Medicinal plants in the protection and treatment of liver diseases

  • Mohammad Saleem College of Pharmacy, G.C. University Faisalabad, Faisalabad, Pakistan
  • Faiza Naseer College of Pharmacy, G.C. University Faisalabad, Faisalabad, Pakistan.
Keywords: Carbon tetrachloride, Hepatotoxicity, Herbs, Paracetamol
DOI: 10.3329/bjp.v9i4.20648

Abstract

Hepatic dysfunction is globally a major health catastrophe that challenges the health care professionals. The existing synthetic drugs to treat liver diseases have not given much pronounced outcomes. So, conventional herbal plants have become progressively more popular and their utilization is more prevalent. The current review is assemblage of few promising medicinal plants used in the protection and treatment of various liver diseases. Extracts of plants ground significant alteration in liver marker enzymes against diverse hepatotoxic agents.

Introduction

The liver plays vital role in maintenance, performance, regulation of homeostasis, secretions of bile, storage of vitamins (Ahsan et al., 2009) and detoxification in the body. It participates in all the biochemical pathways to growth, immune system, nutrient supply, energy provision and reproduction (Ward and Daly, 1999). So, the proper functioning of liver is essential for the healthy living of an individual. Hepatic diseases escort to liver damage. A major contributory factor is the enlarge alcohol utilization in developed countries (Nadeem et al., 1997). Starvation, blood deficiency, communicable diseases and accessibility of over-the-counter hepatotoxic drugs are the most recurrent factors of liver cell injures in developing countries (WHO Bulletin, 1992). Hepatic cell injury caused by various toxicants like chemotherapeutic agents, anti tuberculosis drugs, carbon tetrachloride, paracetamol, chronic alcohol consumption and pathogenic microbes are well reported (Priya et al., 2010). Drugs such as paracetamol, carbon tetrachloride, thioacetamide and isoniazid catabolize the radicals, bring on lipid peroxidation, damage the membranes of liver cells and organelles, cause the inflammation and necrosis of hepatocytes and leads to the liberation of cytosolic enzymes into the systemic transmission (Singh et al., 1998).

The most common disease of the liver is jaundice can be presented as yellow coloration of eye sclera, skin and mucous membrane due to increase amount of bilirubin in body, having prehepatic, hepatic or post-hepatic causes (Tortora and Grabowski, 2002). Enlargement of liver (hepatomegaly) can occur due to increased accumulation of blood in liver, inflammation, pathogenic infection, cysts and increased size of hepatocytes, infiltrative disorders or microhepatic causes. Increased ammonia level in brain causes hepatic encephalopathy. When normal hepatic parenchyma is replaced by fibrosis or regenerative nodules, cirrhosis is formed. This may occur due to alcoholism or viral hepatitis. Carcinoma or bile stone sclerosing cholangitis can cause obstructive jaundice and bile duct obstruction can cause secondary biliary cirrhosis. They may be metabolic disorders include hereditary hyperbolic rubinemias and intermediate metabolism of liver, carbohydrates, proteins and heavy metals. Congenital metabolic disorders include: Congenital hyperbilirubinemia, Gilbert syndromes, Rotor syndrome, Dubin-Jhonson syndrome and alpha 1 antitrypsin deficiency. Aquired metabolic disorder may be due to food, beverages, toxins, drugs or alcohol. Hepatomegaly, alcoholic hepatitis and cirrhosis are the reasons of excessive alcohol intake (Dalia and Nagalakshrni, 2000). 

All forms of liver injuries (microbiologic, toxic, circula tory or traumatic injury) lead to liver necrosis. Necrosis could be diffuse, zonal or focal (Table I). Other liver diseases include followings:

Table I: Classification of hepatotoxins and mechanism of action

Category of agent Mechanism (UNOS) Histological lesion Examples (Avijeet et al., 2008)
Intrinsic toxicity
Direct
Indirect		 Membrane injury
Interference with specific metabolic pathways leads to structural injury		 Necrosis and /or stenosis
Necrosis and or stenosis		 CCl4 , CHCl3
Thioacetamide, paracetamol, ethanol, tetracycline
Host idiosyncrasy
Hypersensitivity		 Drug allergy Necrosis or cholestetosis Sulphonamides, iproniazid, halothane, paraaminosalicylate, isoniazid, pyrazinamide, rifampicin

-Anemia, hemolytic anemia can cause decrease oxygen availability to liver cells and lead to their death.

-Infection: Bacteria, viruses and fungi can cause liver problem.

