Potent Herbs Used in the Treatment of Liver Diseases

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.