TABLE 4.
Metabolic pathways and metabolites of anthraquinones.
| Compound | Animal species | Dose | Administration routines | Metabolic pathway | Metabolites | References |
| Aloe-emodin | SD rats | 10 mL/kg rhubarb decoction | i.g. | Glucuronidation, hydroxylation, hydrogenation, oxidation | Aloe-emodin-8-O-glucoside-1-O-glucuronide or aloe-emodin-1-O-glucoside-8-O-glucuronide, 2-hydroxyaloe-emodin-ω-O-glucuronide | (Song et al., 2010) |
| Aloe-emodin | SD rats | NA | Liver microsomes | Monohydroxylation, hydrogenation, methylation, oxidation in side chain | Aloe-emodin, rhein, 1,8-dihydroxy-3-hydroxymethyl-10-oxanthranol, 1,2,8-trihydroxy-3-hydroxymethylanthraquinon, 1,4,8-trihydroxy-3-hydroxymethylanthraquinon, 1,8,9,10-tetrahydroxy-3-(methoxyl)methyl-9,10-dihydroanthracene, 1,8-dihydroxy-3-(methoxyl)methylanthraquinone, 1,8-dihydroxy-3-hydroxymethyl-4-methylanthraquinone, 1,8-dihydroxy-3-hydroxymethyl-2-methylanthraquinone | (Song et al., 2009a) |
| Aloe-emodin | SD rats | 0.035 mg/mL | Liver microsomes | Hydroxylation, reduction, oxidation | Dihydroxy-aloe-emodin, hydroxy-aloe-emodin, hydroxy-rhein, hydroxyl-1, 8-dihydroxy-3-hydroxymethyl-9-oxanthranol/hydroxyl-1, 8-dihydroxy-3-hydroxymethyl-10-oxanthranol, aloe-emodin, rhein isomer | (Xu et al., 2018) |
| Aloe-emodin | SD rats | NA | Intestinal bacteria | Hydrolysis, hydroxylation, acetylation, demethylation | 3-acetoxy–1,8-dihydroxy-6-hydroxymethyl-10-oxanthranol, 2-formyl-1,8-dihydroxy-3-hydroxymethyl-6-methoxyanthraquinone | (Song et al., 2011) |
| Aloe-emodin | In vitro | 0.0156 mg/mL | Human intestinal bacteria | Reduction, methylation | O-methyl-aloe-emodin, 1,8-dihydroxy-3-hydroxymethyl-9-oxanthranol or 1,8-dihydroxy-3-hydro-xymethyl-10-oxanthranol and aloe-emodin isomer | (Huang et al., 2019) |
| Aloe-emodin 1/8-O-glycoside | In vitro | 0.5 mL | Intestinal bacteria | Hydrolysis, reduction, substitution reaction | aloe-emodin, and reduction and acetoxyl derivatives | (Song et al., 2012) |
| Aloe-emodin-8-O-β-D-glycoside | SD rats | 0.0240 mg/mL | Liver microsomes | Hydrolysis, hydroxylation, reduction, oxidation | aloe-emodin-8- O-β-D -glucopyranoside, aloe-emodin isomer, hydroxy-aloe-emodin, aloe-emodin, rhein | (Xu et al., 2018) |
| Aloe-emdion- O-glucopyranoside | In vitro | 1 ml Xiao-Cheng-Qi Decoction solution (1g/ml raw formula herbs), including rhei Radix et Rhizoma (wine processed), Aurantii Immaturus Fructus and Magnoliae officinalis Cortex | Human intestinal bacteria | Hydrolysis and oxidation | aloe-emdion, rhein and rheinanthrone | (Liu et al., 2018b) |
| 11-O-actyl-aloe-emdion-O-β-glc-xyl | In vitro | 1 ml Xiao-Cheng-Qi Decoction solution (1g/ml raw formula herbs), including rhei Radix et Rhizoma (wine processed), Aurantii Immaturus Fructus and Magnoliae officinalis Cortex | Human intestinal bacteria | Hydrolysis and oxidation | aloe-emdion, rhein and then rheinanthrone | (Liu et al., 2018a) |
