rapid resolution of acute viral hepatitrapid resolution of acute viral hepatitis is by

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1. Prak-20, AN AYURVEDIC DRUG, A POTENT

HEPATOPROTECTIVE AND ANTIFIBROTIC

AGENT – STUDIES IN A MURINE MODEL OFCHRONIC LIVER DISEASE

International Conference, Health and Disease , Delhi ,March 1993

Conference of Indian Association for Study of Liver (INASL,

!ai"ur, #a$asthan, March 1993

2. D!"#$ "#%&' ra&'(%)$' *r%a# + Prak-20, a& A!r$'%

'r!/ %& a& a!*$ %ra# $a*%*% I%th &iennial, Scientific Meetin', Asian acific Associate

for the study of the Liver, )uala*Lu+"ur, Malaysia March 1993

3. PRA4-20 5 A HERBO-MINERAL COMPOUND

Haryana State Ayurvedic Conference, Sone"at, Haryana A"r9-

6. Ra%' R$#!*%& + A!*$ V%ra# H$a*%*% " 7 Prak-208

National .or/sho" on 0ast Actin' Ayurvedic Medicines

2echniues, 4r'ani5ed 6y National Acade+y of Ayurveda,

Ne7 Delhi 0e6 98

National Sy+"osiu+ on Her6al Medicine, Dehradun,

ttaranchal Mar98

South :ast Countries Se+inar on Medicinal lant; atna, &ihar Nov 98



Prak-20, AN AYURVEDIC DRUG, A POTENT

HEPATOPROTECTIVE AND ANTIFIBROTIC

AGENT – STUDIES IN A MURINE MODEL OF

CHRONIC LIVER DISEASESharma G, Sarin S.K, Malhotra V., Mukherjee A.K. and Abdulla M

Department of Gastroentrology and pathology

GB ant !ospital and !amdard "ni#ersity

$e% Delhi, &$D&A

Ayurveda, the ancient Indian medicinal system, describes, several plants with

strong hepatoprotective and antifibrotic properties. It is believed that a combination

of such herbs is more effective with minimal side effects. We investigated Prak-2,

a combination of !" medicinal herbs with an iron ore in a murine model of chronic

liver disease, produced by feeding thioacetamide #$AA%. &wiss albino mice were

e'ually divided into ( groups ) *r I ) control, *r II ) $AA for ! weeks, *r III $AA

for !+ weeks, *r I $AA was prepared as a .glt. a'ueous solution and fed as

!.( mg. ml. Animal ) day by gavage. Prak-2 being insoluble in water was fed by

mi/ing with wkeat flour. Animals were sacrificed according to a fi/ed schedule and

their livers were processed for determination of hepatic 0-hydroo/yproline #11P%

#3amall et al !"4!%, hepatic collagen #*imene5 et al !"4(% and histopathological

studies. $he livers of group II and III animals showed gross micronodularity,

histological evidence of cirrhosis 62 #!7% animals of *r III8, moderate to severe

fibrosis and hepatocellular necrosis in all the liver sections. A several fold increase

in the 11P and hepatic collagen levels was observed in these groups #$able%



Gr! HHRP T*a# $a*% H$a*% C##a/$&

9!./ #%$r: r*$%&9(/: 9!/.(/. r*$%&:

Gr I 23.;±20 0.67±0.19 11.3±3.7

Gr II 476±113*** 0.6±0.19 64.6±8.3***

Gr III 505±37*** 0.6±0.4 532±79.3***

Gr IV 218±60** 0.6±0.2 40.1±6.8*

Gr V 153±51*** 0.7±0.9 27±2.7***

***p < 0.001 between Gr I and II and III; *p;**p <0.01,***p<0.001 between Gr II and III and GrIVand V

Animals treated with Prak-2 after $AA e/posure #*r I%, showed marked

reduction in hepatic necrosis, fibrosis, 11P and hepatic collagen levels. $hese

effects were more pronounced if Prak-2 was started along with $AA from the

beginning #*r %. In conclusion, these results demonstrate that Prak-2, is a potent

hepatoprotective and antifibrotic agent. 9urther studies should be carried out to

identify the active principles in these medicinal plants.



