TABLE 3.
Summary of phenols and flavonoids with significant anti-liver disease activity.
| Compounds | Source | The species investigated | Dose | Mechanisms | References |
|---|---|---|---|---|---|
| Phenols | |||||
| Resveratrol | Polygonum cuspidatum | Male C57BL/6J mice | 60 mg/kg | Through improving insulin sensitivity and glucose levels | Hajighasem et al. (2018); Zhao et al. (2019a) |
| HepG2 cells | 20, 50, 100 μM | ||||
| Male Wistar rats | 25 mg/kg | ||||
| Salvianolic acid B | Salvia miltiorrhiza | Male Kunming mice | 15, 30 mg/kg | Inhibition of MAPK-mediated P-Smad2/3L signaling | Wu et al. (2019b) |
| HSC-T6 cells | 25, 50, 100 μM | ||||
| LX-2 cells | 25, 50, 100 μM | ||||
| Salvianolic Acid C | Salvia miltiorrhiza | Male ICR mice | 5, 10, 20 mg/kg | By attenuating inflammation, oxidative stress, and apoptosis through inhibition of the Keap1/Nrf2/HO-1 signaling | Wu, et al. (2019c) |
| Polydatin | Polygonum cuspidatum | Male Sprague-Dawley rats | 7.5, 15, 30 mg/kg | Through increasing miR-200a to regulate Keap1/Nrf2 pathway, and restoring the antioxidant balance as well as the MMP/TIMP balance | Koneru et al. (2017); Zhao, et al. (2018a) |
| BRL-3A cells | 10, 20, 40 μM | ||||
| HepG2 cells | 10, 20, 40 μM | ||||
| Male C57BL/6 mice | 50, 100 mg/kg | ||||
| Curcumin | Curcumin longa | Pregnant NMRI mice | 10 mg/kg | By suppression of oxidative stress-related inflammation via PI3K/AKT and NF-kB related signaling | Barandeh et al. (2019); Lee et al. (2017b); Zhong et al. (2016) |
| Male Sprague-Dawley rats | 200 mg/kg | ||||
| Male C57BL/6 mice | 20, 40, 80 mg/kg | ||||
| HSCs | 0.5, 1, 2 μM | ||||
| Chlorogenic acid | Oriental Wormwood | Female Sprague-Dawley rats | 50 mg/kg | Inhibition of oxidative stress, JNK pathway and miR-21-Regulated TGF-β1/Smad7 signaling pathway | Shi et al. (2016); Yang et al. (2017) |
| Male Sprague-Dawley rats | 15, 30, 60 mg/kg | ||||
| HSCs | 12.5, 25, 50 mg/ml | ||||
| LX2 cells | 20, 40, 80 μg/ml | ||||
| Lithospermic acid | Salvia miltiorrhiza | Huh-7 cells | 5, 10, 20, 40 μg/ml | Reduction of free radicals, restoration of liver functions and inhibition of caspase activity associated with apoptosis | Chan and Ho (2015) |
| Male BALB/c mice | 50, 100 mg/kg | ||||
| Flavonoids | |||||
| Hesperidin | Citrus | Male Wistar rats | 200 mg/kg | Inhibition of free radicals, NF-κB activation and PI3K/Akt pathway, and activation of the Akt pathway | Li et al. (2020b); Mo'men et al. (2019); Pérez-Vargas et al. (2014) |
| Male C57BL/6J mice | 100, 200, 400 mg/kg | ||||
| Hepatocytes | 10, 20 ng/ml | ||||
| Licochalcone A | Licorice Glycyrrhiza | Nrf2−/− C57BL/6 mice | 50, 100 mg/kg | Up-regulation of the Nrf2 antioxidant and sirt-1/AMPK pathway | Liou et al. (2019); Lv et al. (2018) |
| HepG2 cells | 1.5, 3, 3.7, 6, 12 μM | ||||
| Male C57BL/6 mice | 5, 10 mg/kg | ||||
| Licochalcone B | Licorice Glycyrrhiza | HepG2 cells | 40, 80, 120 μM | Inhibition of Caspase 8 and Caspase 9 proteins | Wang et al. (2019b) |
