Important hepatoprotective botanicals in ISM

Important hepatoprotective botanicals in ISM Important hepatoprotective botanicals in ISM

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Important hepatoprotective botanicals in ISM / Asian Journal of Traditional Medicines, 2012, 7(3) Reviews Important hepatoprotective botanicals in ISM Harish Chander Dutt Department of Botany, University of Jammu, Jammu 180006, India Abstract Liver diseases are among the most serious ailment and can be classified as acute or chronic hepatitis (inflammatory liver disease), hepatosis (non inflammatory diseases) and cirrhosis (degeneration disorders resulting in fibrosis of the liver). Beside expensive and ineffectual modern therapeutic agents like steroids and chemotherapy, south east Asian countries like India and China have an edge in treating hepatic disorders by means of their native botanicals. No doubt, the botanicals need to follow proper standardization and quality control modus operandi before their therapeutic usage in human ailments but the applicability in this regard has shown exceptional success. This review is focused on important botanicals standardized for chemical markers, which have shown promising results as hepatoptotective agents. Key words: hepatoprotective; ISM; botanicals 1 Introduction Liver, the largest glandular organ in the human body, performs over 100 separate bodily functions. However, its sheer complexity and multidimensional functions makes it susceptible to many diseases. Fortunately, most are rare, but there are few that are all too common including hepatitis, cirrhosis, liver disorders in children, alcoholretarded disorders and liver cancer. According to American Liver Foundation, more than 25 million people get infected with liver and gall-bladder diseases each year. Over 27,000 Americans die from cirrhosis annually, making it the country’s third leading cause of death for people between the ages of 25 and 59 years and the seventh leading cause of death overall. World Health Organization (WHO) has estimated about 170 million people (3% of the * Author to whom correspondence should be addressed. Address: Department of Botany, University of Jammu, Jammu 180006, India; Tel.: +91-9906073604; E-mail: duttharish@rediffmail.com Received: 2011-10-11 Accepted: 2012-07-04 world's population) infected with hepatitis - C virus, are at the risk of developing liver cirrhosis and/or liver cancer. Hepatoprotective is a class of therapeutic agents that includes many synthetic as well as natural products used for protection against hepatic damage induced by various toxins. Plant-based therapeutic agents like silybin and silymacin from Silybum marianum (milk thistle) are promising hepatoprotectives [1]. However; further research to explore more plant based hepatoprotectives is always encouraged. It is seen that hepatoprotective botanicals stumble on an important place in Indian Systems of Medicine (ISM), where ISM has proposed many plants like Andrographis paniculata Nees, Berberis aristata DC, Cassia tora L., Phyllanthus amarus Schumach. & Thonn. etc. for hepatoprotection in humans. Most of these botanicals are available as compound drug formulations. Thus, in Indian market a number of herbal formulations are available for liver disorders but in real sense only 129

Important hepatoprotective botanicals in ISM / Asian Journal of Traditional Medicines, 2012, 7(3)

Reviews

Important hepatoprotective botanicals in ISM

Harish Chander Dutt

Department of Botany, University of Jammu, Jammu 180006, India

Abstract

Liver diseases are among the most serious ailment and can be classified as acute or chronic hepatitis (inflammatory liver disease),

hepatosis (non inflammatory diseases) and cirrhosis (degeneration disorders resulting in fibrosis of the liver). Beside expensive

and ineffectual modern therapeutic agents like steroids and chemotherapy, south east Asian countries like India and China

have an edge in treating hepatic disorders by means of their native botanicals. No doubt, the botanicals need to follow proper

standardization and quality control modus operandi before their therapeutic usage in human ailments but the applicability in

this regard has shown exceptional success. This review is focused on important botanicals standardized for chemical markers,

which have shown promising results as hepatoptotective agents.

Key words: hepatoprotective; ISM; botanicals

1 Introduction

Liver, the largest glandular organ in the

human body, performs over 100 separate bodily

functions. However, its sheer complexity and multidimensional

functions makes it susceptible to many

diseases. Fortunately, most are rare, but there are

few that are all too common including hepatitis,

cirrhosis, liver disorders in children, alcoholretarded

disorders and liver cancer. According to

American Liver Foundation, more than 25 million

people get infected with liver and gall-bladder

diseases each year. Over 27,000 Americans die from

cirrhosis annually, making it the country’s third

leading cause of death for people between the ages

of 25 and 59 years and the seventh leading cause of

death overall. World Health Organization (WHO)

has estimated about 170 million people (3% of the

* Author to whom correspondence should be addressed. Address:

Department of Botany, University of Jammu, Jammu 180006, India;

Tel.: +91-9906073604; E-mail: duttharish@rediffmail.com

Received: 2011-10-11 Accepted: 2012-07-04

world's population) infected with hepatitis - C virus,

are at the risk of developing liver cirrhosis and/or

liver cancer.

