Download management of hepatic disorders

MEDICAL RATIONALE OF
LIVOKURE, HEPATOPRETECTIVE
HERBAL FORMULATION
1
MANAGEMENT OF HEPATIC DISORDERS
LIVOKURETM :Corrects liver dysfunction.
LIVOKURETM :Is safe and provides anti-viral effect in infective hepatitis.
LIVOKURETM :
Augments appetite by normalizing liver function.
LIVOKURETM :
Is ideally suited for long term treatment.
LIVOKURETM :
Gives protection in metabolic liver disorders.
HIGHLY EFFECTIVE IN THE MANAGEMENT OF:

Infective Hepatitis, Fatty Infiltration of liver, Anorexia. Alcoholic and Metabolic liver
disorders, Constipation etc.
Livokure is well-researched and clinically proven herbal formulation to act effectively as a
prophylaxis as well as curative drug to any kind of disorder affecting the healthy functioning of the
liver, one of the vital organs of the body. In our daily living we can not escape factors like
consumption of rich and spicy food, polluted drinking water, toxic medicines or possible attack
from hepatitis virus. There is also an increasing trend towards consumption of alcohol. As well
these actors continuously jeopardize functioning of the liver, there is every necessity to ensure a
complete protective shield for this vital organ, which Livokure ensures in a safe and sound
manner.

An essential co-prescription with hepato-toxic drugs, such as:
Antibiotics, Hypotensives, Oral Hypoglycemics, Analgesics, Guinolones, Anti-Tuberculous etc.
COMPOSITION:
Each 500 mg. Capsule contains :
Phyllanthus niruri (bhuiamla)
Picrorhiza kurroa (kutki)
Andrographis paniculata ( kalmegh)
Holarrhena antidysenterica ( kurchi)
Excipient
:
:
:
:
:
100 mg
150 mg
150 mg
100 mg
qs
DOSE :
ADULTS: 1 to 2 capsules twice daily (before food) or as directed by the physician.
CHILDREN:
Half of the adult dose.
MAINTENANCE DOSE: One Capsule twice daily.
ONSET OF ACTION: One to Two hours.
2
Duration of Action: Eight to Twelve hours.
SIDE EFFCT / TOXIC EFFECT:
Not found in the clinical trial. May safely be continued for a longer period.
CONTRAINDICATION :
Hypersensitivity to any of the ingredients.
PRESENTATION :
Strip of 10 capsules.
CLINICAL VALIDATION :

Successful clinical trial was conducted at J. B. Roy State Ayurvedic Medical College &
Hospital, Govt. of West Bengal, Kolkata.

Livokure compound has completely antagonized the toxic effects of Paracetamol on certain
enzymes in serums as well as in isolated hepatic cells. Andrographolide has been found to be
more potent.

The plant p. Kurroa has been found to be having hepatoprotective activities against alcohol,
ccl4 and aflatoxin b1 induced hepatic damage. (ref.1).