| Chrysophanol | SD rats | 10 mL/kg rhubarb decoction | i.g. | Glucuronidation, sulfation | Chrysophanol-1-O-glucoside-8-O-glucuronide, chrysophanol-8-O-glucoside-1-O-glucuronide, chrysophanol-1,8-biglucuronides, chrysophanol-1-O-glucuronide, chrysophanol-8-O-glucuronide | (Song et al., 2010) |
| Chrysophanol | SD rats | 0.0755 mg/mL | Liver microsomes | Hydroxylation, acetylation, demethylation, hydroxylation, reduction, oxidation | Chrysophanol, dihydroxy-chrysophanol, dihydroxyl-1,8-dihydroxy-3-methyl-9-oxanthranol/dihydroxyl-1,8-dihydroxy-3-methyl-10-oxanthranol, hydroxy-chrysophanol, rhein | (Xu et al., 2018) |
| Chrysophanol | SD rats | NA | Liver microsomes | Monohydroxylation, dihydroxylation | Chrysophanol, 1,4,8-trihydroxy-3-hydroxymethylanthraquinone, 2-hydroxychrysophanol, 4-hydroxychrysophanol | (Song et al., 2009a) |
| Chrysophanol | SD rats | NA | Intestinal bacteria | Hydrolysis, hydroxylation, acetylation, demethylation | 3-acetoxy-1,8-dihydroxy-6-methyl-10-oxanthanol, 1,8-dihydroxy-2-(acetoxy) methyl-6-methylanthraquinone, 1,8-dihydroxy-2-(1-hydroxyethoxy) methyl-6-methylanthraquinone | (Song et al., 2011) |
| Chrysophanol | In vitro | 0.0755 mg/mL | Human intestinal bacteria | Reduction, hydrolysis, acetylation, oxidation, demethylation, methylation, hydroxylation, dehydroxylation | Chrysophanol isomer, O-methyl-hydroxy-chrysophanol, aloe-emodin, O-methyl-chrysophanol, 1,8-dihydroxy-3-methyl-9-oxanthranol or 1,8-dihydroxy-3-methyl-10-oxanthranol, emodin, acetyl-1,8-di-hydroxy-anthraquinone, danthron, rhein | (Huang et al., 2019; Tian., et al., 2012) |
| Chrysophanol-1/8-O-glucoside | In vitro | 0.5 mL | Intestinal bacteria | Hydrolysis, reduction, substitution reaction | Chrysophanol and then reduction and acetoxyl derivatives | (Song et al., 2012) |
| Chrysophanol-O-glucopyranoside | In vitro | 1 ml Xiao-Cheng-Qi Decoction solution (1g/ml raw formula herbs), including rhei Radix et Rhizoma (wine processed), Aurantii Immaturus Fructus and Magnoliae officinalis Cortex | Human intestinal bacteria | Hydrolysis and oxidation | Chrysophanol, rhein and then rheinanthrone | (Liu et al., 2018a) |
| Emodin | Wistar rats | 50 mg/kg | i.g. | Methylation, hydroxylation, oxidation | physcion, chrysophanol, aloe emodin, danthron, rhein | (Tian et al., 2012) |
| Emodin | SD rats | 8 g/kg Zhi-Zi-Da-Huang decoction | i.g. | Glucuronidation, sulfation | Emodin-1-O-glucuronide, emodin-1-O-sulfate, emodin-3-O-glucuronide, emodin-3-O-sulfate | (Zhu et al., 2015) |
| Emodin | SD rats | 2.26 mg/kg | i.g. | Oxidation, acidification, methylation, glucuronidation, sulfation | Emodin methylate, ω-hydroxy-emodin, 6-carboxyl emodin, physcion, emodin, sulfonyl emodin, emodin-di-glucuronide, emodin-glucuronide, emodin-glucuronide oxidate, emodin-sulfate oxidate | (Zhang et al., 2018b) |