Hepatoprotective is a class of therapeutic

agents that includes many synthetic as well as

natural products used for protection against hepatic

damage induced by various toxins. Plant-based

therapeutic agents like silybin and silymacin from

Silybum marianum (milk thistle) are promising

hepatoprotectives [1]. However; further research

to explore more plant based hepatoprotectives is

always encouraged.

It is seen that hepatoprotective botanicals

stumble on an important place in Indian Systems

of Medicine (ISM), where ISM has proposed many

plants like Andrographis paniculata Nees, Berberis

aristata DC, Cassia tora L., Phyllanthus amarus

Schumach. & Thonn. etc. for hepatoprotection

in humans. Most of these botanicals are available

as compound drug formulations. Thus, in Indian

market a number of herbal formulations are

available for liver disorders but in real sense only

129

few medicinal herbs are tested methodically for

hepatoprotective activity. Some herbal formulations

claiming to be hepatoprotective may actually contain

chemical constituents having hepatotonic potential.

Ayurveda has already formulated many preparation

for curing hepatic disorders e.g. Bhungaraajaadi

churna, Shadabindu tail, Bhungraaja tail, Bhungraaja

ghrita, Ptnarnavaastake kwatha, Purarnavaadi

kwatha, Punapnavaadi mandur, Katukyadya lauha,

Arozyavardhini, Amritaastak kwatha, Amritarishta

and Yograj gugglu [2]. In spite of the fact ayurvedic

treatment options for common liver diseases such

as cirrhosis, fatty liver, and chronic hepatitis are

not accepted. The effectiveness of treatments

such as interferon, colchicine, penicillamine, and

corticosteroids are inconsistent at best with an

incidence of side-effects. Physicians and patients are

always in need of effective therapeutic agents with

a low incidence of side-effects. Plants potentially

constitute such a group where the side effects are

less and treatment is always permanent.

In recent years many researchers have examined

the effects of plants used traditionally by indigenous

healers and herbalists to support liver function and

treat liver diseases. Several hundred plants have

been examined for cure of wide variety of liver

disorders, but very few have shown activity and are

also mentioned in different classical ayurvedic texts.

However, more than 25 multiple herb preparations

(MHP) are available in Indian market for curing

hepatic disorders. Each of MHP contains plant

species ranging from 5-18 (Table 1). Out of the

ingredients in these MHP, only few plant species are

standardized for their chemical markers.

2 Medicinal plants and hepatic disorders

About 120 distinct chemical substances derived

from plants are considered as important drugs

currently in use in one or more countries of the

world. Now a days, herbs like Salvia miltiorhiza

and fungus like Polyporus umbellatus, or extracts

thereof, are considered as useful drugs in treatment

of hepatic disorders, particularly those with viral

etiology [3]. The important medicinal plants

standardized for the chemical marker in this context

are elaborated below.

2.1 Andrographis paniculata Nees

A. paniculata grows abundantly in moist shady

waste grounds and sometimes in dry forests chiefly

in plains throughout India [4-6]. A. paniculata is an

erect herb, with dark green stem, 0.3-1.0 m in height,

2-6 mm in diameter, quadrangular with longitudinal

furrows and wings on the angles of the younger

part. The herb is commonly known as Bhunimba

and Kalmegha in Sanskrit, Kiryat in Hindi and

the King of bitters or Chiretta in English. Roots,

leaves and aerial parts of the plant are designated

for its medicinal importance. In ayurveda the plant

is described as Yakritvridhi which means to cure

hepatomegaly [4, 5]. A. paniculata extract contains

diterpenes, flavonoids and stigmasterols [7]. The

primary medicinal component of Andrographis is

the diterpene andrographolide. Andrographolide,

described as a “diterpene lactone” due to its ring

like structure, has a very bitter taste and colorless

crystalline appearance. Its leaves contain the highest

concentration of andrographolide (~2.25%) as a

chemical marker, while the seeds contain the lowest.

Beside andrographolide, other important chemical

compounds in the species, include andragrapanin,

deoxyoxoandrographolide, neoandrographolide,

andrographiside, oroxylin, wogonon and

andrographidines A, B, C, D, E and F (Fig. 1) [8-10].

In hepatic disorders this botanical is used in

the treatment of wide variety of conditions such

as jaundice, cholestasis and also an antidote for

hepatotoxins [11-13]. Moreover, andrographolide

from A. paniculata has been found to be more

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Table 1. Trade name and manufacture of multiple herbal preparations (MHP) for hepatoprotection.

Trade name / manufacturer

LIV-52

M/S The Himalaya Drug Co., Makali, Bangalore

HEPATOCARD

M/S Surajmani Enterprises

A-1, Daman, Somnath Road , Dabhei Daman

STIMULIV

M/S Francho-Indian Pharmaceuticals Ltd.

