This article throws light upon the top sixteen potent herbs used in the treatment of liver diseases. Some of the potent herbs are: 1. Silymarin 2. Glycyrrhizin 3. Phyllanthus Niruri 4. Boerhaavia Diffusa 5. Eclipta Alba 6. Berberis Aristata 7. Andrographis Paniculata 8. Picrorhiza Kurroa 9. Cichorium Intybus (Family: Compositae) 10. Solarium Nigrum (Family: Solanaceae) and others.
Potent Herb # 1. Silymarin (Family: Compositae):
Silymarin obtained from Silybum marianum, commonly known as ‘milk thistle’ is one of the oldest and thoroughly researched plants in the treatment of liver diseases. It is the gold standard of hepato-protective agents and has been widely used as comparative standard for test drugs in preclinical studies.
The pharmacological profile of silymarin has been well defined and hepato-protective properties of silymarin were investigated both in vitro and in vivo. Experimental studies demonstrated antioxidant and free radical scavenging properties, improvement of the anti-oxidative defense by prevention of glutathione depletion, and anti-fibrotic activity.
The active constituents of the plant are obtained from the dried seeds and consist of four flavonolignans which are collectively known as silymarin. Silymarin is extracted from the dried seeds of milk thistle plant, where it is present in higher concentrations than in other parts of the plant.
Silymarin is a complex mixture of four flavonolignan isomers, namely silybin, isosilybin, silydianin and silychristin with an empirical formula C25H22O10. The structural similarity of silymarin to steroid hormones is believed to be responsible for its protein synthesis facilitatory actions.
Among the isomers silybin is the major and most active component and represents about 60-70%, followed by silychristin (20%), silydianin (10%), and isosilybin (5%).
The cytoprotective effects of silymarin are mainly attributable to its antioxidant and free radical scavenging properties.
Silymarin can also interact directly with cell membrane components to prevent any abnormalities in the content of lipid fraction responsible for maintaining normal fluidity. Silymarin also has anti-inflammatory actions due to inhibition of 5- lipoxygenase pathway which results in impaired Ieukotriene synthesis.
Liver fibrosis can result in remodeling of liver architecture leading to hepatic insufficiency, portal hypertension and hepatic encephalopathy. These processes involve complex interplay of cells and mediators. In the initial phase there will be proliferation of hepatic parenchymal cells. The conversion of hepatic stellate cells (HSC) into myofibroblast is considered as the central event in fibro genesis.
Silymarin inhibits NF-KB and also retards HSC activation. It also inhibits protein kinases and other kinases involved in signal transduction and may interact with intracellular signaling pathways.
Stimulation of protein synthesis by Silymarin has important therapeutic implications in the repair of damaged hepatocytes and restoration of normal functions of liver.
Drugs in common use can cause toxic effects on the liver which can mimic almost every natural diseases of the liver. This is rarely due to the drug itself and a toxic metabolite is usually responsible. The drug metabolizing enzymes activate chemically stable drugs to produce electrophilic metabolites.
These potent agents bind covalently to liver molecules such as proteins and fatty acids which are essential to the life of the hepatocyte and necrosis ensues. Free radicals are generated which results in lipid peroxidation and membrane damage. The end result is hepatocyte death related to failure to pump calcium from the cytosol and to depressed mitochondrial function.
Drugs like paracetamol and halothane produce zone 3 (centrilobular) necrosis of liver. Silymarin has a regulatory action on cellular and mitochondrial membrane permeability in association with an increase in membrane stability against xenobiotic injury.
It can prevent the absorption of toxins into the hepatocytes by occupying the binding sites as well as inhibiting many transport proteins at the membrane. These actions along with anti-per-oxidative property make silymarin a suitable candidate for the treatment of iatrogenic and toxic liver diseases.
Potent Herb # 2. Glycyrrhizin (Family: Leguminosae):
Glycyrrhizin is an aqueous extract of the liquorice root (Clycyrrhiza glabra) and has been used in traditional medicine to alleviate bronchitis, gastritis and jaundice.
The major constituents are glycyrrhetinic acid, flavonoids, hydroxycoumarins, and β-sitosterol, the latter with probable glucocorticoid and mineralocorticoid properties. Glycyrrhizin is capable of preventing various kinds of liver injury in animals. This drug possesses anti-inflammatory and antioxidant activities.
Glycyrrhizin inhibits CD4+ T-cell and tumor necrosis factor (TNF)-mediated cytotoxicity. Glycyrrhizin has a membrane stabilizing effect and also stimulates endogenous production of interferon. In cell culture experiments, glycyrrhizin modifies glycosylation and blocks sialylation of hepatitis B surface antigen (HBsAg), leading to its retention in the Golgi apparatus.