1.Infectious disease includes canine hepatitis, canine herpes virus, feline infectious peritonitis, leptospirosis, abscesses histoplasmosis, histoplasmosis, coccidiomycosis and toxoplasmosis. HAV, HBV, HCV, HDV, HEV hepatotroipc viruses that cause acute attacks.

2. Hepatitis A virus can cause acute, self-limited disease that is transmitted orally

3.Hepatitis B and C viruses are transmitted by exchange of body fluids such as blood transfusion and sexual contacts.

4.Hepatitis D is a viroid that causes inflammation along with HBV.

5.Hepatitis E is transmitted by enteric route and cause self-limited disease.

6.HBV-HDV cause chronic hepatitis. Methyldopa, nitrofurantoin, ketoconazole and paracetamol cause drug-induced hepatitis.

Medicinal herbal formulations belong to the conventional systems of medication have been considered as liver protective agents from so long. All following plants have momentous hepatoprotective potential all along with other activities.

Lepidium sativum belongs to family Brassicaceae, is commonly known as garden grass and also has hepatoprotective potential against carbon tetrachloride (Figure 1). Figure 2 has presented Vaccinium procyanidins, its hepatoprotective action against two hepatotoxins tetradecanoylphorbol acetate, carbon tetrachloride and D-galactosamine. Figure 3 has presented the one medicinal plant (Ficus carica: Family Umbelliferaceae) with mechanism of action as hepatoprotective agent (Poumale et al., 2008).

Various edible herbs also approved because of their activities in protection and treatment of liver diseases. They have shown their hepatoprotective action by various means. For example: Fruit of Allium sativum belongs to family Liliaceae, is used most commonly in Indian Subcontinent foods and recognizes by the name of "Garlic: Lehsan". It has hepatoprotective potential due to its organosulphur components which is clearly depicted by Figure 4. Like this, roots of Glycyrrhiza glabra belongs to family Fabaceae, commonly known as "Malathi" has proved hepatoprotective action due to glycyrrhetinic acid and liqourice as major chemical constituents against hepatotoxins carbon tetrachloride and D-galactosamine N and viral and non viral hepatitis by controlling oxidative stress and hepatic phase I and II metabolism shown in Figure 5.

Thus the objective of the current review is intended to sum up the maximum medicinal plants those have been using and proved for the protection and treatment of liver Table II.

