TABLE 1.
Metabolites relieves acetaminophen-induced liver injury.
| Categories | Metabolites | Species name | Model | Does or test concentrations | Minimal active does | Positive/negative control | Efficacy | References |
|---|---|---|---|---|---|---|---|---|
| Polyphenols | Silymarin | Silybum marianum (L.) Gaertn. [Asteraceae] | Balb/c mice APAP (300 mg/kg b.wt. i.p.)6 h, 12 h and 24 h | pretreated 100 mg/kg/d (b.wt. per os) 3d | 100 mg/kg | silymarin and 25% xanthan gum i.g. | ↑HO-1, ↓superoxide, GSSG, p-JNK, ROS | Papackova et al. (2018) |
| Domestic pigeons (Columba livia)APAP (3,000 mg/kg PO q24 h) 0 h, 12 h, 24 h, 48 h, 72 h | 35 mg/kg, starting at 12 h after APAP, silymarin treatment q12 h for 0 h, 12 h, 24 h, 48 h, 72 h. | 35 mg/kg | tap water; | ↓mortality | Ihedioha et al. (2020) | |||
| PBS(37°C) | ||||||||
| Male C57/BL6 mice, APAP (350 mg/kg i.p.)6 h, 12 h | oral 35/50/65 mg/kg (dissolved in 4% HP-β-CD (w/v)) 21d | 35 mg/kg | 4% HP-β-CD (w/v); saline | ↓CYP2E1, NAPQI | Yang et al. (2022b) | |||
| Resveratrol | Vitis vinifera L. [Vitaceae], Vaccinium myrtillus L. [Ericaceae], Rubus idaeus L. [Rosaceae], Morus alba L. [Moraceae], Arachis hypogaea L. [Fabaceae] | Male C57BL/6 mice, APAP (400 mg/kg i.p.) 6 h | oral, pretreated 25/50/100 mg/kg, 7 times interval 12 h | 100 mg/kg | 0.5% CMC-Na; saline | ↓JNK, p53, CYP2E1, CYP3A11 and CYP1A2, ↑SIRT1, cyclin D1, CDK4, PCNA | Wang et al. (2015) | |
| Tannins | Osyris lanceolata Hochst. and Steud. [Santalaceae] | Kunming mice, APAP (400 mg/kg, i.p.) 12 h | oral Tannins (25/50mg/kg), silymarin (100mg/kg) 3d | 25 mg/kg | silymarin (100 mg/kg); saline | ↑Nrf2, HO-1,bcl-2,↓IL-1β, TNF-α, c-fos, c-jun, NF-κB (p65), caspase-3, bax | Zhang et al. (2017) | |
| Salvianolic acid B | Salvia miltiorrhiza Bunge [Lamiaceae] | Male Kunming mice, APAP (300 mg/kg,i.g.24 h; HepG2 cells, APAP (10 mM) 24 h | pretreated,25/50 mg/kg,3d; 0.5, 2, 8 μmol/L, 6 h | 25 mg/kg; 8 μmol/L | double-distilled water(37 °C) | ↑PI3K, PKC,Nrf2, HO-1, GCLC | Lin et al. (2015) | |
| Chlorogenic acid | Phyllostachys edulis (Carrière) J.Houz. [Poaceae] | Male ICR mice, oral ,APAP (300 mg/kg) 4 h | pretreated, oral,5/10/20/40 mg/kg, 7 d | 20 mg/kg | ↑MAPK, GCLC, Trx1/2,TrxR1↓ERK1/2,JNK, p38,ASK1, cRaf, MEK1/2, MKK4, MKK3/6, caspase-3/7, | Ji et al. (2013) | ||
| ICR and C57BL/6 mice, oral, APAP (300 mg/kg)6 h; L-02cell, APAP (10/7.5 mM) 4/8/18/24/36/48h | pretreated, oral,20/40 mg/kg,6d; pretreated, 25/50 μM,15/30 min | 20 mg/kg; 25 μM | ↑Nrf2,HO-1,NQO1,p-ERK1/2, ↓PP2A-A, PP5,ROS | Wei et al. (2018) | ||||
| Male C57BL/6 mice, oral APAP (300 mg/kg) 6 h | oral, 40 mg/kg(1 h after APAP) 5h | 40 mg/kg | ↑Nrf2,Lon,↓HSP60,HMGB1, IL-1β,COX2,TNFα,iNOS, NRF1 | Hu et al. (2020) | ||||
| Male Kunming mice, APAP (300 mg/kg, i.g.) 24 h; HepG2 cell | 20/40 mg/kg (i.g.), 14 d; pretreated, 12.5/25/50uM, 15 min | 20 mg/kg; 25uM | Ammonium glycyrrhizinate (AG) (200 mg/kg), 14 d; 0.9% saline (i.g.) | ↑PINK1, Parki, LC3II/LC3I, ↓p62, Tom20 | Hu et al. (2022) | |||
| Caffeic acid | Ilex paraguariensis A.St.-Hil. [Aquifoliaceae] | Male ICR mice, oral, APAP (400 mg/kg)4 h; L-02/HepG2 cells, APAP (7.5/10 mM) 4/8/18/36 h | oral,10/30 mg/kg, 7d; pretreated,10/25/50mM, 15 min | 30 mg/kg; 25 μM | ↑Keap1-Nrf2,Nrf2,HO-1, NQO1,↓ROS,Keap1, CYP2E1, CYP3A4 | Pang et al. (2016) | ||