DOUBLE BLIND RANDOMI<ED PLACEBO

CONTROLLED TRIAL OF PRA4-20, A HERBO-

MINERAL DRUG, IN ACUTE VIRAL HEPATITISBy '( Gupta, B. rakash, A . Mukherjee, SK SarinDept. of Gastroentrology, GB ant !ospital, Delhi,

and V( (an)er 'esear)h *oundation, Dehradun, &ndia

SUMMARY A double blind randomi5ed placebo controlled clinical trial was conducted to

assess the efficacy of Prak-2, a herbo-mineral compound, in fifty cases of acute

viral hepatitis, when used as a dose of 2( mg thrice daily for 0 weeks. Prak-2

was able to hasten symptomatic recovery, especially nausea and vomiting

"p:.(%. Prak-2 treated patients showed a statistically greater fall in serum

bilirubin # p:.!%, serum A;$ # p:.!%, and A&$ #p:.(% within one week as

compared to placebo. $here was no appreciable effect on viral markers. &ide

effects were minor and not significantly different from placebo.

INTRODUCTION

$here are no effective drugs to ameliorate and hasten recovery from acute

hepatitis. Ayurveda has on record a number of plant e/tracts that have been

shown to possess hepatoprotective effects. An offshoot of Ayurveda, called

asayan &hastra, deals with therapy of diseases with salts and o/ides # <hasma%

of minerals, prepared by a very cumbersome, laborious, time consuming and a

very tedious process. $he tedious nature of the process lead to its virtual

abandonment over the course of time. 1owever, lately, there has been a revival of

interest in asayan &hastra because of its ability to provide relief in diseases

where other branches of medicine have little to offer.

=ne such asayan or compound is >andoor <hasma, chemically known as

9erroso-9erric =/ide. When prepared e/actly as per the ancient methodology in a

process lasting + months or more per batch, common iron o/ide #;ouha <hasma%

is transformed into true medicinal 'uality >andoor <hasma, which has an entirely



different set of physiochemical properties. It is then claimed to process

hepatoprotective, anti-to/ic and anti-inflammatory activity in liver. $hese properties

are claimed to make it suitable for the therapy of acute or chronic hepatic in?ury or

inflammation. Ayurveda believes in combining a number of plants e/tracts andor

minerals to decrease the side effect of the principal agent and increase synergism.

With this belief, an Ayurvedic drug called Prak-2 has been prepared, combining a

number of plant e/tracts with >andoor <hasma.

$he composition of Prak-2 is as follows @<aliospermum montanum one part<erberis aristata one part<oerhavia diffusa two partedrus deodara one part

urcuma longa one partyperus rotundus one partBmbellia ribes one partBmblica officinalis one partIpomoea terpethum one partCerium tomentosum one partPicrorhi5a kurroa one partPiper longum #Pipli fruit% one partPiper longum #Pipli-mool% one partPiper nigrum one partPlumbago 5eylanica one part

&ausserea lappa one part$erminalia bellirica one part$erminalia chabula one partDingiber officinale one part>andoor <hasma 2 parts

$he drug was well tolerated in this group of patients and was comparable to

Placebo. It demonstrated useful anabolic activity by increasing serum albumin level

increasing reticulocyte coun and reducing pallor and lethargy better than Placebo.

Bdema was reduced by at least ! degree in 47 patients compared to +7 with

Placebo. &imilarly 0+7 showed decrease in pallor by at least ! degree compared

to !07 with placebo. ;ethargy was reduced by more than ! degree in ++7 s (7

with placebo. $he reticulocyte count increased by at least .(7 in "7 s. 7



with placebo. &erum albumin loss is a characteristic of chronic renal disease. All

0 patients were showing loss of albumin in urine and hypoalbuminaemia. After

therapy 2"7 of patients showed a rise of serum protein levelsE.( gm! ml

compared to 7 with placebo.

