Keywords: Hepatoprotection; Herbal Drugs; Liver Disorders; Nutritional Supplements
• Hepatocellular injury: Elevated levels of serum ALT or ALP [23];
• Cholestatic injury: Serum ALP and bilirubin levels increase [23];
• Mixed injury: Both serum ALT and ALP levels increase [23].
Liver disease |
Agents |
Acute fatty liver infiltration |
Adrenocortical steroids, Phenothiazines, Sulfonamides, Antithyroid drugs, Phenytoin, Tetracyclines, Isoniazid, Salicylates, Valproic acid, Methotrexate |
Acute viral hepatitis |
Acebutolol, Indomethacin, Phenylbutazone, Allopurinol, Isoniazid, Phenytoin, Atenolol, Ketoconazole, Piroxicam, Carbamazepine, Quinine, Diltiazem, Naproxen, Ranitidine, Enflurane, Para-aminosalicylic acid, Sulfonamides, Ethambutol, Penicillins, Sulindac, Labetalol, Probenecid, Cimetidine, Maprotiline, Pyrazinamide, Dantrolene, Metoprolol, Quinidine, Diclofenac, Mianserin, Ethionamide, Phenelzine, Tricyclic antidepressants, Halothane, Phenindione, Valproic acid, Ibuprofen, Phenobarbital, Verapamil |
Cholestasis jaundice |
Actinomycin D, Chlorpropamide, Erythromycin, Amoxicillin/Clavulanate, Cloxacillin, Flecainide, Azathioprine, Cyclophosphamide, Flurazepam, Captopril, Cyclosporine, Flutamide, Carbamazepine, Danazol, Glyburide, Carbimazole, Diazepam, Gold, Cephalosporins, Disopyramide, Griseofulvin, Chlordiazepoxide, Enalapril, Haloperidol, Ketoconazole, Norethandrolone, Sulfonamides, Mercaptopurine, Oral contraceptives, Tamoxifen, Methyltestosterone, Oxacillin, Thiabendazole, Nifedipine, Penicillamine, Tolbutamide, Nitrofurantoin, Phenothiazines, Tricyclic antidepressants, Nonsteroidal, Phenytoin, Troleandomycin, Anti-inflammatory drugs, Propoxyphene, Verapamil |
Chronic active hepatitis |
Acetaminophen, Dantrolene, Methyldopa, Isoniazid, Nitrofurantoin |
Chronic cholestasis |
Chlorpromazine/valproic acid (combination), Imipramine, Thiabendazole, Phenothiazines, Tolbutamide, Chlorpropamide/Erythromycin (combination), Phenytoin |
Liver cirrhosis or fibrosis |
Methotrexate, Terbinafine HCI, Nicotinic acid |
Liver granulomas |
Gold, Phenytoin, Aspirin, Hydralazine, Procainamide, Carbamazepine, Isoniazid, Guinidine, Chlorpromazine, Quinidine, Nitrofurantoin, Sulfonamides, Diltiazem, Penicillin, Tolbutamide, Disopyramide, Phenylbutazone |
Liver tumors |
Anabolic steroids, Oral contraceptives, Thorotrast, Danazol, Testosterone |
Sr. no |
Product |
Mechanism of action |
References |
1 |
L-carnitine |
Essential cofactor for transport of fatty acids into mitochondria for oxidation. |
[36] |
2 |
Milk Thistle (Silymarin) |
Antioxidant; anti-inflammatory; anti-fibrotic; protects against Amanita mushroom toxicity (experimental) in dogs |
[37] |
3 |
N-acetylcysteine |
Glutathione precursor |
[38] |
4 |
SAMe |
Intermediary metabolite: indirect glutathione precursor (antioxidant); choleretic (cats); detoxification; supports membrane function. |
[39] |
|
|
||
5 |
Ursodiol |
Hydrophilic bile acid shifts bile acid pool to less toxic hydrophilic bile acids. Choleretic in dogs (cats unknown). Protects hepatocyte membranes, modulates immune response. |
[40] |
6 |
Vitamin C |
Free radical scavenger; functions in converting Vitamin E back to active form. Acts as prooxidant in the presence of high Fe, Cu levels. |
[31, 41] |
7 |
Vitamin E |
Membrane associated antioxidant, protects liver against oxidative injury. |
[42] |
8 |
Zinc |
Induces intestinal metallothionein, which |
[43] |
|
Sr. No | Name of the Nutritional supplement | Sources | Hepatotoxicity inducing agents | Extracts studied | Mechanism of action | Reference |
1 | Allium flavum (Amaryllidaceae) | Peels | Carbon tetrachloride | Ethanol | Decreased levels of ALT, ALP and improved blood cholesterol profiles | [52] |
2 | Camel | Milk | Paracetamol | Milk | SGOT, SGPT, ALP, TC, TG levels decreased and total protein, albumin levels increased | [53] |
3 | Cocos nucifera (Arecaceae) | coconut | Paracetamol | Dried- and Fermented-Processed Virgin Coconut Oil |
ALT, AST, ALP levels decreased | [54] |
4 | Honey | Honey | Paracetamol | Honey | Prevented the increase in the serum levels of hepatic enzyme markers, and reduced both oxidative stress and inflammatory cytokines | [55] |
5 | Linum usitatissimum L. | Seeds | Carbon tetrachloride | Flaxseed chutney | Reduces the elevated levels of SGOT, SGOT, ALP, cholesterol and hepatic lipid peroxidation | [48] |
(Linaceae) | ||||||
6 | Linum usitatissimum Linn (Linaceae) | Flaxseed | Carbon tetrachloride | n-butanol | Effective in restoration of increased activities of liver function enzymes | [56] |
7 | Malus domestica Borkh (Rosaceae) | Peel | Carbon tetrachloride | Aqueous | Inhibits lipid peroxidation, increases the activities of antioxidant enzyme i.e. SOD, MDA, GSH, Strong free radical scavenging activity | [57] |
