Table 1.
Protective effects of plant extracts against APAP hepatotoxicity and metabolism.
| Animal model | Treatment | Duration | Outcomes | Ref. |
|---|---|---|---|---|
| Mice, B6C3F1 mice (males), receiving a single oral dose of APAP (150–300 mg/kg) | Green tea extract (GTE) (500 or 1000 mg/kg, via oral gavage) | Either before APAP by 3 h or following it by 6 h or once for three days, followed by APAP on the 4th day | GTE after APAP: ↑ hepatotoxicity GTE before APAP: ↓ hepatotoxicity |
[14] |
| Mice, BALB/c (males), receiving daily APAP at 250 mg/kg via oral gavage for seven days | Pineapple vinegar (A. comosus) at 0.08 and 2 ml/kg (oral gavage) | 14 days after seven days of APAP intake | ↓ serum AST, ALT, and triglycerides ↑ tissue GSH and GPX ↓ tissue CYP and iNOS |
[16] |
| Mice, BALB/c (males), receiving a single i.p dose of APAP (350 mg/kg) | Ganoderma amboinense powder (1% and 2% daily, mixed with the standard oral diet) | 6 weeks (pretreatment), followed by APAP i.p injection | ↓ tissue MDA and ROS ↑ tissue GSH and GPX ↓ serum AST and ALT |
[15] |
| Mice, ICR (males), receiving a single i.p dose of APAP (150 mg/kg) | Spirulina platensis (SP) extract (3, 6 and 9%, oral) | 7 days, before APAP injection | SP 6 and 9%: ↓ tissue ROS ↓ serum AST, ALT and IL-18 |
[18] |
| Mice, ICR (males), receiving a single oral APAP (300 mg/kg) | Citrus natsudaidai (CN: 300 and 1000 mg/kg, orally) | 3 days, followed by APAP dose 2 h later | ↑survival rate of APAP-intoxicated mice from 0% to 16.7% (300 mg/kg CN) and 33.3% (1000 mg/kg CN) | [17] |
| Mice, Kunming (males), receiving a single i.p dose of APAP (1000 mg/kg) on the 6th day of the experiment | Tea polyphenols (TP) (100, 200 and 400 mg/kg, intragastric) | 6 days, before APAP injection | ↓ histological damages ↓ tissue CYP2E1 and CYP1A2 |
[19] |
| Mice, Specific-pathogen-free (SPF) BALB/c (males), receiving a single i.p dose of APAP (750 mg/kg) | Green tea polyphenols (GTP) (0.25%, in diet) | 5 days, before APAP injection | ↓ histological damages ↓tissue COX-II and Bax. ↓ serum ALT and TNF |
[20] |
| Mice, Swiss albino (males), receiving i.p APAP (300 mg/kg) | Black tea extract (BTE) (3% and 4.5%, i.p.) | A single dose, 90 min after APAP injection | ↓ histological damages ↑ tissue GSH ↓ serum ALT |
[21] |
| Mice, Wistar (males and females), receiving oral APAP at 1 g/kg per day | Lentinula edodes methanolic extract (200 mg/kg, orally) | 7 days, 3 h after APAP treatment (for seven days) | ↓ histological damages ↓ serum AST, ALT, ALP and bilirubin |
[22] |
| Rats, Specific pathogen-free Sprague–Dawley (males), receiving a single oral dose of APAP (25 mg/kg) | Brassicaceae (kale) extract (2 g/kg orally) | 7 days, followed by a single APAP on the last day | ↑ plasma APAP ↑ tissue UGT |
[23] |
| Rats, Sprague Dawley (males), receiving a single oral dose of APAP (2 g/kg) on the 15th day of the experiment | Auricularia polytricha (AP) aqueous extract (250 and 500 mg/kg, orally once daily) | 14 days, followed by APAP on the 15th day | ↓ histological damages ↑ serum total proteins ↓ serum AST, ALT, ALP, LDH, and total cholesterol |
[24] |
| Rats, Sprague–Dawley (males and females), receiving a single oral dose of APAP at 600 mg/kg | Carica papaya leaf (CPL) and unripe fruit (CPF) aqueous extracts (100 and 300 mg/kg, each orally) | Following APAP adminstration by 2, 6 and 10 h | ↓ histological damages ↓serum AST, ALT, ALP and direct bilirubin |
[25] |
| Rats, Sprague–Dawley (males), receiving a single dose of APAP (10 mg/kg) via oral gavage | Citrus paradise (Grapefruit) juice (GFJ) (10 mg/kg, oral) | A single dose, either 28 or 20 h or 30 min before APAP adminstration | ↓ serum APAP | [26] |
| Rats, Wistar (males) and albino mice (both sexes), receiving a single oral dose of APAP (2 g/kg) | Citrullus colocynthis fruits (MECCF) methanolic extract (300 mg/kg, orally) | 7 days, APAP was provided 30 min after the last MECCF dose | ↓ tissue MDA ↑ tissue SOD and CAT ↓ serum AST, ALT and ALP |
[27] |
| Rats, Wistar (males), receiving oral APAP (500 mg/kg) daily for seven days | Citrus macroptera fruit ethanolic extract (EECM) (250, 500, and 1000 mg/kg, orally) | 30 days, in the last seven days, it was co-administered with APAP | ↓ histological damages ↓ serum AST, ALT, ALP, LDH, total cholesterol, and triglycerides (in particular, 1000 mg/kg dose) |
[28] |
| Rats, Wistar (males), receiving oral APAP (250 mg/kg) thrice (once every five days) | Pouteria campechiana fruit aqueous extract (PCAE) at 50 mg/kg Total phenolic content: 115 ± 1.23 mg GAE/g and a DPPH scavenging activity of 71.6% at 250 μg/ml | Once daily for 15 days (during which APAP was administered once every five days) | ↑ hepatocyte GSH, SOD and CAT ↓serum AST and ALT |
[30] |
| Rats, Wistar (males), receiving intra-peritoneal (i.p) APAP at 500 mg/kg (single dose) | Opuntia robusta (Or) and Opuntia streptacantha (Os) fruit extract (800 mg/kg, orally) | 5 days, before APAP adminstration | ↓ histological damages ↑ tissue GSH ↓ serum AST, ALT, and ALP |
[29] |
ALP: alkaline phosphatase; ALT: alanine aminotransferase; APAP: acetaminophen; AST: aspartate aminotransferase; Bax: BCL2 associated X protein; CAT: catalase; COX: cyclooxygenase; CYP: cytochrome P450; GPX: glutathione peroxidase; GSH: glutathione; IL: interleukin; iNOS: inducible nitric oxide synthase; LDH: lactate dehydrogenase; MDA: malondialdehyde; ROS: reactive oxygen species; SOD: superoxide dismutase; TNF: tumor-necrosis factor; UGT: UDP-glucuronosyl-transferases. Ref.: reference.