Bangladesh Journal of Pharmacology Mini Review Medicinal plants in the protection Medicinal plants in the protection Medicinal plants in the protection and treatment of liver diseasesand treatment of liver diseasesand treatment of liver diseases BJP 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 accu- mulation of blood in liver, inflammation, pathogenic infection, cysts and increased size of hepatocytes, infil- trative 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, pro- teins and heavy metals. Congenital metabolic disorders include: Congenital hyperbilirubinemia, Gilbert syndro- mes, Rotor syndrome, Dubin-jhonson syndrome and alpha 1 antitrypsin deficiency. Aquired metabolic disor- der 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- A Journal of the Bangladesh Pharmacological Society (BDPS); www.bdps.info Bangladesh J Pharmacol 2014; 9: 511-526 Journal homepage: www.banglajol.info Abstracted/indexed in Academic Search Complete, Agroforestry Abstracts, Asia Journals Online, Bangladesh Journals Online, Biological Abstracts, BIOSIS Previews, CAB Abstracts, Current Abstracts, Directory of Open Access Journals, EMBASE/Excerpta Medica, Google Scholar, HINARI (WHO), International Pharmaceutical Abstracts, Open J-gate, Science Citation Index Expanded, SCOPUS and Social Sciences Citation Index ISSN: 1991-0088; 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. Article Info Received: 1 October 2014 Accepted: 16 October 2014 Available Online: 19 October 2014 DOI: 10.3329/bjp.v9i4.20648 Cite this article: Saleem M, Naseer F. Medicinal plants in the protection and treatment of liver diseases. Bangladesh J Pharma- col. 2017; 12: 511-26. This work is licensed under a Creative Commons Attribution 3.0 License. You are free to copy, distribute and perform the work. You must attribute the work in the manner specified by the author or licensor. Medicinal plants in the protection and treatment of liver diseases Mohammad Saleem and Faiza Naseer College of Pharmacy, G.C University Faisalabad, Faisalabad, Pakistan. tory or traumatic injury) lead to liver necrosis. Necrosis could be diffuse, zonal or focal (Table I). Other liver diseases include followings:  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, histo- plasmosis, 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 ex- change of body fluids such as blood trans- fusion 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 conven- tional 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 procya- nidins, its hepatoprotective action against two hepato- toxins tetradecanoylphorbol acetate, carbon tetrachlo- ride and D-galactosamine. Figure 3 has presented the one medicinal plant (Ficus carica: Family Umbelli- feraceae) 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 heap- titis 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. 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 phospha- tase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lipid profile, lactate dehydro- genase (LDH), gamma-glutamyltransferase ( -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 512 Bangladesh J Pharmacol 2014; 9: 511-526 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, etha- nol, tetracycline Host idiosyncrasy Hypersensitivity Drug allergy Necrosis or cholestetosis Sulphonamides, iproniazid, halo- thane, paraaminosalicylate, isonia- zid, pyrazinamide, rifampicin Bangladesh J Pharmacol 2014; 9: 511-526 513 Figure 1: Lepidium sativum juice and powder has hepatoprotective activity against carbon tetrachloride (CCl4) and 2-amino-3- methylimidazole-4, 5-quinoline (IQ). These hepatotoxins disturb the liver regular mechanisms. Plant juice inhibits the hepatocar- cinogenesis via increasing the UDP-glucuronyl-transferase-2 and carcinogen detoxification, inhibits the liver injury via inhibiting the AST, ALT, nitric oxide (NO), leukotriene B4, interleukin 2 (IL-2), tumor necrosis factor (TNF- ) and transforming growth factor (TGF- ) and increases the hepatic detoxification via up regulating the glucuronyltransferase-2 (Afaf et al., 2008) Figure 2: Vaccinium procyanidins inhibits the liver injury via increasing the nuclear factor 2 (NRF-2), NADPH dehydrogenase quinine 1 (NQO1), superoxide dismutase (SOD), glutathione-S-transferase (GST) and hemoxygenase 1, viral hepatitis, fibrogenesis via inhibiting the mitogen activated protein kinase pathways (MAPK) and platelet derived growth factor (PDGF), hepatocarcinogenesis via inhibiting matrix metalloproteinase (MMP), vascular endothelial growth factor (VEGF), nuclear factor kappa light chain enhancer of B cells (NF-ǩB), increases the hepatic detoxification and biliary elimination against hepatotoxins like carbon tetrachloride (CCl4) and D-galactosamine N (Gressner et al., 2012) Figure 3: Ficus carica prevents the liver cell death and LDH leakage by increasing AST, ALT, ALP, TB and MDA levels and decreasing oxidative stress parameters (GSH, SOD, CAT), those were perturbed by CCl4 and Rifampicin hepatotoxins (Poumale et al., 2008) 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. Thioace- tamide, 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/lipopoly- saccharide (3 studies conducted: 2 on rat and 1 on mice), ethanol (3 plants studies on rats), -hexachloro- cyclohexane by Aloe vera on mice, di-methylnitrosa- mine 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 chemi- cal constituents. For example, polyphenolic compounds have an important role in stabilizing lipid oxidation and are associated with anti-oxidant activity. Phenyl propa- noids include phenolic compounds; those have shown remarkable effects on carbon tetrachloride-induced toxic indications in rats while eugenol and acetyleuge- nol from Syzygium aromaticum (Myrtaceae) exhibit 514 Bangladesh J Pharmacol 2014; 9: 511-526 Figure 4: Allium sativum (Family Liliaceae) has shown hepatoprotective potential due to its organosulphur components including: allicin, diallyl sulphide, diallyl disulphide, S-allyl cysteine and allyl marcaptan. These constituents inhibits the hepatocarcinogenesis via inhibiting the genotoxicity, cell proapoptotic activities and increasing the chemosensitivity against carcinogens, aflatoxin B1, H2O2, methyl methanesulfonate (MmeS), bezno-a-pyrene and dimethylnitrosamine. Allicin inhibits the steatosis via inhibiting total serum cholesterol. Its oil and allicin has negative potential against hepatotoxins like CCl4, D-gal-N, Ethanol and heavy metals via inhibiting the AST, ALT, ALP, MDA and ROS and increasing the GSH, SOD, CAT and GPx levels in intrahepatic tissues (Ilyas et al., 2011) Figure 5: Glycyrrhiza glabra (Family: Fabaceae) has hepatoprotective action due to glycyrrhetinic acid and liqourice by inhibiting the liver injuries and inflammation via controlling the oxidative stress parameters and increasing the hepatic detoxification via increasing the cytochrom phase I and glucuronidation phase II metabolism which become affected by hepatotoxins carbon tetra- chloride and D-galactosamine N (Al-Razzuq et al., 2012) Bangladesh J Pharmacol 2014; 9: 511-526 515 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 bidenta- tum (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- hexachlorocyclo- hexane (Lindane) Mice ↓ AST, ALP and ALT levels. Restored depleted liver thiols Etim et al., 2006 8 Amaranthus cau- datus (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 spi- nosus (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 -GT and ↑ TP level Kaleem et al., 2006 11 Arachniodes exilis (Dryopteridaceae) Rhi- zome Ethanol CCl4 Mice ↓ AST, ALT, ALP and CHL. ↑ antioxi- dant enzyme activi- ties of SOD, CAT, MDA and GSH Zhou et al., 2010 12 Asparagus race- mosus (Liliaceae) Whole plant Crude aque- ous PCT Rat ↑ LPO, ↓ GSH and SOD Om et al., 2011 13 Baliospermum montanum (Euphorbiaceae) Leaves Alcohol, Chloroform Thioace-tamide 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 Thioace-tamide 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 516 Bangladesh J Pharmacol 2014; 9: 511-526 Table II Reported medicinal plants having hepatoprotective potential (Continued) SL. No. Botanical plant (Family) Parts used Extract Hepatotoxic agent In vivo models Remarks about liver marker enzymes References 18 Bupleurum kaoi (Umbelliferae) Roots Ethanol Dimethyl nitrosa- mine Rat ↓ SGOT , SGPT, ALP, AST and ALT Yen et al., 2005 19 Butea monosper- ma (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 