8 | Myristica fragrans (Myristicaceae) | Seeds | Carbon tetrachloride | 70% methanol | Reduce the levels of AST, ALT, ALP and TBS. Histology showed degenerative changes, bile duct proliferation, necrosis of hepatocytes. | [58] |
9 | Nigella sativa Linn (Ranunculaceae) | Seeds | Isoniazid, Rifampicin, Pyrazinamide |
Oil | Reverses serum enzyme activity i.e. ALT, AST, ALP, TBS, total protein. | [59] |
10 | Omega -3 polyunsaturated fatty acids |
Fish | Cisplatin | Oil | Intrinsic biochemical antioxidant property | [60] |
11 | Omega -3 polyunsaturated fattyacids |
Fish | Galactosamine | Oil | Reduce the levels of SGOT, SGPT, SLP. Preventive agents for Hepatic cirrhosis in Mus musculus | [61] |
Sunflower | ||||||
12 | Omega-3fatty acids | Fish | Paracetamol | (Cod) liver oil | Decreased level of MDA | [62] |
13 | Punica granatum Linn (Lythraceae) | Fruits | Carbon tetrachloride | Peel Powder |
Restore the biochemical parameters (ALS, AST TBARS and GSH). Improved histological alteration | [63] |
14 | Spirulina platensis | Spirulina | Carbon tetrachloride | Powder extract | Antioxidant property, radical scavenging, and metal chelatin activities | [64] |
15 | Vigna radiata (Fabaceae) | Seed | Ethanol | Aqueous | Improved antioxidant levels (SOD, MDA), serum markers (ALT, AST, TG, cholesterol), NO level and histopathological | [65] |
16 | Vitis vinifera (Vitaceae) (Grape) |
Seed | Carbon tetrachloride | Oil | Reduces the levels of ALT, AST, ALP, liver MDA and hydroperoxides. Improved in glutathione, SOD, CAT, and TP | [66] |
Sr. |
Name of the plant |
Plant |
Hepatotoxicity inducing agents |
Extracts studied |
Mechanism of action |
Reference |
1 |
Acalypha racemose |
Leaves |
Carbon tetrachloride |
Methanol |
Reduced the levels of serum ALT, AST, total protein and albumin and MDA |
[11] |
2 |
Achillea millefolium (Asteraceae) |
Aerial, Seeds, |
Carbon tetrachloride, |
Aqueous, |
Antihepatotoxic property |
[74] |
3 |
Actinidia deliciosa Chev |
Roots |
Carbon tetrachloride |
Ethanol |
ALT, AST serum levels decreased. MDA decreased and GSH increased in liver homogenate |
[75] |
4 |
Adina cordifolia |
Leaves |
Ethanol |
Acetone and aqueous |
SGOT, SGPT, ALP, total bilirubin serum levels decreased and increased the levels of total protein in liver |
[76] |
5 |
Aegle marmelos Corr |
Leaves |
30%Ethanol |
Ethanol |
Enhanced level of TBRS, GSH, SOD, CAT and in both plasma and liver samples |
[77] |
6 |
Aerva lanata Linn |
Fresh bulbs |
Paracetamol |
Ethanol: Water |
Reduces the levels of serum ALT, AST, ALP and bilirubin |
[78] |
7 |
Allium ascalonicum (Amaryllidaceae) |
Whole |
Paracetamol |
Aqueous |
Decreased level of ALT and % of liver lesion (Micro vesicular steatosis, Necrosis area and Lymphocytic infiltration) |
[79] |
8 |
Allium sativum (Amaryllidaceae) |
Garlic |
N-nitrosodiethylamine |
Aqueous |
Reduced the liver toxicity (ALT, AST,ALP, LPO, SOD,GSH) |
[80] |
9 |
Alocasia indica (Araceae) |
Tuber vegetable |
Carbon |
80% Ethanol |
Strong antioxidant property |
[81] |
10 |
Aloe barbadensis Mill |
Aerial |
Carbon tetrachloride |
Aqueous |
Restore the levels of serum ALT, ALP, TBP, triglycerides, MDA, glutathione, glucose-6-phosphatase, microsomal aniline hydroxylase and amidopyrine N-demethylase and integrity of hepatocytes |
[82] |
11 |
Amaranthus caudatus Linn |
Whole plant |
Carbon tertrachloride |
Methanol |
Decreased levels of ALT AST, ALB, TP, TB, DB |
[83] |
12 |
Andrographis paniculata |
|
Ethanol |
Aqueous |
Decreased levels of ALT, AST, ALP and Bilirubin |
[84] |
13 |
Anisochilus carnosus Linn(Lamiaceae) |
Stems |
Carbon tertrachloride |
Ethanol |
Prevents the elevation of all liver marker enzyme |
[85] |
14 |
Annona squamosa |
Leaves |
Isoniazid, |
Ethanol |
Significant decrease in ALP, AST, ALT and γ-GT |
[86] |
15 |
Anthrodia comphorata |
Mycelium |
Alcohol |
Aqueous |
Decreased the activity of SGOT, SGPT, glucose in serum. Increased the activities of hepatic TBARS, SOD and catalase in liver tissue |
[87] |
16 |
Artemisia bsinthium (Asteraceae) |
Whole |
Acetaminophen, |
Aqueous-methanol |
Prevents the elevation of SGOT and SGPT |
[88] |
17 |
Artemisia campestris |
|
Carbon tetrachloride |
Aqueous |
Strong scavenging action of 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl and superoxide anion radicals in liver |
[89] |
18 |
Artemisia maritime (Asteraceae) |
Whole |
Acetaminophen, |
aqueous-methanolic |
Prevents the elevation of SGOT and SGPT |
[90] |
19 |
Aspalathus linearis |
Leaves |
Carbon tetrachloride |
Aqueous |
Inhibits MDA triacylglycerols and cholesterol in liver tissue. suppressed mainly the increase in ALT, AST, ALP and bilirubin in plasma |
[91] |
20 |
Asparagus racemosus Linn(Asparagaceae) |
Roots |
Paracetamol |
Ethanol |
Significantly altered serum marker enzymes and antioxidant levels |
