medicinal plants for treatment of liver disorders

www.wjpps.com Vol 6, Issue 8, 2017.

326

Ghiliyal et al. World Journal of Pharmacy and Pharmaceutical Sciences

MEDICINAL PLANTS FOR TREATMENT OF LIVER DISORDERS

Pallavi Ghiliyal1* and Alok Bhatt

2

1Department of Pharmacology, Uttaranchal University, Premnagar, Dehradun, India.

2Department of Pharmacognosy, Gayani Inder Singh Institute of Professional Studies,

Mussorie Road, Dehradun, India.

ABSTRACT

Liver is the largest organ of the body comprising 2-3% of the total

adult body weight. It is also the central site for the biotransformation of

xenobiotics. In the process of metabolic detoxification, liver is exposed

to high concentrations of toxicants and toxic metabolites making it

susceptible to injury. Liver damage is associated with cellular necrosis,

increase in tissue lipid peroxidation, and depletion in tissue GSH level,

etc. Herbs play a major role in the management of various liver

disorders. Herbal medicines are in great demand in the developed as

well as developing countries for primary health care because of their

wide biological and medicinal properties, higher safety margins, and

lesser costs. Andrographis paniculata, Silybum marianum, Coccinia

grandis, Flacourtia indica, Wedelia calendulacea, Prostechea michuacana, Ficus carica,

Lepidium sativum, Solanum nigrum, Swertia chirata, Phyllanthus emblica, Curcuma longa,

Picrorhiza kurroa, Azadirachta indica, Aegle marmelos etc have been used in poly-herbal

formulations meant for treatment of liver diseases. These hepatoprotective drugs contain

variety of phyto-constituents like phenols, coumarins, lignans, essential oil, monoterpenes,

carotenoids, glycosides, flavonoids, organic acids, lipids, alkaloids and xanthenes etc.

KEYWORDS: Hepatoprotective, liver, herbal drugs.

INTRODUCTION

Ayurveda (Ayur = life, Veda = knowledge), which is “Science of Life”, originated from the

Vedic times and is a part of holistic health care system. The chief source of ancient Indian

Aryan culture and medicine are the four Vedas that are traditionally believed to be revealed to

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

SJIF Impact Factor 6.647

Volume 6, Issue 8, 326-337 Review Article ISSN 2278 – 4357

Article Received on

30 May 2017,

Revised on 20 June 2017,

Accepted on 11 July 2017

DOI:10.20959/wjpps20178-9695

*Corresponding Author’

Pallavi Ghiliyal

Department of

Pharmacology,

Uttaranchal University,

Premnagar, Dehradun,

India.


327


the sages by Brahma (the creator) some 6000 years before Christian era. Ayurveda’s primary

emphasis is on preservation and promotion of health, it also provides treatment for disease.

Many undesirable constitutions (about eight) in the body are mentioned in “CharkaSamhita”,

an authentic source of Ayurveda. Hepatotoxicity is one among them. It is said that it is

comparatively easy to help an liver disorders person.[1]

Liver is considered to be one of the most vital organs that functions as a centre of metabolism

of nutrients such as carbohydrates, proteins and lipids and excretion of waste metabolites.

Additionally, it is also handling the metabolism and excretion of drugs and other xenobiotics

from the body thereby providing protection against foreign substances by detoxifying and

eliminating them. Liver cell injury caused by various toxicants such as certain

chemotherapeutic agents, carbon tetrachloride, thioacetamide etc., chronic alcohol

consumption and microbes is well-studied. Enhanced lipid peroxidation during metabolism of

ethanol may result in development of hepatitis leading to cirrhosis.[2,4]

The Indian Traditional Medicine like Ayurveda, Siddha and Unani are predominantly based

on the use of plant materials. Herbal drugs have gained importance and popularity in recent

years because of their safety, efficacy and cost effectiveness. The association of medical

plants with other plants in their habitat also influences their medicinal values in some cases.