Amoebicidal, anti-tuberculous and other anti-protozoal activity of individual alkaloids specially,
conessine (kurchi) have been extensively investigated. (ref.2).
REFERENCES:
1)
2)
Indigenous Drugs Of India (1982), 2nd Edition Academic Publishers, Calcutta; P – 343-344.
Cultivation and Utilization Of Medicinal Plants. (1982) Rrl, Jammu-Tawi, P-33.
MODE OF ACTION:
 Livokure contains the mixture of picroside I and kutkoside, which has significant
hepatopretective activity and the antiviral effect.
 Livokure contains the active principle of andrographolide, which acts as a cholagogue, and is
used in sluggishness of liver and jaundice.
 Livokure containing lignans blocks DNA polymerase, the enzyme needed for the hepatitis B
virus to reproduce. This is effective in jaundice and also for diarrhoea, dysentery and
dyspepsia.
3
CHEMICAL CONSTITUENTS
AND
PHARMACOLOGICAL ACTIVITIES
OF EACH INGREDIENT OF LIVOKURE
4
Andrographis paniculata Nees
BOTANICAL NAME
:
Andrographis paniculata Nees
COMMON NAME
:
Bengali: Kalmeg, English: The Creat; Sanskrit: Kalmegha,
Bhunimba
FAMILY
:
Acanthaceae
PARTS USED
:
Leaf
HABITAT
:
It grows abundantly in south eastern Asia, India (and Sri
Lanka), Pakistan and Indonesia It grows "serpentine soil,"
which is relatively high in aluminum, copper and zinc.
DESCRIPTION OF PLANT :
Andrographis paniculata is an annual - branched,
erect - running 1/2 to 1 meter in height.
Stem dark green, 0.3 - 1.0 m in height, 2 - 6 mm in
diameter, quadrangular with longitudinal furrows and
wings on the angles of the younger parts, slightly
enlarged at the nodes; leaves glabrous, up to 8.0 cm
long and 2.5 cm broad, lanceolate, pinnate; flowers
small, in lax spreading axillary and terminal racemes
or panicles; capsules linear-oblong, acute at both
ends, 1.9 cm x 0.3 cm; seeds numerous, sub
quadrate, yellowish brown. (Sing, A., Kapoor, L.D.,
and Chandra, V., Pharmaco-botanic studies of
kalmegh, J. ResIndian Med., 7,93,1972)
Photograph 1: whole plant
CHEMICAL CONSTITUENTS:
The highest concentration of the active components is found just before the plant blooms.
The leaves contain the highest amount of andrographolide (2.39%), the most medicinally active
phytochemical in the plant, while the seeds contain the lowest. (Sharma, A., L. Krishan, and
S.S. Handa. 1992. Standardization of the Indian crude drug Kalmegh by high pressure
liquid chromatographic determination of andrographolide. Phytochemical analysis 3:12931).
The
other
medicinal
chemicals
are
also
bitter
principles:
diterpenoids
viz.
deoxyandrographolide, -19ß-D-glucoside, and neo-andrographolide, all of which have been
isolated from the leaves. (Chem Weiming and Liang Xiaotion. Deoxyandrographolide 19ß-D-
5
glucoside from the leaves of A. paniculata, Planta Medica 1982; 15: 245-246.).
The primary medicinal component of Andrographis is andrographolide It has a very bitter taste,
is a colourless crystalline in appearance, and is called a "diterpene lactone" - other active
components
include
14-deoxy-11,12-
didehydroandrographolide
(andrographlide
D),
homoandrographolide, andrographan, andrographon, andrographosterin, and stigmasterol - the
last of which was isolated from an Astrographis preparation (Siripong, P., B. Kongkathip, K.
Preechanukool, P. Picha, K. Tunsuwan, and W.C. Taylor. 1992. Cytotoxic diterpenoid
constituents from Andrographis paniculata, Nees leaves, J. Sci. Soc. Thailand 18(4):18794.).
The roots gave apigenin- 7, 4'- di-O-methyl ether, andrographolide and a new natural flavone, 5hydroxy 7,8,2',3'- tetramethoxy flavone (C19H18O7, mp 150-151˚C; yield, 0.006%). They also
contain a monohydroxy trimethyl flavone, andrographin (C18H16O6, mp 190-191˚C) and a
dihydroxy-di-methoxyflavone, panicolin (C17H4O6, mp 263-264˚C). The presence of α-sitosterol is
also reported. (Chemistry and pharmacology of Andrographis species' by Sudhanshu
Saxena et al published in Indian Drugs 35 (8) August 1998).
PHARMACOLOGICAL ACTION:
Andrographis paniculata, (AP), also known commonly as "King of Bitters," is a member of the
plant family Acanthaceae, and has been used for centuries in Asia to treat GI tract and upper
respiratory infections, fever, herpes, sore throat, and a variety of other chronic and infectious
diseases. It is found in the Indian Pharmacopoeia and is the prominent in at least 26 Ayurvedic
formulas.
Since ancient times, A. paniculata is used as a wonder drug in traditional Siddha and Ayurvedic
systems of medicine as well as in tribal medicine in India and some other countries for multiple
clinical applications. The therapeutic value of Kalmegh is due to its mechanism of action which is
perhaps by enzyme induction. The plant extracts exhibits antityphoid and antifungal activities.
Kalmegh is also reported to possess antihepatotoxic, antibiotic (Gupta et al., 1993), antimalarial,
antihepatitic (Jayaram et al., 1989; Ramfi et al., 1992), antithrombogenic, Jaundice (Tomar et
al., 1983), anti-inflammatory (Tajuddin et al., 1983; Shen et al., 2000), antisnakevenom, and
antipyretic properties to mention a few, besides its general use as an immuno-stimulant agent. A