Table II: Reported medicinal plants having hepatoprotective potential

SL. No. Botanical plant
(Family)		 Parts used Extract Hepatotoxic agent In vivo models Remarks about liver marker enzymes References
1 Abutilon bidentatum (Malvaceae) Leaves, Flowers Aqueous methanol PCT and CCl4 Rabbit ↓ SGPT, SGOT, ALKP and DB Yasmin et al., 2011
2 Aegle marmelos
(Rutaceae)		 Leaves Ethanol CCl4 Mice ↓ SGPT, SGOT, ALP and DB Sumitha and Thirunalasun-dari, 2011
3 Aerva lanata (Amaranthaceae) Leaves Hydro-alcoholic PCT Rat ↓ levels of AST, ALP, DB and serum TB Vertichelvan et al., 2000
4 Allium sativum
(Liliaceae)		 Fruit No extract INH Rat ↓ AST, ALP, SGPT, SGOT and DB Ilyas et al., 2011
5 Alcea rosea
(Malvaceae)		 Aerial parts Aqueous methanol PCT Mice ↓ levels of AST, ALP, DB and serum TB Hussain et al., 2014
6 Aloe barbadensis
(Liliaceae)		 Aerial parts Chloroform, ether and petroleum CCl4 Mice ↓ AST, ALP and ALT levels. Restored depleted liver thiols Chandan et al., 2007
7 Aloe vera
(Liliaceae)		 Leaves Aqueous gamma-hexachlorocyclohexane (Lindane) Mice ↓ AST, ALP and ALT levels. Restored depleted liver thiols Etim et al., 2006
8 Amaranthus caudatus (Amaranthaceae) Whole plant Methanolic extract PCT Rat ↓ ALT, AST, DB, TB and MDA level. ↑ ALB, GSH, TT, TP and CT levels Kumar et al., 2011
9 Amaranthus spinosus (Amaranthaceae) Whole plant Ethanol CCl4 Rat ↓ ALT, AST, DB, TB and MDA level. ↑ ALB, GSH, TT, TP and CT levels Zeashan et al., 2008
10 Annona squamosa (Annonaceae) Leaves Aqueous ethanol INH Rat ↓ TB, ALP, AST, ALT and gamma-GT and ↑ TP level Kaleem et al., 2006
11 Arachniodes exilis
(Dryopteridaceae)		 Rhizome Ethanol CCl4 Mice ↓ AST, ALT, ALP and CHL. ↑ antioxidant enzyme activities of SOD, CAT, MDA and GSH Zhou et al., 2010
12 Asparagus racemosus
(Liliaceae)		 Whole plant Crude aqueous PCT Rat ↑ LPO, ↓ GSH and SOD Om et al., 2011
13 Baliospermum montanum
(Euphorbiaceae)		 Leaves Alcohol, Chloroform Thioacetamide Mice ↓ in SGOT , SGPT and CHL level Kumar and Mishra, 2012
14 Berberis lyceum
(Berberidaceae)		 Bark Alcohol CCl4 Rat ↓ TB, ALP, AST, and ALT levels Khan et al., 2011
15 Bixa orellana
(Bixaceae)		 Seed Methanol CCl4 Rat ↓ in SGOT , SGPT and cholesterol level Ahsan et al., 2009
16 Boerhaavia diffusa
(Nyctaginaceae)		 Roots Aqueous Thioacetamide Rat ↓ TB, ALP, AST, and ALT and ↑ TP Rawat et al., 1997
17 Bombax ceiba
(Bixaceae)		 Flowers Methanol INH, RMP Rat ↓ TB, ALP, AST, and ALT and ↑ TP Ravi et al., 2010
18 Bupleurum kaoi
(Umbelliferae)		 Roots Ethanol Dimethylnitrosamine Rat ↓ SGOT , SGPT, ALP, AST and ALT Yen et al., 2005
19 Butea monosperma
(Fabaceae)		 Flowers Aqueous PCT Rabbit ↓ ALP, AST and ALT Maaz et al., 2010
20 Cajanus cajan
(Fabaceae)		 Whole plant Methanol CCl4 Rat ↓ SGOT, SGPT and CHL level Sing et al., 2011
21 Calotropis procera (Apocynaceae) Flower Aqueous alcohol PCT Rat ↓ SGPT, SGOT, ALP, bilirubin and LDLP, ↑ serum levels of HDL and tissue level of GSH. Setty et al., 2007
22 Carica papaya
(Caricaceae)		 Fruit Aqueous ethanol CCl4 Rat ↓ SGOT , SGPT, ALP, AST, ALT and LDH levels Sadeque and Begum, 2010
23 Carissa opaca (Apocynaceae) Leaves Methanol CCl4 Rat ↓ lipid peroxidation (TBARS), AST, ALT, ALP, LDH and gamma-GT levels Sahreen et al., 2011
24 Carissa spinarum
(Apocynaceae)		 Roots Ethanol PCT and CCl4 Rat ↓ SGOT , SGPT, ALP, AST, ALT and LDH levels Hegde and Joshi, 2010
25 Cassia fistula (Leguminaceae) Leaves Ethanol N-heptane Rat ↓ ALP, AST, ALT, LDH and gamma-GT Bhakta et al., 2001
26 Cassia occidentalis
(Caesalpiniaceae)		 Leaves Aqueous ethanol PCT Rat ↓ SGOT , SGPT, ALP, AST, ALT and LDH levels Rani et al., 2010
27 Casuarina equisetifolia
(Casuarinaceae)		 Leaves and Bark Methanol CCl4 Rat ↓ SGOT , SGPT and cholesterol level Ahsan et al., 2009
28 Cestrum nocturnum
(Solanaceae)		 Leaves Aqueous ethanol PCT Mice ↓ SGOT , SGPT, ALP, AST, ALT and LDH levels Qadir et al., 2014