Bombay

KAMALAHAR

M/S Khatore Ayurvedic Pharmaceutials, Barbil

Orissa

LIV-77

M/S Globe Pharmaceuticals,

Jullundar City

LIVA

M/S Hebid (India), Pvt. Ltd.,

Calcutta

LIVA-16

M/S Maduna Pharmaceuticals Research

Calcutta

LIVARIN

M/S Patiala Ayurvedic Pharmacy

Sirhind

LIVATONA

M/S Scientific Research Industries Pvt. Ltd.

Lucknow

LIVERGEN

M/S Standard Pharmaceuticals, Calcutta

Plant constituents

Capparis spinosa, Cichorium intybus,Solanum nigrum, Cassia occidentalis,

Terminalia arjun, Achillea millefolium,Tamarix gallica, Eclipta alba, Phyllanthus

amarus, Boerhaavia diffusa, Tinospora cordifolia, Berberis aristata, Raphanus

sativus, Phyllanthus emblica, Plumbago zeylanica, Embelia ribes, Terminalia

chebula, Fumaria officinalis.

Picrorhiza kurroa, Andrographis paniculata, Phyllanthus amarus, Boerhaavia

diffusa, Azadirachta indica, Triphala (Terminalia chebula, Terminalia bellirica,

Emblica officinalis), Eclipta alba, Zingiberis officinalis, Piper longum.

Andrographis paniculata, Eclipta alba, Fumaria officinalis, Cynara scolymus.

Tecoma undulata, Phyllanthus urinaria, Embelia ribes, Taraxacum officinale,

Nyctanthes arbortristis, Terminalia arjuna.

Boerhaavia diffusa, Cichorium intybus, Berberis aristata, Eclipta alba,

Heliotropum strigosum, Paunella domestica,Tinospora cordifolia, Trigonella

foenumgraecum.

Andrographis paniculata, Apium graveolens, Berberis aristata, Boerhaavia diffusa,

Carica papaya, Asteracantha longifolia, Cassia angustifolia, Plumbago zeylanica,

Solanum nigrum, Tephrosia hirta, Terminalia arjuna, Trachyspermum ammi.

Alstonia scholaris, Andrographis paniculata, Boerhaavia diffusa, Cassia

angustifolia, Eclipta alba, Hygrophila spinosa, Oldenlandia corymbosa, Piper

longum, Solanum xanthocarpum, Tinospora cordifolia, Vernonia anthelmintica

Andrographis paniculata, Aloe barbadensis, Boerhaavia diffusa, Cassia fistula,

Picrorhiza kurroa, Solanum nigrum, Tecoma undulata.

Andrographis paniculata, Asteracantha longifolia, Glycyrrhiza glabra, Odenlandia

corymbosa, Senna angustifolia, Trachysparmum ammi, Trigonella foenumgraecum

Andrographis paniculata, Apium graveolens, Asteracantha longifolia, Cassia

angustifolia, Trachyspermum ammi, Trigonella foenumgraecum.

LIVER RIN

Andrographis paniculata, Melia azerdarach, Oldenlandia corymbosa, Picrorhiza

M/S Herbs ERA Pharmaceuticals, Udayrajpur (WB). kurroa, Rubia cordifolia, Cassia angustifolia.

LIVERTONE

M/S Gamber Laboratories, Bombay

LIVER

M/S Bhatiya Aushadh Normanshala,

Gujarat

LIVIN

M/S Arya Audhadhi Pharm. Works

Indore

Emblica officinalis, Picrorhiza kurroa, Rheum palmatum, Terminalia bellirica,

Terminalia chebula.

Achillea millifolium, Aconitum heterophyllum, Cassia occidentalis, Embelia ribes,

Piper longum, Solanum nigrum, Tamarix gallias, Swertia chirata.

Acorus calamus, Andrographis paniculata, Aphanamixis olystachya, Baliospermum

montana, Boerhaavia diffusa, Cassia sophera, Citrulus colocynthis, Eclipta alba,

Embelia ribes, Ficus religiosa,Jateorhiza palmata, Ocimum sanctum, Lawsonia

inermis, Operculina turpethum, Piper chaba, Plumbago zeylanica, Salvadora

persica, Tephrosia purpurea, Terminalia chebula, Tinospora cordifolia, Zingiber

officinale, Trachyspermum ammi.

131

Continued Table 1

LIVODIN

M/S Madona Pharm. Res. Calcutta

LIVOKIN

M/S Herbo-Med, Calcutta

aristata

LIVOMYN

M/S Charak Pharmaceuticals

(India) Ltd. Samalkha

LIVOPEP

M/S Anakam Lab. Calcutta

LIVOSIN

M/S Jupiter Pharm. Calcutta

LIVOSPIN

M/S Herbals (ABS) Pvt. Ltd.