| Emodin | SD rats | 10 mL/kg rhubarb decoction | i.g. | Glucuronidation, sulfation, hydroxylation, hydrogenation, oxidation | emodin-O-diglucuronides, emodin-O-glucoside-O-glucuronide, 1,8-Dihydroxy-3-carboxy-6-methylanthraquinone-1or 8-O-glucoside, emodin-1 or 8-O-glucuronide-3-O-sulfate or emodin-1 or 8-O-sulfate-3-O-glucuronide, 1,3,8-trihydroxy-6-methyl-10-oxanthranol glucuronide, emodin-O-diglucuronides, 1,3,8-trihydroxy-6-(glucuronidyl)methylanthrquinone, emodin acid-O-glucuronide, emodin-2-C-glucuronide, emodin-3-O-glucuronide | (Song et al., 2010) |
| Emodin | SD rats | Raw root of P. multiflorum Thunb extract (10 mL/kg/, 2 g/mL) | i.g. | Glucuronidation, sulfation, oxidation | Emodin glucuronide sulfate, emodin 1, 8-O-diglucuronide, emodin 1, 3-O-diglucuronide, emodin 3, 8-O-diglucuronide, 4-hydroxyemodin, 5-hydroxyemodin, emodin acid-3-O-glucuronide, emodin acid-3-O-sulfate, physcion-glucuronides | (Huang et al., 2018) |
| Emodin | SD rats | 0.0156 mg/mL | Liver microsomes | Transhydroxylation, hydroxylation, reduction, dehydroxylation, oxidation | Hydroxy-emodin, 1,3,8-trihydroxy-6-methyl-9-oxanthranol/1, 3,8-trihydroxy-6-methyl -10-oxanthranol, dihydroxy-emodin, hydroxy-emodin, aloe-emodin isomer, hydroxy-rhein, hydroxyl-aloe-emodin, aloe-emodin, emodin | (Xu et al., 2018) |
| Emodin | SD rats | NA | Liver microsomes | Hydroxylation | ω-hydroxyemodin, 2-hydroxyemodin, 4-hydroxyemodin, emodin acid, 3-carbomethoxy-6-methoxy-1,8-dihydroxyanthraquinone, physcion | (Song et al., 2008) |
| Emodin | SD rats | NA | Liver microsomes/intestinal bacteria | Monohydroxylation, methylation, oxidation in side chain | Emodin, physcion, 1, 3, 8-trihydroxy-6-(acetoxy) methyl-10-oxanthranol, ω-hydroxyemodin, 2-hydroxyemodin, 4-hydroxyemodin, emodin acid, 3-carbomethoxy-6-methoxy-1,8-dihydroxyanthraquinone, 1,8-dihydroxy-3-hydroxymethyl-10-oxanthranol | (Song et al., 2008; Song et al., 2009a; Song et al., 2011) |
| Emodin | In vitro | 0.1950 mg/mL | Human intestinal bacteria | Acetylation, hydroxylation, methylation, trans hydroxylation, reduction | Aloe-emodin, isomer of emodin, 8-O-methyl-emodin, 1-O-methyl-emodin,3-O-methyl-emodin, 2-hydroxy-emodin, 4-hydroxy-emodin, ω-hydroxy-emodin, acetyl-1,3,8-trihydroxy-6-methyl-9-oxan-thranol or acetyl-1,3,8-trihydroxy-6-methyl-10-oxanthranol, acetyl-hydroxy-emodin | (Huang et al., 2019) |
| Emodin-1/8- O-glucoside | In vitro | 0.5 mL | Intestinal bacteria | Hydrolysis, reduction, substitution reaction | Emodin and then reduction and acetoxyl derivatives | (Song et al., 2012) |