recent study conducted at Bastyr University, USA confirms anti-HIV activity of andrographolide.
Liver & Gallbladder Protection:
In Ayurvedic medicine (a system used in India), there are 26 different formulations containing AP
that are used to treat liver disorders. AP's four related medicinal compounds were tested for a
protective effect against liver toxicity produced in mice by giving them carbon tetrachloride (a
6
cleaning solvent), alcohol, or other toxic chemicals. (Kapil, A., I.B. Koul, S.K. Banerjee, and
B.D. Gupta. 1993. Antihepatotoxic effects of major diterpenoid constituents of
Andrographis paniculata. Biochemical Pharmacology 46(1):182-85. ). These chemicals
damage the liver by causing lipid peroxidation. This is a process whereby free radicals (reactive
molecules) produced by the chemical attack and destroy cellular membranes that surround liver
cells. When the AP compounds were given to animals three days before the toxic chemicals,
there was a significant protective effect in the liver. This effect was attributed to the antioxidant
ability of the AP compounds, which was effective as silymarin (another plant antioxidant from milk
thistle).
In another study, andrographolide from AP was shown to produce a significant increase in bile
flow. (Shukla, B., P.K.S. Visen, G.K. Patnaik, and B.N. Dhawan. 1992. Choleretic effect of
andrographolide in rats and guinea pigs. Planta Med. 58:146-48. ). Bile is produced in the
liver and stored in the gallbladder and aids in digestion. When a chemical, paracetamol, was
given to animals pretreated with andrographolide, the usual decrease in bile production seen with
this chemical was prevented. In this case. andrographolide was more potent than silymarin.
Infective hepatitis is an acute inflammatory condition of the liver. It is often followed by liver
cirrhosis and may progress to a coma and death. In India, where ancient physicians used AP to
treat similar liver ailments, a study was conducted to evaluate the effect of AP in infective
hepatitis. There was marked improvement in the majority of patients tested, when given a
decoction or infusion of AP. Appetite improved on the fifth day of treatment, jaundice (yellow
colour of conjunctive of the eye and skin) gradually diminished and completely disappeared within
24 days, and fever subsided after 7 days on average. Other indications of effectiveness of AP
included improvement in liver function tests. The researchers concluded that AP was a useful
remedy for treatment of infective hepatitis.
The andrographolides present in AP are potent stimulators of gallbladder function. In animal
experiments, those that received andrographolides for seven consecutive days showed an
increase in bile flow, bile salts, and bile acids. These increases are beneficial and result in
enhanced gallbladder function. Use of AP might, therefore, decrease the probability of gallstone
formation and might also aid fat digestion. The andrographolides also prevented decreases in the
amount of bile that are caused by acetaminophen toxicity. (Holt, Stephen M.D., Linda Comac,
Miracle Herbs: How Herbs Combine with Modern Medicine to Treat Cancer, Heart Disease,
AIDS, and More, Caro Publishing Group, 1998.).
7
REFERENCES:
1.
Chem Weiming and Liang Xiaotion. Deoxyandrographolide 19ß-D-glucoside from the
leaves of A. paniculata, Planta Medica 1982; 15: 245-246.
2.
Chemistry and pharmacology of Andrographis species' by Sudhanshu Saxena et al
published in Indian Drugs 35 (8) August 1998
3.
Gupta et al., 1993
4.
Holt, Stephen M.D., Linda Comac, Miracle Herbs: How Herbs Combine with Modern
Medicine to Treat Cancer, Heart Disease, AIDS, and More, Caro Publishing Group,
1998.).
5.
Jayaram et al., 1989; Ramfi et al., 1992
6.
Kapil, A., I.B. Koul, S.K. Banerjee, and B.D. Gupta. 1993. Antihepatotoxic effects of major
diterpenoid constituents of Andrographis paniculata. Biochemical Pharmacology
46(1):182-85.
7.
Sharma, A., L. Krishan, and S.S. Handa. 1992. Standardization of the Indian crude drug
Kalmegh by high pressure liquid chromatographic determination of andrographolide.
Phytochemical analysis 3:129-31
8.
Shukla, B., P.K.S. Visen, G.K. Patnaik, and B.N. Dhawan. 1992. Choleretic effect of
andrographolide in rats and guinea pigs. Planta Med. 58:146-48.
9.
Siripong, P., B. Kongkathip, K. Preechanukool, P. Picha, K. Tunsuwan, and W.C. Taylor.
1992. Cytotoxic diterpenoid constituents from Andrographis paniculata, Nees leaves, J.
Sci. Soc. Thailand 18(4):187-94.
10.
Sing,A.,Kapoor,L.D.,and Chandra, V., Pharmaco-botanic studies of kalmegh, J.ResIndian
Med .,7,93,1972
11.
Tajuddin et al., 1983; Shen et al., 2000
12.
Tomar et al., 1983
8
Holarrhena antidysenterica Wal.
SCIENTIFIC NAME
:
Holarrhena antidysentericaWal.
COMMON NAME
:
Kurchi (Bengali); Ieory tree (English);
FAMILY
:
Apocynaceae.
PARTS USED
:
Bark.
HABITAT
:
It grows throughout India up to an altitude of 4,000 ft.
It is especially abundant in the sub-Himalayan tract
DESCRIPTION
:
Kureya (Hindi);
A shrub or small tree, glabrous or pubescent, bark with pale.
Leaves 10-20 by 5.11 cm from broadly ovate to elliptic, obtuse.