[92] |
21 |
Azadirachta indica |
Leaves |
Acetaminophen |
Fresh juice |
Decreased levels of SGOT, SGPT, acid phosphatase and ALP |
[93] |
22 |
Azadirachta indica |
Leaf |
Paracetamol |
Aqueous |
Reduced elevated levels of AST, ALT and γ-GT |
[94] |
23 |
Azima tetracantha |
Leaves |
Paracetamol |
Ethanol |
Restore the levels of serum SGOT, SGPT, ALP, TBS and TC |
[95] |
24 |
Ballota glandulosissima |
Aerial |
Carbon tetrachloride, |
Aqueous |
Significantly ameliorated the levels of AST, ALT, ALP and bilirubin in serum, decreased the ballooning degeneration in histopathological examination and significant reduction in rat paw oedema |
[96] |
25 |
Bauhinia varlegate Linn |
Stem bark |
Carbon tetrachloride |
Ethanol |
Reduces the levels of serum marker enzymes, i.e. AST, ALT, ALP and and liver protein and lipids |
[97] |
26 |
Berberis tinctoria |
Leaves |
Acetaminophen |
Methanol |
Decreased the levels of serum SGOT, SGPT, ALP bilirubin and MDA and significantly increased the levels GSH, CAT and SOD in liver |
[98] |
28 |
Boswellia serrate Roxb. |
Oleo gum resin |
Carbon tetrachloride |
Chloroform |
Significantly reduced the elevated levels of serum marker enzymes, prevented the increase in liver weight and supported by changes in histopathology |
[99] |
29 |
Butea superba Roxb. |
Stem bark |
Carbon tetrachloride |
Ethanol |
Decrease in the levels of serum markers, indicating the protection of hepatic cells. |
[100] |
30 |
Cajanus cajan Linn |
Pigeon pea leaf |
D-galactosamine |
Ethanol |
Significantly reduced in serum enzyme such as ALT, AST and increase in reduced MDA and normalized level of SOD, CAT, GSH, and GPx also histopathological improvement in liver tissue. |
[101] |
31 |
Cajanus cajan Linn |
Whole |
Carbon tertrachloride |
70% ethanol |
Significantly reduced in SGOT and SGPT and increased in hepatic total protein. |
[102] |
32 |
Cajanus indicus Linn |
Leaves |
Acetaminophen |
Protein Fraction |
Significantly reversed SGPT, ALP, creatinine and blood urea nitrogen and antioxidant enzymes (namely, MDA, SOD, CAT, GSH almost normal in both liver and kidney homogenates and protects hepatic and renal tissues against oxidative damages |
[103] |
33 |
Cajanus scarabaeoides Linn |
Whole plant |
Paracetamol |
n-butanol, |
significantly and dose dependently decreased the liver marker enzyme activity i.e. SGPT, SGPT, TBS, ALP, total protein, total bilirubin and an almost normal architecture of liver |
[104] |
34 |
Calotropis procera |
Aerial |
Paracetamol |
Chloroform |
Normalize all biochemical parameter |
[105] |
35 |
Calotropis procera Ait |
Latex |
Carbon tetrachloride |
Dried latex |
Significantly and dose-dependent reduction in the serum levels of liver enzymes and inflammatory mediators and attenuated the necro-inflammatory changes in the liver |
[106] |
36 |
Capparis Spinosa Linn |
Roots |
Carbon tetrachloride |
Ethanol |
decreased in the levels of serum markers AST, ALT and duration of sleep, indicating the protection of hepatic cells |
[107] |
37 |
Careya arborea |
Stem bark |
Carbon tetrachloride |
Methanol |
Reduced the activity of serum maker enzymes i.e. SGOT, SGPT, ALP, bilirubin, uric acid, and Liver marker enzymes i.e. decreased lipid peroxidation and significantly increased the levels of SOD, CAT, GSH, vitamin C, vitamin E and protein in a dose dependent manner. |
[108] |
38 |
Carica papaya |
Fruits |
Carbon tetrachloride |
Ethanol and Aqueous |
Reduced all liver damage marker enzyme |
[109] |
39 |
Carissa carandas Linn (Apocynaceae) |
Root |
Carbon tertrachloride, |
Ethanol |
Significantly reduced in the levels of SGOT, SGPT, ALP, total bilirubin, and total cholesterol, significantly maintained the levels of GSH, MDA, and a normal architecture of the liver |
[110] |
40 |
Cassia fistula |
Leaves |
Carbon tetrachloride |
n-Heptane |
Protects against increased serum markers such SGOT, SGPT, bilirubin and ALP |
[111] |
41 |
Cassia auriculata |
Leaves |
Alcohol |
Aqueous |
Significantly reduced in serum enzyme markers |
[112] |
42 |
Cassia occidentalis |
Leaves |
Paracetamol, ethanol |
Aqueous-ethanol |
Normalized in the levels of serum SGOT, SGPT, ALP, cholesterol, total lipids and histopathological alterations. |
[113] |
43 |
Cassia occidentalis Linn |
Roots |
Carbon tetrachloride |
Aqueous |
Decreases AST, ALT and gamma glutamyl |
[114] |
44 |
Cassia roxburghii (Fabaceae) |
Seeds |
Ethanol, carbon tertrachloride |
Methanol |
Inhibit the enhanced SGOT, SGPT, ALP, TB, TP albumin and TC |
[115] |
45 |
Casuarina equisetifolia (Casuarinaceae), |
Leaf and bark, Whole, |
Carbon tertrachloride |
Methanol |
The four plants extract significantly, and dose dependently decreased in the levels of serum markers, indicating the protection of hepatic |
[116] |
46 |
Chamomile |
Capitula flower |