| Emodin-8-O-β-D-glucoside | SD rats | 0.01 mg/mL | Liver microsomes | Transhydroxylation, hydrolysis, oxidation, hydroxylation | Dihydroxyl-1, 3, 8-trihydroxy-6-methyl-9-oxanthranol/dihydroxyl-1, 3, 8-trihydroxy-6-methyl-10-oxanthranol, hydroxy-emodin-O-glucopyranoside, hydroxy-emodin-O-glucopyranoside, emodin-8-O-β-glucopyranoside, emodin | (Xu et al., 2018) |
| Emodin-O-glucopyranoside | In vitro | 1 ml Xiao-Cheng-Qi Decoction solution (1g/ml raw formula herbs), including rhei Radix et Rhizoma (wine processed), Aurantii Immaturus Fructus and Magnoliae officinalis Cortex | Human intestinal bacteria | Hydrolysis and oxidation | Emodin, rhein and then rheinanthrone | (Liu et al., 2018a) |
| Physcion | SD rats | NA | i.g. | Glucuronidation, sulfation | Physcion oxidate, physcion-sulfate, physcion-glucuronide | (Zhang et al., 2018a) |
| Physcion | SD rats | 10 mL/kg rhubarb decoction | i.g. | Glucuronidation, sulfation | Physcion-1-O-glucoside-8-O-glucuronide or physcion-8-O-glucoside-1-O-glucuronide, physcion-1, 8-O-diglucuronides | (Song et al., 2010) |
| Physcion | SD rats | NA | Liver microsomes | Monohydroxylation, oxidation in side chain, demethylation | Emodin, 1,8-dihydroxy-3-methoxyanthraquinone, 1,8-dihydroxy-3-hydroxymethyl-6-methoxyanthraquinone, hydroxyphyscion, emodin acid, ω-hydroxyemodin, 4-hydroxyemodin, 3-carbomethoxy-6-methoxy-1,8-dihydroxyanthraquinone | (Song et al., 2009a) |
| Physcion | SD rats | 0.16 mg/mL | Liver microsomes | Demethylation, hydroxylation, reduction | Dihydroxy-1,8-dihydroxy-3-methoxy-6-methyl-9-oxanthranol/1, 8-dihydroxy-3-methoxy-6- methyl-10-oxanthranol, emodinIsomer, hydroxy-emodin, emodin, physcion | (Xu et al., 2018) |
| Physcion | SD rats | NA | Intestinal bacteria | Hydrolysis, hydroxylation, acetylation, demethylation | 2-Formyl-1,8-dihydroxy-3-hydroxymethyl-6-methoxyanthraquinone, 1,8-dihydroxy-2-(acetoxy) methyl-3-methoxyanthraquinone, 3-acetoxy -1,8-dihydroxy-6-(acetyl) methylanthraquinone | (Song et al., 2011) |
| Physcion | In vitro | 0.1610 mg/mL | Human intestinal bacteria | demethylation, dehydroxylation, transhydroxylation | Chrysophanol isomer, physcion isomer, aloe-emodin, emodin | (Huang et al., 2019) |
| Physcion-O-glucoside | In vitro | 0.5 mL | Intestinal bacteria | Hydrolysis, reduction, substitution reaction | physcion and then reduction and acetoxyl derivatives | (Song et al., 2012) |
| Rhein | SD rats | 8 g/kg Zhi-Zi-Da-Huang decoction | i.g. | glucuronidation, sulfation | Rhein-1-O-sulfate, rhein-8-O-sulfate, rhein-8-O-glucuronide, rhein-1-O-glucuronide | (Zhu et al., 2015) |
| Rhein | SD rats | 10 mL/kg rhubarb decoction | i.g. | glucuronidation, sulfation | rhein, rhein-1-O-glucoside | (Song et al., 2010) |
| Rhein | SD rats | NA | Liver microsomes | Hydrogenation, methylation | 1,8-dihydroxy-3-carboxy-9-oxanthranol, 1,8-dihydroxy-3-carboxy-10-oxanthranol, 2-methylrhein | (Song et al., 2009a) |
