Evidence based Siddha Medical Management of Dengue

http://www.webmedcentral.com/article_view/3808

The link will take you to siddha management in dengue.

Siddha history

When you track Siddha history there are too many confusions . The war between religions also reflected in A system which have a twine witth religion. Siddha is a sect in Jainism .Siddhas are worshipped as liberated souls and people may even not accept this as they are biased with Either Saivism or Vaishnavism But reality is accepted only via history.Read the following doc.

http://www.scribd.com/doc/77642115/Religious-Intolerance

History of Siddha medicine

http://growingeveryday.com/FILES/Sorted/Recipes%20for%20Immortality.pdf


This book has some good points to ponder.

Legal status of Traditional medicine -WHO

http://apps.who.int/medicinedocs/pdf/h2943e/h2943e.pdf

NRHM Mainstreaming

http://nhsrcindia.org/pdf_files/resources_thematic/Public_Health_Planning/NHSRC_Contribution/167.pdf


NRHM -Main Streaming.

http://nhsrcindia.org/pdf_files/resources_thematic/Public_Health_Planning/NHSRC_Contribution/167.pdf

The link will guide you about NRHM Mainstreaming in India.

Varmam Theraphy for Sagana vatham

http://www.webmedcentral.com/article_view/2906

Above link will lead ypu to article

Siddha system Emphasised physicians dress code as white very long back

In Siddha ethics as mentioned by Theraiyar in Thiala varka Churukkam, regarding Physicians dress code,

White is the dress preferred and blue,red and dresses with designs are un acceptable.If we take Theraiyar period as 14-15 th century , this concept came into existence in western medicine only in late 19 century .Read the link below regarding historical background of medical coats.


http://virtualmentor.ama-assn.org/2007/04/mhst1-0704.html#GrossClinic

National Formulary of India

http://www.ipc.gov.in/writereaddata/linkimages/NFI__2011_14Aug%202012%20(web%20download)4550225372.pdf

As a member in Healing profession Every one of Us should have this .

Amendments in Drugs and Cosmetic act in the past two years

http://indianmedicine.nic.in/showfile.asp?lid=337

Click the above link to read the Story. Industries in Siddha ayurvedha and Unani - Attention on Amendment will save Money energy and Time.

DGCI - AYUSH -Finance ministers approval

http://www.safemedicinesindia.in/blog/2012/06/finance-ministry-gives-in-principle-approval-to-create-post-of-dcgi-for-ayush-sector/


click the link and read FM'S Approval for DCGI For AYUSH.

http://www.ijrap.net/admin/php/uploads/822_pdf.pdf

Physico chemical studies in arumuga chenduram. Congrats to the scientific team behind.

Amuri the elixir unique to Siddha

http://nopr.niscair.res.in/handle/123456789/9350

Above link take you to a Process of Preparation Unique to Siddha. Amuri has too many health benefits as kayakalpam.

Sivanar amirtham - Siddha medicine Effective drug in chronic ailments.



PHARMACOLOGICAL ACTIVITIES OF 
SIVANAR AMIRTHAM – A SIDDHA 
PREPARATION
 Journal Of Research In Ayurvedha and Siddha.
Sudesh Gaidhani , M. Anantharaman , 
T.Thenammal2, E. Krishnakumari2 and G. Veluchamy 

(Received on 04.10.2006)

Sivanar amirtham, is a combination of eight ingredients have long since been used as antiarthritic in Siddha medicine. The drug was screened for anti-inflammatory, antiarthritic and analgesic activities in different suitable pharmacological experimental models. The study confirmed the anti-inflammatory, anti-arthritic and analgesic properties of Sivanar amirtham claimed in the Siddha medicine by orally treating to rats. Sivanar amirtham showed significant anti-inflammatory activity at the doses of 50,100,200 and 500 mg/kg, orally. The analgesic study with acetic acid induced writhing episode on albino mice produced significant analgesia in the dose of 50,100,200 and 500 mg/kg, orally. By using analgesic response using hot plate Sivanar amirtham showed significant analgesia at the doses of 50,100,200 and 500 mg/kg, orally. The analgesic study with acetic acid induced writhing episode on albino mice produced significant analgesia in the dose of 50,100,200 and 500 mg/kg, orally. By using analgesic response using hot plate Sivanar amirtham showed significant analgesia at the doses of 50,100,200 and 500 mg/kg, orally.

http://www.japsonline.com/admin/php/uploads/540_pdf.pdf


The ethno medicinal effects of Siddha in Combating Hepatitis is repeatedly proved  .Click the above link to read the hepatoprotetive Review on Pidangu nari kudineer.

http://timesofindia.indiatimes.com/india/Mandatory-clinical-trials-for-herbal-drugs-soon/articleshow/15412133.cms


The above link will address you why Siddha Doctors should be exposed in Conducting Clinical Trials.

Musk deer -Musk - Kasthuri man- Kasthuri

http://archive.org/stream/muskdeerlittleun97gree/muskdeerlittleun97gree_djvu.txt

click the above link to read about Musk deer (Kasthuri)

http://www.biomedcentral.com/1471-2407/8/294/


Read the above link for Triphala and pancreatic cancer

http://www.biomedcentral.com/1471-2407/8/294/


Read the above link for Triphala and pancreatic cancer

Ethanolic extract of nilavembu answers pyrexia

http://www.ncbi.nlm.nih.gov/pubmed/22014740

read the above link.

Varmam protocol

Cervical spondylosis Research Protocol

http://www.webmedcentral.com/article_view/2968



Read the above said link for varmam protocol

safety studies in metallic drugs

Safety Issues in Metallic drugs
Dr. P. Sathiyarajeswaran
Dr. M. Kannan
Dr. K. Gopakumar
Central Council for Research in Siddha
Rationale in using metallic drugs
When
How much
How long
What are all the Do’s and Dont’s
What are all the possible side effects
How to choose a efficacious, non toxic SOP
Which anti dotes are available in literature


Safety studies - Protocol
Pre clinical – Standardization
Animal studies – Efficacy testing
Toxicological profiling
Phase 1 trial
Enzymatic
Sonologic
Tissue Biopsy
Bone teeth
LFT/KFT

Phase 1
Safety
Human healthy volunteers
Males are preferred
Non addictive
Occupationally hazard free subject
CTRI Compulsory
Out come socially Viable
Standardization
Traditional standards- Organoleptic / Five senses
PLIM Standards
Develop our own standards for High order Forms
Nano studies
Chemical Profiling(XRD/SEM/TEM/ICPMS/ICPOES)
Ligands / Chelating testing
Purification understanding
First step in drug manufacturing.
Select the best process.
Is purification alone enough.
Detoxification.
Ore dressing.
Debris removal

Understanding the risk in Phase I
IEC Approval
Pre screening
Consent
Compensation
Out come benefit


Our experience
Linga chenduram
Aya veeram
Aya brinuga raja karpam
Phase II
Minimal sample size
No enzymatic / Sonological Changes
Quality of life Prospectively observed.
To end with
Half baked cakes reach the masses.
Physicians have to think out of the box.
A Metallic study without Clinical trial testing will end up in Bias results.
Use metallic drugs as much you can but Rationally.