29 Chamomile recutita (Asteraceae) Flower Methanol CCl4 Rat ↑ Conc. of glutathione in Liver & blood and Na+K+ATPase activity. ↓ ALT, AST, ALP, TB and liver glycogen levels Gupta et al., 2006
30 Chenopodium murale
(Chenopodiaceae)		 Whole plant Aqueous methanol PCT Mice ↓ ALP, AST, ALT and TB levels Saleem et al., 2014
31 Cinnamomum tamala
(Lauraceae)		 Leaves Methanol PCT Mice ↓ SGOT, SGPT, ALP, lipid profile, TB and ↑ TP Selvam et al., 2010
32 Clerodendron inerme (Verbenaceae) Leaves Ethanol PCT Rat ↓ SGOT, SGPT, SALP, TB and ↑ TP levels Haque et al., 2011
33 Coccinia grandis (Curcubitaceae) Leaves Aqueous, Ethanol CCl4 Rat ↓ SGOT, SGPT, ALP, TB and CHL levels Sunilson et al., 2009
34 Cocculus hirsutus
(Menispermaceae)		 Aerial parts Methanol Bile duct ligation Rat ↓ ALT, AST, LDLC, HDL TC and STG. ↑ antioxidant enzyme activities of SOD, CAT, GSH-Px and GST Thakare et al., 2009
35 Cochlospermum planchoni
(Coclospermaceae)		 Rhizome Aqueous CCl4 Rat ↓ ALP, AST and TB levels Nafiu et al., 2011
36 Convolvulus arvensis
(Convolvulaceae)		 Whole plant Ethanol PCT Mice ↓ ALP, AST, ALP and TB levels Ali et al., 2013
37 Cordia macleodii
(Boraginaceae)		 Leaves Ethanol CCl4 Rat ↓ SGPT, SGOT, ALP and TB levels Qureshi et al., 2009
38 Cuscuta chinensis
(Convolvulaceae)		 Seeds Aqueous ethanol PCT Rat ↑ antioxidant enzyme activities of SOD, CAT, GSH-Px, GST and GSH Yen et al., 2007
39 Cyathea gigantea (Cyatheaceae) Leaves Methanol PCT Rat ↓ SGPT, SGOT, ALP,TB, TP and reverse the hepatic damage Kiran et al., 2012
40 Decalepis hamiltonii
(Asclepiadaceae)		 Roots Aqueous Ethanol Rat ↓ ALT, AST, LDLC, HDL TC and STG.↑ SOD, CAT, GSH-Px, GST, and GSH Srivastava and Shivanandappa, 2006
41 Dodonaea viscose (Sapindaceae) Leaves Methanol Alloxan Rabbit ↓ ALT, AST, LDLC, HDL TC and STG Ahmad et al., 2011
42 Eclipta alba
(Asteraceae)		 Whole plant Ethanol PCT Mice ↓ ALT level, fatty degeneration and centrizonal liver necrosis Tabassum et al., 2004
43 Emblica officinalis
(Phyllanthaceae)		 Leaves Ethanol CCl4 Rat ↓ ALT, AST, LDLC, HDL TC and STG Jose and Kuttan, 2000
44 Equisetum arvense
(Equisetaceae)		 Aerial parts Methanol Tacrine Hep G2 cells ↓ AST, ALT, TP, TB and ALP levels Oh et al., 2004
45 Eucalyptus maculata (Myrtaceae) Leaves Chloroform PCT Rats and Mice ↓ AST, ALT and ALP Mohamed et al., 2005
46 Euphorbia fusiformis
(Euphorbiaceae)		 Tubers Ethanol RMP Rat ↓ AST, ALT, ALP, SGPT and SGOT Anusuya et al., 2010
47 Feronia elephantum (Rutaceae) Fruit Aqueous CCl4 Rat ↓ ALT, AST, billirubin level and ↑ TP levels Kamat et al., 2003
48 Ficus cordata
(Moraceae)		 Roots Methanol/ ethylacetate CCl4 Rat Prevent liver cell death and LDH leakage Donfack et al., 2011
49 Foeniculum vulgare (Apiaceae) Leaves and fruit Ethanol CCl4 Rat ↓ AST, ALT, ALP, SGPT and SGOT Ozbek et al., 2003
50 Galium aparine (Rubiaceae) whole plant Alcohol CCl4 Rat ↓ ALP, AST, and ALT levels Khan et al., 2011
51 Glycosmis pentaphylla
(Rutaceae)		 Leaves and bark Methanol PCT Mice ↓ in SGOT, SGPT and cholesterol level Nayak et al., 2011
52 Glycyrrhiza glabra (Fabaceae) Roots Aqueous CCl4 Rabbit ↑ antioxidant enzyme activities of SOD, CAT, GSH-Px, GST and GSH Al-Razzuqi et al., 2012
53 Gundelia tourenfortii
(Asteraceae)		 Stalk Hydro alcoholic CCl4 Rat ↓ ALP, AST, TB and ALT levels Jamshidzadeh et al., 2005
54 Halenia elliptica
(Gentianaceae)		 Whole plant Methanol CCl4 Rat ↓ SGOT, SGPT, ALP, AST and TB levels Huang et al., 2010
55 Haloxylon salicornicum (Chenopodiaceae) Aerial parts Ethanol CCl4 Rabbit ↓ SGOT, SGPT, ALP and TB levels Ahmad and Erum, 2011
56 Hemidesmus indicus (Apocynaceae) Roots Methanol INH and RMP Rat ↓ ALP, AST, TB and ALT Prabhakaran and Rangasamy, 2000
57 Hygrophila auriculata
(Acanthaceae)		 Roots Aqueous CCl4 Rat ↓ AST , ALT, ALP, TB and CHL levels Dhanaraj et al., 2012
58 Hypericum japonicum