One of the important and well-documented uses of plant products is their use as

hepatoprotective agents. Hence, there is an ever in-creasing need for safe hepatoprotective

agent.[3,4]

Liver is a vital organ play a major role in metabolism and excretion of xenobiotics from the

body.[3,5]

Liver injury or liver dysfunction is a major health problem that challenges not only

health care professionals but also the pharmaceutical industry and drug regulatory agencies.

Liver cell injury caused by various toxic chemicals (certain antibiotic, chemotherapeutic

agents, carbon tetrachloride (CCL4), thioacetamide (TAA) etc.), excessive alcohol

consumption and microbes is well-studied. The available synthetic drugs to treat liver

disorders in this condition also cause further damage to the liver. Hence, Herbal drugs have

become increasingly popular and their use is wide-spread. Herbal medicines have be used in

the treatment of liver diseases for a long time.

Hepatotoxicity implies chemical-driven liver damage and the chemicals that cause liver

injury are called hepatotoxins. Liver plays a vital role in bio-transformation and sometimes


328


clearing of chemicals that are susceptible to the toxicity. Certain medicinal agents in

overdoses and sometimes even at therapeutic ranges may injure the liver. Other chemical

agents, such as those used in laboratories and industries, herbal remedies can also cause

injury to liver cell. Most of the drugs have been implicated in causing liver damage and is the

most common reason for a drug to be withdrawn from the market.[6]

Hepatotoxicity and drug-

induced liver injury of drugs of different origin is one of leading cause of compound failures,

highlighting the need for drug screening assays such as stem cell-derived hepatocyte-like

cells that are capable of detecting toxicity early in the drug development process. The

diseases and disorders of liver is a worldwide problem in the absence of reliable liver

protective drugs in allopathic medical practices.[7,8]

According to the office for National

Statistics in the United Kingdom, liver disease is now the fifth most common cause of

death.[9]

Liver is considered to be one of the most vital organs that functions as a centre of metabolism

of nutrients such as carbohydrates, proteins, lipids and excretion of waste metabolites.

Additionally, it is also handling the metabolism and excretion of drugs and other xenobiotics

from the body thereby providing protection against foreign substances by detoxifying and

eliminating them. The bile secreted by the liver has, among other things, plays an important

role in digestion. Hepatic disease (Liver disease) is a term that affects the cells, tissues,

structures, or functions of the liver. Liver has a wide range of functions, including

detoxification, protein synthesis, and production of biochemical necessary for digestion and

synthesis as well as breakdown of small and complex molecules, many of which are

necessary for normal vital functions.[10.11]

Herbal drugs are more widely used than allopathic drugs as hepatoprotective because of them

are inexpensive, better cultural acceptability, better compatibility, with the human body and

minimal side effects. These herbal drugs have shown the ability to maintain the normal

functional statues of the liver with or without fewer side effects. The liver plays an

astonishing array of vital functions in the maintenance, performance and regulating

homeostasis of the body. It is involved with almost all the biochemical pathways to growth,

fight against disease, nutrient supply, energy provision and reproduction. Therefore,

maintenance of a healthy liver is essential for the overall well being of an individual. Liver

cell injury caused by various toxicants such as certain chemotherapeutic agents, carbon


329


tetrachloride, thioacetamide etc., chronic alcohol consumption and microbes is well-

studied.[12,13]

The Indian Traditional Medicine like Ayurveda, Siddha and Unani are predominantly based

on the use of plant materials. Herbal drugs have gained importance and popularity in recent

years because of their safety, efficacy and cost effectiveness. Several Indian medicinal plants

have been extensively used in the Indian traditional system of medicine for the management

of liver disorder. The use of natural remedies for the treatment of liver diseases has a long

history and medicinal plants and their derivatives are still used all over the world in one form

or the other for this purpose.[14]

Some indigenous plants that have hepatoprotective properties such as Andrographic

paniculata, Chamomile capitula, Silybum marianum, Coccinia grandis, Flacourtia indica,

Wedelia calendulacea, Annona squamosa, Prostechea michuacana, Ficus carica, Lepidium

sativum, Sargassum polycystum, Solanum nigrum, swertia chirata, Phyllanthus emblica,

Curcuma longa, Picrorhiza kurroa, Azadirachta indica, Aegle marmelos, Cassia roxburghii,

Orthosiphon stamineus, Jatropha curcas, Foeniculum vulgare, Trigonella foenum graecum,

Eclipta alba, Garcinia mangostana Linn.


