Table 2 Some major phytoconstituents with hepatoprotective activity

1

Phenylethanoid glycoside: acteoside

Plantago major L

Aerial parts

Aqueous methanolic

500 mg/kg orally

CCl₄

Inhibited the serum elevation of ALT, AST, ALP, and GGT enzymes as well as total and direct bilirubin. Decrease LPO and increased GSH in the liver

Blocks the P50-mediated CCL4 bioactivation and exhibits superoxide-free radical scavenging effects

[40, 192]

2

Pentacyclic triterpene: alpha-amyrin

Alstonia scholaris Linn

Stem bark

Ethanol extract

20 mg/kg/day orally

CCl₄

Decreased serum liver markers like GGT, AST, ALT, LDH, ALP, acid phosphatase (ACP), sorbitol dehydrogenase (SDH), glutamate dehydrogenase (GDH), and total bilirubin, total protein

Increased glutathione, ceruloplasmin, β-carotene, vitamin C, and vitamin E

Increased hepatic antioxidants like SOD, CAT, GPx, GR, GST, LPO, 5′-ribonucleotidase, acid ribonuclease, succinic dehydrogenase

Exhibits antifibrotic, anti-inflammatory, antiapoptotic, and free radical scavenging effects

[149, 162]

3

Triterpenoid: asiatic acid

Potentilla chinensis

4 or 8 mg/kg/day orally

Lipopolysaccharide/D-galactosamine

Decreased the serum ALT and AST and showed improvement of liver pathology

Inhibits MAPK and NF-κB via the partial induction of PDCD4 and upregulation of Nrf2 in an AMPK/GSK3β pathway activation-dependent manner resulting in the inhibition of oxidative stress and inflammation

[91, 126]

4

Pentacyclic triterpenoid saponin: asiaticoside

Centella asiatica

5, 10, and 20 mg/kg/day orally

Lipopolysaccharide/D-galactosamine

Decreased the elevated serum level of ALT, hepatocytes apoptosis, caspase-3, improvement of liver pathological injury in dose-dependent manner. Also reduced the elevation of phospho-p38 MAPK, phospho-JNK, phospho-ERK protein, and TNF-alpha mRNA expression in liver tissue

Inhibits TNF alpha and MAPKs

[13, 191]

5

Saponin: cristatain

Celosia cristata L

Seeds

50% ethane

1, 2, and 4 mg/kg/day orally

CCl₄ and N,N-dimethyl formamide

Significantly reduced in the values of AST, ALT and ALP of serum and histopathological examinations compared to controls

Downregulates caspase-3 and caspase-8 activities and prevents hepatic cell apoptosis. Exhibits antioxidant activities through scavenging hydroxyl and DPPH-free radicals

[4, 177]

6

Oleanolic acid saponins: celosin A and celosin B

Semen celosiae

Seeds

Ethanolic extract

1, 2, and 4 mg/kg orally

CCl₄

Inhibited the serum elevation of AST, ALT, and ALP while improve the serum level of GSH_PX, MDA, CAT, and SOD

Both have significant hepatoprotective effects due to the antioxidant property by decreasing the serum liver biochemical markers and liver antioxidant enzymes

[183, 184]

7

Sesquiterpene glycoside: cichotyboside

Cichorium intybus

Seeds

-

CCl₄

Exhibited a significant anti-hepatotoxic activity by reducing the elevated levels of liver enzymes such as AST and ALT

Reduces liver weight and liver protein; inhibits oxidative stress by increasing reduced glutathione content and decreasing lipid peroxidation

[64, 94]

8

Flavonol glycoside: visconoside C

Cleome viscosa L

Leaves

Methanolic extract

100 µM

CCl₄-induced hepatotoxicity on HepG2 cells

Exhibited a significant hepatoprotective activity by antioxidant mechanism and quercetin taken as standard control

Shows free radical scavenging activity and normalizes impaired membrane function activity

[118, 151]

9

Dehydrocavidine

Corydalis saxicola

-

1, 0.5 and 0.25 mg/kg/day intraperitoneally

CCl₄-induced hepatic fibrosis in rats

Inhibited the serum level of ALT, AST, ALP, TB and increased the SOD, CAT, GPx

Alleviates liver damage by reducing the formation of fibrous septa, decreasing the MDA concentration, reducing oxidative stress, promoting collagenolysis, and regulating fibrosis-related genes

[175]

10

Isoflavones: puerarin

Kudzu roots/Pueraria lobelia

Roots

30, 60, and 120 mg/kg/day orally

Chronic alcohol-induced liver injury

Decreased the serum levels of ALT, AST, ALP, and intrahepatic contents of alcohol dehydrogenase (ADH); aldehyde dehydrogenase (ALDH) were elevated

Inhibits endogenous activities of CYP2E1, CYP1A2, and CYP3A which potentially sustain metabolic homeostasis

[28, 84]

11

Rubiadin

Rubia cordifolia Linn

-

50, 100, and 200 mg/kg orally

CCl₄-induced hepatic damage in rats

Normalized serum level of ALT, AST, ALP, and GGT and decrease activities of glutathione S-transferase and glutathione reductase

Shows glutathione mediated detoxification as well as free radical scavenging effect

[103, 138]

12

Ursolic acid

Hedyotis corymbosa L

Whole plant

Ethane

0.75 mg/ml/kg body weight orally

Paracetamol-induced liver injury

Decreased serum enzyme levels of ALT, AST, ALP, total bilirubin, and also normalized histological architecture of the liver compared to the paracetamol-treated group

Suppresses the nuclear factor-kappa beta (NF-κB) activation, inhibits Cytochrome P4502E1 expression, enhances hepatic-glutathione regeneration capacity, and upregulates metallothionein expression

[56, 157]

13

Coumarin: wedelolactone

Eclipta prostrata L

NA

NA

50 and 100 mg/kg intraperitoneally

Concanavalin A-induced hepatitis in mice

Significantly reduced leukocyte infiltration and T-cell activation in liver. Suppress the activity of nuclear factor-kappa B, tumor necrosis factor, interferon gamma, and interleukin (IL)-6

Inhibits the infiltration of leukocytes into the liver via suppression of NF-κB signaling pathway

[89]

14

Betulinic acid and ricinine

Tetracarpidium conophorum

Seeds

Hexane fraction

100 mg/kg betulinic acid and 50 mg/kg ricinine orally

CCl₄-induced hepatotoxicity

Both betulinic acid and ricinine exhibited hepatoprotective potential in CCl₄ rat model in vivo. Both possess strong affinity and better interaction in the active sites of hepatitis B virus DNA polymerase

Improves tissue redox system, decrease lipid peroxidation, and maintain antioxidant system

[122, 189]

15

Coumarin analogues: meranzin hydrate I

Citrus grandis

Pericarp

70% ethanol and 30% water

20-µM concentration

D-Galactosamine-induced cell survival inhibition in LO2 cells by MTT assay

Increased superoxide dismutase and glutathione peroxidase and decreased the level of malondialdehyde in liver toxic model

Modulates cellular antioxidant pathway and improves the free radical scavenging property

[164]