TABLE 3.

The protective mechanisms of quercetin on INH-ILI.

Dose and model	Dosage and time of drug administration	Changes of indexes after administration	Mechanisms of action
10 mmol/L INH. L02 cells	25, 50 μmol/L for 24 h	Cell DNA tailing↓; cell mitochondrial ROS level↓; ΔΨm↑; The effect of the high dose group was stronger than that of the low dose group	Inhibition of ROS-mediated mitochondrial damage reduces cellular mitochondrial ROS generation and enhances cellular mitochondrial membrane potential Chen T Y et al. (2016)
10 mmol/L INH. L02 cells	25, 50 μmol/L for 24 h	Cell survival rate↑; cell apoptosis rate↓; LDH activity↓; mitochondrial ROS level↓; ΔΨm↑; Caspase-3 protein↓	Inhibition of ROS released, improvement of mitochondrial function, inhibition of ROS/Caspase-3 signaling pathwayChen et al. (2019)
10 mmol/L INH. L02 cells	25, 50 μmol/L for 24 h	Cell survival rate↑; cell mitochondrial ROS level↓; MDA↓; GSH, SOD↑; HO-1 protein in the cytoplasm and Nrf2 protein in the nucleus↑	Regulate the Nrf2/ARE signaling pathway and inhibit mitochondrial oxidative damage Chen et al. (2021a)
10 mmol/L INH. L02 cells	50 μmol/L for 24 h	Cell survival rate↑; cell apoptosis rate↓; LDH activity↓; relative Caspase-3 activity ↓; mitochondrial ROS ↓; p-JNK protein↓	Inhibit ROS/JNK pathway to decrease apoptosis Chen et al. (2021b)
52 mmol/L INH. HepG2 cells	0.1, 1 mg/L for 24 h	Cell survival rate↑; ALT, AST↓; GSH, SOD↑; Bcl-2↑; Bax, Caspase-3, Caspase-9↓; SIRT1 and ERK phosphorylation↑; apoptosis rate↓; ΔΨm↑	Inhibition of mitochondrial oxidative stress, activation of SIRT1/ERK pathway and inhibition of apoptosis Zhang et al. (2019b)
300 mg/kg INH. Male SD rats; 50 mmol/L INH, L02 cells	Male SD rats: 50, 100 mg/kg for 10 days; L02 cells: 5 and 10 μmol/L for 24 and 48 h	ALT, AST↓; ASC, NLRP3 inflammasome, Caspase-1 and IL-1 proteins↓; SIRT1 protein↑; Caspase-3, Bax/Bcl2↓; cell apoptosis rate↓; ΔΨm↑	Activate SIRT1 signaling pathway, inhibite the activation of NLRP3 inflammatory bodies to decrease cell apoptosis Zhang and Lu. (2020)

Notes: INH, isoniazid; RFP, rifampicin; SOD, superoxide dismutase; LDH, lactate dehydrogenase; SDH, sorbitoldehydrogenase; GSH, glutathione; MDA, malonic dialdehyde; ROS, reactive oxygen species; ΔΨm, mitochondrial membrane potential; Nrf2, nuclear erythroid 2-related factor 2; ARE, antioxidant response element; HO-1, heme oxygenase 1; JNK, c-jun N-terminal kinase; SIRT1, silent information regulator 1; ERK, extracellular signal-regulated kinases; NLRP3, NLR, pyrin domain containing 3; ASC, adaptor protein apoptosis speck-like protein containing CARD.