TABLE 2.
Toxicity of triptolide and celastrol.
| Component | Toxicity | In vivo/In vitro | Effects and mechanisms | References |
|---|---|---|---|---|
| Triptolide | Hepatotoxicity | in vivo; wistar rats | causes necrosis of hepatocytes with inflammatory cell infiltration, involving alteration of hepatic redox status and reduction of serum glucose | Wang et al. (2013a) |
| in vivo; SD rats | inhibits mitochondrial respiratory chain, thus impairing secondary β-oxidation, which is involved in liver injury | Fu et al. (2011) | ||
| in vitro; human liver L02 cells | induces hepatotoxicity, which is associated with mitochondrial fission-associated mitophagy | Hasnat et al. (2019) | ||
| Nephrotoxicity | in vivo; SD rats | impairs the antioxidant system and induces oxidative stress, which contributes to nephrotoxicity | Yang et al. (2012) | |
| in vivo and vitro; wistar rats, HK-2 and HEK-293T cells | causes nephrotoxicity, involved the expression of organic cation transporter 2 (which transported more TP into kidney cortex) | Shen et al. (2019) | ||
| Reproductive toxicity | in vivo; male mice | disrupts testicular structure and inhibit spermatogenesis, which may be associated with downregulation of PPAR and abnormal energy and lipid metabolism | Ma et al. (2015) | |
| in vivo; female mice | decreases the expression levels of estradiol and progesterone, and the cyclic adenosine monophosphate/protein kinase A pathway may be involved | Zhang et al., 2012a; Zhang et al., 2012b | ||
| Celastrol | Hepatotoxicity | in vivo; SD rats | causes liver damage, and it may be related to the inhibition of the activity of cytochrome P450s | Sun et al. (2014) |
| in vitro; rat primary hepatocytes | induced hepatotoxicity mediated by hepatic CYP450s | Jin et al. (2019) | ||
| Cardiotoxicity | in vivo; zebrafish embryos | results in severe edema in the pericardial sac | Wang et al. (2011) | |
| in vivo; HEK 293 cells | reduces potassium conductance (QT prolongation) by inhibiting K+ channels (hERG and Kir2.1) activity | Sun et al. (2006) | ||
| Hematological toxicity | in vivo; BALB/c mice | regulates the hematopoietic cell subsets, thus impairing the development of erythrocytes and B cells | Kusy et al. (2012) |