I(r$($&* $$& & *!' ara($*$r 5 = Ca&/$

0 10 20 30 40 50 60 70 80

Energet! "e e#

$r. %#b&'n

(et)arg*

+et! ,-&nt

a##-r

#a!eb-

+%/20

&t&re #an

Fevelopment of in process 'uality controlled techni'ue and standardi5ation of raw

anf finished product should be carried out.

%!n-w#edge'ent

We acknowledge anba/y ;aboratories ;td., Felhi. Fepartment of

*astroentrology, Fepartment of Cephrology, *.<.Pant 1ospital and ;.C.3.P.

1ospital. Cew Felhi for conducting various studies on Prak-2.

We thank Fr. A. >ukher?ee, >edical onsultant, Galka?i, Cew Felhi for his

continued help and guidance in carrying out all the research pro?ects. We are also

thankful to <harat <haisha?ya &hala Private ;imited, Fehradun for providing study

material.



Ta"#$ >%&/ '%++$r$&$ + ra%'%* + #%&%a# r$&$ "$*>$$& Prak-

20 /r! $r P#a$".

S+A+&S+&(A- S+A+&S+&(A-

S&G$&*&(A$+ S&G$&*&(A$+

&M'V/M/$+ Vs. &M'V/M/$+ Vs.

A(/B A(/B

0&+!&$ 1 0//K S//$ &$ D"'&$G '2 S//$ &$3 4 nset of relief in G& 4 'ate of fall in fe#er

Symptoms

4 *all in Sr. Bilirubin in 4 &mpro#ement in appetite 1 %k 5p67.7718

4 *all in Sr. A+ in 4 *all in Sr. A+ at 9 %k

1 %k 5p67.7718

4 *all in Sr. AS+ in 1 %k 4 &n)iden)e of heartburn

5p67.7:8

$de e""e!t

<oth the groups tolerated the test drugs very well with minor side effects that

included heartburn in and ! patients respectively in both the groups.

-#eran!e r-"#e

Prak-2 is a ?udicious combination of !" herbs and >andoor <hasma. >andoor is

an iron ore described in asa te/t as an anti-inflammatory agent. Iron is known as

1epato to/ic specially in the liver diseases. $o rule out any potential side effects on

the body following studies had been conducted on animal prior to initiation of

human studies.

Came of the study #year%

!. Indian Institute of $o/icology, <ombay, !"".

1epatoprotective studies on liver $onic of anba/y ;aboratories ;td.,

Felhi



Na*%&a# S(%!( & H$r"a# M$'%%&$, 1??@

PRA4-20 5 A HERBO-MINERAL COMPOUND

VA&D-A BA/$D" 'AKAS!

V( (A$(/' '/S/A'(! *"$DA+&$, D/!'AD$

Prak-2 is a ?udicious combination of !" herbs and >andoor <hasma, derived from

the ancient treatise of asayan &hastra. It has strong hepatoprotective ,

deto/ifying, anti-fibrotic and anti-inflammatory properties in a diverse range of liver

disorders with no significant to/icity or side effects. Prak-2 has been studiede/tensively in animals and man.

>andoor <hasma is chemically ferrous ferric o/ide. It ia an Ayurvedic anti-

inflammatory agent. It is purified in sesame seed oil, butter milk, cowHs urine, and

decoction of $riphala and Gulthi. It is then ground in the e/tract of <, diffused for

about !2 hours in wet grinders. $he resultant is sun-dried and then baked in

specially designed pits using dried cow-dung crackery. $his cycle is repeated 0

times, the resultant powder meets with the specifications of a <hasmaJ as defined

earlier.

