecan and collagen-I/-II were analyzed by real-time RT-PCR. The molecular mechanisms underlying the effects observed upon TPL treatment were investigated by analyzing involvement of Toll-like receptors TLR2/4 (real-time RT-PCR, n = 5), NF-jB, MAP kinases p38, ERK and JNK (immunoblotting and immunocytochemistry, n = 4) as well as RNA polymerase II (immunoblotting, n = 3). Results Results showed that 50 nM TPL exhibited an anti-inflammatory, anti-catabolic and anabolic effect on the mRNA level for IL-6/-8, PGE2S, MMP1/2/3/13, aggrecan, collagen-II and TLR2/4, with most pronounced changes after 18 h for proinflammatory cytokines and MMPs or 30 h for TLRs and matrix proteins. However, we also observed an up-regulation of TNF-a at higher concentrations. The effects of TPL did not seem to be mediated via an inhibition of NF-jB or a decrease of RNA polymerase II levels, but TPL influenced activity of MAP kinases p38 and ERK (but not JNK) and expression of TLR2/4. Conclusions In conclusion, TPL may possess promising potential for the treatment of inflammation-related discogenic back pain in vitro, but its analgetic effect will need to be confirmed in an appropriate in vivo animal model.

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“…It was suggested that triptolide may use multiple signaling pathways, some of which involve p53 in cells with wild-type p53, growth arrest and induction of apoptosis (Kiviharju et al, 2002). Clinical and experimental studies have demonstrated that triptolide has anti-inflammatory and immunosuppressive activities, and effectively prolongs allograft survival in organ transplantation including bone marrow, cardiac, renal and skin transplantation (Liu, 2011). PG490-88Na (Pharmagenesis Inc.), a water-soluble prodrug of triptolide (14-succinyl sodium salt) that is converted into triptolide in the serum, has been elucidated as a new immunosuppressant (Fidler et al, 2003).…”

Section: Triptolidementioning

confidence: 99%

“…However, the safety and side effects of triptolide for PC therapy need to be further elucidated. Further development of triptolide derivatives may produce promising anticancer drug candidate (Liu, 2011).…”

Section: Triptolidementioning

confidence: 99%