(Clusiaceae)		 Whole plants Aqueous CCl4 Mice ↓ SGPT, SGOT, AST , ALT and ALP levels Wang et al., 2008
59 Hyptis suaveolens
(Lamiaceae)		 Leaves Aqueous PCT Rabbit ↓ TP and TB levels Babalola et al., 2011
60 Ipomoea staphylina
(Convolvulaceae )		 Levaes Hydro- alcohol CCl4 Rat ↓ ALP, AST, ALT, SGPT, SGOT and CHL levels Bag and Mumtaz, 2013
61 Kohautia grandiflora
(Rubiaceae)		 Leaves Aqueous PCT Rat ↓ AST, ALT, ALP, TB and TP Garba et al., 2009
62 Laggera pterodonta
(Asteraceae)		 Whole plant Ethyl alcohol CCl4 Rat ↓ AST , ALT, ALP, TB and TP Wu et al., 2007
63 Launaea procumbens
(Asteraceae)		 Whole plant Methanol CCl4 Rat ↓ ALT, AST, ALP, LDH, LDL, HDL, TC and
Triglycerides levels		 Khan et al., 2012
64 Lepidium sativum
(Brassicaceae)		 Whole plant Methanol CCl4 Rat ↓ AST , ALT, ALP, TB and TP Afaf et al., 2008
65 Luffa echinata
(Cucurbitaceae)		 Fruit Petroleum, acetone and methanol CCl4 Rat ↓ SGOT, SGPT, ALP and AST levels Ahmed et al., 2001
66 Malva parviflora
( Malvaceae)		 Whole plant Methanol PCT Mice ↓ ALP, AST, TP and ALT Mallhi et al., 2014
67 Momordica dioica
(Cucurbitaceae)		 Leaves Aqueous
methanol		 CCl4 Rat ↓ ALP, AST, TP and ALT Jain et al., 2008
68 Mimosa Pudica
(Mimosaceae)		 Leaves Methanol CCl4 Rat ↓ AST , ALT, ALP, TB and TP. ↓ SGOT, SGPT Rajendran et al., 2009
69 Moringa oleifera
(Moringaceae)		 Roots, flowers Methanol INH, RMP, PZA Rat ↑ Antioxidant enzyme activities of SOD, CAT, GSH-Px, GST and GSH. ↓ AST , ALT, ALP, TB and TP. ↓ SGOT, SGPT Pari and Kumar, 2002
70 Nigella sativa (Ranunculaceae) Seeds Alcohol Galactosamine/ lipo polysaccharide Rat ↓ ALP, AST, TB, TP and ALT Gani and John, 2013
71 Ocimum gratissium (Lamiaceae) Fresh leaves Methanol CCl4 Rat ↓ ALT, AST and ALP levels Friday et al., 2012
72 Ocimum sanctum
(Lamiaceae)		 Leaves Alcohol PCT Rat ↓ SGPT, SGOT, ALT, AST and ALP Lahon et al., 2011
73 Orthosiphon stamineous
(Lamiaceae)		 Leaves Methanol PCT Rat ↓ SGPT, SGOT, LPO, ALT, AST and ALP Maheswari et al., 2008
74 Parkinsonia aculeata (Fabaceae) Leaves Ethanol PCT Rat ↓ SGOT, SGPT, LDH, ALP, TB and ↑ TP levels Shah and Deval, 2011
75 Phoenix dactylifera
(Arecaceae)		 Fruits Methanol Thioacetamide Rat Ameliorated the increased level of MDA and decline of GSH and amelioration of ALT, ALP and AST Okwuosa et al., 2014
76 Picrorhiza kurroa
(Scrophulariaceae)		 Roots rhizomes Ethanol CCl4 Rat ↓ ALP, AST, ALT, SGPT, SGOT and CHL levels Arsul et al., 2011
77 Piper chaba
(Piperaceae)		 Fruit Aqueous acetone Galactosamine/lipo polysaccharide Mice ↓ ALP, AST, ALT, SGPT and SGOT levels Matsuda et al., 2009
78 Pistacia integerrima (Anacardiaceae) Bark Ethyl acetate PCT Rat ↓ ALP, AST, and ALT levels Joshi and Mishra, 2010
79 Plumbago zeylanica (Plumbaginacea) Aerial parts Methanol PCT Rat ↓ serum TB, SGPT, SGOT and ALP levels Kanchana and Sadiq, 2011
80 Phyllanthus emblica (Euphorbiaceae) Fruits Aqueous PCT Rat Significant ↑ TBC and less necrosis Malar and Mettilda, 2009
81 Phyllanthus niruri (Euphorbiaceae) Leaves, fruits Aqueous methanol PCT Mice ↑ Antioxidant enzyme activities of SOD, CAT, GSH-Px, GST and GSH. Tabassum and Agrawal, 2005
82 Phyllanthus polyphyllus
(Euphorbiaceae)		 Leaves Methanol PCT Mice ↓ ALP, AST, ALT, SPGT and SGOT levels.
↑ Antioxidant enzyme activities of SOD, CAT, GSH-Px, GST and GSH.		 Srirama et al., 2012
83 Physalis minima
(Solanaceae)		 Whole plant Methanol CCl4 Rat ↓ SGPT, SGOT, LPO, TP, ALT, AST and ALP Ahsan et al., 2009
84 Plantago major
(Plantaginaceae)		 Whole plant Methanol CCl4 Rat ↓ TB, TP, SGPT, SGOT, AST and ALP levels Turel et al., 2009
85 Pterospermum acerifolium
(Sterculiaceae)		 Leaves Ethanol CCl4 Rat ↓ ALP, AST, ALT, SGPT, SGOT and CHL levels Kharpate et al., 2007
86 Rheum emodi (Polygonaceae) Roots Petroleum benzene, chloroform CCl4 Rat ↓ serum TB, TP, SGPT, SGOT, AST and ALP levels Ibrahim et al., 2008