| Wogonin | Scutellaria radix | Male C57BL/6 mice | 10, 20, 40 mg/kg | Regulation of hepatic stellate cell activation and apoptosis | Du et al. (2019) |
| HSC-T6 cells | 1.25 μg/ml | ||||
| LX-2 cells | 20 μg/ml | ||||
| Quercetin | Radix Bupleuri | Male C57BL/6J mice | 0.05% (wt/wt) | By ameliorating inflammation, oxidative stress, and lipid metabolism, and modulating intestinal microbiota imbalance and related gut-liver axis activation | Li et al. (2018b); Porras et al. (2017); Yang et al. (2019a); Zhu et al. (2018a) |
| Male BALB/c mice | 50 mg/kg | ||||
| Raw 264.7 cells | 50 μM | ||||
| Male db/db mice | 100 mg/kg | ||||
| Male Sprague-Dawley rats | 100 mg/kg | ||||
| HepG2 cells | 100 μM | ||||
| Baicalin | Scutellariae radix | Male C57BL/6 mice | 15, 30, 60 mg/kg | By regulating the ERK signaling pathway, TLR4-Mediated NF-κB pathway and miR-3595/ACSL4 axis | Cheng et al. (2017); Liao et al. (2017); Wu et al. (2018a) |
| HSC-T6 cells | 50, 100, 150 μM | ||||
| Young chicken | 50, 100, 200 mg/kg | ||||
| Baicalein | Scutellariae radix | BEL-7402 cells | 5, 10 μg/ml | By activating apoptosis and ameliorating P-glycoprotein activity | Li. et al. (2018a) |
| BEL-7402/5-FU cells | 5, 10 μg/ml | ||||
| Rutin | Forsythia suspensa | Male db/db mice | 60, 120 mg/kg | By interfering with oxidative stress, inflammation and apoptosis, and facilitating signal transduction and activated state of insulin IRS-2/PI3K/Akt/GSK-3β signal pathway | D'Atanasio et al. (2018); Elsawy et al. (2019); Liang et al. (2018); Liu et al. (2017) |
| HepG2 cells | 8, 16, 32, 64 μg/ml | ||||
| Male albino rats | 70 mg/kg | ||||
| Male Sprague Dawley rats | 50, 100 mg/kg | ||||
| Male C57BL/6 mice | 200 mg/kg | ||||
| Calycosin | Radix astragali | Male C57BL/6 mice | 12.5, 25, 50 mg/kg | By activating farnesoid X receptor | Duan et al. (2017) |
| Silybin | Silybum marianum | Male C57BL/6 mice | 105 mg/kg | By reducing oxidative damage to mitochondria, proteins, lipids, and involvement with the NF-κB pathway | Goh et al. (2020); Ou et al. (2018) |
| LO2 cells | 25, 50 μM | ||||
| Isorhamnetin | / | Male C57BL/6J mice | 50 mg/kg | By inhibiting de novo lipogenic pathway, by inhibiting TGF-β/Smad signaling and relieving oxidative stress, inhibiting Extracellular Matrix Formation via the TGF-β1/Smad3 and TGF-β1/p38 MAPK Pathways (via inhibition of TGF-β1-mediated Smad3 and p38 MAPK signaling pathways.) | Ganbold et al. (2019); Liu et al. (2019a); Yang et al. (2016b) |
| LX-2 cells | 25, 50, 100 μM | ||||
| HepG2 cells | 25, 50, 100 μM | ||||
| Male ICR mice | 10, 30 mg/kg | ||||
| Oroxylin A | Scutellaria baicalensis | Male ICR mice | 30 mg/kg | Inhibition of hypoxia inducible factor 1alpha, and activation PKM1/HNF4 alpha | Jin et al. (2018); Wei et al. (2017) |
| LO2 cells | 10, 20, 40 μM | ||||
| HepG2 cells | 6, 8, 10 μM | ||||
| SMMC-7721 cells | 15, 20, 25 μM | ||||
| C57BL/6J mice | 75 mg/kg |