Thank you all…

Antibacterial activity of Vallarai Chooranam against Human Pathogens

International Journal of PharmTech Research
CODEN (USA): IJPRIF        ISSN : 0974-4304
                                                                                                              Vol.4, No.1, pp 162-168,          Jan-Mar 2012
Antibacterial activity of Vallarai Chooranam
against Human Pathogens
T.G.Nithya
1
, S.Sivakumar
2
, K.Sangeetha
1
1
Department of Biotechnology, Faculty of Science and Humanities, SRM University,
Kattankulathur,India.
2
Department of Gunapadam , National institute of Siddha, Tambaram Sanitorium,
Chennai,India.
*Corres. Author: nithya_245@yahoo.co.in
Mobile : +919841404193
Abstract:Vallarai chooranam is a polyherb,comprised of 10 different herbs,used for treatment of diabetics,urinary
tract infection,leucorrhea,veneral disesase and also to improve memory power.The present investigation was
carried out to study the unexplored area of the Vallarai  chooranam towards their antibacterial activity against both
Gram positive and Gram negative organisms by Disc diffusion method.Aqueous and solvent extracts of the
chooranam were tested against selected human pathogens viz. S.aureus, P.aeruginosa, B.subtilis ,K.pneumoniae
and E.coli.   B o t h   t h e   e x t r a c t s   w e r e   f o u n d   t o   b e   m o r e   e f f e c t i v e   a g a i n s t   a l l   t h e   t e s t   p a t h o g e n s .B.Subtilis was more
susceptible to the aqueous extracts among the tested organisms.The results of antibacterial activity revealed that
both the extracts exhibited good inhibitory activity against all test pathogens.The presence of phytochemicals in the
formulation were also assayed.The results showed positive response for significant secondary metabolites.
Key words: Polyherbal, antibacterial,Qualitative analysis,Aqueous extract,Solvent extract,Vallarai Choornam.
Introduction:
Herbal medicines derived from plant extracts
are being increasingly utilized to treat a wide variety of
clinical diseases, mainly in developing countries, for
p r i m a r y   h e a l t h   c a r e   b e c a u s e   o f   b e t t e r   c u l t u r a l
acceptability, better compatibility with the human
body and fewer side effects. Nowadays multiple drug
resistance has developed due to the indiscriminate use
of commercial antimicrobial drugs commonly used in
the treatment of infectious disease
1
. In addition to this
problem, antibiotics are sometimes associated with
adverse effects on the host including hypersensitivity,
immune-suppression and allergic reactions
2
.
It has been reported that there has been an
alarming increase in number of diseases and disorders
caused by synthetic drugs prompting a switch over to
traditional herbal medicine
3
.The earliest record of
human civilization and culture of China, Egypt,
Assyria, and Indies valley reveals that the elders and
w i s e   m e n   o f   t h o s e   t i m e s   u s e d   h e r b s   t o   t r e a t   v a r i o u s
diseases. Many of the indigenous medicinal plants are
used as spices for cooking
4
.The ancient use of plants
for healing purposes forms the origin of much of
modern medicine. Many traditional drugs originate
from plant sources: a century ago, most of the effective
drugs were plant based
5
.
It is estimated that there are 250,000 to 500,000
species of higher plants on earth. But relatively smallT.G.Nithya et al /Int.J.PharmTech Res.2012,4(1) 163
percentage (5-15%) has been systematically
investigated for the presence of bioactive compounds
6
.
Microorganisms are the causative agents of almost all
kinds of acute and chronic diseases.
Plants based antimicrobials have enormous therapeutic
potential. They are effective in the treatment of
infectious diseases while simultaneously mitigating
m a n y   o f   t h e   s i d e   e f f e c t s   t h a t   a r e   o f t e n   a s s o c i a t e d   w i t h
synthetic antimicrobials.The use of plant extracts with
known antimicrobial properties, can be of great
significance in therapeutic treatments.Although
hundreds of plant species have been tested for
antimicrobial properties, the vast majority of them
have not been adequately evaluated
7
.Many efforts have
been made to discover new antimicrobial compounds
from various kinds of sources such as micro-organisms,
animals,and plants.One of such resources is folk
medicines. Systematic screening of them results in the
discovery of novel effective compounds
8
.The
increasing prevalence of multidrug resistant strains of
bacteria and the recent appearance of strains with
reduced susceptibility to antibiotics raises the specter
of untreatable bacterial infections and adds urgency to
the search for new infection-fighting
strategies
9
.Considering the vast potentiality of plants
as sources for antimicrobial drugs with reference to
antibacterial agent, a systematic investigation was
undertaken to screen the polyherbal formulation
Vallarai chooranam for its antibacterial activity
against selected human pathogens.
 This polyherbal formulation is a composition
of 10 different herbs viz.,(In tamil) Vallarai, Jaadhikai,
Jaadhipathiri,Lawangam,Elakkai,Thaaleesapathiri,Ma
asikkai,Kadukkai,Nellikai,Thaantrikkai.(Table 1).The
powder form of this sidhha  Chooranam is used to treat
diabetics,Urinary tract infection,Leucorrhea,Veneral
disesase and also used to improve memory power and
blood purification
10
.The use of alchocol or water as
solvent  is efficient in extracting a wide variety of
active components. Therefore, we analysed the
Vallarai chooranam for the presence of
phytochemicals and evaluated the antimicrobial
activity against selected human pathogens.
Materials and Methods:
Preparation of Formulation:
The ingredients were procured from reputed
commercial Siddha supplier (Dr.Sivakumar and
Dr.Juliet, Selaiyur.Chennai) and authenticated [Table
1]. All the ingredients were shade dried, powdered and
mixed thoroughly in same proportion.The mixture was
further boiled in distilled water at 100ºC for 60
minutes and filtered.The filtrate was evaporated to
dryness, used for subsequent experiments and they are
designated as Chooranam since they are comprised of
multiple herbs.
Solvent extract preparation:
1 0   g r a m s   o f   a i r   d r i e d Vallarai chooranam
powder was extracted with 100ml of Organic solvent
(Ethanol) and kept on rotary shaker at 190-220 rpm for
24 hours.The supernatant was collected and solvent
was evaporated to make the final volume one – fourth
of the original volume and stored at 4
0
C in air tight
bottles
11
.
Aqueous extract preparation:
The aqueous extract is prepared by soaking
100grams of Vallarai chooranam powder in 200 ml of
distilled water for 12hours.The extracts were filtered
using Whatman filter paper (125 mm).
12
Table 1:Polyherbal formulation of Vallarai chooranam
S.No Siddha Name Botanical Name Quantity Family Name
1 Vallarai Centella asiatica 50gms Mackinlayaceae
2 Jaadhikai Myristica fragrans 10gms Myristicaceae
3 Jaadhipathiri Myristica fragrans 10gms Myristicaceae
4 Lawangam Syzgium aromaticum 10gms Myrtaceae
5 Elakkai Eletteria cardamomum 10gms Zingiberaceae
6 Thaaleesa pathiri Taxus beccata 10gms Taxaceae
7 Maasikkai Quercus infectoris 10gms Fagaceae
8 Nellikai Emblica officinalis 10gms Phyllanthaceae
9 Kadukkai Terminalia chebula 10gms Combretaceae
10 Thaantrikkai Terminalia belerica 10gms CombretaceaeT.G.Nithya et al /Int.J.PharmTech Res.2012,4(1) 164
Phytochemical screening :
The qualitative tests were carried out in both
the extract of Vallarai chooranam using standard
procedures
13-15
.Both the extacts were analysed for the
presence of significant secondary metabolites viz
Alkaloids, Tannins, Flavonoids ,Cardiac glycosides,
Steroids and Saponins.
Growth and Maintenance of Test
Microorganism for Antimicrobial Studies:
Bacterial cultures of Bacillus subtilis (B.
subtilis), Escherichia coli (E. coli), Pseudomonas
aeruginosa (P.aeruginosa),Staphylococcus aureus (S.
aureus) and Klebsiella pneumoniae
(K.pneumoniae)were obtained from  Department of
Microbiology, SRM Medical College, India, and the
studies were performed at Department of
Biotechnology,FSH,SRM University.The bacteria
were maintained on Nutrient Agar(NA) slants at
4°C.For further study, cultures have been grown in
Nutrient Broth (NB) for 24hrs as overnight cultures.
Disc diffusion Method:
 The antibacterial assay of aqueous and
ethanolic extracts was performed by Disc diffusion
method
16
. T h e   N u t r i e n t   a g a r   m e d i a   ( 2 0 m l )   w a s   p o u r e d
into sterilized petri dishes and left to solidify at room
temperature. The overnight bacterial cultures have
b e e n   s p r e a d   p l a t e d   o n   t h e s e   p e t r i d i s h e s   u s i n g   s t e r i l e   L
rod.Taking the crude extract concentration as
100%,different concentration of aqueous and ethanolic
extracts was prepared viz., 20%,40%, 60%, and 80%.
W h a t t m a n ’ s   N o . 1   f i l t e r   p a p e r   d i s c s   ( 3 m m )   w e r e
soaked in 0.1 ml of Ethanol extract of varying
concentrations  from 20% -80%.The similar procedure
was carried out for aqueous extract with varying
concentration from 20% -80% simultaneously.
T h e   f i l t e r   p a p e r   d i s c s   w e r e   p l a c e d
equidistantly on inoculated media and diffusion of
solution was allowed to occur for 30 minutes at room
t e m p e r a t u r e .   P l a t e s   w e r e   i n c u b a t e d   a t   3 7˚C   f o r   2 4
hours. The average zone of inhibition was recorded.
Sterile distilled water and Ethanol were maintained as
control. The diameters of the inhibition zones were
measured in mm.
Table 2 :Antibacterial screening of the extract showing the range of zone of inhibition (mm)
Table 3 :Zone of inhibition of Ethanolic extract (mm)
 Zone of Inhibition (mm) by varying concentration(%)
Test Organism 20% 40% 60% 80%
E.coli 3.12±0.12 6.22±0.15 8.27±0.13 11.22±0.12
S.aureus 6.53±0.11 10.16±0.10 11.13±0.16 12.15±0.19
P.aeruginosa 2.32±0.10 3.85±0.17 5.61±0.13 7.16±0.18
B.subtilis 7.21±0.13 9.45±0.20 11.33±0.19 14.33±0.16
K.pneumoniae 4.33±0.20 6.27±0.14 9.13±0.10 12.33±0.12
Test
Organism
Ethanol
Extract
Aqueous
Extract
E.coli 3 to 11 2 to 11
S.aureus 6 to 12 3 to 10
  P.aeruginosa 2 to 7 2  to  6
B.subtilis 7 to 14 7  to 14
K.pneumoniae 4 to 12 4 to   9T.G.Nithya et al /Int.J.PharmTech Res.2012,4(1) 165
Ethanolic extract Zone of inhibition
0
5
10
15
20 40 60 80
P e r c e n ta g e   o f   e th a n o l i c   Ex t r a c t
Inhibition (mm)
E . c o l i S . a u r e  u s P . a e  ru  g i  n  o s a
B . s u b t i l i s K . p n e  u m o n i a e
Graph 1:
Table 4 : Zone of inhibition by Aqueous extract (mm)
 Zone of Inhibition (mm) by varying concentration(%)
Test Organism 20% 40% 60% 80%
E.coli 2.75± 0.11 4.51±0.14 6.13±0.13 11.24±0.16
S.aureus 3.87 ± 0.14 5.31±0.15 9.19±0.11 10.16±0.17
P.aeruginosa 2.37 ± 0.20 4.22±0.12 5.31±0.12 6.15±0.18
B.subtilis 7.62±0.15 8.32±0.12 10.14±0.14 14.31±0.20
K.pneumoniae 4.53±0.14 5.12±0.15 7.16±0.13 9.56±0.15
 GRAPH 2:
Aqueous  extrac t  Zone  of  inhibition
0
5
10
15
20 40 60 80
Percentage of Aqueous Extract
Inhibition in mm
E.coli S.aureus P.aeruginosa
B.subtilis K.pneumoniaeT.G.Nithya et al /Int.J.PharmTech Res.2012,4(1) 166
GRAPH 3:
Comparision of Antibacterial activity of Ethanolic and
Aqueous extract
0
5
10
15
20E 20A 40E 40A 60E 60A 80E 80A
Percentage of Extracts %
Inhibition(mm)
E.coli S.aureus P.aeruginosa
Table 5: Phytochemical screening results of
Vallarai Chooranam
Compound Result
Alkaloids +
Cardiac glycosides +
Flavonoids +
Steroids +
Saponins +
Tannins +
+  =  Positive
Results :
Antimicrobial activity results obtained in the
present study revealed  that the tested extracts posses
potential antibacterial activity against B. subtilis, S.
aureus,E. coli,K.pneumoniae ,P.auregenosa (Table
2).The diameters of the inhibition zones against all the
tested bacteria were measured in mm. The results
showed that increase in concentration of extract
increased the zone of inhibition .When tested by the
disc diffusion method, the Ethanolic extracts of
Vallarai Chooranam showed significant activity
against S.aureus, K.pneumoniae  around 12mm.The
zone of inhibition for E.coli was observed as 11
mm.The highest antibacterial  activity of 14 mm was
observed in B. subtilis and least activity was  recorded
in P.auergenosa  o f   7 m m.The range of zone of
inhibition by ethanolic extracts against pathogens were
in the following order of higher to
lower,viz.,B.subtilis,S.aureus, E.coli, K.pneumoniae,
P.auregenosa(Table:3&Graph1).
The antimicrobial results for aqueous extract
of Vallarai Chooranam showed maximum activity
against B. subtilis o f     1 4   m m   a n d     l e a s t   a c t i v i t y
observed in P.aueregenosa of 6 mm .Inhibitory
activity against E.coli. S.aureus, K.pneumoniae was
around 9-11mm ( T a b l e   4   &   G r a p h   2 ) . T h e   r e s u l t s
elucidated that the activity was higher against Gram
+ve strains than Gram –ve pathogens.In classifying
the antibacterial activity as Gram-Positive or Gramnegative, it would generally be expected that a much
greater number would be active against Gram-positive
than Gram-negative bacteria
17
, however, in our study
b o t h   G r a m   p o s i t i v e   a n d   G r a m   n e g a t i v e   b a c t e r i a   w e r e
inhibited by the extracts of the Vallarai Chooranam.
On comparison of both the extracts the activity against
pathogens showed similar results with effective and
significant inhibitory action(Graph 3).The aqueous and
s o l v e n t     e x t r a c t s   w e r e   u s e d   t o   i d e n t i f y   t h e   p r e s e n c e   o f
various phytochemicals .Standard test for Flavonoids,
Alkaloids, Saponins, Cardiac glycosides, Tannins and
Steroids showed positive response(Table 5 ).
Discussion:
Ayurveda is a traditional Indian Medicinal
System practiced for thousands of years. Considerable
research on pharmacognosy, chemistry, pharmacology
and clinical therapeutics has been carried out on
ayurvedic medicinal plants. The polyherbal
formulations described in Ayurveda have been the
basis of treatment of various human diseases.
Biological evaluation of herbal formulations based on
their  medicinal uses forms the basis for development
of new drugs from plants
18
. Historically, plants have
provided a source of inspiration for novel drug
compounds,as plant derived medicine have made large
contribution to human health and well-being.
The combination of multiple herbs has
increased the efficacy of the Vallarai Chooranam to a
greater extent, since they possess medicinal values
exerted by the presence of phytochemicals.Flavonoids
a r e   k n o w n   t o   b e   s y n t h e s i z e d   b y   p l a n t s   i n   r e s p o n s e   t o
microbial infection.Hence it should not be surprising
that they have been found to be effective as
antibacterial substances against a wide array of
infectious agents
19
.Tannins (commonly referred to as
tannic acid) are also known as antimicrobial
agents.They are water-soluble polyphenols and
precipitated proteins present in many plant foods.T.G.Nithya et al /Int.J.PharmTech Res.2012,4(1) 167
Tannins have been reported to prevent the
development of microorganisms by precipitating
microbial protein.The growth of many fungi, yeasts,
bacteria, and viruses were inhibited by this Tannins.
20
According to World Health Report on
infectious diseases 2000, overcoming antibiotic
r e s i s t a n c e   i s   t h e   m a j o r   i s s u e   o f   t h e   W H O   f o r   t h e   n e x t
millennium.Hence,the last decade witnessed an
increase in the investigations on plants as a source of
human disease management
21
and not many reports are
available on the exploitation of plants for
the management of plant diseases
22
.This is mainly due
to lack of information on the screening and evaluation
of diverse plants for their antibacterial
potential.Therefore, in the present investigation of
Vallarai Chooranam,a multiherbal formulation was
evaluated for its antibacterial potential for the first
time against selected human pathogenic bacteria which
are known to cause many infectious diseases.
Conclusion:
In the present investigation Vallarai
Chooranam was evaluated for its antibacterial potential
for the first time against selected human pathogenic
bacteria which are known to cause many infectious
diseases and also the phytoanalysis revealed the
presence of medicinally active constituents. The
antibacterial activity of this polyherbal formulation
would help for development of a new alternative
medicine system which has no side effects. Both the
extracts of this formulation possess a broad spectrum
of activity and open the possibility of finding new
clinically effective antimicrobial compounds.Hence
the study has provided  biochemical basis for
ethanopharmacological claims of the Chooaranam in
treatment and prevention of various diseases and
disorders.
References:
1) Ahmad I, Mehmood Z, Mohammad F.Screening
of some Indian medicinal plants for their
antimicrobial properties. J Ethnopharmacol 62:
183-193, 1998. 3
2) C l a r k   A M   N a t u r a l   p r o d u c t s   a s   r e s o u r c e   f o r   n e w
drugs. Pharm Res 13: 1133-1141
3) Ghule ST, Patil DK. Kisan World. 2001; 28: 33-
34.
4) Okwu DE , Phytochemicals and vitamin content
of indigenous spices of South   Eastern Nigeria.
J. Sustain. Agric. Environ. 6: 30-34.
5) Andrew Vickers, Herbal medicine:  W e s t   J   M e d .
2001 August; 175(2): 125–128.
6) Taylor, L. (2000), Plant Based Drugs and
Medicine, Raintee Nutrition Inc.,pp. 1-5.
7) B a l a n d r i n ,   M . F . ,   J . A .   K l o c k e ,   E . S .   W u r t e l e   a n d
2006. Phytochemical analysis and   antibacterial
W.H. Bollinger, 1985. My. Science., 1: 72-78.
Science, 228: 1154-1160
8) Tomoko.N. Takashi A., Hiromo T., Yuka I.,
(2002): Antibacterial activity of    extracts
preparated from tropical and subtropical plants
on methicillin-resistant Staphylococcus aureus. J.
Health Sci., 48: 273–276
9) Sieradzki K., Roberts R.B.., . (1999):
Thedevelopment of vancomycin resistance  ina
patient with methicillin-resistantStaphylococcus
aureus infection. N. Engl.J. Med., 340: 517–523.
10) Winston, D., Maimes, S., Adaptogens: Herbs
F o r   S t r e n g t h ,   S t a m i n a ,   a n d   S t r e s s   R e l i e f ,   2 0 0 7 ,
pp. 226-7
11) Harborne JB;Phytochemical Methods: A Guide
To Modern Technique of Plant Analysis.3rd
ed .London, England: Chapman and Hall;
1998:114-118.
12) H . O .   E d e o g a ,   D .   E .   O k w u ,     P h y t o c h e m i c a l
constituents of some Nigerian medicinal Plants;
African Journal of Biotechnology Vol. 4 (7), pp.
685-688 July 2005
13) Sofowora AE (1993). Medicinal Plants and
Traditional Medicines inAfrica.. 2nd edition.
Spectrum Books, Ibadan, Nigeria. p. 289.
14) Trease E.G., Evans W.C 1978. Pharmacognosy.
11th Edition, Balliere Tindall, London. 115-222.
15) Harborne JB;Phytochemical Methods: A Guide
To Modern Technique of Plant Analysis.3rd
ed .London, England: Chapman and Hall;
1998:114-118.
16) Bauer, A.W., Kirby, W.M.M., Sherris, J.C.,
Turck, M., 1966. Antibiotic susceptibility testing
by a standardized single disk method. Am. J.
Clin. Pathol. 45: 493-496.
17) McCutcheon AR, Roberts TE, Gibbons E, Ellis
S M ,   B a b i u k   L A ,   H a n c o c k   R E W ,   T o w e r s   G H N
(1995). Antiviral screening of British Columbian
medicinal plants. J. Ethnopharmacol. 49: 101-
110.T.G.Nithya et al /Int.J.PharmTech Res.2012,4(1) 168
18) Krishnan Kannabiran; Antibacterial activity of
saponin isolated from the leaves of  Solanum
trilobatum Linn; Journal of Pharmacy
Research, Vol 2, No 2 (2009)
19) Jasmine. R, Daisy.P and Selvekumar. B.N., 2007.
In vitro Efficacy of Flavonoids from Eugenia
jambolana Seeds Against ESL-Producing
Multidrug-Resistant Enteric Bacteria. Research
Journal of Microbiology. 2 (4):369–374.
20) P r a s a d ,   N .   R . , e t   a l . ,   2 0 0 8 .   P r e l i m i n a r y
phytochemical screening and antimicrobial
activity of Samanea saman . Journal of
Medicinal Plants Research. 2: 268-270.
21) Aiyelaagbe et al. 2000. Fitoterapia. 72: 544–546.
22) Satish S., Raveesha K. A. and Janardhana G. R.
1999. Lett. Applied Microbiol.28: 145–147.
*****