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 -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 equise- tifolia (Casuarinaceae) Leaves and Bark Methanol CCl4 Rat ↓ SGOT , SGPT and cholesterol level Ahsan et al., 2009 28 Cestrum noctur- num (Solanaceae) Leaves Aqueous ethanol PCT Mice ↓ SGOT , SGPT, ALP, AST, ALT and LDH levels Qadir et al., 2014 29 Chamomile recuti- ta (Asteraceae) Flower Methanol CCl4 Rat ↑ Conc. of glutathi- one 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 Bangladesh J Pharmacol 2014; 9: 511-526 517 Table II Reported medicinal plants having hepatoprotective potential (Continued) SL. No. Botanical plant (Family) Parts used Extract Hepatotoxic agent In vivo models Remarks about liver marker enzymes References 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) Rhi- zome 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 en- zyme 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 hamilto- nii (Asclepiadaceae) Roots Aqueous Ethanol Rat ↓ ALT, AST, LDLC, HDL TC and STG. ↑ SOD, CAT, GSH-Px, GST, and GSH Srivastava and Shivanan dappa, 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 arven- se (Equisetaceae) Aerial parts Methanol Tacrine Hep G2 cells ↓ AST, ALT, TP, TB and ALP levels Oh et al., 2004 45 Eucalyptus macu- lata (Myrtaceae) Leaves Chloroform PCT Rats and Mice ↓ AST, ALT and ALP Mohamed et al., 2005 46 Euphorbia fusi- formis (Euphorbiaceae) Tubers Ethanol RMP Rat ↓ AST, ALT, ALP, SGPT and SGOT Anusuya et al., 2010 47 Feronia elephan- tum (Rutaceae) Fruit Aqueous CCl4 Rat ↓ ALT, AST, billiru- bin 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 vul- gare (Apiaceae) Leaves and fruit Ethanol CCl4 Rat ↓ AST, ALT, ALP, SGPT and SGOT Ozbek et al., 2003 http://www.sciencedirect.com/science/article/pii/S1386634606001598 http://www.sciencedirect.com/science/article/pii/S1386634606001598 http://www.sciencedirect.com/science/article/pii/S1386634606001598 518 Bangladesh J Pharmacol 2014; 9: 511-526 Table II Reported medicinal plants having hepatoprotective potential (Continued) SL. No. Botanical plant (Family) Parts used Extract Hepatotoxic agent In vivo models Remarks about liver marker enzymes References 50 Galium apari- ne (Rubiaceae) whole plant Alcohol CCl4 Rat ↓ALP, AST, and ALT levels Khan et al., 2011 51 Glycosmis pen- taphylla (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 en- zyme activities of SOD, CAT, GSH-Px, GST and GSH Al-Razzuqi et al., 2012 53 Gundelia touren- fortii (Asteraceae) Stalk Hydro alco- holic 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 salicor- nicum (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 auric- ulata (Acanthaceae) Roots Aqueous CCl4 Rat ↓ AST , ALT, ALP, TB and CHL levels Dhanaraj et al., 2012 58 Hypericum japon- icum (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 staph- ylina (Convolvulaceae ) Levaes Hydro- alco- hol CCl4 Rat ↓ALP, AST, ALT, SGPT, SGOT and CHL levels Bag and Mumtaz, 2013 61 Kohautia grandi- flora (Rubiaceae) Leaves Aqueous PCT Rat ↓ AST , ALT, ALP, TB and TP Garba et al., 2009 62 Laggera pterodon- ta (Asteraceae) Whole plant Ethyl alcohol CCl4 Rat ↓ AST , ALT, ALP, TB and TP Wu et al., 2007 63 Launaea procum- bens (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 Bangladesh J Pharmacol 2014; 9: 511-526 519 Table II Reported medicinal plants having hepatoprotective potential (Continued) SL. No. Botanical plant (Family) Parts used Extract Hepatotoxic agent In vivo models Remarks about liver marker enzymes References 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 en- zyme activities of SOD, CAT, GSH-Px, GST and GSH. ↓ AST , ALT, ALP, TB and TP. ↓ SGOT, SGPT Pari and Ku- mar, 2002 70 Nigella sativa (Ranunculaceae) Seeds Alcohol Galactosa-mine/ lipo- polysaccha- ride Rat ↓ALP, AST, TB, TP and ALT Gani and John, 2013 71 Ocimum gratissi- um (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 acule- ata (Fabaceae) Leaves Ethanol PCT Rat ↓ SGOT, SGPT, LDH, ALP, TB and ↑ TP levels Shah and Deval, 2011 75 Phoenix dac- tylifera (Arecaceae) Fruits Methanol Thioaceta-mide Rat Ameliorated the increased level of MDA and decline of GSH and ameliora- tion of ALT, ALP and AST Okwuosa et al., 