Flowen white in terminal corymbose eymes, white. Fruit follicles of
20-38 cm long. A tall perennial woody plant have a main trunk and
branches forming a distinct elevated crown; includes both
gymnosperms and angiosperms. This is a small tree, glabrous or
pubescent, bark with pale colour. Leaves 10-20 by 5.11 cm from
broadly ovate to elliptic, obtuse. Flowers white in terminal
corymbose eymes, white. Fruit follicles of 20-38 cm long (Ref:
Indian
Journal
of
Pharmaceutical
Sciences
(Scientific
Publication of the Indian Pharmaceutical Association) March
April 2002 Poonam G. Daswani Tannaz J. Birdi D. S.
Antarkar1 and N. H. Antia. The Foundation for Medical
Research Mumbai Holarrhena antidysenterica (L).
Fig.1 Portion of a flowering twig
9
Photograph-1&2: Whole plant
CHEMICAL CONSTITUENTS:
1.
Around 30 alkaloids have been isolated from the plant, mostly from the bark. These
include conessine, kurchine, kurchicine, holarrhimine, conarrhimine, conaine,
conessimine,
iso-conessimine,
conimine,
holacetin
and
conkurchin.
Aminoglycosides are important; the bark also gave nonalkaloids.(Ref: Indian J. Chem.,
1981, 20B: 62.).
2.
Three new bases isolated from bark are conesi'mine, holarrhine and holarrhimine'.
Further, two new alkaloids from the. seeds and bark were isolated -conimine and
isoconessimine".The gum resin contains caoutechoue, lettoresinol-A and lettoresinol-B'.
The formulation Kutajarishta has been studied for distribution of alkaloids.
3.
The principal alkaloid of kurchi is conessine. The other alkaloids reported to be present in
the bark are: conamine, conkurchine, connessimine, kurchine, conarrhinine, holarrhinene
and isoconcessimine
10
PHARMACOLOGICAL ACTIVITIES:
1.
The bark is used as an astringent, anthelmintic, antidontalgic, stomachic, febrifuge,
antidropsical, diuretic, in piles, colic, dyspepsia, chest affections and as a remedy in
diseases of the skin and spleen. It is a well known drug for amoebic dysentery and other
gastric disorders. It is also indicated in diarrhoea, indigestion, flatulence and colic. [Ref:
Dictionary of Indian Medicinal Plants, CIMAP, Lucknow (1992) ,Singh, K.P.: Ancient
Sci. Life 5:228 (1986) , Selected Medicinal Plants of India, CHEMEXCIL, Mumbai
(1982). ]
2.
Conessine from the bark killed free living amoebae and also kills Entamoeba
histolytica in the dysenteric stools of experimentally infected kittens. It is markedly lethal
to the flagellate protozoon. It is antitubercular also. Conkurchine is hydrochloride
hypotensive and vasodilator. (Ref: J.Pharm. (London), 1049, 1:340. ,
3.
Antibacterial activity of Holarrhena antidysenterica [kurchi] Against The Enteric
pathogens. The present study was undertaken to find the anti-bacterial activity of the
crude aqueous and alcoholic extracts of stem bark of Holarrhena antidysenterica
against the known enteric pathogens. Our present work suggests that clinical trial of both
aque-ous and alcoholic extracts of the stem bark of H. antidysenterica can be carried out
against a battery of enteric pathogens, casuative agents of diarrhea in infants and adults.
(Ref: M. BALLAL, D. SRUJAN, K.K. BHAT, A. SHIRWAIKAR, P.G. SHIVANANDA
Department of Microbiology, Kasturibai Medical college, Manipal Department of Botany,
Poorna Prajna College, Udupi,Department of Chemistry, Kasturibai Medical College,
Manipal-576 119.) (Ref: Indian Journal of Pharmacology 2001; 33: 392-393, Brown HC.
Holarrhena antidysenterica. Br Med J 1992; 306:903-10).
4.
Investigation of the Antidiarrhoeal activity of holarrhena antidysenterica. Holarrhena
antidysenterica (L)- Apocyanaceae, well known for its antidiarrhoeal activity was studied
for its effect on diarrhoeagenic Escherichia Escherichia coil. Different dilutions of the
decoction of the plant were assayed for its effect on the adherence and toxin production of
2 groups of E. coli enteropathogenic (EPEC) and enterotoxigenic (ETEC.) Adherence per
se was not affected though disruption of the characteristic `microcolonies' of EPEC on
HEp-2 cell line was observed. The decoction was more effective in inhibiting stable toxin
production as compared with labile toxin. (Ref: Daswani PG; Birdi TJ; Antarkar DS;
Antia NH. Indian Journal of Pharmaceutical Sciences. 2002 Mar-Apr; 64(2): 164-7).
11
5.
Chopra and his associates (1972) showed that conessine killed free living amoebae,
proteus and limax in dilutions of 1 in 2,80,000. Its action on the vegetative forms of
E.histolytica was tested on the dysenteric stools of experimentally infected kittens. In
mucus flakes in such stools motile amoebae were killed in dilutions of 1 in 2,80,000 in 8
minutes in the presence of an alkali and in 18 minutes in the absence of alkali, as
compared with 1 in 2,00,000 of emetine. (Ref: Chopra, R. N.: Indigenous Drugs of
India, Acadernic Publishers, Calcutta (1982).
6.
Conessine from the bark kills free living amoebae; it also kills Entamoeba histolytica in
dysenteric stools of experimentally infected kittens. Conessine produces little effect on
Trichomonas hominis but is lethal to the flagellate protozoon.
7.
In a clinical study on 40 cases of amoebiasis and giardiasis, the efficacy of Holarrhena