ICDS – Scope of Siddha in Enhancing the Scheme

Traditional medical knowledge  twined with culture and community health   are inherited or spread transplacentally. Usage of certain herbal combinations in safe delivery and compound drugs in lactation enhancement are the scientific Secrets which emerged from Grandmas Pandora box.  Adapting the same in life is the secret behind less statistics of Anemia in Tamilnadu when compared with other states. The knowledge may be transferred and translated by products to a successful completion of ICDS.
                        Immune Enhancement:
Seinei and Uraimathirai should be fed from day 1 up to 1 yr of child growth.
Dosage: 100 mcg of uraimathirai daily/ 0.5 ml ofSeinei.
Vit A Supplementation
This can be achieved through Karisalaikarpam tab and Murungailai chooranam.
 Dosage: 250 mg tab of Karisalaikarpam / 500 mg of Murungai ilai chooranam.
Ante natal care drugs
 Advocacy of Antenatal drugs as mentioned in the text.
 Usage of Pavana panchagulathylam – Internally.
 Application of Ulunthu thylam externally.
               Ayabringa raja karpam / Satavari lehyam – Iron & Folic acid supplementation.    
            For prevention of Vomiting
Mathulai Manappagu   - 10 ml Daily Two times a day
           Post natal care
               Sowbakya chuntee – 10 gms daily from the day 2 of delivery.
              Thaneer vittan kilangu nei /lehyam for promoting lactation.
              Thripala chooranam for douching in excess lochia discharge.
      Anaemia Eradication
              Advocacy of Ayabringarajakarpam - 200 mg –b.i.d for 90 days.
            Advocacy of Anna bedhi Chenduram – 200 mg –Cap for 30 days.
            Advocacy of Muthuchippi parpam -200 mg for calcium supplementation
           Advocacy of  Nellikai lehyam for Vit C – benefit and enhancement of Iron absorption.