Acetaminophen |
50% ethanol |
Suppresses the elevated levels of Na+ K+- ATPase activity, serum marker enzymes, glycogen and TBARS in blood and liver, normalized impair membrane function activity. |
[117] |
47 |
Chenopodium album Linn. |
Aerial |
Alcohol |
Petroleum ether |
Restore physiological integrity of hepatocytes |
[118] |
48 |
Silybam marianum |
Seeds |
Thioacetamide |
Ethanol |
Significantly decreased in the activity of ALT, AST, ALP and bilirubin, significantly altered the level of Na+, K+ and liver weight |
[119] |
49 |
Cichorium intybus |
Leaves |
Carbon tetrachloride |
Ethanol |
Prevents the elevation levels of serum ALT, AST and ALP, and significant hepatoprotection |
[120] |
50 |
Cichorium intybus |
Root and root callus |
Carbon tetrachloride |
Aqueous |
SGOT, SGPT, ALP and bilirubin levels decreased |
[121] |
51 |
Cleome viscosa Linn |
Seeds |
Carbon tetrachloride |
Aqueous |
Prevents the elevation of all liver marker enzyme |
[122] |
52 |
Clerodendrum inerme Linn |
Leaves |
Carbon tetrachloride |
Ethanol |
SGOT, SGPT, ALP, TG, TC serum levels decreased, significantly increased the glutathione level |
[123] |
53 |
Clitoria ternatea Linn (Fabaceae) |
Leaves |
Paracetamol |
Methanol |
Antioxidant property |
[124] |
54 |
Commiphora opobalsamum |
Aerial |
Carbon tetrachloride |
Ethanol |
significantly protected SGOT, SGPT, ALP and bilirubin |
[125] |
55 |
Cryptolepis buchanani |
Leaves |
Acetaminophen |
Ethanol |
Hepatoprotective and antioxidant property |
[126] |
56 |
Cucumis trigonus Roxb (Cucurbitaceae) |
Fruit |
Carbon tertrachloride |
Ether, chloroform, alcohol, aqueous |
High significantly decreased in the levels of serum markers, indicating the protection of hepatic cells |
[127] |
57 |
Curculigo orchioides |
Rhizomes |
Carbon tetrachloride |
Methanol |
Antioxidant property |
[128] |
58 |
Curcuma longa |
Rhizomes |
7-12 Dimethylbemzamthracene |
Aqueous |
Antioxidant property, reverse ALT, AST, ALP, bilirubin urea and creatinine levels |
[129] |
59 |
Curcuma longa |
Rhizomes |
Acetaminophen, isoniazid, |
Ethanol |
Lowered serum liver enzyme activities, normal histology |
[130] |
60 |
Curcuma longa |
Rhizomes |
Carbon tetrachloride |
Aqueous |
Decreased antioxidant enzyme activities such as SOD, CAT, GPx, GST, GSH, total TSH, protein (PSH), non-protein (NPSH) thiols and ascorbic acid in the liver, decreased ALT, AST, Glucose-6-phosphatase (G6Pase) and the membrane bound ATPase activities |
[131] |
61 |
Cuscuta chinensis Linn. |
Seeds |
Acetaminophen |
Ethanol |
Reduce SGPT, SGPT, ALP levels, prevent hepatic injuries |
[132] |
62 |
Cyperus articulatus Linn. |
Whole rhizome |
Paracetamol |
Methanol |
SGPT, SGOT, ALP, total protein and total bilirubin levels decreased in serum. Improvement or normalized the level of MDA, SOD, CAT, GSH in liver homogenate |
[133] |
63 |
Diospyros malaborica |
Bark |
Carbon tetrachloride |
Methanol |
Hypoglycemic activity, antioxidant activity, antidiabetic activity |
[134] |
64 |
Eclipta alba |
Whole |
Acetaminophen, |
Ethanol |
Significantly reduced in serum marker enzyme |
[135] |
65 |
Eclipta alba |
|
Carbon tetrachloride |
Ethanol, water |
Hepatoprotective activity, Reduced in serum marker enzymes |
[136] |
66 |
Enicostema axillare Lam |
Leaves |
Carbon tetrachloride |
Ethanol |
Decrease in the levels of serum markers, indicating the protection of hepatic cells. |
[137] |
67 |
Epaltes divaricata Casso |
Whole |
Carbon tetrachloride |
Aqueous |
Improved liver marker enzyme |
[138] |
68 |
Ervatamia coronaria |
Leaves |
Carbon tetrachloride |
Methanol |
Hepatoprotective activity |
[139] |
69 |
Euphorbia antiquorum |
Aerial |
Carbon tetrachloride |
Aqueous |
Hepatoprotective and antioxidant property |
[140] |
70 |
Euphorbia hirta Linn |
Whole |
Carbon tetra chloride |
Ethanol |
Enhanced level of SGPT, SGOT, ALP, bilirubin in the dose dependent manner |
[141] |
71 |
Ficus carica Linn |
Leaves |
Carbon tetrachloride |
Methanol |
Lowed the serum levels of ALT,AST, ALP, total bilirubin, and malondialdehyde |
[142] |
72 |
Ficus religiosa Linn |
Stem bark |
Paracetamol |
Methanol |
Significantly reduced serum enzyme levels. |
[143] |
73 |
Foeniculum vulgare |
Seeds |
Carbon tetrachloride |
Essential oil |
Decreased levels of serum AST, ALT, ALP and bilirubin. |
[144] |
74 |
Garcinia indica Linn |
Fruit |
Carbon tertrachloride |
Ethanol |
Antioxidant and hepatoprotective activity |
[145] |
75 |
Ginkgo biloba |
Leaves |
Carbon tetrachloride |
Dry extract |
AST, ALT, ALP, and TP, albumin levels decreased |
[146] |
76 |
Glycyrrhiza glabra |
Roots |
Lipopolysaccharide / |
|
Prevents inflammatory responses and IL-18 production, significantly inhibited IL-18 production in liver injury |
[147] |
77 |
Gmelina asiatica Linn (Lamiaceae) |
Aerial |
Carbon tertrachloride |
