Triptolide alters barrier function in renal proximal tubular cells in rats

Sun, Lixin; Li, Han; Huang, Xin; Wang, Tao; Zhang, Shuang; Yang, Jing; Huang, Shan; Mei, Huifang; Jiang, Zhenzhou; Zhang, Luyong

doi:10.1016/j.toxlet.2013.08.014

Cited by 37 publications

(18 citation statements)

References 18 publications

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“…f. possesses multiple pharmacological activities, including anti-inflammatory ( Wang et al, 2014c ), anti-fertility ( Li et al, 2015 ), anti-cystogenesis, and anticancer activities ( Li et al, 2015 ). However, triptolide has a narrow therapeutic window, and its clinical applications are limited due to its severe toxicities, including hepatotoxicity ( Li X. et al, 2014 ), nephrotoxicity ( Sun et al, 2013 ), immunotoxicity ( Wang et al, 2014a ), and developmental and reproductive toxicities ( Ni et al, 2008 ; Ma et al, 2015 ). Among the adverse effects of triptolide, hepatotoxicity is non-negligible and has a high incidence.…”

Section: Introductionmentioning

confidence: 99%

Sex-Related Differences of Lipid Metabolism Induced by Triptolide: The Possible Role of the LXRα/SREBP-1 Signaling Pathway

Jiang

Huang

et al. 2016

Front. Pharmacol.

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Triptolide, a diterpenoid isolated from the plant Tripterygium wilfordii Hook. f., exerts a unique bioactive spectrum of anti-inflammatory and anticancer activities. However, triptolide’s clinical applications are limited due to its severe toxicities. Fatty liver toxicity occurs in response to triptolide, and this toxic response significantly differs between males and females. This report investigated the pathogenesis underlying the sex-related differences in the dyslipidosis induced by triptolide in rats. Wistar rats were administered 0, 150, 300, or 450 μg triptolide/kg/day by gavage for 28 days. Ultrastructural examination revealed that more lipid droplets were present in female triptolide-treated rats than in male triptolide-treated rats. Furthermore, liver triglyceride, total bile acid and free fatty acid levels were significantly increased in female rats in the 300 and 450 μg/kg dose groups. The expression of liver X receptor α (LXRα) and its target genes, cholesterol 7α-hydroxylase (CYP7A1) and Sterol regulatory element-binding transcription factor 1(SREBP-1), increased following triptolide treatment in both male and female rats; however, the female rats were more sensitive to triptolide than the male rats. In addition, the expression of acetyl-CoA carboxylase 1(ACC1), a target gene of SREBP-1, increased in the female rats treated with 450 μg triptolide/kg/day, and ACC1 expression contributed to the sex-related differences in the triptolide-induced dysfunction of lipid metabolism. Our results demonstrate that the sex-related differences in LXR/SREBP-1-mediated regulation of gene expression in rats are responsible for the sex-related differences in lipid metabolism induced by triptolide, which likely underlie the sex-related differences in triptolide hepatotoxicity. This study will be important for predicting sex-related effects on the pharmacokinetics and toxicity of triptolide and for improving its safety.

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Section: Introductionmentioning

confidence: 99%

Sex-Related Differences of Lipid Metabolism Induced by Triptolide: The Possible Role of the LXRα/SREBP-1 Signaling Pathway

Jiang

Huang

et al. 2016

Front. Pharmacol.

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“…Triptolide (TPL) is diterpenoid extracted from the plant, Tripterygium wilfordii Hook F (TWHF), which is a traditional Chinese medicinal herb (10). TPL has been shown to possess a unique and wide bioactivity, including immunosuppressive, anti-fertility and anti-cystogenesis activities (11). Recent studies have revealed that TPL is effective against a broad range of cancer types, including lung cancer (12,13), breast cancer (14,15), colon cancer (16), gastric cancer (15) and pancreatic cancer (17).…”

Section: Introductionmentioning

confidence: 99%

Triptolide inhibits tumor growth by induction of cellular senescence

Zhang

Tian

et al. 2016

Oncology Reports

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Cellular senescence, an irreversible growth arrest of cells, is involved in protection against cancer. Triptolide (TPL) plays an important role in immunosuppressive, anti-fertility, anti-cystogenesis and anticancer activities. However, effect and mechanism of TPL on cellular senescence-associated antitumor is rarely reported. Herein HepG2 cells were used to explore the effect of TPL on tumor growth and cellular senescence. We showed that TPL inhibited tumor cell proliferation and growth in vitro and in vivo, accelerated cellular senescence and arrested cells at G0/G1 phase. We further demonstrated that TPL accelerated HepG2 cell senescence by regulating the AKT pathway. In addition, TPL could also enhance cellular senescence and inhibit tumor growth by negatively regulating human telomerase reverse transcriptase (hTERT) signaling pathway. These findings reveal a regulatory mechanism of TPL on cellular senescence, indicating that TPL promotes HepG2 cell senescence through AKT pathway and hTERT pathway simultaneously. Altogether, TPL-induced senescence can be regarded as a promising strategy for anticancer therapy and drug development.

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“…Triptolide is a diterpenoid isolated from the plant Tripterygium wilfordii Hook F, which is a member of the Celastraceae family. Triptolide has been shown to display a unique bioactive spectrum of immunosuppressive, anti-fertility and anticystogenesis activities [8] . Recent studies of triptolide have revealed many properties relevant to its anti-inflammatory and anticancer activities [9][10][11] .…”

Section: Introductionmentioning

confidence: 99%

Triptolide inhibits human breast cancer MCF-7 cell growth via downregulation of the ERα-mediated signaling pathway

et al. 2015

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Aim: To investigate the anticancer mechanisms of triptolide, a diterpenoid isolated from the plant Tripterygium wilfordii Hook F, against human breast cancer cells and the involvement of the estrogen receptor-α (ERα)-mediated signaling pathway in particular. Methods: Human breast cancer ERα-positive MCF-7 cells and ERα-negative MDA-MB-231 cells were tested. PrestoBlue assay was used to evaluate the cell viability. The levels of ERα mRNA and protein were detected with real-time PCR and immunoblotting, respectively. Mouse models of MCF-7 or MDA-MB-231 xenograft tumors were treated with triptolide (0.4 mg·kg, po) or a selective estrogen receptor modulator tamoxifen (mg·kg -1 ·d

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Triptolide alters barrier function in renal proximal tubular cells in rats

Cited by 37 publications

References 18 publications

Sex-Related Differences of Lipid Metabolism Induced by Triptolide: The Possible Role of the LXRα/SREBP-1 Signaling Pathway

Sex-Related Differences of Lipid Metabolism Induced by Triptolide: The Possible Role of the LXRα/SREBP-1 Signaling Pathway

Triptolide inhibits tumor growth by induction of cellular senescence

Triptolide inhibits human breast cancer MCF-7 cell growth via downregulation of the ERα-mediated signaling pathway

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