Compatible nutrition package
        1.Pancha mutti Kanchi
       2.Pea nut / Ellu mittai
       3.Ulunthu kali / Ulunthu kanchi
       4.Athipalam
       5.Pasumpal .

Saya chooranam -Immuno modulator

Santhammal et al, JAPHR 2011, Vol 1 Issue 3 Research Article
8
Content list available at: www.iaphp.in
Journal of Advances in Pharmacy and Healthcare Research
Journal home page: http://www.japhr.iaphp.in
ISSN 2231-6817
Evaluation of Immunomodulatory Activity of Saya Churnam (A Poly Herbal Formulation) on Albino rats.
Y. Santhammal1, S. Arthika1, N. Sharly Elgal1, R. Ganesan2, P. Satyarajeswaran2, S.N. Gaidhani2, G.Pramod Reddy2* and T. Anadan2
1Department of Bio-technology, Bishop Heber College, Tirucharappalli, T.N. India.
2Department of Pharmacology, Siddha Central Research Institute, Chennai, T.N., India.
Key words:
Saya churnam, Immunomodulation, Antibody titer,
Delayed type hyper sensitivity, Ig E.
Corresponding Author:
Dr. G. Pramod Reddy, Department of Pharmacology, Siddha Central Research Institute, Anna hospital Campus, Arumbakkam, Chennai, T.N., India.
gpramod01@gmail.com
Abstract:
The immunomodulatory activity of Saya churnam (a poly herbal formulation) on Albino rats was evaluated by using Cyclophosphamide as an immunosuppressant. The Poly herbal formulation was administered orally at the dosage levels of 200mg/kg/day and 400mg/kg/day body weight of rat. The assessment of immunomodulatory activity on specific and non- specific immunity were studied by Hemagglutination antibody (HA) titer, delayed type hypersensitivity (DTH), Identification of Ig E, hematological , biochemical analysis. Induction of immune suppression in rats was achieved by using Cyclophosphamide (CP) (100mg/kg/day, p.o). Oral administration of Saya Churnam (SC) showed a significant increase in the production of circulating antibody titer in response to sheep red blood cells (SRBCs). A significant (p< 0.001) increase in the both primary and secondary HA titer was observed when compared to control group, where as in Cyclophosphamide treated group Saya Churnam showed significant (p<0.01) increase in HA titer. Saya churnam showed significant (p<0.01) Delayed type hypersensitivity (DTH) reaction by facilitating the foot pad thickness response to SRBCs in sensitized rats. Also biochemical and hematological analysis showed a significant (p<0.001) increase in Serum Glutamate Oxaloacetate Transaminase (SGOT), Serum Glutamate Pyruvate Transaminase (SGPT), Alkaline Phosphatase (ALP) and WBCs. The study demonstrates that Saya churnam triggers both specific and non-specific responses to a greater extent. The study showed significantly increased results in Heme agglutination (HA) titer, DTH response, Ig E test, biochemical, hematological analysis.
INTRODUCTION
Indian traditional systems of medicines like Siddha and Ayurveda which generally involve herbal formulations have suggested the body’s natural resistance to disease (Sagrawat and Khan, 2007). Recent studies with plants have revealed many compounds with potent antioxidant, antineoplastic, antiulcer, anti-inflammatory and immunostimulating potential (Wanger, 1990). Immune activation is an
effective as well as protective approach against emerging infectious diseases, and this immune system known to be involved in etiology and pathophysiological mechanisms of several diseases. It is believed that the immunomodulatory drugs promote positive health and maintain organic resistance against infections by establishing body’s equilibrium and conditioning the body tissues (Dasgupta et
Santhammal et al, JAPHR 2011, Vol 1 Issue 3 Research Article
9
al., 1998). The restorative and rejuvenating power of these herbal remedies might be due to their action on the immune system and thereby responsible for the protection of the organism from extraneous substance and maintaining homeostasis.
Plant and plant products are being used as a source of medicine since long. Non – toxic herbal preparations are used to improve the general health by stimulating body’s immunity. In this poly herbal formulation (Terminalia chebula, Piper longum, Piper cubeb, Alpinia galangal, and Myristica officinalis) each herb have a capacity to induce immune response and each herb have anti-inflammatory, anti-ulcer, and other activities.
The Siddha system of medicines not only provides hat alternative, but also scores over the side effects and cost factors of allopathic medicine. Herbal preparation can be more effective and safer (Vinothapooshan et al., 2011) than conventional medicines. Non-toxic herbal drug preparations that are used to improve general health by stimulating body’s immunity (Kumar et al., 1999).
Herbal medicine has become an integral part of standard health care (Agarwal et al., 2010). This formulation of Saya churnam was obtained from the ancient Siddha text (Agasthiar, 1995). In Siddha normally this Saya churnam is prescribed for Tuberculosis, Jaundice, Anemia, Diabetes mellitus, Arthritis. On the basis of literature there are no reports on Saya Churnam for immunomodulatory system.
The present study was undertaken to investigate and to validate the Immunomodulatory activity of Saya churnam.
MATERIALS AND METHODS
Site of the experiment: The experiment was conducted at the Department of Pharmacology, Siddha Central Research Institute, Chennai, in February, 2011.
Plant material: Fruits and rhizome of the plants were procured from local market and it was authentified by Sasikala Ethirajulu, Assistant Director, Department of Pharmacognosy, Siddha Central Research Institute, Chennai.
Preparation of poly herbal formulation: Fruits of Terminalia chebula, Piper longum, Piper cubeb, Myristica officinalis and Rhizome of Alpinia galangal was collected. It was cleaned without any dust particles or other unwanted materials. Each herb is finely powdered and it was mixed in different ratio. The collected fruits and rhizome are fried little and powdered as mentioned in the ancient text. Then the poly herbal powder was used for the further studies. Now this formulation is used for the evaluation study.
Drug and chemicals: All the drugs and chemicals are analytical grade while the other drugs procured were Cyclophosphamide (Biochem pharmaceutical, Mumbai), ELISA commercial kit from Biotran Diagnostics, U.S.A.
Animals: Healthy Wistar albino rats both male and female (180-230 gm) were used for the study. All the animals were housed which were under standard conditions of temperature (25 ± 2? C), 12h light/ dark cycles and fed with standard pellet food and water. The animals were divided into four groups consisting of six animals each. A group of
Santhammal et al, JAPHR 2011, Vol 1 Issue 3 Research Article
10
six un- treated rats were taken as control (group I). Group II animals received standard drug Cyclophosphamide on day 9th and 16th orally in a dosage range of 100mg/kg/day. The Saya churnam was fed orally for 21 days at a dosage of 200 mg/kg/day (group III), 400) mg/kg/day, (group IV) mg/kg/day for assessment of immunomodulatory activity.
Test compound formulations: The different ratio of all the fruit and rhizome powder was measured and prepared in honey with water in the ratio of 7:3 prior to oral administration of animals. Freshly prepared drug solution was used. The vehicle alone served as control.
EXPERIMENTAL PROCEDURE
Antigenic material: Preparation of sheep RBCs (SRBCs): Sheep blood was collected in sterile Alsever’s solution in 2:1 proportion of Alsever’s solution (Freshly prepared). Blood was kept in the refrigerator and processed, for the preparation of SRBCs batch, by centrifugating at 2000rpm for ten minutes and washing with physiological saline 4-5 times and then suspending into buffered saline for further use (Kirtikar et al., 1961).
Heamagglutinating Antibody (HA) Titer: The rats of all groups are pre-treated with drug for 21 days. And each rat immunized with 0.1X109 SRBC/rat by i.p. route, including control rats. The immunization (Agarwal et al., 1999) was given on day 7th and 14th. The animals were treated with Saya churnam for 21 days. The titer was determined by titrating serum dilutions with SRBCs. The micro titer plates were incubated at room temperature for one hour and examined visually for agglutination has been expressed as HA titer.
Delayed Type Hypersensitivity (DTH) Response: Each group of animals (group I-IV) was immunized with SRBCs on day 7th and 14th. On day 21st Rats are administered 0.1ml of 1% SRBCs in the left hind foot pad by subcutaneous (Fulzele et al., 2003) injection, in the right hind foot pad administered 0.1 ml of 0.9% of normal saline was injected and the increased level of paw volume was measured by plethysmometer (Gayathri et al., 2005) in three different time (0 hour, 1 hour, 3 hour) intervals. The thickness between left and right hind paw volume was measured.
Identification of Ig E: On 21st day serum was obtained from all the group of animals. 25µl of serum was added to all the wells, add 100µl of Ig E biotin reagent then allowed to incubation of an hour. Discard the contents and add 300 µl of wash buffer and discarded that it was carried out four times. Then added 100 µl of Ig E enzyme reagent allowed it for incubation of half an hour. Discard the contents and added 300 µl of wash buffer and discarded it was carried out 4 times after that.1 ml of working substrate solution was added allowed for 15 minutes incubation then added 0.05ml of stop solution read the absorbance at 450 nm.
Liver function and blood parameters test: Activities of Serum Glutamate Oxalate Transaminase (Sharififa et al., 2009) (SGOT), Serum Glutamate Pyruvate Transaminase (SGPT), Alkaline Phosphatase (ALP) and Hematological parameters (RBC, WBC, Hb, PLT) were estimated by using kits (Span Diagnostics, India). For this purpose four groups of animals (one control+three
Santhammal et al, JAPHR 2011, Vol 1 Issue 3 Research Article
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Table 1: Effect of Saya Churnam on primary and secondary antibody titer.
Treatment
Primary antibody titer
Secondary antibody titer
Control
6.88±0.83
7.66 ± 0.98
CP 100mg/kg
5.23±0.63**
4.86 ± 1.04**
SCLD 200mg/kg
5.72 ± 1.04***
6.12 ± 0.89***
SCHD 400mg/kg
7.76 ± 1.32***
8.56 ± 0.98***
The values are expressed as (Mean ± S.D), n=6,**p<0.01 and *** p<0.001
Treatments) as described above were used and treated with drug for 21 days.
Statistical analysis: The statistical analysis was performed by using student t Test followed by one way analysis (ANOVA).
RESULTS
Heamagglutination antibody (HA) Titer: Effect of Saya churnam low dose (SCLD) and Saya churnam high dose (SCHD) on primary and secondary antibody response on HA titer is shown in (Table 1). Primary antibody response on day 14th in saya churnam (200mg, 400mg/kg/p.o) treated group with normal immune status showed significant increase (p<0.01) in HA titer when compared with the control group. A significant decrease in the antibody titer was observed in the Cyclophosphamide–treated group when compared with the control group. In immunosuppressed groups, where the immunity was suppressed by administration of Cyclophosphamide on day nine, Saya churnam (400mg/kg/p.o) administration produced a significant (p<0.01) rise in the antibody titer when compared with the Cyclophosphamide – treated group. Secondary antibody titer on twenty first day in Saya churnam both low dose and high dose treated groups with normal immune status group showed a significant rise (p<0.01) in the antibody titer when compared with the control group. In the immunosuppressed groups where the immunity was suppressed by administration of Cyclophosphamide on day sixteenth Saya churnam both low dose and high dose showed a significant rise (p<0.01) in HA titer when compared with the Cyclophosphamide group.