Ethanol chloroform |
Antioxidant and hepatoprotective activity |
[148] |
78 |
Hibiscus rosa-sinensis |
Petals |
Carbon tetrachloride |
Ethanol |
Antidiabetic and antioxidant property, therapeutic |
[149] |
79 |
Hyptis suaveolens Linn |
Leaves |
Acetaminophen |
Aqueous |
Significantly reduced in the levels of albumin, TP, total globulin, |
[150] |
80 |
Ichnocarpus frutescens Linn |
Whole |
Acetaminophen |
Chloroform |
Decreased the activity of serum enzymes, bilirubin, and lipid peroxidation, significantly increased the levels of GSH, SOD, CAT, in a dose dependent manner. |
[151] |
81 |
Indigofera trita Linn |
Whole |
Carbon tetrachloride |
Ethanol |
Significantly and dose dependent decreased in the levels of SGOT, SGPT, ALP and TBARS and significantly increased in the levels of albumin, TP, SOD and CAT |
[152] |
82 |
Kalanchoe pinnata |
Leaves |
Carbon tetrachloride |
Fresh juice |
Hepatoprotective Activity |
[153] |
83 |
Lannea coromandelica Linn. |
Bark |
Thioacetamide |
Aqueous and ethanol |
Hepatoprotective and antioxidant activity |
[154] |
84 |
Launaea pinnatifida |
Leaves and roots |
Carbon tetrachloride |
Ethanol |
Significantly restored all the serum and liver parameters near to the normal levels |
[155] |
85 |
Lawsonia alba |
Bark |
Carbon tetrachloride |
50% Ethanol |
Reduced GSH level and inhibits the production of free radicals and peroxidation of microsomal lipids in a dose-dependent manner. |
[156] |
86 |
Lawsonia inermis |
Roots |
Paracetamol and anti-tubercular drugs |
Alcoholic and aqueous |
Significantly reversed the levels of cytosolic enzymes, a marker of oxidative damage to hepatocytes and significantly increased the levels SOD, GSH |
[157] |
87 |
Leucas cilita Linn |
Whole |
Carbon tertrachloride |
Ethanol |
Strong free radical scavenging and hepatoprotective activity. |
[158] |
88 |
Leucas lavandulaefolia Rees |
Aerial |
Carbon tetrachloride |
Chloroform |
Hepatoprotective activity |
[159] |
89 |
Leucophyllum frutescens Berl. (Scrophulariaceae) |
Aerial |
Carbon tetrachloride |
Methanol |
ALT, AST levels decreased |
[160] |
90 |
Luffa echinata |
Fruit |
Carbon tetrachloride |
Petroleum ether, acetone, methanol |
Hepatoprotective activity |
[161] |
91 |
Lycium chinense (Solanaceae) |
Fruits |
Carbon tetrachloride |
Aqueous |
AST, ALT and ALP levels decreased, strong free radical scavenging activity in a dose-dependent manner, significantly decreased in the level of cytochrome P450 2E1 (CYP2E1) mRNA and protein in liver |
[162] |
92 |
Lygodium flexuosum Swartz |
Whole |
D-galactosamine |
n-Hexane |
Prevents the elevation of AST, ALT, LDH, hepatic MDA and GSH levels and normal histological index |
[163] |
93 |
Momordica subangulata |
Leaves, whole |
Acetaminophen |
Aqueous |
Hepatoprotective and choleretic activities |
[164] |
94 |
Melia azadiracta Linn |
Leaves |
Carbon tetra chloride |
Ethanol |
Restore the levels of biochemical parameters like total protein, total bilirubin, total cholesterol, triglycerides, and urea |
[165] |
95 |
Melia azedarach Linn |
Leaves |
Simvastatin |
Ethanol |
Hepatoprotective activity |
[166] |
96 |
Mentha arvensis |
Whole |
Alcohol and carbon tetra chloride |
Aqueous |
Restored all biochemical parameters in serum and liver |
[167] |
97 |
Momordica dioica |
Leaves |
Acetaminophen |
Aqueous |
Hepatoprotective, antioxidant and anti-inflammatory property |
[168] |
98 |
Morinda citrifolia Linn |
Fruit |
Streptozotocin |
Aqueous |
Hypoglycemic and hepatoprotective property |
[169] |
99 |
Mussaenda frondosa Linn |
Leaves |
20% alcohol |
Petroleum ether, chloroform, alcohol |
Decreased the level of AST, ALP, ALT, bilirubin, cholesterol, triglyceride, VLDL, MDA in serum and increased the level of protein, HDL and antioxidants (SOD, GSH and CAT) in liver |
[170] |
100 |
Myrtus communis |
Leaves |
Paracetamol |
Aqueous |
Significant reduction in serum hepatic enzymes |
[171] |
101 |
Nelumbo nucifera Gaerth |
Flowers |
Carbon tetrachloride |
Ethanol |
Protects against hepatocytic necrosis, fatty changes and oxidative damage |
[172] |
102 |
Nigella sativa |
Seeds |
Carbon tetrachloride |
Ethanol |
Prevents MDA, increase anti-oxidant defense system activity and also prevent liver damage |
[173] |
103 |
Ocimum gratissimum |
Leaves |
2-Acetylaminoflourene |
Aqueous |
Hepatoprotective potential |
[174] |
104 |
Ocimum sanctum |
Leaves |
Carbon tetrachloride isoniazid, |
Ethanol |
Hepatoprotective action, antioxidant activity and revers the biochemical and histological changes |
[175] |
105 |
Parkinsonia aculeata Linn |
Leaves |
Carbon tetrachloride |
Ethanol |
Potential therapeutic and preventive, antioxidative property |
[176] |
106 |
Pergularia daemia Forsk (Apocynaceae) |
Aerial |
Carbon tetrachloride |
Ethanol |
Hepatoprotective activity |
[177] |
107 |
Phoenix dactylifera |
