Medicinal plants in the protection and treatment of liver diseases

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-thecounter 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).
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.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.
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  1: Lepidium sativum juice and powder has hepatoprotective activity against carbon tetrachloride (CCl4) and 2-amino-3methylimidazole-4, 5-quinoline (IQ).These hepatotoxins disturb the liver regular mechanisms.Plant juice inhibits the hepatocarcinogenesis 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.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), -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 anti-oxidant 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, 4,7dihydroxy 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 -amanitin to infiltrate through the membrane into the cell nucleus (Valan et al., 2013) (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 anti-oxidant 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.

Figure 4 :Figure 5 :
Figure4: 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) 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 Figure4.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 heaptitis by controlling oxidative stress and hepatic phase I and II metabolism shown in Figure

Table II Reported medicinal plants having hepatoprotective potential (Continued)
Various diterpenoids, triterpinoids and sesquiterpenoids mostly from Lauraceae, Acanthaceae, Compositae families have active components -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: 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 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, -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