| Morin | Maclura pomifera (Raf.) C.K.Schneid. [Moraceae], Maclura tinctoria (L.) D.Don ex G.Don [Moraceae], Psidium guajava L. [Myrtaceae] | Male Wistar rats, oral APAP (1 g/kg/d, 0.5 %CMC) 28d | oral 30 mg/kg/d, 0.5% CMC, 28 d | 30 mg/kg | 0.5% CMC | ↑Nrf2,HO-1,NQO1, Nrf2 nuclear transfer and ARE-Nrf2 affinity,↓PHLPP2, pFyn,GSK3β,HMGB1,caspase-12, Nrf2 ubiquitination | Rizvi et al. (2015b) | |
| Procyanidins | Prunus amygdalus Batsch [Rosaceae] | Male Balb/c mice, APAP (300 mg/kg,i.p.)8 h; HepG2 | oral, Procyanidins 1/10 mg/kg, silymarin (50 mg/kg), three times per week; 10/25/50 μg/mL, 12 h | 1 mg/kg; 25 μg/mL | silymarin (50 mg/kg); Sulforaphane (25 μM); | ↑Nrf2/ARE, ERK, PI3K/Akt, NQO1, GPX, SOD | Truong et al. (2014) | |
| 50% polyglycol; | ||||||||
| 0.1%DMSO | ||||||||
| Curcumin | Curcuma longa L. [Zingiberaceae] | Male B6C3F1 mice, APAP (400 mg/kg, i.p.) 24 h | 17 mg/kg/day (p.o.) 12 d | 17 mg/kg | ↓Bax, caspase-3, p53,↑Bcl-XL | Bulku et al. (2012) | ||
| Male BALB/c mice, APAP 300 mg/kg (i.p.) 16 h | 10/20 mg/kg (i.p.) 2 h | 10 mg/kg | PBS; 1% CMC | ↑Bcl-2/Bax,↓liver necrosis | Li et al. (2013) | |||
| Male mice, fed, APAP 400 mg/kg, 24 h | fed, 200/600 mg/kg, 24 h | 200 mg/kg | corn oil; | ↓necrosis, IL-12, IL-18 | Somanawat et al. (2013) | |||
| distilled water | ||||||||
| Male CD1 mice, APAP (350 mg/kg bw i.p.) 14 h | 35/50/100 mg/kg, bw, 90min | 35 mg/kg | 0.05% CMC | attenuated the decrease in oxygen consumption, membrane potential, ATP synthesis, aconitase, respiratory complexes I, III, IV | Granados-Castro et al. (2016) | |||
| Terpenes | Ginsenosides | Panax ginseng C.A.Mey. [Araliaceae] | Male ICR mice, oral APAP (200-500 mg/kg) 18 h; H4IIE cells |
oral, 10/30/100/300/500 mg/kg/day, 1/5weeks; 0.1/0.5/1 mg/ml, 12 h | 30 mg/kg; 0.1 mg/ml | 40% PEG400; distilled water | ↓LD50, P450 2E1, CYP2E1 ↑GSTA2, Nrf2, C/EBPβ, C/EBPb, GSTA2 | Gum and Cho (2013b) |
| Tanshinone IIA | Salvia miltiorrhiza Bunge [Lamiaceae] | male C57BL/6J mic, APAP (i.p.,300 mg/kg) 24 h; HepG2 cells | oral,10/30 mg/kg,4 d; 10 μM, 24 h | 30 mg/kg; 10 μM | 0.5% CMC-Na (20 ml/kg) | ↑Nrf2, GCLC, NQO1, HO-1 | Wang et al. (2016) | |
| Andrographolide | Andrographis paniculata (Burm.f.) Nees [Acanthaceae] | C57BL/6 mice, APAP (300 mg/kg, i.g.)6weeks | 20/40 mg/kg (i.g.), 4 weeks | 20 mg/kg | 4% methyl-cyclodextrin | ↑Nrf2,GCL, NQO1, HO-1, P62,↓Keap1, ROS | Yan et al. (2018) | |
| Anthraquinones | Rhein | Rheum palmatum L. [Polygonaceae] | Male Sprague–Dawley rats, 2.5 g/kg APAP (i.g.) 48 h | 10/20/40 mg/kg (i.g.) 48 h | 10 mg/kg | 5%CMC-Na; | ↓ROS, NO, MDA, ↑GSH | Zhao et al. (2011) |
| Saline+0.2% gum (i.g.) | ||||||||
| Emodin | Rheum palmatum L. [Polygonaceae] | Female Sprague-Dawley albino rats, APAP (2 g/kg, po) 48 h | 20, 30 and 40 mg/kg (po) 24 h | 30 mg/kg | silymarin (50 mg/kg, po); NaHCO3; hot distilled water | ↓MDA, SALP, LDH, LFTs, ↑GSH | Bhadauria (2010) | |
| Male C57BL/6 mice, APAP (300 mg/kg,i.p.) 24 h | pretreated, oral 15/30 mg/kg, 5 d | 30 mg/kg | 40% PEG; saline | ↑Nrf2,NQO1, HO-1,↓NLRP3,IL-1β, IL-6, TNF-α,IFN-α, cGAS, STING,CYP2E1 | Shen et al. (2022) | |||
| Sulfur-containing NPs | Sulforaphane | Brassica oleracea L. | Male, C57BL/6 mice APAP (300 mg/kg,i.p.)6 h; Primary hepatocytes, APAP (15 mM) 14 h | pretreated, oral 5 mg/kg,30min; pretreated SFN (10 μM) 6 h | 5 mg/kg; 10 μM | PBS | ↑Nrf2,Gclc, Gclm, Cu/Zn SOD, HO-1,↓ROS,4-HNE | Noh et al. (2015) |
| Male Sprague-Dawley rats, oral APAP 1 g/kg (3 h after Sulforaphane), 24 h | oral 500 μg/kg/d, 3 d | 500 μg/kg | water; hot saline | ↓neopterin, CRP, cellular inflammation, liver damag, protect normal hepatic architecture | Dokumacioglu et al. (2017) |