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Types of Hepatic Injury

[19]

Type of injury or

damage Representative toxins

Fatty liver Amiodarone, CCl4, ethanol, fialuridine, tamoxifen, valproic

acid

Hepatocyte death Acetaminophen, allyl alcohol, Cu, dimethylformamide,

ethanol

Immune-mediated

response Diclofenac, ethanol, halothane, tienilic acid

Canalicular cholestasis Chlorpromazine, cyclosporin A, 1,1-dichloroethylene,

estrogens, Mn, phalloidin

Bile duct damage Alpha-naphthylisothiocyanate, amoxicillin, methylene

dianiline, sporidesmin

Sinusoidal disorders Anabolic steroids, cyclophosphamide, microcystin,

pyrrolizidine alkaloids

Fibrosis and cirrhosis CCl4, ethanol, thioacetamide, vitamin A, vinyl chloride

Tumors Aflatoxin, androgens, arsenic, thorium dioxide, vinyl

chloride

Today every herbal company is marketing formulations for liver disorders but the actual

scene is that only selected medicinal herbs have been tested for hepatotprotective activity.

Some herbal formulations claiming to be hepatoprotective may actually contain chemical

constituents having hepatotoxic potential. Andrographolide (Andrographis paniculata),

Glycyrrhizin (Glychyrrhiza glabra), Picrrorihzin (Picrorrhiza kurroa) and Hypo-phyllanthin

(Phyllanthus niruri) are potential candidates with hepatoprotective activity. The article

reviews latest trends in testing of isolated constituents with hepatoprotective activity.[20]

Liver Diseases and Medicinal Plants

Liver has a pivotal role in regulation of physiological processes. It is involved in several vital

functions such as metabolism, secretion and storage. Furthermore, detoxification of a variety

of drugs and xenobiotics occurs in liver. The bile secreted by the liver has, among other

things, an important role in digestion. Liver diseases are among the most serious ailment7.

They may be classified as acute or chronic hepatitis (inflammatory liver diseases), hepatosis

(non inflammatory diseases) and cirrhosis (degenerative disorder resulting in fibrosis of the

liver). Liver diseases are mainly caused by toxic chemicals (certain antibiotics,

chemotherapeutics, peroxidised oil, aflatoxin, carbon-tetrachloride, chlorinated hydrocarbons,

etc.), excess consumption of alcohol, infections and autoimmune/disorder.[21,20]


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Liver protective herbal drugs contains a variety of chemical constituents like phenols,

coumarins, lignans, essential oil, monoterpenes, carotinoids, glycosides, flavonoids,

lipids, alkaloids and xanthines.[5]

Liver Protective Herbal Drug Along With Their Main Phytoconstituents.

S.NO Main Phytoconstituent Liver protective drug Part used

1. Phenols

Arnica Montana Linn.

Cichorium intybus Linn.

Picrorriza kurroa Royle

Syzygium aromaticum Linn.

Plant

Plant

Root

Plant

2. Coumarin

Armillaria tabescens Scop.

Artemisiae capillaries herba

Hemidesmus indicus

Fungus

Plant

Roots

3. Lignans

Schisandra chinensis Turcz.

Schisandra sphenanthera

Silybum marianum Gaertn

Thujopsis dolabrata

Fruit

Fruit

Seed

Leaves

4. Essential oil

Anethum graveolens Linn.