Glycyrrhizin counteracts several forms of experimental hepatic injury and partly inhibits the activity of 11 -beta- hydroxysteroid dehydrogenase, prostaglandin E2 production by macrophages, and may have anti-oxidative properties through the induction of glutathione-S-transferees and catalase. Some evidence points to an anti-fibrotic effect in the rat CCl4 model, possibly through inactivation of NFkB.
Potent Herb # 3. Phyllanthus Niruri (Family: Euphorbiaceae):
Phyllanthus niruri is a small, erect, annual herb that grows 30-40 cm in height. It is indigenous to the rainforests of the Amazon and other tropical areas throughout the world, including the Bahamas, southern India, and China.
The main plant chemicals include alkaloids, astragalin, brevifolin, carboxylic acids, corilagin, cymene, ellagic acid, ellagitannins, gallocatechins, geraniin, hypophyllanthin, lignans, lintetralins, lupeols, methyl salicylate, niranthin, nirtetralin, niruretin, nirurin, phyllanthin, phyllanthine, phyllanthenol, phyllochrysine, phyltetralin, repandusinic acids, quercetin, quercetol, quercitrin, rutin, saponins, triacontanal, and tricontanol.
Whole plant, fresh leaves and fruits are used to treat various ailments, particularly hepatitis. This herb has shown potent antioxidant activity and hepato-protective activity.
Methanolic and aqueous extract of leaves and fruits of P. niruri showed inhibition of membrane lipid peroxidation (LPO), scavenging of 1,1-diphenyl-2 picrylhydrazyl (DPPH) radical and inhibition of reactive oxygen species (ROS) in vitro.
Antioxidant activities of the extracts were also demonstrable in vivo by the inhibition of the CCI4 induced formation of lipid peroxides in the liver of rats by pretreatment with the extracts. CCI4 induced hepatotoxicity in rats, as judged by the raised serum enzymes, glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) was prevented by pre-treatment with the extracts, demonstrating the hepato-protective action of P. niruri.
Treatment with the protein isolates of P. niruri significantly increase SOD and catalase which were reduced due to CCI4 administration. Phyllanthin and hypo-phyllanthin have been established as the hepato-protective agents.
Potent Herb # 4. Boerhaavia Diffusa (Family: Nyctaginaceae):
Boerhaavia diffusa is a vigorous, low-growing, spreading vine with a long, tuberous tap root. It can be found in many tropical and warm-climate countries and is indigenous to Brazil. It is also found in abundance in warmer parts of India and called punarnava.
It has a long history of use by indigenous and tribal people and in Ayurvedic herbal medicine systems. The roots of Boerhaavia diffusa are used by a large number of tribes in India for the treatment of various hepatic disorders.
The Boerhaavia diffusa plant contains a large number of such compounds as flavonoids, alkaloids, steroids, triterpenoids, lipids, lignins, carbohydrates, proteins, and glycoproteins. Punarnavine, punarnavoside and liirodendrin are the major active constituents.
Punarnavoside and liirodendrin are thought to be responsible for the hepatopotective activity. The hepato-protective activity of roots of Boerhaavia diffusa was examined in thioacetamide intoxicated rats. The results showed that an aqueous extract (2 ml/kg) of roots exhibited marked protection of a majority of serum parameters, i.e. AST, ALT and ALP.
Potent Herb # 5. Eclipta Alba (Family: Compositae):
It is widely used herbal medicine. Folklore suggests its hepato-protective activity. It is widely distributed throughout India, China, Thailand, and Brazil. In Ayurvedic medicine, the leaf extract is considered a powerful liver tonic, rejuvenative, and especially good for the hair.
Phyto-chemically, Eclipta alba is rich in coumestans i.e. wedel lactone (I) and demethylwedelolactone (II), polypeptides, P-amyrin, stigmasterol, luteolin-7- Glucoside, poly-acetylenes, thiophene-derivatives, steroids, triterpenes and flavonoids.
Wedelolac-tone possesses a wide range of biological activities and is used for the treatment of hepatitis and cirrhosis and for direct inhibition of IKK complex resulting in suppression of LPS-induced caspase- 11 expression.
The hepato-protective activity has been experimentally established. The hepato-protective effect of the ethanol/water (1:1) extract of Eclipta alba has been studied in rats against CCI4 induced hepatotoxicity.
It significantly counteracted CCI4 induced inhibition of the hepatic microsomal drug metabolizing enzyme amidopyrine N-demethylase and membrane bound glucose 6-phosphatase, but failed to reverse the very high degree of inhibition of another drug metabolizing enzyme aniline hydroxylase.