1erbs used in Prak-2 have following properties @

Anti-nauseant, Antispasmodic, Anti-pyretic, Appeti5er, Astringent, holagogue,

arminative, Fiuretic, Fyspepsia, 1eratoprotective, Improves Gidney 9unction,

Improves liver function, Prokinetic Purgative K ;a/ative action, elieves diarrhea,

relieves hepatomegaly, eleives 3aundice, elieves &plenomegaly.

%$$E$$E : E%:+:EIVE %IVIIE$ : +%/20

%n'a# $t&de



Animal studies were done in rats and mice under controlled conditions, using high

doses of arbon $etrechloride, Paracetamol or $hio-Acetamide as the 1epato-

to/in, to produce predictable degrees of liver cell in?ury, dysfunction, rise in liver

en5ymes, and necrotic changes followed by cirrhotic processes.

oncomitant therapy with Prak-2 produced significant attenuation of liver cell

in?ury, protected the cell against necrosis and cirrhosis, and significantly

normali5ed raised serum en5yme changes. $he studies demonstrated a rapid

onset of anti-inflammatory effect, deto/ifying effect, anti-cirrhotic effect, and

regenerative effect in all the animal models studied.

&'an t&de

!. 1uman studies were initiated with a study of the tolerance of the drug in

kidney impairement cases undergoing renal dialysis at the Fept. of

Ceprology, ;C3P 1ospital using a Fouble <lind placebo ontrolled protocol,

Prak-2 produced a marked improvement in serum albumin levels,

eticulocyte count, pallor and edema. $here were no side effects observed

e/cept one case of minor skin rashes that disappeared on drug withdrawal.

2. $he study was followed by the second Fouble <lind Placebo ontrolled

study in Acute viral hepatitis, at the Fept. of *astroenterology, *< Pant

1ospital, Cew Felhi. =nce again, Prak-2 gave statistically significant faster

resolution in improving *I$ symptoms, and in reducing &r. <iluribin, &r A;$

and &r. A&$ within one or two weeks of therapy as compared to placebo.

. $he third study was an open evaluation of Prak-2 in treating admitted

cases of liver damage due to a variety of causes. $hey included #a% Acute

iral 1epatitis, cL2, #b% Alcohol induced 1epatitis, nL+, #c% Anti-$< $herapy

Induced 1epatitis, nL, and #d% irrhosis of ;iver, nL(

All 0 studies showed a significant resolution in &r. <ilrubin, &r. A;$, &r. A&$, and

Alkaline Phosphatase.



esearch in progress on Prak-2

!. &tandardi5ation of raw materials

2. Fevelopment of in-process 'uality controlled techni'ues

. &tandardi5ation of finished products

0. >ulticentric research pro?ects

RAPID RESOLUTION OF ACUTE VIRAL HEPATITIS

BY 7PRA4-208Vaidya Balendu rakash, Dehradun

Acute viral 1epatitis is an auto immune disorder which may occur sporadically or in

epidemics. $he ;iver involvement is part of a generali5ed infection but dominates

the clinical picture. $he diagnosis is based on clinical findings associated with

abnormal liver tests #markedly elevated transminases% early in the course.

$he clinical course morbidity, and mortality of viral 1epatitis may vary

considerably. In most cases clinical recovery is complete in -!+ weeks. $he

overall mortality rate is less than !7 but the rate is reportedly higher in older

people #particularly postmenopausal women%. Fietary management consisting of

giving palatable meals as tolerated without over feeding and bed rest are

commonly prescribed in western system of medicines and the patients should

avoid atrenuous physical e/certion, alcohol and other hepatoto/ic agents.

Acute viral 1epatitis is also termed as 3aundiceJ. In Ayurvedic te/t the disease is

mentioned as Pandu, Gamla, 1aleemak depending upon the severity of the

?aundice. A number of formulations have been described in various asa granthas.

=ut of these Punarnava >andoor, Cavyas ;oha, Galmegh asayan, Arogya



ardhani figures prominently. $he above formulations have been used for years in

the reduction of ?aundice, however no statistical data is available for reference.