Pits and flesh |
Carbon tetrachloride |
Aqueous |
Effective prophylactic or treatment against liver cytotoxicity |
[178] |
108 |
Phyllanthus longiflorus (Phyllanthaceae) |
Leaves |
Acetaminophen |
Ethanol |
Reduced the necrosis and swelling of the hepatocytes in liver histology, ALT, AST, ALP, TP, albumin and total bilirubin levels in serum. |
[179] |
109 |
Phyllanthus maderaspatensis |
Whole |
Acetaminophen |
n-Hexane |
Antihepatotoxic activity |
[180] |
110 |
Phyllanthus niruri |
Leaves |
Acetaminophen |
Alcohol |
Regenerative changes, presence of |
[181] |
111 |
Phyllanthus polyphyllus Willd(Phyllanthaceae) |
Leaves |
Acetaminophen |
Methanol |
Significantly altered serum marker enzymes and antioxidant levels to near normal |
[182] |
112 |
Phyllanthus rheedi (Phyllanthaceae) |
Whole |
D-galactosamine |
Ethanol |
Antioxidant and choleretic activity |
[183] |
113 |
Platycodon grandiflorum |
Roots |
Acetaminophen |
Aqueous |
Inhibits P450 lA2-dependent methoxyresorufin O-deethylase activities and the P450 2E1-dependent p-nitrophenol and aniline hydroxylase, blocked P450-mediated APAP bioactivation. |
[184] |
114 |
Pleurotus ostreatus |
Whole |
Carbon tetrachloride |
Ethanol |
SGOT, SGPT and ALP levels reverted, GSH, CAT, SOD and Gpx levels increased and MDA significantly lowered |
[185] |
115 |
Polygala arvensis Wild |
Leaves |
D-galactosamine |
Chloroform |
Normalized the levels of SGOT, SGPT, ), ALP, lactate dehydrogenase TC, TGL, albumin, TP |
[186] |
116 |
Pterocarpus santalinus Linn |
Stem bark |
Carbon tetrachloride |
Aqueous |
Decrease in levels of liver enzyme markers, significantly increased in total protein, indicating the recovery of hepatic cells, revealed normal hepatic cords without any cellular necrosis and fatty infiltration |
[187] |
117 |
Raphanus sativus Linn (Brassicaceae) |
Seeds |
Carbon tetrachloride |
Aqueous, methanol |
Inhibits increased SGOT, SGPT, bilirubin and histopathological changes |
[188] |
118 |
Rhodococcum vitis |
Leaves |
D-galactosamine |
Aqueous |
Antioxidant activity |
[189] |
119 |
Rhododendron arboretum |
Leaves |
Carbon tetrachloride |
Ethanol |
Hepatoprotective property, anti-oxidant activity |
[190] |
120 |
Ricinus communis |
Leaves |
Carbon tetrachloride, |
n-Hexane chloroform |
Protects against hepatotoxicity |
[191] |
121 |
Rubia cordifolia |
Roots |
Thioacetamide |
Methanol |
Hepatoprotective property |
[192] |
122 |
Saccharum officinarum (Poaceae) |
Cane |
20% Ethanol |
Juice |
Significantly prevented the physical, biochemical, histological and functional changes |
[193] |
123 |
Saponaria officinalis Linn |
Carbon tetrachloride |
Powdered |
Ameliorated the histopathological alteration in liver section |
[194] |
|
124 |
Sarcostemma brevistigma |
Stem |
Carbon tetrachloride, |
Ethyl acetate |
Hepatoprotective property |
[195] |
125 |
Schisandra chinensis |
Seeds |
Carbon tetrachloride |
Alcoholic |
Reduced in the levels of ALT, AST, and GGT, glucose, triglycerides, and cholesterol in serum, found new flavonoids |
[196] |
126 |
Sida cordifolia |
Leaves |
Ethanol |
Petroleum ether, chloroform |
Analgesic, anti-inflammatory, hypoglycemic activities |
[197] |
127 |
Sida cordifolia |
Whole |
Carbon tetrachloride, paracetamol and |
Methanol |
Immunomodulator and pharmacological properties |
[197] |
128 |
Sida veronicaefolia (Malvaceae) |
Leaves |
Ethanol |
Aqueous and ethanol |
SGPT, SGOT, ALP, total bilirubin levels decreased and increased the levels of total protein. |
[198] |
129 |
Smilax chinensis (Smilaceae) |
Roots |
Acetaminophen |
Ethyl acetate |
Hepatoprotective and antioxidant activities |
[199] |
130 |
Solanum nigram Linn |
Fruits |
Carbon tertrachloride |
Ethanol |
Reduce the serum biochemical indicators like AST, ALT, TB, TP and oxidative stress like GSH, SOD, LPO levels decreased |
[200] |
131 |
Solanum trilobatum |
Whole |
Carbon tetrachloride |
Ethanol |
Antioxidant and hepatoprotective |
[201] |
132 |
Swertia longifolia Boiss |
Aerial |
Acetaminophen |
Ethanol |
Significantly reduced AST, ALT ALP |
[202] |
133 |
Syzgium aromaticum Linn |
Flowers buds |
Acetaminophen |
Ethanol |
Antioxidant activity |
[203] |
134 |
Tecomella undulate |
Leaves |
Alcohol and paracetamol |
Methanol |
Hepatoprotective potential and presence of flavonoids, quinones and other bioactive constituents |
[204] |
135 |
Tectona grandis Linn. |
Leaves |
Carbon tetra chloride |
Hydroalcoholic |
Significantly and dose dependently decreased the levels SGOT, SGPT and ALP |
[205] |
136 |
Tephrosia purpurea (Fabaceae) |
Aerial |
Arsenic |
Aqueous |
ALT, AST, ALP levels decreased and reduced necrosis and inflammation in liver section |
[206] |
137 |
Terminalia bellerica Roxb |
Fruits |
Alcohol |
Aqueous |
Prevents the physical and biochemical changes against hepatotoxins |