antidysenterica in intestinal amoebiasis was 70%. Good response was also observed in
Entamoeba histolytica cyst-passers, when treated with H. antidysenterica bark. (Ref:
Encyclopedia of Indian Medicinal Plants – C.P.Khare. Published by Springer-Verlag
Berlin Heidelberg, Printed in Germany.
REFERENCES:
1.
Chopra, R. N.: Indigenous Drugs of India, Acadernic Publishers, Calcutta (1982).
2.
Prasad, S. and P. N. Kaul,: Ind. J. Pharm, Oct. 423 (1956).
3.
Anandakumar, A. et al.: Ancient Sci. Life 3: 203 (1983).306:903-10.
4.
Roy, A. C. and Mukherjee,. J. Sci. Indus. Res. 17A: 158 (1958).
5.
Siddiqui, S. and Pillai: Ind. J. Chem. Soc. 9: 553 (1932).
6.
Siddiqui, S. et al.: J. Sci. Indus. Res. 25: 20 (1982).
7.
Peacock and Choudbury: J. Chem. Soc. 1129 (1935).
8.
Singh, K. P.: Ancient Sci. Life 5: 228 (1986).
9.
Khorana, M. L. and T. N. Vasudevan: Ind. J. Pharin. 29: 149 (1967).
10.
Chopra, R. N.: Indigenous Drugs of India, Acadernic Publishers, Calcutta (1982). Daswani
PG; Birdi TJ; Antarkar DS; Antia NH. Indian Journal of Pharmaceutical Sciences. 2002
Mar-Apr; 64(2): 164-7
11.
Dictionary of Indian Medicinal Plants,CIMAP, Lucknow(1992) ,Singh, K.P.: Ancient Sci.
Life 5:228 (1986) , Selected Medicinal Plants of India, CHEMEXCIL, Mumbai (1982).
12
12.
Encyclopedia of Indian Medicinal Plants – C.P.Khare. Published by Springer-Verlag Berlin
Heidelberg, Printed in Germany.
13.
Indian J. Chem., 1981, 20B: 62.
14.
Indian Journal of Pharmacology 2001; 33: 392-393, Brown
antidysenterica. Br Med J 1992; J.Pharm. (London), 1049, 1:340.
13
HC.
Holarrhena
Phyllanthus niruri
BOTANICAL NAME
:
Phyllanthus niruri
FAMILY
:
Euphorbiaceae
SYNONYMS
:
Phyllanthus carolinianus, P, sellowianus,
COMMON NAMES
:
Chanca piedra
PART USED
:
Entire plant
HABIT
:
Shrubs, trees, and annual or biennial herbs
HABITAT
:
Distributed throughout the tropical and subtropical regions of
both hemispheres.
DESCRIPTION OF PLANT:
Phyllanthus niruri is an annual, herb; height varies between 30–60 cm. Stem is angular with
numerous distichous, elliptic-oblong leaves. Flowers are yellow and very numerous; monoecious
with 1–3 staminate flowers and solitary pistillate flower borne axillary. Fruits capsule, very small,
globose, smooth, seeds 3-gonous, longitudinally ribbed on the back. Seed to seed cycle occurs in
two or four weeks. The flowering time in Indian conditions is July to August. Keys for identification
of different species of Phyllanthus are found in Caius (1986), Agharkar (1991), and Gupta (984).
Fig: 1 Portion of Phyllanthus niruri
Fig: 2 Inflorescence
Photograph: Whole plant
14
CHEMICAL CONSTITUENTS:
Alkaloids, astragalin, brevifolin, carboxylic acids, corilagin, cymene, ellagic acid, ellagitannins,
gallocatechins, geraniin, hypophyllanthin, lignans, lintetralins, lupeols, methyl salicylate, niranthin,
nirtetralin, niruretin, nirurin, nirurine, niruriside, norsecurinines, phyllanthin, phyllanthine,
phyllanthenol, phyllochrysine, phyltetralin, repandusinic acids, quercetin, quercetol, quercitrin,
rutin, saponins, triacontanal, tricontanol (Ref: Ueno, H., et al. “Chemical and pharmaceutical
studies on medicinal plants in Paraguay. Geraniin, an angiotensin-converting enzyme
inhibitor from ‘paraparai mi,’ Phyllanthus niruri.” J. Nat. Prod. 1988; 51(2): 357–59.
PHARMACOLOGICAL ACTION:
Its root, leaves, fruits, milky juice, and whole plants are used as medicine. According to
Ayurvedic system of medicine it is considered acrid, cooling, alexipharmic and useful in thirst,
bronchitis, leprosy, anemia, urinary discharge, anuria, biliousness, asthma, for hiccups, and as a
diuretic.
According to Unani system of medicine herb is stomachic and good for sores and useful in
chronic dysentery. Fruits useful for tubercular ulcers, wounds, sores, scabies and ring worm
(Agharkar 1991; Krishnamurty 1993). The fresh root is believed to be an excellent remedy for
jaundice. A poultice of the leaves with salt cures scabby affection and without salt applied on
bruise and wounds. The milky juice is a good application to offensive sores. The bark yields a
bitter principle phyllanthin. The infusion of the root and leaves is a good tonic and diuretic when
taken cold in repeated doses.
In different parts of India, specially, in Chhattisgarh state, there is a rich traditional medicinal
tradition concerning this weed (Caius 1986; Oudhia and Tiwari 2001). In many parts of India, it
is commonly used for the treatment of snake bite. The active compounds phyllanthin and
hypophyllanthin have been isolated from leaves. Recently, lignansniranthin, nirtetralin, and
phyltetralin have been isolated from leaves. (Rastogi and Mehrotra, 1991) It is a major component
of many popular liver tonics in India. Fresh juice and powder of dried plant are used most
frequently in Ayurvedic preparations (Sastry and Kavatherkar, 1991). (Ref: Rastogi, R.P. and
B.N. Mehrotra. 1991. Compendium of Indian medicinal plants Vol. II. Central Drug Research
Institute, Lucknow and publications and Information Directorate, New Delhi).
15
ETHNOBOTANY:
India
Anemia, asthma, astringent, bronchitis, conjunctivitis, cough, deobstruent, dropsy, diabetes,
