Table 4 The toxicity of PCL
Toxicology | Active extract/fraction/compounds | Mechanism | Toxic dose | Material or mode | Study design | References |
|---|---|---|---|---|---|---|
Hepatotoxicity | ||||||
Oxidative Stress | Bavachinin A | ROS accumulation and P38 and JNK proteins activation | IC50 = 11.97 μM | HepaRG cells | In vitro | [144] |
Isobavachalcone | ROS accumulation and Akt suppression | IC50 = 155.9 μM | HepG2 cells | In vitro | [145] | |
Psoralen | Increased the expression and transcription levels of endoplasmic reticulum stress-related markers | 80 mg/kg | Mice | In vivo | [147] | |
Cholestasis | Aqueous extracts of PCL | Induced cholestasis by PPAR α pathway | LD50 = 40.29 g/kg | Rats | In vivo | [149] |
Psoralen | Led to the disorder of bile acid transport and accumulation in hepatocytes by affecting bile acid transporter | 60 mg/kg | Rats | In vivo | [150] | |
8-Methoxypsoralen | Disrupted MDR3-mediated phospholipids efflux and bile acid homeostasis | 200, 400 mg/kg; 100 μM | Rats; Human liver cell line L02 | In vivo | [151] | |
Bakuchiol | Promoted the expression of NTCP and resulted in the abnormal increase of bile acid concentration in hepatocytes | 50 mg/kg | Mice | In vivo | [152] | |
Mitochondrial dysfunctions | Aqueous and ethanol extracts of PCL | Mitochondrial dysfunction-mediated apoptosis | 5.14 g/kg | Mice | In vivo | [154] |
Bavachinin A | Damaged the structure and function of mitochondria | 6.25, 12.5, 25 μM | HepaRG cells | In vitro | [155] | |
Metabolic disorders | Psoralen | Caused disturbances in amino acid metabolism, especially valine, leucine, and isoleucine biosynthesis in serum and liver | 60 mg/kg | Rats | In vivo | [157] |
Isopsoralen | Induced disorders of phenylalanine, tyrosine, and glycine, serine, and threonine metabolism | 3.5, 7.0, 14 mg/kg | Rats | In vivo | [158] | |
Abnormal liver regeneration | Psoralen | Upregulated cyclin E1 and p27, inhibited mTOR signaling and induced mitochondrial injury | LD50 = 1673 mg/kg; IC50 = 450 μM | Mice; L02 cells | In vivo and in vitro | [160] |
Nephrotoxicity | 70% ethanol extracts of PCL | Interfered with phospholipid metabolism, amino acid metabolism, purine metabolism and antioxidant system activity | 0.54, 1.08, 1.62 g/kg | Rats | In vivo | [161] |
Furanocoumarins | Affected the renal organic ion transport system | 20, 40 mg/kg | Mice | In vivo | [162] | |
Bakuchiol | Damaged the cell membrane, triggered apoptosis and inhibited DNA synthesis in cells | 40 μM | HK-2 cells | In vitro | [163] | |
Phototoxicity | 8-Methoxyepsoralen | Metabolized slowly and accumulated in the serum and epidermis | 3–5 mg/kg | Guinea pigs | In vivo | [167] |
Developmental toxicity | Psoralen | Induced the oxidative stress, apoptosis, and energy metabolism Disorder | LC50 = 18.24 µM | Zebrafish Embryos/Larvae | In vivo | [168] |
Reproductive toxicity | Ethanol extracts of PCL | Impaired testicular interstitial cell function and interfered the pituitary–testicular axis | 10 g/kg | Rats | In vivo | [169] |
Psoralen | Decreased ovarian follicular function and reduced ovulation by enhancing estrogen metabolism levels | 18, 90, 180 mg/kg | Rats | In vivo | [170] | |