[207] |
138 |
Terminalia catappa |
Leaves |
Carbon tetrachloride |
Chloroform |
Protects against liver mitochondrial damage |
[208] |
139 |
Teucrium polium |
Aerial |
Carbon tetrachloride |
Ethyl acetate |
Restore the normal histomorphology pattern of liver cells |
[209] |
140 |
Thespesia lampas Dalz and Gibs (Malvaceae) |
Roots |
Carbon tertrachloride |
Methanol |
Revealed normal liver section without any hepatic steatosis, centrilobular necrosis, and swelling of the hepatic cytoplasm |
[210] |
141 |
Tinospora cordifolia |
Stem, leaves |
Carbon tertrachloride |
Aqueous |
Antioxidant or free radical scavenger property and hepatic regeneration ability |
[211] |
142 |
Tinospora cordifolia (Menispermaceae) |
Leaf, stem, roots |
Carbon tertrachloride |
Pet ether, Ethanol, Aqueous |
Biologically and hepatoprotective activity |
[212] |
143 |
Tinospora cordifolia (Menispermaceae) |
Stem |
Carbon tetrachloride |
Aqueous |
Liver function and immune functions |
[213] |
144 |
Tinospora cordifolia (Menispermaceae), |
Stem and bark |
Carbon tertrachloride |
Aqueous |
Restoration of improved level of SOD, CAT, MDA |
[214] |
145 |
Tinospora sinensis (Menispermaceae) |
Stem |
Acetaminophen |
Satwa |
Improved hepatic function normalized the lipid profile in the serum and liver, and improvements in the levels of antioxidant enzymes and oxidative-stress markers. |
[215] |
146 |
Tinospora cordifolia Wild. |
Roots |
Isoniazid, |
Ethanol |
Hepatoprotective potential and prevents immunosuppression |
[216] |
147 |
Trianthema portulacastrum |
Leaves |
Acetaminophen, |
Ethanol |
Significant hepatoprotective activity |
[217] |
148 |
Tridax procumbens |
Aerial |
D-galactosamine |
Ethanol |
Alteration in biochemical marker enzymes |
[218] |
149 |
Trigonella foenum-graecum Linn (Fabaceae) |
Seeds |
Carbon tetrachloride |
Diethyl ether |
Anti-inflammatory and hepatoprotective |
[219] |
150 |
Tylophora indica |
Leaves |
Ethanol |
Aqueous |
Significantly prevented the physical (liver weight and volume), biochemical (ALT,AST, ALP, TP,TBP, TC, triglycerides), histological (damage to hepatocytes) and functional changes (thiopentone-induced sleeping time) histological (damage to hepatocytes) |
[220] |
151 |
Uetica parviflora Roxb. |
Leaves |
Carbon tetrachloride |
Ethanol |
Restore of the levels of serum bilirubin, proteins and hepato protective enzymes, revealed the centrilobular necrosis in a dose dependent manner |
[221] |
152 |
Veronica ciliata (Plantaginaceae,) |
Herbs |
Carbon tetra chloride |
Petroleum ether, ethyl acetate |
Antioxidant |
[222] |
153 |
Vetiveria zizanioides |
Root |
Paracetamol |
Methanolic |
Antioxidant |
[223] |
154 |
Vetiveria zizanioides Linn (Poaceae) |
Roots |
Alcohol |
Methanol |
Hepatoprotective property |
[224] |
155 |
Vicia calcarata Desf |
Aerial |
Carbon tetrachloride |
Ethanol |
Inhibits lipid peroxidation, revealed the flavanol glycosides of F-2 protect against hepatic damage |
[225] |
156 |
Vitex negundo Linn (Lamiaceae) |
Fresh bark |
Paracetamol |
Methanol |
Significantly altered in all biochemical and histopathological sections |
[226] |
157 |
Xylopia phloiodora Mildbr. |
Stem bark |
Carbon tetrachloride, |
Crude extract |
Antihepatotoxicity activity |
[227] |
158 |
Zizyphus mauritian Lamk |
Seed |
Isoniazid, Pyrazinamide |
Ethanol |
Hepatoprotective, strong antioxidant property and indicated probable presence of flavonoids, phenolic compounds, tannins and saponins |
[228] |
159 |
Zizyphus mauritian Lamk |
Seed |
Isoniazid, Pyrazinamide |
Ethanol |
Hepatoprotective, strong antioxidant property and indicated probable presence of flavonoids, phenolic compounds, tannins and saponins |
[228] |
More than 700 mono and poly-herbal preparations from more than 100 plants are in clinical use as hepatoprotective agents in the form of decoction, tincture, tablets and capsules [232, 233]. In recent years, the use of herbal drugs for the treatment of liver diseases has increased all over the world [233]. The herbal drugs are easily available and believed to be harmless and free from serious adverse reactions [234]. The usage of alternative medicine, including herbal preparations, has increased due to limited therapeutic options and disappointing success of modern medicine in treating liver ailments [235]. Several commercial hepatoprotective herbal formulations are known to be effective in liver diseases and are used to treat different types of liver disorders [236-255].
The synchronous activity of ingredients from polyherbal formulation is believed to be responsible for hepatoprotective activities of these formulations mention in Table 5.
The mechanism of action of promising hepatoprotective therapies (Hepatoprotective agents, nutritional supplement, medicinal plants, herbal formulation) is shown in Figure 1.