diarrhea, diuretic, dysentery, fevers, eye disorders, galactagogue, genitourinary disorders,
gonorrhea, hepatitis, jaundice, leucorrhea, menorrhagia, oligogalactia, ringworm, scabies,
stomachic, thirst, tuberculosis, tumor (abdomen), urogenital tract infections, warts.
REFERENCES:
1.
Rastogi, R.P. and B.N. Mehrotra. 1991. Compendium of Indian medicinal plants Vol. II. Central
Drug Research Institute, Lucknow and publications and Information Directorate, New Delhi
2.
Dhar, M. L., et al. “Screening of Indian plants for biological activity: Part I.” Indian J. Exp. Biol. 1968;
6: 232–47.
3.
Kitisin, T., et al. “Pharmacological studies. 3. Phyllanthus niruri.” Sirriaj. Hosp. Gaz. 1952; 4: 641–
49.
4.
Umarani, D., et al. “Ethanol induced metabolic alterations and the effect of Phyllanthus niruri in their
reversal.” Ancient Sci . Life 1985; 4(3): 174–80.
5.
Ueno, H., et al. “Chemical and pharmaceutical studies on medicinal plants in Paraguay. Geraniin,
an angiotensin-converting enzyme inhibitor from ‘paraparai mi,’ Phyllanthus niruri.” J. Nat. Prod.
1988; 51(2): 357–59.
6.
Sreenivasa, R. Y., “Experimental production of liver damage and its protection with Phyllanthus
niruri and Capparis spinosa (both ingredients of LIV52) in white albino rats.” Probe 1985; 24(2):
117–19.
7.
Prakash, A., et al. “Comparative hepatoprotective activity of three Phyllanthus species, P. urinaria,
P. niruri and P.simplex, on carbon tetrachloride induced liver injury in the rat.” Phytother. Res. 1995;
9(8): 594–96.
8.
Bhumyamalaki , et al. “Phyllanthus Niruri and jaundice in children.” J. Natl. Integ. Med. Ass. 1983;
25(8): 269–72.
9.
Thabrew, M. R., et al. “Phytogenic agents in the therapy of liver disease.” Phytother. Res. 1996;
10(6): 461–67.
10.
Wang, M. X., et al. “Observations of the efficacy of Phyllanthus spp. in treating patients with chronic
Hepatitis B.” Zhongguo Zhong Yao Za Zhi 1994; 19(12): 750–52.
11.
Farouk, A. “Antimicrobial activity of certain Sudanese plants used in folkloric medicine. Screening
for antibacterial activity (I). Fitoterapia 1983; 54(1): 3–7.
12.
Mesia, L.T.K., et al. “In-vitro antimalarial activity of Cassia occidentalis, Morinda morindoides and
Phyllanthus niruri.” Ann. Trop. Med. Parasitol. 2001; 95(1): 47–57.
13.
“Antimalarial activity of 20 crude extracts from nine African medicinal plants used in Kinshasa,
Congo.” J. Ethnopharmacol. 1999; 68(1/3): 193–203.
14.
Rao, M. V., and K. M. Alice. “Contraceptive effects of Phyllanthus amarus in female mice.
Phytother. Res. 2001; 15(3): 265–67.
16
Picrorhiza kurroa Royle ex Benth
BOTANICAL NAME
:
Picrorhiza kurroa Royle ex Benth
COMMON NAME
:
Hellbore, Katuka, Katuki, Kurri, Kutki, Katuko, Kuru,
Katukarogani.
PARTS USED
:
Dry rhizomes and roots.
HABITAT
:
Found in the Himalayan region growing at elevations of
3,000-5,000 meters
DESCRIPTION OF PLANT:
Picrorhiza kurroa has a long, creeping rootstock that is bitter in taste, and grows in rock crevices
and moist, sandy soil. The leaves of the plant are flat, oval, and sharply serrated. The flowers,
which appear June through August, are white or pale purple and borne on a tall spike.
Photograph 1: Whole plant
17
PHYTOCHEMISTRY:
The active constituents are obtained from the root and rhizomes
Kutkin is the active principal 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. [Weinges K, Kloss P, Henkels WD. Natural products from
medicinal plants. XVII. picroside-II, a new 6-vanilloyl-catapol from Picrorhiza kuroa Royle
and Benth. Justus Liebigs Ann Chem 1972;759:173-182. [Article in German]; Stuppner H,
Wagner H. New cucurbitacin glycosides from Picrorhiza kurroa. Planta Med 1989;55:559563.] Apocynin is a catechol that has been shown to inhibit neutrophil oxidative burst in addition to
being a powerful anti-inflammatory agent, [Simons JM, `t Hart BA, Ip Vai Ching TR, et al.
Metabolic activation of natural phenols into selective oxidative burst agonists by activated
human neutrophils. Free Radic Biol Med 1990;8:251-258.] while the curcubitacins have been
shown to be highly cytotoxic and possess antitumor effects. [Stuppner H, Wagner H. New
cucurbitacin glycosides from Picrorhiza kurroa. Planta Medica 1989;55:559.]
Kutkin, a bitter glycosidal principle, was reported by Rastogi et al. They also isolated D-mannitol,
vanillic acid and some steroids.Kutkin was later shown to be a stable mixed crystal of two C-9
iridoid glycosides-Picroside I and Kutakosid. Apocynin has been isolated from the plant. Picroside
II has been isolated and shown to have hepatoprotective activity. With the help of preparative
HPLC, larger Quantities of picrosides have been isolated, permitting precise structure
identification and biological experiments.
ETHNOBOTANY:
For thousands of years, the bitter rhizomes of Picrorhiza have been used in India to treat people
with indigestion, but it is also a remedy for constipation accompanied with insufficient digestive
secretion, and fevers caused by all types of infection. Scientific studies have shown Picrorhiza to
have antioxidant properties, particularly in the liver.
PHARMACOLOGICAL ACTION:

Hepatoprotective,

Anticholestatic,

Antioxidant,

Immune-modulating activity.
18
[Atal CK, Sharma ML, Kaul A, Khajuria A. Immunomodulating agents of plant origin. I:
preliminary screening. J Ethnopharmacol 1986;18:133-141.Subedi BP. Plant profile: Kutki
(Picrorhiza scrophulariifiora). Himalayan Bioresources 2000;4.
1.
Picrorhiza kurroa (Kutaki) Royle ex Benth as a hepatoprotective agent--experimental &
clinical studies. Vaidya AB, Antarkar DS, Doshi JC, Bhatt AD, Ramesh V, Vora PV,
Perissond D, Baxi AJ, Kale PM Year : 1996 Vol: 42 Issue : 4 Page : 105-8
Picrorhiza kurroa (Pk), a known hepatoprotective plant, was studied in experimental and
clinical situtations. The standardization of active principles--Picroside 1 and 2 was done
with High Performance Liquid Chromatography. Picroside 1 ranged from 2.72 to 2.88
mg/capsule and picroside 2 from 5.50 to 6.00 mg/capsule. In the galactosamine-induced
liver injury in rats, Pk at a dose of 200 mg/kg p.o. showed a significant reduction (p < 0.05)
in liver lipid content, GOT and GPT. In a randomised, double-blind placebo controlled trial
in patients diagnosed to have acute viral hepatitis (HBsAg negative), Pk root powder 375
mg three times a day was given for 2 weeks (n = 15) or a matching placebo (n = 18) was
given. Difference in values of bilirubin, SGOT and SGPT was significant between placebo
and Pk groups. The time in days required for total serum bilirubin to drop to average value
of 2.5 mg% was 75.9 days in placebo as against 27.44 days in Pk group. The present
study has shown a biological plausability of efficacy of Pk as supported by clinical trial in
viral hepatitis, hepatoprotection in animal model and an approach for standardizing
extracts based on picroside content.
19
2.
Hepatic Insult and Damage
Numerous animal studies, primarily in rats, have demonstrated that the active constituents
of Picrorhiza kurroa are effective at preventing liver toxicity and the subsequent
biochemical changes caused by numerous toxic agents. Hepatocytes damaged by
exposure to galactosamine, thiocetamide, and carbon tetrachloride were incubated with
Picrorhiza constituents. A concentration-dependent restorative effect was observed in
regard to normal hepatocyte function. [Visen PK, Saraswat B, Dhawan BN. Curative
effect of picroliv on primary cultured rat hepatocytes against different hepatotoxins:
an in vitro study. J Pharmacol Toxicol Methods 1998;40:173-179.]
A similar effect was seen when 25 mg/kg/day oral Picrorhiza extract was administered to
rats poisoned by aflatoxin B1 exposure. Picrorhiza kurroa significantly prevented the
biochemical changes induced by aflatoxin B1. [ Rastogi R, Srivastava AK, Rastogi AK.
Biochemical changes induced in liver and serum aflatoxin B1-treated male wistar
rats: preventive effect of picroliv. Pharmacol Toxicol 2001;88:53-58.]
Picrorhiz extract, when given at a dose of 3-12 mg/kg orally for 45 days, was also shown
to be effective in reversing ethanol-induced liver damage in rats. [ Saraswat B, Visen PK,
Patnaik GK, Dhawan BN. Ex vivo and in vivo investigations of picroliv from
Picrorhiza kurroa in an alcohol intoxication model in rats. J Ethnopharmacol
1999;66:263-269.]
In an animal model of hepatic ischemia, rats given Picrorhiza orally at 12 mg/kg daily for 7
days,
prior to induced ischemia, demonstrated improved hepatocyte glycogen
preservation and reduced apoptosis, compared to control animals. [ Singh AK, Mani H,
Seth P. Picroliv preconditioning protects the rat liver against ischemia-reperfusion
injury. Eur J Pharmacol 2000;395:229-239]
Picrorhiza principals have also shown to be effective in treating Amanita mushroom
poisoning in an in vivo animal model. [ Dwivedi Y, Rastogi R, Garg NK, et al. Effects of
picroliv, the active principle of Picrorhiza kurroa, on biochemical changes in rat
liver poisoned by Amanita phalloides. Chung Kuo Yao Li Hsueh Pao 1992;13:197200.]
20
An in vitro study demonstrated Picrorhiza's antioxidant activity by subjecting human
Glioma and Hep 3B cells to a hypoxic state. Picrorhiza treatment reduced the cellular
damage cause by hypoxia, indicating Picrorhiza constituents may protect against
hypoxia/reoxygenation-induced injuries. [ Gaddipati JP, Madhavan S, Sidhu GS, et al.
Picroliv -- a natural product protects cells and regulates the gene expression during
hypoxia/reoxygenation. Mol Cell Biochem 1999;194:271-281.]
REFERENCES:
1. Atal CK, Sharma ML, Kaul A, Khajuria A. Immunomodulating agents of plant origin. I: preliminary
screening. J Ethnopharmacol 1986;18:133-141.Subedi BP. Plant profile: Kutki (Picrorhiza
scrophulariifiora). Himalayan Bioresources 2000;4.
2. Dwivedi Y, Rastogi R, Garg NK, et al. Effects of picroliv, the active principle of Picrorhiza kurroa, on
biochemical changes in rat liver poisoned by Amanita phalloides. Chung Kuo Yao Li Hsueh Pao
1992;13:197-200.]
3. Gaddipati JP, Madhavan S, Sidhu GS, et al. Picroliv -- a natural product protects cells and
regulates the gene expression during hypoxia/reoxygenation. Mol Cell Biochem 1999;194:271-281.]
4. Justus Liebigs Ann Chem 1972;759:173-182. [Article in German];
5. Saraswat B, Visen PK, Patnaik GK, Dhawan BN. Ex vivo and in vivo investigations of picroliv from
Picrorhiza kurroa in an alcohol intoxication model in rats. J Ethnopharmacol 1999;66:263-269.
6. Simons JM, `t Hart BA, Ip Vai Ching TR, et al. Metabolic activation of natural phenols into selective
oxidative burst agonists by activated human neutrophils. Free Radic Biol Med 1990;8:251-258.
7. Singh AK, Mani H, Seth P. Picroliv preconditioning protects the rat liver against ischemiareperfusion injury. Eur J Pharmacol 2000;395:229-239].
8. Stuppner H, Wagner H. New cucurbitacin glycosides from Picrorhiza kurroa. Planta Med
1989;55:559-563.].
9. Stuppner H, Wagner H. New cucurbitacin glycosides from Picrorhiza kurroa. Planta Medica
1989;55:559.].
10. Vaidya AB, Antarkar DS, Doshi JC, Bhatt AD, Ramesh V, Vora PV, Perissond D, Baxi AJ, Kale PM
Year : 1996 Vol: 42 Issue : 4 Page : 105-8.
11. Rastogi R, Srivastava AK, Rastogi AK. Biochemical changes induced in liver and serum aflatoxin
B1-treated male wistar rats: preventive effect of picroliv. Pharmacol Toxicol 2001;88:53-58.
12. Weinges K, Kloss P, Henkels WD. Natural products from medicinal plants. XVII. picroside-II, a new
6-vanilloyl-catapol from Picrorhiza kuroa Royle and Benth.
21
QUALITY CONTROL PARAMETERS
OF `API’ OF LIVOKURE
22
QUALITY CONTROL PARAMETERS OF `API’ OF LIVOKURE
Sl.
Extracts
No.
01.
Phyllanthus niruri
Plant
parts
used
Type of
form used
Organoleptic
test
Particle
size
L.O.D.%
w/w
at 1050C
pH of 1%
soln. in
water
Assay
Whole
plant
Dry powder
extract with
fine granules
Brown
coloured,
aromatic odour
and bitter taste
passed
thru 20#
NMT 6%
4.0-7.0
Root
Dry powder
extract with
white specks
passed
thru 20#
NMT 5%
4.0-7.0
Leaf
Brown dry
powder
passed
thru 20#
NMT 5%
4.0-7.0
Andrograph
olides NLT
5% by
gravimetry
Bark
Fine powder
extract
Dark brown
coloured,
characteristic
odour and
bitter taste
Dark greenish
brown
coloured,
aromatic odour
and bitter taste
Brown
coloured,
aromatic odour
and bitter taste
By
gravimetry.
Bitters
NLT
2%(d/b)
Bitters by
gravimetry.
NLT 6%
(d/b).
passed
thru 20#
NMT 10%
4.0-7.0
Alkaloids by
gravimetry
NLT 4%
(d/b)
(Bhuiamla)
02.
Picrorhiza kurroa
(Kutki)
03.
Andrographis
paniculata
(Kalmegh)
04.
Holarrhena
antidysenterica
(Kurchi)
23
CLINICAL DATA ON
LIVOKURE
24
Fig. 1. Effect of the Plant extract of Livokure on lipid content
of the liver in rats during CCl4 liver injury (S.E.)
Total lipid in mg/kg liver tissue
200
150
Normal
100
CCl4 administered +
vehicle
CCl4 administered +
Livokure
50
0
Groups
Sl. No.
1)
2)
3)
Group
Normal
CCl4 administered + Vehicle
CCl4 administered + Plant extract
No. of animal used 65, * P<0.001
25
Total lipids in
mg/kg liver tissue
67.0  2.0
180.5  3.5
71.2  2.5*
Fig. 2 Effect of plant extract of Livokure on serum triglyceride
level during CCl4 intoxication in rats (+S.E.)
200
180
160
140
Groups
120
Normal
100
80
CCl4 administered +
Vehicle
60
40
CCl4 administered +
Livocure
20
0
Triglyceride level (mg/100ml)
Sl. No.
1)
2)
3)
Group
Normal
CCl4 administered + Vehicle
CCl4 administered + Plant extract
No. of animal used 65, *P<0.01
26
Total lipids in
mg/kg liver tissue
180.5  5.5
135.6  6.2
167.2  3.9*
Fig. 3. Effect of Livokure on serum cholesterol in CCl4
induced liver intoxication in rats (S.E)
Cholesterol level (mg/100 ml)
60
50
40
Normal
30
CCl4 administered +
vehicle
CCl4 administered +
Livokure
20
10
0
Groups
Normal
CCl4 administered
CCl4 administered Livokure
No. of animal used 65, * P<0.02
27
50.2  2.9
41.1  3.2
53.5  3.1
Fig. 4. Effect of Livokure on SGPT and SGOT level of source
of rats during the CCl4 treatment (S.E.)
120
Unit/ml serum
100
80
Normal
60
CCl4 administered +
vehicle
CCl4 administered +
Livokure
40
20
0
SGPT
Sl.
No.
1)
2)
3)
SGOT
Group
Normal
CCl4
CCl4 administered + Plant extract
No. of animal used 65, * P<1.9
28
SGPT
(unit/ml serum)
14.4  0.8
110.0  2.1
15.6  0.9
SGOT
(Unit/ml serum)
51.6  2.0
86.2  3.0
52.6  1.9*
CLINICAL TRIAL OF LIVOKURE :