Aloe indica, Aphanamixis polystachya, Andrographis paniculata, Boerhaavia

diffusa, Carum copticum, Cassia angustifolia,Eclipta alba, Embelia

ribes,Holarrhaena antidysentrica, Hygrophila spinosa, Oldenlandia corymbosa,

Piper nigrum, Solanum xanthocarpum, Tinospora cordifolia.

Andrographis paniculata, Apium graveolens, Carum copticum, Berberis aristata,

Cichorium intybus, Cyperus rotundus, Eclipta erecta, Ipomoea turpethum,

Oldenlandia corymbosa, Picrorhiza kurroa, Plumbago zeylanica, Solanum nigrum,

Tephrosia purpurea, Terminalia chebula, Trigonella foenumgraecum.

Andrographis paniculata,Aphanamixis polystachya, Boerhaavia diffusa,

Caesalpinia bonduc, Casearia esculenta, Cassia sophera, Eclipta alba, Embelia

ribes, Fumaria officinalis, Holarrhaena antidysentrica, Hordeum vulgare,

Lagenaria siceraria, Lawsonia (Haryana) inermis, Ocimum sanctum, Operculina

turpethum, Oryza sativa, Piper longum, Plumbago zeylanica, Rosa hinensis,

Swertia chirata, Tephrosia purpurea, Tinospora cordifolia, Zingiber officinale.

Andrographis paniculata,Apium graveolens, Asteracantha longifolia, Oldenlandia

corymbosa, Trachyspermum ammi, Trigonella fornumgraecum.

Avena sativa, Carica papaya, Ferula asafoetida, Mentha longifolia, Strychnos

nuxvomica, Panicum miliaceum, Podophyllum hexandrum, Cassia angustifolia,

Zingiber officinale.

Ammora rohituka, Andrographis paniculata, Embelia ribes, Tephrosia purpurea,

Ipomoea turpethum, Moringa oleifera, Oldenlandia corymbosa, Salvia plebia,

Swertia angustifolia.

LIVOTONE

M/S Herbals (ABS) Pvt. Ltd.M/S East India Pharm.

Works., Calcutta

LIVOTRIT

M/S Zandu Pharmaceuticals

Bombay

TEFROLI

M/S TTK Pharm Madras

Andrograhis paniculata, Apium graveolens, Asteracantha longifolia, Holarrhaena

antidysentrica, Rhamnus purshiana, Trigonella foenumgraecum.

Andrographis paniculata, Boerhaavia diffusa, Eclipta alba, Operaculina

turpethum, Picrorhiza kurroa, Plumbago zeylanica, Rhamnus wightii, Tinospora

cordifolia.

Andrographis paniculata, Eclipta alba, Ocimum sanctum, Tephrosia purpurea,

Terminalia chebula.

VIMLIV

M/S Solumiks Bombay

BILGERIN

M/S Standard Pharma-Remedies Calcutta

LIVOZON

M/S Hind Chemicals, Kanpur

BONLIV

M/S Pharm Products. Thanjavur

Boerhaavia diffusa, Cichorium intybus, Eclipta alba, Phyllanthus simplex,

Picrorhiza kurroa.

Andrographis paniculata, Apium graveolens, Asteracantha longifolia, Operaculina

turpethum, Swertia chirata, Trachyspermum ammi, Trigonella foenumgraecum.

Phyllanthus niruri, Tinospora cordifolia, Triphala (Terminalia chebula, Terminalia

bellarica, Emblica offficinalis).

Eclipta alba, Wedelia calendulacea, Phyllanthus niruri, Tribulus terrestris,

Glycyrrhiza glabra.

potent than silymarin, a standard hepatoprotective

agent [13]. Reduction of glutathione (GSH)

in liver (4.8+/-0.21nmol/mg protein) and in

intestinal mucosa (13+/-0.67 nmol/mg protein) of

cyclophosphamide- treated controls was significantly

reversed by A. paniculata administration (liver:

6.4+/-0.13, intestinal mucosa: 17.11+/-0.06),

with amelioration of changes in serum and

132

Fig. 1. Important molecules of Andrograhis paniculata, Picrorhiza kurroa, Swertia chirata, Terminalia chebula, Zingiber

officinale, Emblica officinalis, Phyllanthus amarus and Boerhaavia diffusa

liver ALP, GPT, LPO (lipid peroxidation) [14].

A. paniculata has been found to exert the cell

membrane stabilizing property which may lead in

the prevention of the toxic effect of bile salts in

various hepatic disorders [15]. Its treatment prevents

benzene hexachloride (BHC) induced increase in

the activities of enzymes y-glutamyl transpeptidase,

glutathione-S-transferase and lipid peroxidation.

Andrographolide also show in vivo hepatoprotective

effect against galactosamine or paracetamolinduced

hepatotoxicity in rats [16]. Its leaf extract

has been found to have more protective action on

carbon tetrachloride induced hepatic toxicity than

its bitter principle, andrographolide [17, 18]. The

133

greater protective activity of andrographolide and

neoandrographolide could be due to their glucoside

groups which may act as strong antioxidants [19].