Apium graveolens Linn.

Azadirachta indica

Carapa guianensi Aublet

Cynara scolumus Linn.

Foenuculum vulgare Mill.

Petroselinum sativum Hoffm.

Pimpinella anisum Linn.

Fruit

Seed

Leaves

Seed

Leaves, Flower

Plant

Plant

Plant

5. Triterpens

Glycyrrhiza glabra Linn.

Hedyotis corymbosa Linn.

Protium heptaphyllum Aubl.

Sambucus chinesis Lindley

Tetrapanax papyriferus

Root

Whole plant

Trunkwood

Plant

Leaves

6. Glycosides

Aloe barbadensis Mill

Dianthus superbus Linn.

Panax ginseng

Polygonum cuspidatum

Polygonum multiflorum Thunb.

Leaves

Plant

Rhizome

Root

Root

7. Flavonoids

Acacia catechu Willd.

Aegiceras corniculatum

Artemisia capillaries Thunb.

Calotropis gigantean R. Br.

Canscora decussate Roxb.

Cassia occidentals Linn

Clausena dentate Willd.

Garcinia kola Heckel

Helichrysum arenarium Linn.

Mentha longifolia Linn.

Phyllanthus emblica Linn.

Scrophularia grossheimi

Tagetes patula Linn.

Hard wood

Stem

Plant

Leaves

Plant and Juice

Leaves

Plant

Inflorescences

Plant

Leaves

Leaves

Plant

Seeds


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Uncaria gambir (Hunter)Roxb Heartwood

8. Alkaloids

Aristolochia clematis

Fumaria parviflora Lam.

Fumaria officinalis Linn.

Herniaria glabra Linn.

Peumus boldus Molina.

Physalis peruviana

Plant

Plant

Plant

Whole Plant

Plant

Plant

Mechanism of Action[23,24,27]

Hepatotoxicity as injury to the liver that is allied with diminished liver function caused by

acquaintance to a drug. the dissimilarity between function and damage is important because it

is mainly when function is impaired that symptom and clinically significant disease follow.

The serious drug related hepatotoxicity is incapacitating life-threatening. drug related

hepatotoxicity is uncommon for many drugs, its true rate is difficult to determine. After

acetaminophen overdose the use of N-acetylcysteine and intravenous carinitine for valproate

induced mitochondrial injury are allowances drug related hepatotoxicity is now leading cause

of acute liver failure, among patient referred for liver transplantation because of an

intentional and intentional overdose of acetaminophen. Hepatotoxicity leads to some liver

disease such as.

Hepatitis, inflammation of liver mainly caused by various viruses but also by some poison

like alcohol, autoimmunity.

Non alcoholic fatty liver disease, a spectrum in disease associated with obesity and

characterized by an abundance in fat of liver; may lead to hepatitis.

Cirrhosis is the formation of fibrous tissue in the liver can be caused by viral hepatitis,

alcoholism or contact with other liver toxic chemicals.

Haemochromatosis, a hereditary disease causing the accumulation of iron in the body,

eventually leading to liver damage.

Cancer of the liver(primary hepatocellular carcinoma of cholangiocarcinoma and

metastatic cancers, usually from other parts of the gastrointestinal tract).

Wilson’s disease, a hereditary disease which causes the body to retain copper.

Primary sclerosing cholangitis, an inflammatory disease of the bile duct, likely

autoimmune in nature.

Primary biliary cirrhosis, autoimmune disease of small bile ducts.

Budd-chiari syndrome, obstruction of the hepatic vein.

Gilbert’s syndrome, a genetic disorder of bilirubin metabolism.


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Glycogen storage type II, the build up of glycogen causes progressive muscle weakness

throughout the body and effect various body tissue, particularly in the heart, skeletal

muscle, liver and nervous system.

AYURVEDIC OR HERBAL TREATMENT[6,9,12]

These are generally classified at three categories.