87 Rosa damascene
(Rosaceae)		 Fruit Aqueous methanol CCl4 Rat ↓ SGPT, SGOT, LPO, TP, ALT, AST and ALP levels. Achuthan et al., 2003
88 Rubia cordifolia (Rubiaceae) Roots Methanol Thioactamide Rat ↓ ALP, AST, ALT , SPGT and SGOT levels Babita et al., 2007
89 Rumex dentatus
(Polygonaceae)		 Whole plant Aqueous-methanol PCT Mice ↓ ALP, AST, TB and ALT levels Saleem et al., 2014
90 Sarcostemma brevistigma
(Asclepiadaceae)		 Stem Ethyl acetate CCl4 Rat ↓ AST, ALT, ALP, TP, SGOT and TB levels and liver necrosis Singh and Mehta, 2003
91 Saururus chinensis
(Saururaceae)		 Whole plant Ethanol CCl4 Rat ↓ AST, ALT, ALP and CHL. ↑ antioxidant enzyme activities of SOD, CAT, MDA and GSH Wang et al., 2009
92 Schouwia thebica
(Arecaceae)		 Aerial parts Diethyl ether, chloroform CCl4 Rat ↓ ALT, AST, SGPT, SGOT, levels of glucose, triglycerides and CHL Awaad et al., 2006
93 Scoparia dulcis
(Scrophulariaceae)		 Leaves Ethanol CCl4 Mice ↓ SGPT, SGOT, ALP, AST, TB and ALT levels Tsai et al., 2010
94 Silybum marianum
(Asteraceae)		 Whole plant Ethanol CCl4 Rat ↓ AST, ALT, ALP and CHL. ↑ antioxidant enzyme activities of SOD, CAT, MDA and GSH Ramadan et al., 2011
95 Spondias pinnata
(Anacardiaceae)		 Stem wood Ethyl acetate,
methanol		 CCl4 Rat ↓ SGPT, SGOT, CHL, AST, ALT, ALP, TP and TB levels Rao and Raju, 2010
96 Solanum nigram (Solanaceae) Fruit Ethanol CCl4 Rat ↓ AST, ALT, ALP, TP and TB levels Raju et al., 2003
97 Stachytarpheta indica
(Verbenaceae)		 Whole plant Ethanol CCl4 Rat ↓ SGPT, SGOT, CHL, AST, ALT, ALP, TP and TB levels Joshi et al., 2010
98 Suaeda fruticosa
(Amaranthaceae)		 Leaves Aqueous methanol PCT Rabbit ↓ SGPT, SGOT, AST, ALT, ALP, TP and TB levels. Rehman et al., 2013
99 Tecomella undula
(Bignoniaceae)		 Aerial parts Aqueous ethanol PCT Rat ↓ ALP, AST, ALT, SPGT and SGOT levels .
↑ Antioxidant enzyme activities of SOD, CAT, GSH-Px, GST and GSH.		 Singh and Gupta, 2011
100 Tephrosia purpurea L
(Fabaceae)		 Aerial parts Aqueous ethanol Thioacetamide Rat ↓ ALP, AST, ALT, SPGT and SGOT levels.
Ameliorated the increased level of MDA and decline of GSH and amelioration of ALT, ALP and AST		 Khatri et al., 2009
101 Terminalia chebula
(Combetraceae)		 Fruit Ethanol RIF, INH, PZA Rat ↓ AST, ALT, ALP, TP and TB levels Tasduq et al., 2006
102 Thunbergia laurifolia
(Acanthaceae)		 Leaves Aqueous Ethanol Rat ↓ SGOT, SGPT, AST, ALP and TB levels Pramyothin et al., 2005
103 Thymus linearis
(Lamiaceae)		 Leaves Aqueous and ether PCT and CCl4 Mice ↓ SGOT, SGPT, ALT, AST, ALP and TB levels Alamgeer et al, 2014
104 Trianthema decandra
(Aizoaceae)		 Leaves Aqueous CCl4 Rat ↑ GSH, SOD, CAT levels. ↓ SGPT, SGOT, AST, ALT, ALP, TP and TB Balamurugan and Muthu-samy, 2008
105 Trichodesma sedgwickianum
(Boraginaceae)		 Leaves Ethanol CCl4 Rat ↑ GSH, SOD, CAT levels. ↓ AST, ALT, ALP, TP and TB levels. Saboo et al., 2013
106 Tridax procumbens
(Asteraceae)		 Aerial parts Ethanol Galactosamine/lipopolysaccharide Rat ↑ GSH, SOD, CAT levels. ↓ AST, ALT, ALP, TP and TB levels. Ravikumar et al., 2005
107 Tylophora indica
(Asclepiadaceae)		 Leaf powder Aqueous alcohol Ethanol Rat ↓ AST, ALT, ALP, TP and TB levels Gujrati et al., 2007
108 Vernonia amygdalina
(Compositae)		 Leaves Aqueous PCT Mice ↓ SGOT, SGPT, LDH, ALP, DB and TB, TBAR and iron. ↑ CAT and TP Iwalokun et al., 2006
109 Viola odorata
(Violaceae)		 Leaves Aqueous methanol PCT Mice ↓ SGOT, SGPT, TB, AST, ALP, ↑ CAT, GSH levels Qadir et al., 2014
110 Vitex trifolia
(Verbenaceae)		 Leaves Aqueous ethanol CCl4 Rat ↓ tissue necrosis, SGPT, SGOT, CHL, AST, ALT, ALP, TP and TB levels Manjunatha and Vidya, 2008
111 Vitis vinifera
(Vitaceae)		 Roots Ethanol CCl4 Rat ↓ SGOT, SGPT, TB, AST, ALP levels. ↑ CAT and GSH levels Sharma et al., 2012
112 Zanthoxylum armatum
(Rutaceae )		 Bark Ethanol CCl4 Rat ↓ SGOT, SGPT, TB, AST, ALP, ↑ CAT, GSH levels Verma et al., 2010