Andrographolide also completely antagonize the

toxic effects of paracetamol on certain enzymes

(glutamate oxaloacetate transaminase, glutamic

pyruvic tramsaminase and alkaline phosphatase)

in serum as well as in isolated hepatic cells [12].

A. paniculata in a formulation alongwith some

other plants like Terminalia arjuna, Eclipta erecta,

Trianthema decandra, Piper chaba, Saxifraga

ligulata, Achyranthes aspera, Onosma bracteatum

and Tinospora cordifolia has been observed to

express hepatoprotective properties in adult goats of

either sex [20]. The effects of A. paniculata extract

and andrographolide on hepatic cytochrome p450

expression after in vivo administration to rats only

and in vitro in rat and human liver microsomes and

hepatocyte cultures have been confirmed and it is

reported that Andrographolide and A. paniculata

extract could cause herb-drug interactions in humans

through modulation of cytochrome p450 (2C9) and

cytochrome p450 (3A4) expression and activities

[21, 22].

2.2 Emblica officinalis Gaertn.

Emblica officinalis is a small or medium sized,

tree found growing in the plains and sub-mountain

tracts, all over the India from 200msl to 1500msl.

Small or medium-sized deciduous tree with smooth,

greenish-grey, exfoliating bark possess depressed

globose, fleshy and obscurely 6-lobed fruits. The

plant as well as the fruits of the species is known as

Amla in Hindi and Indian gooseberry in English [2,

5, 23].

Due to high nutritive value in the fruit pulp like

protein (0.5%), fat (0.1%), mineral water (0.7%),

fiber (3.4%), carbohydrates (14.1%), calcium

(0.05%), potassium (0.02%), iron (1.2 mg/100 g),

moisture (81.2%), nicotinic acid (0.2 mg/100 g),

and vitamin C (600 mg/100 g), it is an important

ingredient in many ISM formulations. Beside a

rich source of Vitamin C (>720 mg/100 g in fresh

pulp and 921 mg/100 cc of pressed juice), fruit is

also a good source of pectin. Fruit also contains

phyllemblic acid (6.3%), lipids (6.0%), gallic acid

(5.0%) and emblicol as important biomolecules.

Fruit find its presence in ayurvedic medicine,

because of its contents like vitamins, carbohydrates,

auxins, growth inhibitors and important alkaloids

[23, 24]. The fruits are known for hepatoprotective

potential [25].

E. officianlis fruit extract has been standardized

on the basis of ellagic acid (Fig. 1). Much

interest surrounds the potential for Emblica in

cancer; however, the published clinical trial or

epidemiological data is not available in this concern.

Emblica has inhibited induced mutagenesis in

Salmonella strains. An aqueous extract of Emblica

also inhibit dose-dependent hepatocarcinogenesis.

E. officinalis also has a potential to suppress

carcinogen-induced response in rat liver. The

antitumour activity of aqueous extract of E.

officinalis extract may partially be due to its

interaction with cell cycle regulation [26, 27].

Moreover, extracts of E.officinalis, Phyllanthus

amarus Schumach. & Thonn. and Picrorhiza kurroa

Royle significantly inhibited hepatocarcinogenesis

[28]. Pepticare, a herbomineral formulation of the

ayurvedic medicine consisting of Glycyrrhiza glabra

L., Tinospora cordifolia Miers and E. officinalis

possesses anti-ulcer activity, which can be attributed

to its anti-oxidant mechanism of action [29]. The

acute effects of thioacetamide in rat liver can be

prevented by pre-treatment with E. officinalis extract

[30]. Histopathological studies have confirmed

the beneficial roles of E. officinalis extract against

ethanol induced liver injury in rats. E. officinalis and

Chyavanaprash extracts could inhibit the induction

of liver fibrosis by CCl 4 in rats [31]. Alcoholic and

134

aqueous extracts of the fruits of Emblica have shown

hepatoprotective properties in experimental rats

[32]. Amalkadi Ghrita, a polyherbal formulation,

has been evaluated for its hepatoprotective activity

against carbon tetrachloride (CCl 4 )-induced hepatic

damage in rats, but hepatoprotective effect of

formulation is defined probably due to combined

action of all the ingredients [33].

2.3 Phyllanthus amarus Schumach. & Thonn.

Phyllanthus amarus is distributed throughout

the hotter parts of India below 700msl. It is known

as Bhumyamalalaki in Sanskrit, Jar amla in Hindi

and Stone breaker in English [34, 35]. The taxa

is an annual or biennial, rarely perennial, erect or

prostrate, glabrous about 10-170 cm tall branched

herb. The secondary metabolites isolated from P.

amarus are alkaloids, flavanoids, hydrolysable

tannins and major lignans. Thus botanical is

standardized for phyllanthin as the marker

compound (Fig. 1) [35]. In ayurveda the species

is described for Yakritvridhi (hepatomegaly),

Kamala (jaundice) and Yakrituttejaka (liver tonic).