Delayed type hypersensitivity: Effect of Saya churnam on cell mediated immune response by DTH induced foot pad oedema is shown in (Table 2). In the all groups of rats with normal immune status, of Saya churnam low dose (200mg/kg/p.o) and Saya churnam high dose(400mg/kg/p.o) showed significant (**p<0.01,*P<0.05) potentiated DTH response in terms of increase in the mean difference of paw thickness when compared with control group. The drug treated group of rats showed significant (p<0.01) potentiated DTH response in terms of increase in the mean difference of paw thickness. Heightened delayed type hypersensitivity reaction suggests activation of cellular immune system.
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Table 2: Effect of Saya churnam treatment on cell mediated immune response by delayed type hypersensitivity induced footpad oedema.
Treatment
SRBC’s (in left hind paw)
Saline (in right hind paw)
0 hrs
1 hrs
3 hrs
0 hrs
1 hrs
3 hrs
Control
0.81±0.14
1.14±0.32
2.04±0.33
0.81± 0.15
0.91±0.19
0.96±0.36
SCLD200mg/kg
0.78±0.20**
1.30±0.42**
2.35±0.45**
0.88±0.16*
0.87±0.15*
0.86±0.23**
SCHD400mg/kg
0.98±0.12**
1.36±0.32**
3.64±0.36**
1.00±0.21*
0.65±0.15*
1.05±0.40**
The values are expressed as (Mean ± S.D), n=6.*P<0.05 and **p<0.01.
Identification of Ig E: The administration of Saya churnam both low dose and high dose (200mg/kg/day and 400mg/kg/day) showed significantly increased (*p<0.05) levels of immunoglobulin level when compared to control in the animal serum sample
Table 3: Effect of Saya churnam on Ig E
Treatment
Ig E
Control
16±4.5
SCLD 200 mg/kg
13.6±2.8*
SCHD 400mg/kg
14.3±4.9*
The values are expressed as (Mean ± S.D), n=6.*p < 0.05.
Liver function and test: There was a significant elevation in SGOT, SGPT, ALP as a result of treatment with Saya churnam on both low dose and high dose in this study (***p<0.001,*p<0.01) (Table 4). The drug treated group compared with control group which showed significantly increased values.
Hematological parameter test: In hematological analysis observed significant differences in hematological parameters and drug treated groups are compared with control and Cyclophosphamide treated group. Result shows increased level of WBC, RBC, HGB, PLT on low dose and high dose treated group when compared with control group.
DISCUSSION
Immunostimulatory agents of plant and animal origin enhance the (Fulzele et al., 2003) immune responsiveness of an organism against a pathogen by activating the immune system. However these
poly herbal formulations should be subjected to systematic studies to substantiate the therapeutic
claims made with regard to their clinical utility (Joshi et al., 2003). Immunomodulation is a procedure which can alter the immune system of an organism by interfering with its functions; if it results in an enhancement of immune reaction it is named as immunostimulative drug which primarily implies stimulation of specific and non- specific system. Immunomodulation through natural substances may be considered an alternative for the prevention (Zhang et al., 2011) and cure of disease. Immuno-suppression implies mainly reduce resistance against infections, stress and may occur on account of environmental or chemotherapeutic factor (Makare et al., 2001). The results obtained in the present study indicate that Saya churnam is a potent immunostimulant, stimulating specific and non-specific immune mechanisms.To evaluate the effect of Saya churnam on humoral response, its influence was tested on sheep erythrocyte specific
Santhammal et al, JAPHR 2011, Vol 1 Issue 3 Research Article
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HA titer in rats (Benaceraf et al., 1978). Cyclophosphamide showed significant inhibition in
Table 4: Effect of Saya churnam on liver enzymes.
Treatment
SGOT U/L
SGPT U/L
ALP U/L
Control
56.42 ± 11.9
19.18 ± 3.72
88.8 ± 16.1
CP 100mg/kg
111.3 ± 18.42***
31.58 ± 9.11**
120.02 ±14.1***
SCLD 200mg/kg
59.73 ± 11.12***
36.68 ± 10.7 **
150.55 ± 16.88 ***
SCHD 400mg/kg
62.85 ± 10.98 ***
47.58 ± 7.06**
270.9 ± 73.65 ***
The values are expressed as (Mean ± S.D), n=6.**p<0.01 and ***p<0.001.
antibody titer response, while saya churnam counteract the suppression of both primary and secondary humoral (Kulkarni et al., 2007)
responses induced by Cyclophosphamide. It indicates that the Saya churnam has the significant effect on humoral antibody response. In DTH test, the DTH response, which directly correlates with cell mediated immunity (CMI), was found to be the highest at maximum dose of 400mg/kg/day tested in this study. Increase in the DTH response indicates that Saya churnam has stimulatory effect on lymphocytes and accessory cell types (Mitra et al., 1999) required for the expression of the reaction Cell mediated immunity the mechanism behind this elevated DTH during the CMI responses could be due to sensitized T- lymphocytes. When challenged by antigen they are converted to lymphoblast and secrete variety of molecules including pro-inflammatory lymphokines, attracting more scavenger cells to the site of reaction (Fulzele et al., 2003).
Increase in the DTH response indicates that the drug has a stimulatory effect on lymphocytes and accessory cell types required for the expression of the reaction (Mitra et al., 1999). Foot volume was enhanced after Saya churnam treatment suggesting cell (Sen et al., 1992) mediated immune enhancement. Immunoglobulin level is a direct measure to detect the humoral immunity. Serum immunoglobulin refers to a group of serum molecules produced by B- lymphocytes, they are soluble and secreted from of B-cell receptors and are produced to a maximum level to counter the invasion by an antigen, and hence they are also called as (Ismail and Asad, 2009) antibodies.
Identification of Ig E also showed the presence Ig E in the tested animals. The results shown significantly increased level of immunoglobulin in Saya churnam treated group when compared with control and Cyclophosphamide treated group. Estimation of LFT enzymes did not show any toxicity effect which was concomitant with any
Table 5: Effect of Saya churnam on Hematological parameters
Groups
WBC
RBC
HGB
PLT
Control
6.7± 3.5
5.32±1.11
9.0 1 ±1.93
406.9±108.3
CP 100mg/kg
3.81± 4.01*
6.96±2.81*
12.42±5.4 *
169.5±200.1**
SCLD 200mg/kg
5.52±2.34 ***
6.61±2.52***
11.32±4.46***
267.2±105.4***
SCHD 400mg/kg
7.63±2.07 ***
6.69±2.33***
11.56±4.43***
342.1±155.7***
The values are expressed as (Mean ± S.D),n=6.*P<0.05, **p<0.01and ***p<0.001.
Santhammal et al, JAPHR 2011, Vol 1 Issue 3 Research Article
14
significant increase in relative weight of liver. High dosage 400mg/kg/day showed increased level of SGPT, SGOT, and ALP. And the results of the presence study revealed that significant difference in the blood parameters. Findings of the present study showed an overall stimulatory effect of Saya churnam on humoral as well as cell-mediated immunity in rats.
CONCLUSION
On the basis of the results obtained in the current study, it can be concluded that the saya churnam has the potential to stimulate cell-mediated and humoral immunity and it may be a potential therapeutic candidate in several immunosuppressed clinical conditions. However, more exhaustive work needs to be performed to substantiate the claim.
REFERENCES
Agarwal, R., S. Diwanay, P. Pakti and B. Patwardhan, 1999. Studies on immunomodulatory activity of Withania somnifera (Ashwagandha) extracts in experimental immune inflammation. J. Ethnopharmacol., 67: 27-35. 10616957
Agasthiar, G.N., 1995. Agasthiar Gowmathi Nool 400. Thamarai Pathippagam., 94.
Benacerraf, B., 1978. A hypothesis to relate the specificity of T lymphocytes and the activity of I region specific Ir genes in macrophages and B lymphocytes. J of Immunology. 120:1809-1812.
Dasgupta, P.S.C. and A. Gomes, 1998. Immunopotentiating activity of immune-21: A poly herbal product. Indian J. Pharmacol., 30:163-168.
Fulzele, S.V., P.M. Satturwar, S.B. Joshi and A.K. Dorle, 2003. Study of the immunomodulatory activity of Haridradi ghrita in rats. Indian J Pharmacology., 35:51-54.
Sharififar, F., S. Pournourmohammadi and M. Arabnejad, 2009. Immunomodulatory activity of aqueous extract of Achillea wilhelmsii C. Koch in mice. Indian J. Exp. Biol., 47: 668-671.
Fulzele, S.V, P.M. Satturwar, S.B. Joshi and A.K. Dorle, 2003. Study of the immunomodulatory activity of Haridradi ghrita in rats. Indian J Pharmacology., 35:51-54.
Gayathri, V., V.V. Asha and A. Subramoniam, 2005. Preliminary studies on the immuno-modulatory and antioxidant properties of selaginella species. Indian J. Pharmacol., 37:381-385.
Joshi, S.B., P.M. Satturwar, S.V.Fulzele and A.K. Dorle, 2003. Study of the immunomodulatory activity of Haridradi ghrita in rats. Indian J Pharmacology., 35:51-54.
Kirtikar, K.R. and B.D. Basu, 1961. Indian Medicinal Plants. Lalit Mohan Basu Publications, Allahabad.
Kulkarni, A.V, B.D. Siraskar, S.S. Jadhav, S.M. Dhonde, A.S. Kulkarni and S.S. Bingi, 2007. Study of hydroalcoholic extract of <I>Portulaca oleracea</I> L. for immunomodulatory activity in mice. Indian J. Green pharmacy., 1,pp:45-49.
Kumar, P.V. R. Kuttan and G. Kuttan, 1999. Effect of “ Rasayanas” a herbal drug preparation on cell-mediated immune responses in tumor bearing mice. Indian J. Exp. Biol., 37:23-26.
Makare, N., S. Bodhankar and V. Rangari, 2001. Immunomodulatory activity of alcoholic extract of Mangifera indica L. in mice. J thnopharmacology., 78:133-137.
Santhammal et al, JAPHR 2011, Vol 1 Issue 3 Research Article
15
Mitra, S.K, M. Gupta and D.N.K Sharma, 1999. Immunomodulatory effect of IM-133 Phytother Res., 13:341-343.
Sagrawat, H. and Y. Khan, 2007. Immunomodulatory plants: A phytopharmacological. pharmacognosy Rev., 1,pp: 248-260.
Fulzele, S.V., P.M. Satturwar, S.B. Joshi and A.K. Dorle, 2003. Study of the immunomodulatory activity of Haridradi ghrita in rats. Indian J Pharmacology., 35:51-54.
Sen, P., P.K. Mendiratta and A. Ray, 1992. Effects of Azadirachta indica on some biochemical, immunological and visceral parameters in normal and tressed rats. Indian J Exp Biol., 30: 1170-1175
Agarwal, S.S., S.C. Khadase and G.S. Talele, 2010. Studies on immunomodulatory activity of Capparis zeylanica leaf extracts. Int. J. Pharmaceutical sci. Nanotechnol., 3(1): 887-892
Ismail, S. and M. Asad, 2009.Immunomodulatory activity of Acacia catechu. Indian J Physiol Pharmacol., 53(1):25-33.
Vinothapooshan, G. and K. Kumar, 2011. Immunomodulatory activity of various extracts of Adhatoda vasica Linn. in experimental rats. African j. Pharmacy Pharmacl., 5(3):306-310
Wanger, H., 1990. Search for plant derived natural products with Immunostimulatory activity (recent advances). Pure Appl. Chemistry.,62:7:1217-1222.
Zhang, Z., Y. Yang and G. Xing, 2011. Immunomodulatory activity of polysaccharides from roots of actinidia kolomicta on macrophages. Int. j. biol., 3(2):