Alteration in liver markers: The consequences of hepatoprotective activity of extract of medicinal plants are considerable decline in liver marker enzymes: Total bilirubin (TB), direct bilirubin (DB), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lipid profile, lactate dehydrogenase (LDH), gamma-glutamyltransferase (γ-GT), thiobarbituric acid reactive substances (TBARS) and markers for oxidative defense namely malondialdehyde (MDA), accompanied by significant enhance in the level of total protein (TP), glutathione (GSH), total thiols (TT), conjugated dienes (CD), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione-S-transferase (GST) and glutathione peroxidase (GSH-Px) in treatment group as compared to the hepatotoxic group and these also estored the depleted liver thiol levels significantly.

Analysis of Table II indicates that there are compiled 112 Asian herbs which have been reported for their hepatoprotective activity against hepatotoxins. Among these 35 plants have proved their hepatoprotective activity against paracetamol, in which 17 studies were conducted on rats, 15 on mice and 3 on rabbits. 53 botanical herbs have shown their potential for protection and treatment of liver against carbon tetrachloride (inorganic substance), in which rat has been used as biological animal in 45, mice in 5 and rabbit in 3 studies. Anti-tuberculosis drugs (isoniazid, rifampicin, pyrazinamide etc) also act as hepatotoxin. In Table II, 7 plants have proved their activity against them and all studies were conducted on rats. Thioacetamide, an organosulphur compound has ability to destroy the hepatocyte. Five plants were reported against this hepatotoxin, in which 4 studies were conducted on rats and 1 on mice. Other hepatotoxins which become the reason of high magnitude of liver marker enzymes include D-galactosamine/lipopolysaccharide (3 studies conducted: 2 on rat and 1 on mice), ethanol (3 plants studies on rats), γ-hexachlorocyclohexane by Aloe vera on mice, di-methylnitrosamine on rat, alloxan on rabbit, n-heptane on rat, bile duct ligation on rat and tacrine (centrally acting anti-cholinesterase) on human liver-derived Hep G2 cells. Among all listed plants, for only few acute toxicity studies were conducted. For example, Aloe barbadensis did not show any sign of toxicity up to oral dose of 2 g/kg in mice (Chandan et al., 2007) and Euphorbia fusiformis ethanol extract single dose LD50 was found to be 10,000 mg/kg body weight when administered orally in mice (Anusuya et al., 2010).