P. amarus is one of the widely used plant species

in the mono- and polyherbal preparations with

potent antihepatotoxic activity [36, 37]. It is further

reported that niranthin, nirtetralin, hinokinin and

geraniin at the non-cytotoxic concentration of

50g, suppress effectively both HBsAg and HBeAg

expression. Of these, niranthin show the best anti-

HBsAg activity, while the most potent anti-HBeAg

activity has been observed with hinokinin [38, 39].

P. amarus administration has been found to be

ineffective in controlling the liver weight, elevation

of tissue gamma-glutamyl transpeptidase, serum

alkaline phosphatase and serum glutamate pyruvate

transaminase of HCC harboring animals, therefore

increases the life span of rats with hepatocellular

carcinoma [40].

Silymarin with ethanolic extract of P. amarus

show better activity due to high concentration of

phyllanthin in ethanolic extract in comparison to

aqueous extract of P. amarus. Moreover, P. amarus

leaf extract could protect the liver against ethanolinduced

oxidative damage by possibly reducing

the rate of lipid peroxidation and increasing the

antioxidant defence mechanism in rats [41, 42].

Histopathological observations has confirmed the

beneficial roles of P. amarus and silymarin against

ethanol induced liver injury in rats. It also possesses

a potent protective effect against aflatoxin B-1

induced hepatic damage [43, 44]. In complementary

medicine many plants are used for the of chronic

hepatitis-B and hepatitis-C where P. amarus is

recognized as one of important component [45].

Oral administration of aqueous extract of P. amarus

along with carbon tetrachloride cause significant

mitigation of CCl 4 induced changes in mice liver

[46]. The hepatoprotective mechanism of this plant

is neither related to inhibition on cytochrome p450,

nor induction on sulfate and glucuronide conjugation

pathways of paracetamol, but partly due to the

antioxidant activity and the protective effect on the

decrease of hepatic reduced glutathione [47].

2.4 Picrorhiza kurroa Royle ex Benth.

Picrorhiza kurroa is distributed from Kashmir

to Sikkim in Himalaya between 2700-4500msl.

The herb is hairy with 15-25 cm long, bitter,

clothed rootstock with withered leaf bases

[24]. In ayurveda the species is described for

Yakritvridhi (hepatomegaly) Kamala (jaundice) and

Yakrituttejaka (liver tonic). Iridoid glycosides and

pikuroside, has been isolated from the roots of P.

kurroa, together with three known iridoids, picroside

I, picroside II, and 6-feruloyl catalpol. A number of

other biomolecules are also isolated from the species

(Fig. 1) [48].

P. kurroa is used traditionally in mono or

poly herbal preparation for the hepatic diseases

135

[37]. Picroliv, a standardized mixture of iridoid

glycosides, prepared from the alcoholic extract

of the root and rhizome of P. kurroa has shown

strong hepatoprotective activity against several

models of hepatotoxicity. During Leishmania

donovani infection, a marked hepatoprotective

effect of Picroliv indicate that it can be utilized

as an adjunct to chemotherapy or in combination

therapy along with sodium stibogluconate in kala

azar. This augments the efficacy of antileishmanials

[49]. Hepatoprotective activity of Picroliv

against aflatoxin B1 toxicity in rats has also

been confirmed [50]. When Picroliv has been

administered orally (25 mg/kg) with monocrotaline,

alters the biochemical parameters along with the

histopathological changes in liver. Moreover,

beside the hepatoprotective effects of Picroliv, it

is also reported as an immunomodulator [51, 52].

Hepatoprotection afforded by oral pretreatment of

CCl 4 intoxicated rats with multiple doses of Picroliv

has evidenced by a significant improvement in

the activities of various enzymes related to drug

metabolism [53]. Beside, its hepatoprotection

activities against galactosamine-induced hepatic

damage, Picroliv also have a marked anticholestatic

effect [54]. It is also known that hepatoprotective

drug silymarin on comparison was found to be

less active than Picroliv and also more potent

choleretic and anticholestatic agent [55, 56].

Picroliv is reported for its significant reversal of

the paracetamol induced biochemical changes and

prevent biochemical changes due to thioacetamide

in liver and serum [57, 58]. But it is also seen that

mixture of Picroside I and Kutkoside in the ratio

of 1:1.5 at 12 mg/kg dose elicited lesser response

than Picroliv [59, 60]. Moreover, Picroliv show

the protective effect against Amanita phalloides

induced hepatotoxicity in rats [61]. Picroliv also

show the protection against alcohol induced chronic

hepatotoxicity and also stimulate the regeneration of

the liver [62, 63]. The extract of P. kurroa has been

found to offer significant protection against liver

damage by CCl 4 . It probably acts as free-radical

scavenger and inhibitor of lipid peroxidation of liver

plasma membrane [64].