Monograph on Athimathuram

Copyright© 2005 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission. Alternative Medicine Review Volume 10, Number 3 September 2005

Glycyrrhiza glabra Monograph

Page 230 Alternative Medicine Review u Volume 10, Number 3 u 2005

Glycyrrhiza

glabra

Introduction

Glycyrrhiza glabra, also known as licorice and sweetwood, is native to the Mediterranean and certain areas

of Asia. Historically, the dried rhizome and root of this plant were employed medicinally by the Egyptian, Chinese,

Greek, Indian, and Roman civilizations as an expectorant and carminative. In modern medicine, licorice extracts

are often used as a flavoring agent to mask bitter taste in preparations, and as an expectorant in cough and cold

preparations. Licorice extracts have been used for more than 60 years in Japan to treat chronic hepatitis, and also

have therapeutic benefit against other viruses, including human immunodeficiency virus (HIV), cytomegalovirus

(CMV), and Herpes simplex. Deglycyrrhizinated licorice (DGL) preparations are useful in treating various types

of ulcers, while topical licorice preparations have been used to sooth and heal skin eruptions, such as psoriasis and

herpetic lesions.

Description

The licorice shrub is a member of the pea family and grows in subtropical climates in rich soil to a height

of four or five feet. It has oval leaflets, white to purplish flower clusters, and flat pods. Below ground, the licorice

plant has an extensive root system with a main taproot and numerous runners. The main taproot, which is harvested

for medicinal use, is soft, fibrous, and has a bright yellow interior.1 Glycyrrhiza is derived from the ancient Greek

term glykos, meaning sweet, and rhiza, meaning root.

Active Constituents

A number of components have been isolated from licorice, including a water-soluble, biologically active

complex that accounts for 40-50 percent of total dry material weight. This complex is composed of triterpene saponins,

flavonoids, polysaccharides, pectins, simple sugars, amino acids, mineral salts, and various other substances.2

Glycyrrhizin, a triterpenoid compound, accounts for the sweet taste of licorice root. This compound represents a

mixture of potassium-calcium-magnesium salts of glycyrrhizic acid that varies within a 2-25 percent range. Among

the natural saponins, glycyrrhizic acid is a molecule composed of a hydrophilic part, two molecules of glucuronic

acid, and a hydrophobic fragment, glycyrrhetic acid.2 The yellow color of licorice is due to the flavonoid content of

the plant, which includes liquiritin, isoliquiritin (a chalcone), and other compounds.3 The isoflavones glabridin and

hispaglabridins A and B have significant antioxidant activity,4 and both glabridin and glabrene possess estrogen-like

activity.5

O

O

H

H

H

COOH

O

HO O

HO

HO

HO

HO COOH

COOH

O

Glycyrrhizin

Copyright© 2005 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission. Alternative Medicine Review Volume 10, Number 3 September 2005

Monograph Glycyrrhiza glabra

Alternative Medicine Review u Volume 10, Number 3 u 2005 Page 231

Pharmacokinetics

After oral administration of licorice in humans,

the main constituent, glycyrrhizic acid, is hydrolyzed

to glycyrrhetic acid by intestinal bacteria

possessing a specialized ß-glucuronidase.6,7 Glycyrrhetic

acid is 200-1,000 times more potent an inhibitor

of 11-ß-hydroxysteroid dehydrogenase (involved

in corticosteroid metabolism) than glycyrrhizic acid;

therefore, its pharmacokinetics after oral intake are

more relevant. After oral dosing, glycyrrhetic acid

is rapidly absorbed and transported via carrier molecules

to the liver. In the liver it is metabolized to

glucuronide and sulfate conjugates, which are subsequently

rehydrolyzed to glycyrrhetic acid. Glycyrrhetic

acid is then reabsorbed, resulting in a significant

delay in terminal clearance from plasma.8 After

oral administration of 100 mg glycyrrhizin in healthy

volunteers, no glycyrrhizin was found in the plasma

but glycyrrhetic acid was found at < 200 ng/mL. In

the 24-hour period after oral administration, glycyrrhizin

was found in the urine, suggesting it is partly

absorbed as an intact molecule.3

Mechanisms of Action

The beneficial effects of licorice can be attributed

to a number of mechanisms. Glycyrrhizin

and glycyrrhizic acid have been shown to inhibit

growth and cytopathology of numerous RNA and

DNA viruses, including hepatitis A9 and C,10,11 herpes

zoster,12 HIV,13,14 Herpes simplex,15,16 and CMV.17

Glycyrrhizin and its metabolites inhibit hepatic

metabolism of aldosterone and suppress 5-ßreductase,

properties responsible for the well-documented

pseudoaldosterone syndrome. The similarity

in structure of glycyrrhetic acid to the structure of

hormones secreted by the adrenal cortex accounts for

the mineralocorticoid and glucocorticoid activity of

glycyrrhizic acid.18

Licorice constituents also exhibit steroidlike

anti-inflammatory activity, similar to the action

of hydrocortisone. This is due, in part, to inhibition

of phospholipase A2 activity, an enzyme critical to

numerous inflammatory processes.19 In vitro research

has also demonstrated glycyrrhizic acid inhibits cyclooxygenase

activity and prostaglandin formation

(specifically prostaglandin E2), as well as indirectly

inhibiting platelet aggregation, all factors in the

inflammatory

process.

19,20

Certain licorice constituents possess significant

antioxidant and hepatoprotective properties.

Glycyrrhizin and glabridin inhibit the generation of

reactive oxygen species (ROS) by neutrophils at the

site of inflammation.21,22 In vitro studies have demonstrated

licorice isoflavones, hispaglabridin A and B,

inhibit Fe3+-induced mitochondrial lipid peroxidation

in rat liver cells.23 Other research indicates glycyrrhizin

lowers lipid peroxide values in animal models of

liver injury caused by ischemia reperfusion.24 Licorice

constituents also exhibit hepatoprotective activity by

lowering serum liver enzyme levels and improving

tissue pathology in hepatitis patients.25

Glycyrrhizin and other licorice components

appear to possess anticarcinogenic properties as well.

Although the exact mechanisms are still under investigation,

research has demonstrated they inhibit abnormal

cell proliferation, as well as tumor formation

and growth in breast,26 liver,27 and skin28,29 cancer.

Deglycyrrhizinated licorice formulations

used in the treatment of ulcers do not suppress gastric

acid release like other anti-ulcer medications. Rather,

they promote healing by increasing mucous production

and blood supply to the damaged stomach mucosa,

thereby enhancing mucosal healing.30,31

Copyright© 2005 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission. Alternative Medicine Review Volume 10, Number 3 September 2005

Glycyrrhiza glabra Monograph

Page 232 Alternative Medicine Review u Volume 10, Number 3 u 2005

Clinical Indications

Chronic Hepatitis

In Japan, glycyrrhizin has been used for more

than 60 years as a treatment for chronic hepatitis C.