Sr. |
Name of the formulation |
Plants used in |
Hepatotoxicity inducing agents |
Mechanism of action |
Reference |
||
1 |
Blood wort |
Rumex acetosa L. (Polygonacease; bark) |
Carbon tetrachloride |
Hepatoprotective property |
[236] |
||
2 |
BR-16A (Mentat) |
Bacopa monnieri (Scrophulariaceae), |
Ethanol |
Anxiogenic response |
[237]
|
||
3 |
Clearliv polyherbal formulation |
Phyllanthus niruri (Phyllanthaceae), |
Thioacetamide D-Galactosamine and |
Reduces plasma liver markers, and elevated antioxidants levels. |
[238] |
||
4 |
DHC-1 |
Bacopa monnieri Linn. (Scrophulariaceae; whole), |
Carbon tetrachloride |
Reduces the levels of serum markers and decreased in tissue MDA levels and increased in SOD, catalase, GSH and membrane bound enzymes indicated the hepatoprotective and antioxidant property |
[239] |
||
5 |
HD-03 |
Solanum nigrum L. (Solanaceae;whole plant), |
D-Galactosamine |
Hepatoprotective property |
[240] |
||
6 |
Hepax, a polyherbal formulation, |
Plumbago zeylanica (Chitraka, Plumbaginaceae), |
Carbon tetrachloride, paracetamol and thiocetamide |
Decreased the levels SGPT, SGOT, ALP and total bilirubin |
[241] |
||
7 |
Herbal formulation |
Andrographis paniculata (Acanthaceae; leaves), |
Carbon tetrachloride and ethanol |
Restores the cellular integrity of liver architecture, |
[242] |
||
8 |
Herbal Preparation (HP-4) |
Aloe vera (Xanthorrhoeaceae; leaves), |
D-Galactosamine |
Free radical scavenging properties, Antioxidants property, Hepatoprotective activity, Synergistic protection |
[243] |
||
9 |
HPN-12 |
Glycyrrhiza glabra (Papilionaceae),
|
Carbon tetrachloride |
Improved serum, liver function marker such as AST, ALT, ALP |
[244] |
||
10 |
Jigrine |
Cichorium intybus Linn. (Asteraceae), |
Alcohol, carbon tetrachloride and paracetamol |
Hepatoprotective activity of Jigrine and antioxidant property |
[245] |
||
11 |
Liv 52 |
Achillea millefolium (Asteraceae), |
Carbon tetrachloride and |
all the six herbal formulations (Ayurvedic medicine) showed marked beneficial effects in the studied pharmacological, biochemical and histological parameters. |
[246] |
||
12 |
Livergen |
Andrographis paniculata (Acanthaceae), |
Carbon tetrachloride and paracetamol |
Gastrointestinal and hepatic regulator |
[246] |
||
14 |
Livokin |
Andrographis paniculata (Acanthaceae), |
Carbon tetrachloride and paracetamol |
Herbal formulation, for hepatic dysfunction |
[246] |
||
15 |
Octogen |
Arogyavardhini rasa, |
Carbon tetrachloride and paracetamol |
Highly potent hepatoprotective |
[246] |
||
16 |
Stimuliv |
Andrographis paniculata (Acanthaceae), |
Carbon tetrachloride and paracetamol |
Liver stimulant and tonic |
[246] |
||
17 |
Tefroliv |
Andrographis paniculata (Acanthaceae), |
Carbon tetrachloride and paracetamol |
Standardized liver formulation for effective hepatic regeneration |
[246] |
||
18 |
Liv. 100 |
Cichorium intybus (Asteraceae), |
Isoniazid, rifampicin, and |
Decreased in the activity of Na+K+ ATPase Ca2+ ATPase and Mg2+ ATPase, restores antioxidant enzymes and scavenge reactive oxygen species |
[247] |
||
19 |
Liv. 52 |
Achillea millefolium (Asteraceae), |
Carbon tetrachloride |
Significantly decreased in MDA |
[248] |
||
20 |
Mandur bhasma |
Ferric oxide/hematite or red iron oxide |
Carbon tetrachloride |
Prevents the paraffin mediated and CC14 mediated changes in the enzyme activities, |
[249] |
||
21 |
Panchagavya ghrit. |
cow milk, |
Carbon tetrachloride |
Prevents elevated levels of serum GPT, GOT, ACP and ALP, normal architecture and reduced the CCl4 induced hepatotoxicity |
[250] |
||
22 |
Polyherbal formulation |
Curcuma longa (Zingiberaceae; rhizomes), Emblica officinalis (Phyllanthaceae; fruit), Terminalia chebula (Combretaceae;fruit), Terminalia belirica (Combretaceae; fruit) and Myrica nagi (Myricaceae; fruit)and bees wax. |
Paracetamol |
Hepatoprotective property |
[251] |
||
23 |
Polyherbal formulation |
Emblica officinalis (Euphorbiaceae;leaves), Phyllanthus acidus (Phyllanthaceae; leaves), |
Paracetamol |
Inhibits against various hepatotoxicants, SGPT, SGOT, ALP, DB and LDH levels decreased |
[252] |
||
25 |
Polyherbal formulation tablets |
Andrographis paniculata (Acanthaceae), Phyllanthus niruri Linn. (Euphorbiaceae), |
Alcohol, carbon tetrachloride and paracetamol |
[252] |
|||
24 |
Polyherbal formulation |
Acacia catechu (Fabaceae), |
Carbon tetrachloride and paracetamol |
Prophylactic and therapeutic efficacy |
[253] |
||
26 |
Polyherbal formulation tablets |
Phyllanthus niruri (Phyllanthaceae), |
Carbon tetrachloride |
Antioxidant activity |
[254] |
||
27 |
Rhinax |
Withania somnifera L. (Solanaceae; root), Asparagus racemosus Wild. (Liliaceae; root), Mucuna pruriens Baker non-DC (Papilionaceae; root), |
Carbon tetrachloride |
Anti-hepatotoxic activity, increased activity of cytochrome P450, |
[255] |
Note: SGOT: Serum glutamic oxaloacetic transaminase; SGPT: Serum glutamic pyruvic transaminase; ALP: Alkaline phosphatase; γ-GT: Gamma-Glutamyl Transferase; MDA: Malondialdehyde; SOD: Superoxide dismutase; GSH: Reduced glutathione; CAT: Catalase; GPx: Glutathione peroxidase; LPO; Lipid hydroperoxide; TC: Total cholesterol; TG: Triglycerides
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