| Rhein | SD rats | 0.1950 mg/mL | Liver microsomes | Hydroxylation, reduction | rhein, rhein isomer, dihydroxyl-1,8-dihydroxy-3-carboxyl-9-oxanthranol/dihydroxyl-1,8-dihydroxy-3-carboxyl-10-oxanthranol | (Xu et al., 2018) |
| Rhein | SD rats | NA | Intestinal bacteria | Hydrolysis, hydroxylation, acetylation, demethylation | 2-acetoxy -6-carboxy -1,8-dihydroxyanthraquinone, 3-acetoxy–1,8-dihydroxy-6-hydroxymethyl-10-oxanthranol | (Song et al., 2011) |
| Rhein | In vitro | 0.0350 mg/mL | Human intestinal bacteria | methylation, hydroxylation, reduction | rhein, O-methyl-rhein, 1,8-dihydroxy-3-carboxyl-9-oxanthranol, 1,8-dihydroxy-3-carboxyl-10-oxanthranol, hydroxy-rhein, chrysophanol isomer | (Huang et al., 2019) |
| Rhein | In vitro | 1 ml Xiao-Cheng-Qi Decoction solution (1g/ml raw formula herbs), including rhei Radix et Rhizoma (wine processed), Aurantii Immaturus Fructus and Magnoliae officinalis Cortex | Human intestinal bacteria | Hydrolysis | Rheinanthrone | (Liu et al., 2018a) |
| Rhein-8-O-glucoside | SD rats | 0.025 mg/mL | Liver microsomes | Hydrolysis, hydroxylation, reduction | Rhein-8-O-glucopyranoside, dihydroxy-3-carboxyl-9-oxanthranol-O-glucopyranoside/1, 8-dihydroxy-3-carboxyl-10-oxanthranol-O-glucopyranoside, rhein, emodin isomer | (Xu et al., 2018) |
| Sennoside A | Human | 0.0250 mg/mL | Intestinal bacteria | Hydrolysis, methylation, hydroxylation, dehydroxylation, reduction | sennidine A-8-O-monoglucoside, rheinanthrone, dehydroxy-rheinanthrone, O-methyl-hydroxy-rheinanthrone, rhein | (Huang et al., 2019) |
| sennoside A | In vitro | 1 ml Xiao-Cheng-Qi Decoction solution (1g/ml raw formula herbs), including rhei Radix et Rhizoma (wine processed), Aurantii Immaturus Fructus and Magnoliae officinalis Cortex | Human intestinal bacteria | Hydrolysis | Rheinanthrone | (Liu et al., 2018a) |
| Sennoside B | Human | 0.0393 mg/mL | Intestinal bacteria | Hydrolysis, methylation, hydroxylation, dehydroxylation, reduction | Sennoside A, dehydroxy-rheinanthrone, O-methyl-rheinanthrone, sennidine B-8-O-monoglucoside, sennidine A-8-O-monoglucoside, aloe-emodin, O-methyl-hydroxy-rheinanthrone, O-methyl-rheinanthrone, rhein | (Huang et al., 2019) |
| Sennoside C | Human | 0.0398 mg/mL | Intestinal bacteria | Hydrolysis, oxidation, methylation, dehydroxylation, reduction | sennoside C, sennidine C-8-monoglucoside, sennidine C-8′-monoglucoside, rheinanthrone-8-O-monoglucoside, dehydroxy-rheinanthrone, rhein, aloe-emodin, O-methyl- rheinanthrone | (Huang et al., 2019) |
| Sennoside D | Human | 0.0263 mg/mL | Intestinal bacteria | Hydrolysis, oxidation, methylation, dehydroxylation, reduction | Chrysophanol isomer, sennidine D-8-O-monoglucoside or sennidine D-8′-O-monoglucoside, O-methyl-rheinanthrone, aloe-emodin, rhein | (Huang et al., 2019) |
NA: not available; i. g.: intragastrical administration; I.V.: intravenous injection.