Stronger Neo-Minophagen C (SNMC), a glycyrrhizin

preparation, has been extensively used with considerable

success. In two clinical trials, SNMC has

been shown to significantly lower aspartate transaminase

(AST), alanine transaminase (ALT), and gamma-

glutamyltransferase (GGT) concentrations, while

simultaneously ameliorating histologic evidence of

necrosis and inflammatory lesions in the liver.25,32 In

recent years, several studies have been performed

supporting this action.10,11 Presently, interferon (IFN)

therapy is a predominant treatment for chronic hepatitis.

Because its efficacy is limited, an alternative

treatment is desirable. SNMC has profound effects on

the suppression of liver inflammation and is effective

in improving chronic hepatitis and liver cirrhosis. It

also appears to have considerably fewer side effects

than IFN.33

In a double-blind, randomized, placebo-controlled

trial investigating IV infusions of SNMC,

short-term efficacy of licorice was confirmed with

regard to ALT levels. The study showed the need for

daily IV administration of SNMC, which may be impractical

for patients. The study also demonstrated

that after cessation of therapy the ALT-decreasing effect

of licorice disappeared, suggesting the need for

long-term administration.25

Oral Lichen Planus

Patients with chronic hepatitis C often experience

oral lichen planus, an inflammatory disease characterized

by lymphocytic hyperkeratosis of the oral

mucosa. It is rarely cured and effective treatments are

limited. In an open clinical trial, 17 hepatitis C-positive

patients with oral lichen planus were given either

routine dental care or 40 mL IV glycyrrhizin daily for

one month. Among nine patients taking glycyrrhizin,

six (66.7%) noted improved clinical symptoms, such

as decreased redness, fewer white papules, and less

erosion of the mucosa. In the non-glycyrrhizin group

of eight patients, only one (14.3%) reported any improvement.

34

Other Viral Illnesses

It has been reported that licorice inhibits

growth and cytopathology of many unrelated DNA

and RNA viruses, while not affecting cell activity or

cellular replication.15

Hepatitis A virus (HAV) causes acute hepatitis,

a major public health concern in numerous countries.

In vitro research with glycyrrhizin and a human

hepatoma cell line has demonstrated glycyrrhizin

completely suppresses the expression of the HAV antigen.

In comparison to ribavirin (an antiviral agent

used to treat hepatitis), glycyrrhizin proved to be 10

times more potent at reducing infectivity of HAV, as

measured by reduction in viral titres. Glycyrrhizin

also exhibited a five-fold greater cell selectivity than

ribavirin in that it was less cytotoxic to the hepatoma

cells. These results indicate glycyrrhizin may be a

potential therapeutic adjunct in fighting HAV infections.

9

Studies show licorice and its constituents,

specifically glycyrrhizin, have antiviral activity

against Herpes simplex and are capable of irreversibly

inactivating the virus.16,35,36 Glycyrrhizin has also

been shown to inhibit viral replication and infectivity

of HIV,14,36 herpes zoster,37 Varicella zoster,12 and

CMV.17,38,39

A case report demonstrated a two-percent topical

glycyrrhizic acid cream (carbenoxolone sodium)

applied six times daily in 12 patients with acute oral

herpetic (Herpes simplex) infections resolved pain

and dysphagia within 24-48 hours of beginning use.

Moreover, the accompanying ulceration and lymphadenopathy

gradually healed within 24-72 hours.16

A clinical study of three HIV patients with

hemophilia investigated the effect of glycyrrhizin on

HIV replication. Glycyrrhizin was administered IV at

400-1600 mg on six separate occasions over a onemonth

period. The HIV p24 antigen was detected in

all patients at the beginning of treatment courses. At

the end of one month, p24 antigen levels had either

decreased significantly or become negative. Tapering

of the glycyrrhizin dose resulted in an immediate elevation

in p24 antigen levels, suggesting the higher

doses of glycyrrhizin were responsible for decreased

antigen levels, probably via suppressed viral replication.

13

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Monograph Glycyrrhiza glabra

Alternative Medicine Review u Volume 10, Number 3 u 2005 Page 233

In a clinical trial of 31 patients with severely

painful herpes zoster lesions, 12 patients were given

20 mg IV glycyrrhizin on six separate occasions. The

remaining 19 patients received either zoster immune

gamma-globulin, recombinant interferon-ß, or acyclovir.

Glycyrrhizin ranked next to acyclovir for pain

resolution at the end of one month.37

CMV is the most common cause of congenital

and perinatal viral infections throughout the world.

It manifests with profound liver dysfunction and poor

weight gain. In a series of studies, both oral and IV

preparations of licorice (SNMC) were administered

to infants with CMV. Liver dysfunction and weight

gain improved in nearly all cases compared to groups

without treatment.17,38,39

Hepatocellular Carcinoma

In a retrospective study, long-term licorice

administration for hepatitis C infection was effective

in preventing hepatocellular carcinoma (HCC). Four

hundred fifty-three patients diagnosed with hepatitis

C were divided into three groups and given either

licorice, in the form of SNMC at a dose of 100 mL

daily for two months, or other natural treatments,

such as vitamin K. The remaining group of patients

was treated with a wider number of agents, including

SNMC, corticosteroids, and immunosuppressive

agents; as a result of the mixed medication regimen,

this group was excluded from the study. After 10

years, analysis of the results showed 30/84 patients

(35.7%) employing SNMC had normalized AST levels,

compared with seven patients (6.4%) not treated

with IV SNMC. Moreover, the 10- and 15-year appearance

rate of HCC was 7 and 12 percent in the

treated group compared to 12 and 25 percent in the

untreated group, respectively.40 A summary of the literature

on HCC and the use of SNMC has confirmed

that IV glycyrrhizin not only decreases ALT levels

but also improves liver histology and decreases incidence

of hepatic cirrhosis.41

Aphthous Ulcers

In a double-blind, placebo-controlled trial,

24 patients with recurrent aphthous ulcers were randomly

allocated to consume 2 g glycyrrhizin (carbenoxolone

sodium) in 30 mL of warm water or a

placebo three times daily following meals for four

weeks. In contrast to the placebo group, the use of the

oral licorice mouthwash significantly reduced the average

number of ulcers per day, pain scores, and the

development of new ulcers.42 In a study of 20 patients

instructed to use a DGL mouthwash four times daily,

15 experienced 50-75 percent clinical improvement

after only one day, with complete healing of canker

sores after three days.43

Peptic Ulcer Disease

Licorice has been used as a demulcent and

emollient for 2,000 years to promote the healing of

ulcers by acting on the mucosal layer. Glycyrrhizin

(as carbenoxolone sodium) speeds healing of gastric

ulcers and protects against aspirin-induced damage to

the gastric mucosa. In a double-blind, placebo-controlled

study, 70 patients with endoscopically-confirmed

gastric or duodenal ulcers were given carbenoxolone

sodium 300 mg or placebo daily during the

first seven days, followed by 150 mg daily over the

next 3-5 weeks. The authors concluded the carbenoxolone

group had an increase in pH at the stomach

antrum from 1.1 to 6.0, and a reduction in basal and

histamine-induced gastric acid secretion at pH 3 and

5. Overall, 70 percent of ulcers in the glycyrrhizin

group healed within 3-5 weeks of beginning therapy,

compared to 36 percent employing placebo.44

Unfortunately, the side effects of licorice

limit its potential to be used on a long-term basis for

treatment of peptic ulcer disease. A processed form

of licorice, DGL (removal of the glycyrrhizin), was

produced to eliminate potential adverse effects, including

licorice-induced hypertension.45 In a double-

blind trial, 100 patients were randomly chosen

to chew Caved S (DGL plus antacid), 760 mg three

times daily, or take cimetidine (Tagamet®) 200 mg

three times daily and 400 mg at night for 12 weeks.

Endoscopy showed the healing rate between the two

regimens was comparable at six (63 percent) and 12

(91 percent) weeks. Although both therapies reduced

pain symptom scores in a comparable fashion during

the day, cimetidine was more effective during the first

two weeks at reducing nighttime pain.46 A two-year

follow-up trial comparing the two therapies in the

prevention of gastric ulcer recurrence noted the outCopyright

© 2005 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission. Alternative Medicine Review Volume 10, Number 3 September 2005

Glycyrrhiza glabra Monograph

Page 234 Alternative Medicine Review u Volume 10, Number 3 u 2005

comes were similar, with a reported relapse rate of 29

percent (9/31) in the Caved S group and 25 percent

(8/32) in the cimetidine group.47

Other clinical trials have demonstrated the

effectiveness of DGL for gastric ulcer.48,49 A fourweek

clinical trial by Turpie et al demonstrated a

statistically significant greater reduction in ulcer size

in patients receiving 760 mg of a DGL preparation

compared to placebo.48

Helicobacter pylori infection is prevalent in

individuals with peptic ulcer and is also a known risk

factor for gastric cancer.50,51 Consequently, an in vitro

study was performed to investigate the effects of licorice

flavonoids on the growth of H. pylori. These flavonoid

components showed promising anti-H. pylori

activity against clarithromycin- and amoxicillin-resistant

strains. As the antimicrobial property seems to

be attributed to the flavonoid constituents of licorice,

DGL preparations may provide therapeutic benefit

for H. pylori infection.52

Other studies have demonstrated DGL’s benefit

in healing duodenal ulcers. In a trial of 40 patients

receiving either 3.0 or 4.5 g DGL daily for eight

weeks, all patients showed significant improvement

after 5-7 days. Patients were assessed for relief from

epigastric pain, nausea, vomiting, x-ray of ulcer craters

to determine changes in size, and frequency of

relapse (return of ulcer pain for two days per week).