1. Anti-hepatotoxic agent: antagonize the effect of any hepatotoxic causing hepatitis.

2. Hepatotropic agents: promote the healing process of liver.

3. Hepatoprotective agents: prevent various types of liver affection.

Medicinal plants having hepatoprotective activity.

Botanical name Family Parts

used Extract

Chemical

constituents

Screening

method

Amaranthus

caudatus Linn Amaranthacee

Whole

plant Methanol

Flavonoids,

saponins,

glycosides

Carbon

tetrachloride

Anisochilus

carnosus Linn Lamiaceae Stems Ethanol

Alkaloids,

flavanoids,

Glycosides

Carbon

tetrachloride

Asparagus

racemosus Linn Asparagaceae Roots Ethanol

Phenols,

coumarins

Paracetamol

Azima tetracanthas Salvadoracaee Leaves Ethanol Flavonoids,

triterpenoids

Paracetamol

Calotropis procera

R.Br Asclepediaceae

Root

bark Methanol

Terpinoidsglycosi

des, flavonoids

Carbon

tetrachloride

Cajanus cajan

Linn Leguminosae

Pigeon

pea leaf Ethanol

Flavonoids,

stibenes D-galactosamine

Cajanus

scarabaeoides Linn Fabaeceae

Whole

plant

n-butanol,

ethanol Flavonoids

Paracetamol

Induced

Carissa carindas

Linn Apocyanaceae Root Ethanol

Alkaloids,

tannins, steroids

Carbon tetra

chloride induced

Clitoria ternatea

Linn Fabaceae Leaves Methanol

Phenolic

Flavonoids

Paracetamol

Induced

Cucumis trigonus

Roxb Cucurbitaceae Fruit

Pet ether,

chloroform,

alcohol,

aqueous

Flavonoids Carbon tetra

chloride induced

Ficus religiosa

Linn Moraceae

Stem

bark Methanol

Glycosides,

steroids, tannins

Paracetamol

Induced

Desmostachya

bipinnata Poaceae

Whole

Plant Ethanol

Flavanoids

glucoside, trycin,

trycin-7-

glucoside,

Carbon tetra

chloride induced

Garcinia indica

Linn Clusiaceae

Fruit

rind Ethanol

Benzophenones,

garcinol

Carbon tetra

chloride induced

http://pick4.pick.uga.edu/mp/20q?go=http://plants.usda.gov/java/ClassificationServlet%3Fsource%3Dprofile%26symbol%3DPoaceae%26display%3D31


334


Herbs that are hepatoprotective.

S.NO Common

name Scientific name Ingredients Liver pathologies treated

1. Green tea Camellia sinensis Leaves and seeds of

Camellia sinensis

Acute liver injury

NAFLD (Non-alcoholic

fathyliver disease)

2. Silymarin Silybum marianum Milk thisle seeds

Oxidative stress.

Inflammation and fibrosis

Alcohol-induced cirrhosis.

Mushroom poisoning

Viral hepatitis

3. Liv-52

Combination of

Capparis spinosa, C.

intybus, S. nigrum,

Terminalia arjuna,

Cassia occidentalis,

Achillea millefolium,

Mixture of leaves,

roots, flowers, fruits

and seeds of Capers,

blue daisy, Black

Nightshade, Arjuna,

NegroCoffee,Yarrow.

Jaundice, Alcoholic liver

disease, Viral hepatitis,

Liver cirrhosis,

4. Kamilari

Combination of

Thespesia populnea,

Elettari

cardamomum,

Zingiber officinale,

Glycyrrhiza glabra

Mixture of Leaves,

roots, barks, fruits,

seed pods and rhizome

of Portia Tree, Green

cardamom, Ginger and

Licorice

Jaundice Alcoholic liver

disease Viral hepatitis

Liver cirrhosis

5. Livfit

Combination of E.

alba, P. niruri, C.