The loss of hepatic lysosomal acid phosphatase and alkaline phosphatase by CCI4 was significantly restored by extract of Eclipta alba. The study shows that hepato-protective activity of extract of Eclipta alba is by regulating the levels of hepatic microsomal drug metabolizing enzymes.
Potent Herb # 6. Berberis Aristata (Family: Berberida-Ceae):
Berberis aristata is an erect, spine scent and glabrous shrub, ranging between 2 and 3 metres in height with lanceolate, simple spiny, toothed, leathery, sessile, acuminate leaves.
The flowers are yellow coloured and are present in corymbose racemes. Fruits are in form of ovoid berries. It is an edible plant employed in the South Asian Traditional Medicine, particularly its fruits being used as a tonic remedy for liver and heart.
It is rich in alkaloids like berberine, oxyberberine, berbamine, aromoline, karachine, and oxycanthine. Berberine is the major active constituent. Berberine has experimentally established hepato-protective activity. In an investigation, berberine, a known compound from this plant, was studied for its possible anti- hepatotoxic action in rats.
Pretreatment of animals with berberine (4 mg/kg; orally twice daily for 2 days) prevented the acetaminophen or CCl4 induced rise in serum levels of alkaline phosphatase (ALP) and amino transaminases (AST and ALT), suggestive of hepato-protection.
Post-treatment with three successive oral doses of berberine (4 mg/kg every 6 h) reduced the hepatic damage induced by acetaminophen, while CCl4 induced hepatotoxicity was not modified, suggesting a selective curative effect against acetaminophen.
Pretreatment of animals with a single oral dose of berberine (4 mg/kg) induced prolongation of the pentobarbital (60 mg/kg, i.p.) induced sleeping time as well as increased strychnine (0.3 mg/kg; i.p.) induced toxicity, suggestive of inhibitory effect on microsomal drug metabolizing enzymes, cytochrome P450s (CYPs).
Potent Herb # 7. Andrographis Paniculata (Family: Acan- Thaceae):
Andrographis paniculata is a herbaceous plant in the family Acanthaceae, native to India and Sri Lanka. Andrographis paniculata, is an erect annual herb extremely bitter in taste in each and every part of the plant body. The stem is quadrangular with longitudinal furrows. The leaves are glabrous, dark green and arranged opposite decussate. Flowers are small and in terminal racemes.
Mostly the leaves and roots were used for medicinal purposes. The principal constituents are 14- Deoxy-11 -dehydroandrographolide, 14-Deoxy- 11-oxoandrographolide, andrographolide, an-drographine, neoandrographolide, panicoline, panicufide-A, paniculide-B and paniculide-C.
Andrographolide, chief constituent extruded from the leaves of the plant, is a bitter water-soluble lactone exhibiting protective effects in carbon tetrachloride induced hepatopathy in rats. It is very popular for its hepato-protective activity. Andrographolide is the major active constituent and it has been established that it is responsible for the hepato-protective activity of Andrographis paniculata.
Andrographolide, the active constituent isolated from the plant Andrographis paniculata, showed a significant dose dependent (0.75-12 mg/kg p.o.x 7) protective activity against paracetamol-induced toxicity on ex vivo preparation of isolated rat hepatocytes.
It significantly increased the percent viability of the hepatocytes as tested by trypan blue exclusion and oxygen uptake tests. It completely antagonized the toxic effects of paracetamol on certain enzymes (GOT, GPT and alkaline phosphatase) in serum as well as in isolated hepatic cells. Andrographolide was found to be more potent than silymarin, a standard hepato-protective agent.
Potent Herb # 8. Picrorhiza Kurroa (Family: Scrophulari-Aceae):
Picrorhiza kurroa is a well-known herb in the Ayurvedic system of medicine and has traditionally been used to treat disorders of the liver and upper respiratory tract, reduce fevers, and to treat dyspepsia, chronic diarrhea, and scorpion sting.
It is a small perennial herb from the Scrophulariaceae family, found in the Himalayan region growing at elevations of 3,000-5,000 meters. The active constituents are obtained from the root and rhizomes.
Kutkin is the active principle of Picrorhiza kurroa and is comprised of kutkoside and the iridoid glycoside picrosides I, II, and III. Other identified active constituents are apocynin, drosin, and nine cucurbitacin glycosides. Picroliv is a standardized iridoid glycoside mixture isolated from the roots and rhizomes of the plant Picrorhizakum.