$he formulation of Prak-2J is derived from asayan &hastra which is one of the

eight clinical specialties of Ayurveda. In the present study we will discuss the

therapeutic effect of Prak-2 in the rapid resolution of Acute viral 1epatitis, in a 0

weeks long double blind randomi5ed Placebo controlled clinical trial which was

held at *.<.Pant 1ospital, Cew Felhi.

9ifty patients were selected who were randomi5ed in double blind manner to

receive 0 weeks of either Prak-2 2( mg capsules or matching Placebo $IF for 0

weeks. =nly early untreated cases of definite viral 1epatitis with the disease

process still on the upswing in severity with the following inclusions and e/clusions

criteria were selected for the study.

E!#&-n rtera Pregnancy, lactation, encephalopathy, pedal edema, ascitis,

uncontrolled respiratory &I renal or C& disease, uncontrolled diabetes, steroid

or immune suppressive drug intake, children : !2 yrs.

In!#&-n rtera 3aundice : ! week, &erum <ilirubin E .( mgdl and A;$ E

times normal

-##-w &p

&erology, I*>, Anti 1A, 1bs Ag and Anti 1 #2nd generation% by Abbott BIA.

=ut of the 2( cases in each group, 2 in Prak-2 group completed the trial,

compared to !M in the Placebo group. Patients were followed up weekely clinically

on severity grade of ! to 0 and by serial estimations of the following biochemical

tests.

esult #$able% In patients receiving Prak-2, the decrease in fever , anore/ia,

bilirubin, A;$, A&$ was more dramatic than with Placebo.



At ! week Prak-2 achieved significantly more reduction in bilirubin #( & =%, A;$

#M" & (2% and A&$ # +4 & 0% levels than Placebo.

Parameter Prak-2 #nL2% Placebo #nL!M%

! week 2 week ! week 2 week

9ever MM 2".0NN - (4 (.2N -

Anore/ia#N% 44 2.(NN - 0! !!.MN -

& <il#mgdl%

4.4O2 (.MO!.2NN 2.O. M.!O!.M 4.(O! 0.4O.4

A;$ #I;% !24O2+" 2M2O4NN !("O(M M+"O2! +"O4(N !(4O+!

A&$ #I;% 42MO(2NN 2++O(2NN !0(O(" +!O!+4 2("OM( !4(O2

eferences @

!. &harma *, amanamurthy <, Abduliah >, >alhotra ., >ukher?ee A,

Prakash <,&arin.&.G. #!""2%

Bfficasy of Prak-2, an Indian Ayurvedic medicine as an Antifibrotic Frug in

a >urine >odel of hronic ;iver Fisease. *astronerologyJ ol. !2. Co.

I..&.A.

2. &harma *, &arin &G, >alhotra ., >ukher?ee A and Abdulla > #!""% Prak-

2. An Ayurvedic drug a potent hepatoprotective an anti fibrotic agent-

studies in >urine >odel of hronic ;iver Fisease.

International 3ournal of $o/icology, =ccupational K Bnvironmental 1ealth,

ol. 2 Co. I. 3an.".

. *upta , Prakash <., >ukher?ee A., &arin &G #!""0% Fouble blind

randomi5ed trial of Prak-2, an Ayurvedic drug in an Acute iral 1epatitis.

IQth <ienniel &cientific >eeting. Asian Pacific Association for the syudy of

;iver, Guala-;umpur, >alasia. 3an."0.

0. >ehta imal, 3ain &G #!""(% Preliminary- eport of ole of 1epato-

Protective Frug #Prak-2% in the treatment of Acute iral 1epatitis. Annual

onference of Indian &ociety of *astroentrology !""( uttak.

Firector,



P ancer esearch 9oundation #&I=s%>andir >arg, turner oad, lement $own, Fehradun- 2042, ICFIA

Bmail @ vcpcrfRsancharnet.in

rapid resolution of acute viral hepatitrapid resolution of acute viral hepatitis is by

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