intybus, Rheum

emodi, Tephrosia

purpurea

Mixture of Leaves,

roots, barks, and

flowers of false daisy,

stonebreaker, blue

daisy, Himalayan

rhubarb and Wild

indigo

Oxidative and Toxic Liver

injury

6. Stimuliv Combination of A. Mixture of Leaves, Viral Hepatitis,

Gmelina asiatica

Linn Verbenaceae

Aerial

parts

Ethanol,

Chloroform Flavonoids

Carbon tetra

Chloride

Hyptis suaveolens

linn Lamiaceae leaves Aqueous Flavonoids

Acetaminophn

Induced

Leucas cilita Linn Lamiaceae Whole

plant Ethanol Flavonoids

Carbon

tetrachloride

Induced

Melia azhadirecta

Linn Piperaceae leaves Ethanol

Spectro photo

metric method

Carbon tetra

chloride,

silymarin

Morinda citrifolia

Linn Rubiaceae Fruit Aqueous

Saponins,

triterpins, steroids

Streptozotocin

Induced

Myoporum lactum

Linn Myoporaceae Leaves

Methanol, n-

Butanol Flavonoids

Profenofos

induced

Myrtus communis

Linn Myrtaceae Leaves Silymarin

Flavonoids,

terpenoids,

Steroids

Paracetamol

Induced


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paniculata, P. niruri,

E. alba,

P. kurroa,

Boerhaavia diffusa,

Azadirachtica indica,

Berberis aristata,

Ipomoea turpethum,

T. purpurea

roots, barks, and

flowers of False daisy,

Creat, stonebreaker,

kutki, red spiderling,

Indian Lilac, Tree

Turmeric, St. Thomas

lidpod and wild indigo

Hepatomegaly

7. Himoliv

Combination of P.

kurroa, B. diffusa,

Tinospora cordifolia,

A. paniculata, P.

emblica

Mixture of Leaves,

roots, barks, and

flowers of Creat, red

spiderling, Giloy,

kutki, and emblic

hepatic dysfunction

8. Tefroliv

Combination of A.

paniculata, E. alba,

Ocimum sanctum, P.

niruri, P. kurroa,

Piper longum, S.

nigrum, Tephrosia

purpurea, Terminalia

chebula

Mixture of Leaves,

roots, barks, fruits,

seed pods and rhizome

of Creat, kutki,

stonebreaker, false

daisy, holy basil,

Indian long pepper,

Black Nightshade,

Wild indigo and

Yellow Myrobalan.

Acute and chronic hepatitis

Alcoholic liver damage

Cirrhosis

Fatty liver and drug-induced

hepato toxicity

9. Wolfberry Lycii fructus Dried berries and root

bark of Lycii fructus Hepatoma, NAFLD

10. Garlic Allium sativum Garlic cloves NAFLD, Steatosis, Fibrosis

Chronic liver injury

11. Amla Emblica officinalis Toxic-induced liver

inflammation

12. Mahanimba Ailanthus excelsa Chemically- induced liver

injury

13. Bitter leaf Vernonia amygdalina Leaves Chemical liver injury

14. Fennel Foeniculum vulgare Stems of foeniculum

vulgare

Anti-inflammatory,

acute hepatotoxicity

15. Curcumin Curcuma longa

Acute liver damage by

chemicals, e.g. Ethanol,

CCl4, Dimethylnitrosamines

Marketed Formulations

Liv.52, Liverite Liver Aid, Microhydrin, Liv.52 syrup, Zandu pancharishta, Zandu livotrit,

Kailari Cap., Livwin cap., Sidoliv syrup etc.

CONCLUSION

Different methods have been used to reduce hepatotoxicity and its complications for many

years. Disappointing results after cessation the lifestyle modification or pharmacotherapy

compeleted the researchers and physicians tore think to find a new, safe and striking


336


therapeutic alternative for this global health concern. Herbal medicines have been in attention

as an effective option to reduce hepatotoxicity.

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medicinal plants for treatment of liver disorders

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