It contains at least 60% of a i ;1.5 mixture of picroside I and kutkoside; the remainder (40%) is a mixture of iridoid as well as cucurbitacin glycosides and some still unidentified substances. This herb is one of the most important natural remedies for liver diseases. Picroliv has been found to possess potent hepatoprotective activity against different hepatotoxins.
The hepato-protective activity of Picroliv, a standardized iridoid glycoside fraction of Picrorhiza kurroa, has been investigated by studying the protection of biochemical and histological changes induced in livers of rats given single oral doses (7 mg/kg) of aflatoxin B1.
Administration of antitoxin B1 resulted in a significant increase in 52-nucleotides, y-glutamyl trans peptidase, acid ribonuclease, total lipids, cholesterol and lipid peroxides in liver and transaminases, alkaline phosphatase and bilirubin in serum.
However, the activity of glucose 6-phosphatase and levels of cytochrome P450, cytochrome b5, DNA, RNA, proteins and glycogen in liver and total proteins in serum decreased. The liver histology showed ballooned hepatocytes, degeneration, micro-vesicular fat, focal necrosis, bile duct hyperplasia and proliferation of oval and spindle cells in portal tracts.
When Picroliv (25 mg/kg x 7 days) was given to aflatoxin B1 toxieated rats, the majority of the biochemical and histological changes were significantly protected. The findings indicate a hepato-protective activity of Picroliv against aflatoxin B1 toxicity in rats.
Potent Herb # 9. Cichorium Intybus (Family: Compositae):
Cichorium intybus is a bushy perennial herb with a fleshy tap root and blue or lavender flowers. The leaves are broadly oblong, lanceolate, crowded at the base and arranged spirally on the stem. Principal chemical constituents are inulin (polysaccharide), cichoriin, lactucin and lactucopricin.
The plant Cichorium intybus is used as liver tonic, cardio tonic, diuretic, stomachic, cholagogue, depurative, emmenagogue, hepatomegaly, cephalalgia, inflammations, anorexia, dyspepsia, flatulence, colic, jaundice, splenomegaly, amenorrhea dysmenorrhea, and asthma. It has been experimentally established as a potent hepato-protective agents.
The different fractions of alcoholic extract and one phenolic compound AB-IV of seeds of Cichorium intybus were screened for anti-hepatotoxic activity on carbon tetrachloride induced liver damage in albino rats. The degree of protection was measured using biochemical parameters like AST, ALT and ALP.
The methanol fraction and compound AB- IV were found to possess a potent anti-hepatotoxic activity comparable to the standard drug Silymarin. The histopathological study of the liver was also carried out, wherein the methanolic fraction and compound AB-IV showed almost complete normalization of the tissues as neither fatty accumulation nor necrosis was observed.
Potent Herb # 10. Solarium Nigrum (Family: Solanaceae):
Solanum nigrum has been widely used as hepato-protective and anti-inflammation agent. The principal constituents are solamargine-A, solamargine-B, solasodine and solasodine. Its hepatoprotective and antioxidant activity has been established experimentally.
In this study, the protective effects of aqueous extract of Solanum nigrum (SNE) against liver damage were evaluated in CCI4 induced chronic hepatotoxicity in rats. Solanum nigrum extract was orally administered (0.2, 0.5 and 1.0 g/kg) along with administration of CCI4 (20% CCI4/corn oil; 0.5 mL/ kg) for 6 weeks.
The results showed that the treatment of SNE significantly lowered the CCI4 induced serum levels of hepatic enzyme markers (COT, CPT, ALP, and total bilirubin), superoxide and hydroxyl radical. The hepatic content of GSH, and activities and expressions of SOD, GST Al, and GST that were reduced by CCl4 were normalized by the supplement of SNE.
Liver histopathology confirmed hepato-protection by SNE. The results of this study suggest that SNE could protect liver against the CCl4 induced oxidative damage in rats, and this hepato-protective effect might be contributed to its modulation on detoxification enzymes and its antioxidant and free radical scavenger effects.
Potent Herb # 11. Plumbago Zeylanica (Family: Plumbagi-Naceae):
Plumbago zeylanica or White Leadwort is native to SE Asia. It is a highly branched, evergreen rambling subscandent shrub with white flowers that reaches about 6 feet (2 meters) in height. Leaves are Dark green, ovate and glabrous.
Plumbago zeylanica is a very useful medicinal plant. The root of the plant and its constituents are credited with potential therapeutic properties including anti-atherogenic, cardiotonic, hepato-protective and neuro-protective properties. The anti-oxidant activity of this herb has been established. Plumbagin is the main active constituent responsible for antioxidant and hepato-protective activity.