Botanical herbs have been used for protection and treatment of liver diseases due to the presence of chemical constituents. For example, polyphenolic compounds have an important role in stabilizing lipid oxidation and are associated with antioxidant activity. Phenyl propanoids include phenolic compounds; those have shown remarkable effects on carbon tetrachloride-induced toxic indications in rats while eugenol and acetyleugenol from Syzygium aromaticum (Myrtaceae) exhibit cholagogue activity in biological models which increase the contractile activity and promote the discharge of bile from the liver and the gall bladder. Coumarin derivatives like 7-hydroxy, 7-s- hydroxy, 4-hydroxy, 4,7-dihydroxy and 4,7-dimethyl-5-hydroxy coumarin, coumarin-3-carboxylic acid and dicoumarol has ability to stimulate choleresis in rats (Vonk et al., 1978). Family Compositae (Artemisia abrotanum, Cichorium intybus) produce poly phenolic compounds and all those chemical compounds which have hydroxyl group at C-7 are become able to exerting a strong choleretic action (Dey et al., 2013). Silymarin is a most potent hepatoprotective compound and a mixture of isomeric flavolignans- silybin, silydianin and silychristen. It produces its defensive mechanism by competitively blocking the binding of phalloidin to receptors on the membrane of liver cell and obstructing the α-amanitin to infiltrate through the membrane into the cell nucleus (Valan et al., 2013). Essential oil also has shown its protective potential on liver histology, liver metabolic and serum profile. Myrtaceae, Umbelliferae, Labiatae and Rosaceae families increase the bile secretion and organic components to protect the liver by producing essential oils through choleretic activity. Umbelliferae has also ability to regenerate the hepatocytes by decreasing the liver damage and tissue necrosis.

Various diterpenoids, triterpinoids and sesquiterpenoids mostly from Lauraceae, Acanthaceae, Compositae families have active components β-eugenol and hinesol exhibited significant liver protecting effects by decreasing the SGPT and SGOT levels. Curcurbitiacin B, a triterpene compound obtained from Cucurbitaceae family has shown it’s inflammatory and choleretic activity in biological models. Active constituents: Glycyrrhizin and glycyrrhetic acid from of Glycyrrhiza glabra (Fabaceae) prevent the cirrhosis in rats (Al-Razzuq et al., 2012). Carotenoids include crocin and crocetin isolated from the fruits Rubiaceae family increase the bile secretion when administered into rabbits. Extracts from Scrophulariaceae, Rubiaceae and Plantaginaceae families produce glycosides like picroside I and picroside II, acubin, iridoid and geniposidic acid have  shown liver protective  effects against liver intoxication by carbon tetrachloride in mice. Saponins like saikosaponin D and saikosamponin A are produced by Leguminosae, Polygonaceae, Caryophyllaceae and Arleaceae families protect the liver in rabbits from hepatotoxin like carbon tetrachloride and inhibit the deposition of lipid peroxides in the liver of rats. Catechin, quercetin, kaempferol, narringenin, isohelichrysin, luteolin stachyrin, α-tocopherol (vitamin E) belong to flavonoid group of compounds. All families like Compositae, Liliaceae, Euphorbiaceae, Scrophulariaceae, Labiatae etc have flavonoids as their major constituents and that’s why having potent potential for protection and treatment of liver diseases correlating with radical scavenging activity by donating hydrogen atom [H+]. Flavonoids also have ability to scavenge the superoxide anion and hydroxyl radicals and terminate chain radical reactions (Kumar et al., 2011).

Conclusion

The purpose of clustering maximum plants having potential for treatment and protection of liver against various hepatotoxic agents is to develop an encyclopedia. Although we know the traditional hepatoprotective and antioxidant plants those are easily available in their crude form but their use in this form is so difficult or some time useless to cure the disease. So, still there is a strong need to develop some effective agents based on plant principles.

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Published
2014-10-09

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Issue
Vol 9 No 4 (2014)
Section
Mini Review
Financial Support
Conflict of Interest
Authors declare no conflict of interest.