2014 76 Picrorhiza kurroa (Scrophulariaceae) Roots rhi- zomes Ethanol CCl4 Rat ↓ALP, AST, ALT, SGPT, SGOT and CHL levels Arsul et al., 2011 77 Piper chaba (Piperaceae) Fruit Aqueous acetone Galactosa-mine/ lipo- polysaccha- ride Mice ↓ALP, AST, ALT, SGPT and SGOT levels Matsuda et al., 2009 78 Pistacia integerri- ma (Anacardiaceae) Bark Ethyl acetate PCT Rat ↓ ALP, AST, and ALT levels Joshi and Mishra, 2010 79 Plumbago zeylan- ica (Plumbaginacea) Aerial parts Methanol PCT Rat ↓ serum TB, SGPT, SGOT and ALP levels Kanchana and Sadiq, 2011 80 Phyllanthus em- blica (Euphorbiaceae) Fruits Aqueous PCT Rat Significant ↑ TBC and less necrosis Malar and Mettilda, 2009 81 Phyllanthus niru- ri (Euphorbiaceae) Leaves, fruits Aqueous methanol PCT Mice ↑ Antioxidant en- zyme activities of SOD, CAT, GSH-Px, GST and GSH. Tabassum and Agrawal, 2005 82 Phyllanthus poly- phyllus (Euphorbiaceae) Leaves Methanol PCT Mice ↓ ALP, AST, ALT, SPGT and SGOT levels. ↑ Antioxidant en- zyme activities of SOD, CAT, GSH-Px, GST and GSH. Srirama et al., 2012 520 Bangladesh J Pharmacol 2014; 9: 511-526 Table II Reported medicinal plants having hepatoprotective potential (Continued) SL. No. Botanical plant (Family) Parts used Extract Hepatotoxic agent In vivo models Remarks about liver marker enzymes References 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 ne- crosis Singh and Mehta, 2003 91 Saururus chinen- sis (Saururaceae) Whole plant Ethanol CCl4 Rat ↓ AST, ALT, ALP and CHL. ↑ antioxi- dant enzyme activi- ties of SOD, CAT, MDA and GSH Wang et al., 2009 92 Schouwia thebica (Arecaceae) Aerial parts Diethyl ether, chloro- form CCl4 Rat ↓ ALT, AST, SGPT, SGOT, levels of glucose, triglycer- ides 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 maria- num (Asteraceae) Whole plant Ethanol CCl4 Rat ↓ AST, ALT, ALP and CHL. ↑ antioxi- dant enzyme activi- ties 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 Bangladesh J Pharmacol 2014; 9: 511-526 521 Table II Reported medicinal plants having hepatoprotective potential (Continued) SL. No. Botanical plant (Family) Parts used Extract Hepatotoxic agent In vivo models Remarks about liver marker enzymes References 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 en- zyme activities of SOD, CAT, GSH-Px, GST and GSH. Singh and Gupta, 2011 100 Tephrosia pur- purea L (Fabaceae) Aerial parts Aqueous ethanol Thioaceta-mide Rat ↓ ALP, AST, ALT, SPGT and SGOT levels. Ameliorated the increased level of MDA and decline of GSH and ameliora- tion of ALT, ALP and AST Khatri et al., 2009 101 Terminalia chebu- la (Combetraceae) Fruit Ethanol RIF, INH, PZA Rat ↓ AST, ALT, ALP, TP and TB levels Tasduq et al., 2006 102 Thunbergia lauri- folia (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 decan- dra (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 procum- bens (Asteraceae) Aerial parts Ethanol Galactosa-mine/ lipopolysa- ccharide 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 amygda- lina (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 http://www.ncbi.nlm.nih.gov/pubmed/?term=Manjunatha%20BK%5Bauth%5D http://www.ncbi.nlm.nih.gov/pubmed/?term=Vidya%20SM%5Bauth%5D cholagogue activity in biological models which increase the contractile activity and promote the discharge of bile from the liver and the gall bladder. Coumarin deri- vatives like 7-hydroxy, 7-s- hydroxy, 4-hydroxy, 4,7- dihydroxy and 4,7-dimethyl-5-hydroxy coumarin, cou- marin-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 hepatopro- tective compound and a mixture of isomeric flavolig- nans- 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 -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 sesquiterpe- noids mostly from Lauraceae, Acanthaceae, Compositae families have active components -eugenol and hinesol exhibited significant liver protecting effects by decrea- sing 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: Glycy -rrhizin 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 saikosa- ponin D and saikosamponin A are produced by Legu- minosae, 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 stachy- rin, -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+]. 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