Potent Herb # 12. Tinospora Cordifolia (Family: Menisper-Maceae):
Tinospora cordifolia is a large, glabrous, deciduous climbing shrub belonging to the family Menispermaceae. It is distributed throughout tropical Indian subcontinent and China, ascending to an altitude of 300 m. In Hindi, the plant is commonly known as Giloya, which is a Hindu mythological term that refers to the heavenly elixir that have saved celestial beings from old age and kept them eternally young.
Its principle chemical constituents are tinosporine, tinosporide, cordifol, cordifolide, heptacosanol, clerodane furano diterpene, columbin and β-sitosterol. It is widely used in Ayurvedic medicine in India as tonic, vitalizer and as a remedy for diabetes mellitus and metabolic disorders.
It has been experimentally established that this herb also possess significant hepato-protective and antioxidant activities.
Potent Herb # 13. Embelia Ribes (Family: Myrsinaceae):
It is large scandent shrub with slender branches and elliptic-lanceolate and gland dotted leaves. The fruit is globular and wrinkled varying in color from dull red to black. The plant contains embelin, christembine, quercitol and resins.
It is a widely used herb for its anthelmintic, analgesic, antifertility properties hepato-protective and anti-tumour properties. Embelin is the major active constituent and is responsible for the antioxidant and hepato-protective activity.
Potent Herb # 14. Cassia Occidentalis (Family: Caesalpini- Aceae):
Cassia occidentalis commonly known as ‘Kason- di’, is used in Unani medicine for liver ailments and is an important ingredient of several poly- herbal formulations marketed for liver diseases.
The hepato-protective effect of aqueous-ethanol- ic extract (50%, v/v) of leaves of Cassia occidentalis was studied on rat liver damage induced by paracetamol and ethyl alcohol by monitoring AST, ALT, ALP, serum cholesterol, serum total lipids and histopathological alterations. The extract of leaves of the plant produced significant hepato- protection.
Potent Herb # 15. Achillea Millefolium (Family: Composi-Tae):
The herb is used as antiseptic, antispasmodic, hepato-protective, astringent, carminative, cholagogue, diaphoretic, digestive and stimulant. The crude extract of Achillea millefolium was studied for its possible hepato-protective effect against d- galctosamine and lipopolysaccharide (LPS) induced hepatitis in mice to rationalize some of the folklore uses.
Co-administration of d-golactos amine (700 mg/kg) and LPS (25 n/kg) produced 100% mortality in mice. Pre-treatment of animals with Achillea millefolium extract (300 mg/kg) reduced the mortality to 40%.
Co-administration of d-galactosamine (700 mg/kg) and LPS (1 µg/ kg) significantly raised the plasma ALT and AST levels compared with values in the control group. Pre-treatment of mice with crude extract (150- 600 mg/kg) significantly prevented the toxins induced rise in plasma ALT and AST.
The hepato-protective effect of Achillea millefolium extract was further verified by histopathology of the liver, which showed improved architecture, absence of parenchymal congestion, decreased cellular swelling and apoptotic cells, compared with the toxin group of animals.
Potent Herb # 16. Vernonia Amygdalina (Family: Compo- Sitae):
Vernonia amygdalina is widely used in tropical countries for treatment of fever, jaundice, stomach disorders and diabetes. The possible modulatory effect of methanolic extract of Vernonia amygdalina, on the toxicity of CCI4, was investigated in rats.
Oral administration of CCI4 at a dose of 1.2 g/kg body weight 3 times a week for 3 weeks significantly induced marked hepatic injury as revealed by increased activity of the serum enzymes ALT, AST, SALP and y-CT.
Methanolic extract of V. amygdalina administered 5 times a week for 2 weeks before CCI4 treatment at 250 and 500mg/kg doses of the extract ameliorated the increase in the activities of these enzymes.
Likewise the methanolic extract of V. amygdalina reduced the CCl4 induced increase in the concentrations of cholesterol, triglyceride and phospholipid by 37.8%, 30.6% and 8.5%, respectively, and a reduction in the cholesterol/phospholipids ratio. CCI4 induced lipid peroxidation was likewise attenuated by 57.2% at 500mg/kg dose of the methanolic extract of V. amygdalina.
Similarly, administration of the extract increased the activities of the antioxidant enzymes:
SOD, glutathione S-transferase and reduced glutathione concentration significantly at 500mg/kg and catalase activity at 500-1 000mg/kg doses. These results suggest that methanolic extract of V. amygdalina leaves possesses protective effect against CCI4 induced hepatotoxicity by the antioxidant mechanism of action.