Efficacy of Picroliv in protection against hepatic

ischemia-reperfusion injury in vivo, has been

evaluated [65]. Picroliv also possesses therapeutic

activity against Entamoeba histolytica induced

hepatic damage, while picroside II can protect

hepatocytes against injury and prevent apoptosis

[66, 68]. In the galactosamine induced liver

injury in rats, P. kurroa (200 mg/kg p.o.) show a

significant reduction (P

observed in this experiment. The mechanism of action

in this activity is noted as prevention of necrosis

and improvement in biochemical parameters [73].

However, the methanol extract of the whole plant of

S. chirata dose (100 mg/kg i.p.) was investigated for

its hepatoprotective activity against paracetamol and

galactosamine induced hepatotoxicity. The activity

was retained in the chloroform soluble fraction, which

was most active at a dose level of 25 mg/kg i.p. with

overall protection of 81 and 78% against paracetamol

and galactosamine respectivly [74, 75].

2.6 Boerhavia diffusa L.

The plant species is found throughout India,

up to an altitude of 2000msl in Himalaya. The plant

species is a perennial herb where stems are trailing

upto 200 cm, and are glabrous or sparsely pubescent.

In auyrveda the species is mentioned to cure Kamala

(jaundice) and Pandu (anemia) [5]. Number of organic

compounds are identified from the plant species viz

a viz boeravinone A-C, E, G-J; coccinenine B & E;

boerhavisterol; boerhadiffusene; diffusaarotenoid;

boerhavilanostenyl etc (Fig. 1) [76, 77].

The aqueous extract of roots of B. diffusa (2

ml/kg) show more hepatoprotective activity than

the powder form, this is probably due to the better

absorption of the liquid from the intestinal tract.

Moreover, hepatoprotective action of B. diffusa is

well understood in rats [78, 79]. B. diffusa (100

mg/100 g body weight/day) has protective effects

on the rats from hepatotoxicity induced by country

made liquor [80]. An alcoholic extract of whole

plant given orally exhibited hepatoprotective

activity against experimentally induced CCl 4

hepatotoxicity in rats and mice. The extract also

produced an increase in normal bile flow in rats

suggesting a strong choleretic activity. It is also

seen that extract does not show any signs of

toxicity up to an oral dose of 2 g/kg in mice [81].

The claims made by the different tribes of India for

the use of B. diffusa root in hepatic ailments is also

authenticated while standard operation procedure

(SOP) for collecting the species has also been

standardized [82].

2.7 Terminalia chebula Gertn.

Terminalia chebula is distributed in plains of

sub-tropical India. Globally the species is found in

countries like Bangladesh, Bhutan, Cambodia, Laos,

Myanmar, Nepal, Sri Lanka, Thailand, Vietnam.

Measuring about 30 m tall tree is characterised with

greyish black to grey, coarsely splited and thick bark.

The fruit of the species are ovoid or elliposide and

yield a black colour used to dye cloth. The fruits

of the species are described for Kamala (jaundice),

Yakritvridhi (hepatomegaly) and Yakrituttejaka (liver

tonic) in ayurvedic texts. Fruits contain astringent

substances like tannic acid, chebulinic acid, gallic acid

etc. (Fig. 1). Resin and a purgative principle of the

nature of anthraquinone and sennoside are also present

[8]. T. chebula also called as “King of Medicines”

in Tibet and is always listed first in the Ayurvedic

Materia Medica because of its extraordinary powers

of healing with a wide spectrum of biological activity.

The fruit of T. chebula is being used for the treatment

of different types of diseases and disorders since

antiquity. During the last five decades, apart from the

chemistry, considerable progress has been achieved

regarding the biological activities and medicinal

applications of T. chebula. It is now considered as

a valuable source of unique natural products for

development of medicines against various diseases

and also for the development of industrial products.

The biological and pharmacological activities of T.

chebula extracts and some of its isolated compounds,

has been confirmed for clinical studies, plausible

medicinal applications along with their safety

evaluation.

In a crude multi-herb formulation (Boerhavia

diffusa, Tinospora cordifolia, Berberis aristata,

137

Terminalia chebula and Zingiber officinale) a maximum

cure rate of 73% (dose: 800 mg/kg/day) in hepatic

amoebiasis reducing the average degree of infection

(ADI) to 1.3 as compared to 4.2 for sham-treated

controls has been reported [83]. Hepatoprotective

compound chebulic acid and its minor isomer,

neochebulic acid has been isolated from the ethanolic

extract of the fruits of the species [84]. T. chebula

is an important herbal drug described in Ayurvedic

Pharmacopea, and the fruit of the species are

chemically characterised on the basis of chebuloside

II. T. chebula extract has been found to prevent

the hepatotoxicity caused by the administration

of rifampicin, isoniazid and pyrazinamide (in

combination) in a sub-chronic mode [85].