Clinical trials on effectiveness of Phyllanthus for HBV have been mixed, the picies
P.urinaria and P.niruri seem to work better than P.amarus (Ref 8). Clinical trials with
hepatitis B patients have been used 900-2700 mg of Phyllanthus per day (Ref. 1.).

It completely antagonized the toxic effects of paracetamol on certain enzymes in
serums as well as in isolated hepatic cells. Andrographolide was found to be more
potent (Ref 2).

The plant has found experimentally that it has hepatoprotective activities against
alcohol CCl4 and aflatoxin B1 induced hepatic damage (Ref. 3,4).

Amoebicidal, antituberculous and other antiprotozoal activity of individual alkaloids
specially, conessine have been extensively investigated (Ref 5).
References :
1)
Meixa W, Haoweei C, Yanjun L, et al. Herbs of the genus Phyllanthus in the treatment of
chronic hepatitis B: observation with three preparations from different geographic sites. J
Lab Clin Med 1995; 126:350-2.
2)
J. Ethnopharmacol 1993 Oct; 40(2):131-136.
3)
Ibid., Abstract No. 36.
4)
Indigenous Drugs of India (1982), 2nd Ed. Acedemic Publishers, Calcutta, P-242.
5)
J. Ethnopharmacol 1999 Dec 15;68(1-3):399-44.
29
A CLINICAL TRIAL REPORT OF `LIVOKURE’
DONE BY
“J. B. ROY STATE AYURVEDIC MEDICAL COLLEGE & HOSPITAL”
GOVERNMENT OF WEST BENGAL
Date : 17.06.2001
The Ayurvedic medicine `LIVOKURE’ [Drug License no. AL-828(M)] manufactured by
Herbicure (P) Ltd. Calcutta was supplied to me in capsule form for clinical trial.
LIVOKURE was given to the patients (male 11, female 13, age group 10 – 60 years)
through p.o. route (dose: One capsule t.i.d.). The patients were suffering from haemolytic
jaundice, cirrhosis of liver, hepatitis, alcoholic liver diseases.
After 7 days’ consecutive treatment with LIVOKURE, biochemical studies revealed that
lipid level was normalised significantly. It was also noted that serum bilirubin level
(conjugated & unconjugated) was reduced markedly. Most of the patients were relieved
from griping pan and irregular bowel movement and revival of loss of appetite was
noticed within a week. SGPT & SGOT levels were normalized after 14 days’ consecutive
treatment of LIVOKURE. It is suggested that the Ayurvedic medicine LIVOKURE is very
much effective remedy against all sorts of acute and chronic liver disorders. LIVOKURE
can also be used as prophylactic medicine to root out liver disorders. It is free from any
side effects.
30