2.8 Zingiber officinale Roscoe

Zingiber officinale is widely cultivated in

tropics, probable in tropical Asia, South East Asia

and through out India. This is a native plant of

Asia and commonly known as Ginger. However,

presently, the ginger is cultivated throughout the

tropical regions of the world. The dividing of

the rootstock is the usual way by which ginger is

propagated around the world. Ideal habitats for the

ginger are areas of fertile soil and the plant requires

plenty of rain. Ginger is a perennial aromatic herb

with knotty, fibrous, and whitish or buff-colored

rootstock. It produces a simple, leafy stem covered

with the leaf sheaths of the lanceolate-oblong to

linear leaves. The plant reaches a height of about

one meter with leaves growing 15-30 cm long. The

sterile flowers are white with purple streaks and

grow in spikes [2, 24].

Pungent components of ginger inhibit

cycloxygenase and lipoxygenase activity in the

arachidonic acid metabolic pathway and thereby

probably reduce inflammation and relieve pain

in rheumatic disorders and migraine headache.

Consumption of ginger reduces plasma thromboxane

B2 (TXB2) levels in humans. Ginger is reported to

reduce nausea, vertigo and vomiting for which the

mechanism of action is, however, not yet understood.

Hepatic intoxication with CCl 4 , elevated the plasma

concentration of gingerol at the terminal phase [86].

Ginger contains mutagenic (gingerol and

shogaol) and anti-mutagenic (zingiberone)

compounds (Fig. 1). Ginger extract exhibits

cytotoxic effects in cultured plant cells but it is not

known whether ginger can suppress tumour growth

in experimental animals or humans. Some of the

chemical compounds from ginger may prove to

have anti-inflammatory, anti-emetic, cardiotonic and

gastroprotective properties in humans without side

effects [87].

Ginger is well known in the form of ginger

sticks. If these are consumed during travel, the

traveler imbibes, albeit subconsciously. Thus the

plant is called as a healing plant for motion sickness.

The efficacy of ginger rhizome for the prevention

of nausea, dizziness, and vomiting as symptoms

of motion sickness (kinetosis), as well as for

postoperative vomiting and vomiting of pregnancy,

has been well documented and proved beyond

doubt in numerous high-quality clinical studies.

The use of this ancient medicine for gastrointestinal

problems (stimulation of digestion) has been given

scientific approval. Today, medicinal ginger is

used mainly for prevention of the symptoms of

travel sickness. Essential oil of the rhizomes of the

species is characterized by presence of heptane,

octane, isovaleraldehyde, nonanol, ethyl pinene,

camphene, β pinene, sabinene, myrecene, limonene,

β-phellandrene and 1, 8-cineole. Through GC-MS

the presence of gingediol, methylgingediol and

their diacetates is reported. New sesquiterpenes

(sequithujene, cis-sesquisabinene hydrate) and

zingiberenol are isolated and their structures are

also determined. car-3-ene, α-terpinene, α-terpineol,

nerol, 1, 8-cineole, zingiberene, neral, geranial,

138

geraniol and geranyl acetate are also identified

in essential oil. The oil from the rhizome of Z.

officinale could be useful in preventing chemically

induced acute liver injury [88]. The hepatoprotective

effect of aqueous ethanol extract of Z. officinale

against acetaminophen induced acute toxicity

is mediated either by preventing the decline of

hepatic antioxidant status or due to its direct radical

scavenging capacity [89]. Liver damage by CCl 4 can

also be prevented by the roots of the plant species

[90]. Ginger oleoresin when administered orally

significantly lowered serum and hepatic cholesterol

and increased faecal cholesterol excretion [91].

3 Discussion

Silybin and silymacin are worldwide accepted

plant based hepatoprotective agent, however in

various systems of medicine other complementary

and alternative medicine are also in practice.

Although a very scanty scientific research is carried

out on such medicines, but there continuous use

in human health system has influenced the native

manufacturers for huge production. About 25

multi herbal formulations are available in Indian

market with one or more important botanical

of hepatoprotection. Andrographolide from

Andrographis paniculata, iridoid glycosides from

Picrorhiza kurroa, extract of Swertia chirata,

aqueous extract of Boerhavia diffusa, chebulic

acid from Terminalia chebula, aqueous extract of

Zingiber officinale and crude multidrug formulations

are proved as the best hepatoprotective either parallel

to or above Silybin and Silymacin in action. It is also

observed that either one or more plants are among

the important ingredients in polyherbal formulations

of ISM (Table 1). Because of the critical threat to the

biodiversity, it is obligatory that all these polyherbal

formulations should be analysed properly for the

hepatoprotetction using new technique, so that that

minimum required plant species can be utilised for

the preparation of hepatoprotective drugs.

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