Patients receiving the higher DGL dose showed the

most improvement.53 In a large study of 874 patients

with chronic duodenal ulcers, patients received either

DGL, cimetidine, or antacids. Ninety-one percent of

all ulcers healed, regardless of treatment type. Differences

among treatment groups were not statistically

significant, but patients in the DGL group experienced

the fewest relapses.54

Other Therapeutic Considerations

In a trial of 15 normal-weight subjects (seven

males, eight females, ages 22-26), 3.5 mg of a commercial

licorice preparation daily for two months resulted

in a decrease in body fat mass. Plasma renin

activity and aldosterone were also suppressed. No

changes in body mass index were noted. These results

indicate licorice and its constituents can reduce

body fat by inhibiting 11-ß-hydroxysteroid dehydrogenase

in fat cells.55

Armanini et al investigated the effect of licorice

on serum testosterone in nine healthy women,

ages 22-26, using the same licorice preparation as

above, and found total serum testosterone decreased

from 27.8 (± 8.2) to 19.0 (± 9.4) ng/dL after one

month, and further decreased to 17.5 (± 6.4) ng/dL

after the second month of therapy. This is likely due

to inhibition of 17-hydroxysteroid dehydrogenase,

indicating

licorice may be of benefit in treating women

with hirsutism and polycystic ovary syndrome.56

Several animal and in vitro studies indicate

glycyrrhizin and its constituents possess anticarcinogenic

activity against a variety of cancers, warranting

further investigation in clinical trials.26-29

Studies also show licorice constituents to be

effective in the treatment of eczema,57 melasma,58 eosinophilic

peritonitis,59 postural hypotension,60 erosive

gastritis,61 and as anti-malarial62 and anti-Leishmanial

agents.63 More recently, animal studies indicate aqueous

extracts of G. glabra may have memory-enhancing

activity via reversal of chemically-induced amnesia,

as measured by maze and passive avoidance

testing in mice.64

Drug-Botanical Interactions

There is an increased likelihood of cardiac

arrhythmias, particularly in individuals with ischemic

heart disease, when licorice is used in conjunction

with digoxin.65

Estrogen-based oral contraceptives may enhance

the mineralocorticoid side effects of licorice in

susceptible individuals. This may be due in part to estrogens

reacting with mineralocorticoid receptors or

inhibition of 11â-hydroxysteroid dehydrogenase.66

Hypokalemia, commonly associated with

metabolic acidosis, may co-present with essential

benign hypertension in patients using diuretics and

licorice simultaneously.67

Side Effects and Toxicity

One of the most commonly reported side effects

with licorice supplementation is elevated blood

pressure. This is thought to be due to the effect of

licorice on the renin-angiotensin-aldosterone system.

It is suggested licorice saponins are capable of potentiating

aldosterone action while binding to mineralocorticoid

receptors in the kidneys. The phenomenon

Copyright© 2005 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission. Alternative Medicine Review Volume 10, Number 3 September 2005

Monograph Glycyrrhiza glabra

Alternative Medicine Review u Volume 10, Number 3 u 2005 Page 235

is known as “pseudoaldosteronism.” In addition to

hypertension, patients may experience hypokalemia

(potassium loss) and sodium retention, resulting

in edema. All symptoms usually disappear with

discontinuation of therapy.25 Many studies report no

side effects during the course of treatment.32,33 Generally,

the onset and severity of symptoms depend on

the dose and duration of licorice intake, as well as

individual susceptibility. Patients with delayed gastrointestinal

transit time may be more susceptible to

these side effects, due to enterohepatic cycling and

reabsorption of licorice metabolites. The amount of

licorice ingested daily by patients with mineralocorticoid

excess syndromes appears to vary over a wide

range, from as little as 1.5 g daily to as much as 250

g daily.68

Dosage

Because individual susceptibility to various

licorice preparations is vast, it is difficult to predict

a dose appropriate for all individuals. Nevertheless,

a daily oral intake of 1-10 mg of glycyrrhizin, which

corresponds to 1-5 g licorice (2% glycyrrhizin), has

been estimated to be a safe dose for most healthy

adults.69 Studies of DGL for peptic ulcers employed

dosages ranging from 760-2,280 mg DGL daily.

References

1. Olukoga A, Donaldson D. Historical perspectives

on health. The history of liquorice: the plant, its

extract, cultivation, and commercialisation and

etymology. J R Soc Health 1998;118:300-304.

2. Obolentseva GV, Litvinenko VI, Ammosov AS,

et al. Pharmacological and therapeutic properties

of licorice preparations (a review). Pharm Chem J

1999;33:24-31.

3. Yamamura Y, Kawakami J, Santa T, et al.

Pharmacokinetic profile of glycerrhizin in

healthy volunteers by a new high-performance

liquid chromatographic method. J Pharm Sci

1992;81:1042-1046.

4. Vaya J, Belinky PA, Aviram M. Antioxidant

constituents from licorice roots: isolation, structure

elucidation and antioxidative capacity toward LDL

oxidation. Free Radic Biol Med 1997;23:302-313.

5. Tamir S, Eizenberg M, Somjen D, et al. Estrogenlike

activity of glabrene and other constituents

isolated from licorice root. J Steroid Biochem Mol

Biol 2001;78:291-298.

6. Hattori M, Sakamoto T, Yamagishi T, et al.

Metabolism of glycyrrhizin by human intestinal

flora. II. Isolation and characterization of human

intestinal bacteria capable of metabolizing

glycyrrhizin and related compounds. Chem Pharm

Bull (Tokyo) 1985;33:210-217.

7. Akao T, Akao T, Hattori M, et al. Hydrolysis

of glycyrrhizin to 18 beta-glycyrrhetyl

monoglucuronide by lysosomal beta-Dglucuronidase

of animal livers. Biochem Pharmacol

1991;41:1025-1029.

8. Ploeger B, Mensinga T, Sips A, et al. The

pharmacokinetics of glycyrrhizic acid evaluated by

physiologically based pharmacokinetic modeling.

Drug Metab Rev 2001;33:125-147.

9. Crance JM, Biziagos E, Passagot J, et al. Inhibition

of hepatitis A virus replication in vitro by antiviral

compounds. J Med Virol 1990;31:155-160.

10. Van Rossum TG, Vulto AG, Hop WC, et al.

Intravenous glycyrrhizin for the treatment of

chronic hepatitis C: a double-blind, randomized,

placebo-controlled phase I/II trial. J Gastroenterol

Hepatol 1999;14:1093-1099.

11. Su XS, Chen HM, Wang LH, et al. Clinical and

laboratory observation on the effect of glycyrrhizin

in acute and chronic viral hepatitis. J Tradit Chin

Med 1984;4:127-132.

12. Baba M, Shigeta S. Antiviral activity of

glycyrrhizin against Varicella-zoster virus in vitro.

Antiviral Res 1987;7:99-107.

13. Hattori T, Ikematsu S, Koito A, et al. Preliminary

evidence for inhibitory effect of glycyrrhizin on

HIV replication in patients with AIDS. Antiviral

Res 1989;11:255-261.

14. Ito M, Sato A, Hirabayashi K, et al. Mechanism of

inhibitory effect of glycyrrhizin on replication of

human immunodeficiency virus (HIV). Antiviral

Res 1988;10:289-298.

15. Pompei R, Flore O, Marccialis MA, et al.

Glycyrrhizic acid inhibits virus growth and

inactivates virus particles. Nature 1979;281:689-

690.

16. Partridge M, Poswillo DE. Topical carbenoxolone

sodium in the management of herpes simplex

infection. Br J Oral Maxillofac Surg 1984;22:138-

145.

17. Numazaki K, Umetsu M, Chiba S. Effect of

glycyrrhizin in children with liver dysfunction

associated with cytomegalovirus infection. Tohoku

J Exp Med 1994;172:147-153.

18. Armanini D, Karbowiak I, Funder JW. Affinity

of liquorice derivatives for mineralocorticoid and

glucocorticoid receptors. Clin Endocrinol (Oxf)

1983;19:609-612.

Copyright© 2005 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission. Alternative Medicine Review Volume 10, Number 3 September 2005

Glycyrrhiza glabra Monograph

Page 236 Alternative Medicine Review u Volume 10, Number 3 u 2005

19. Okimasu E, Moromizato Y, Watanabe S, et al.

Inhibition of phospholipase A2 and platelet

aggregation by glycyrrhizin, an antiinflammation

drug. Acta Med Okayama 1983;37:385-391.

20. Ohuchi K, Tsurufuji A. A study of the antiinflammatory

mechanism of glycyrrhizin. Mino

Med Rev 1982;27:188-193.

21. Akamatsu H, Komura J, Asada Y, Niwa Y.

Mechanism of anti-inflammatory action of

glycyrrhizin: effect on neutrophil functions

including reactive oxygen species generation.

Planta Med 1991;57:119-121.

22. Wang ZY, Nixon DW. Licorice and cancer. Nutr

Cancer 2001;39:1-11.

23. Haraguchi H, Yoshida N, Ishikawa H, et al.

Protection of mitochondrial functions against

oxidative stresses by isoflavans from Glycyrrhiza

glabra. J Pharm Pharmacol 2000;52:219-223.

24. Nagai T, Egashira T, Yamanaka Y, Kohno M. The

protective effect of glycyrrhizin against injury of

the liver caused by ischemia-reperfusion. Arch

Environ Contam Toxicol 1991;20:432-436.

25. Van Rossum TG, Vulto AG, Hop WC, Schalm

SW. Glycyrrhizin-induced reduction of ALT in

European patients with chronic hepatitis C. Am J

Gastroenterol 2001;96:2432-2437.

26. Tamir S, Eizenberg M, Somjen D, et al. Estrogenic

and antiproliferative properties of glabridin from

licorice in human breast cancer cells. Cancer Res

2000;60:5704-5709.

27. Shiota G, Harada K, Ishida M, et al. Inhibition

of hepatocellular carcinoma by glycyrrhizin in

diethylnitrosamine-treated mice. Carcinogenesis

1999;20:59-63.

28. Nishino H, Kitagawa K, Iwashima A. Antitumorpromoting

activity of glycyrrhetic acid in mouse

skin tumor formation induced by 7,12 dimethylbenz[

a]anthracene plus teleocidin. Carcinogenesis

1984;5:1529-1530.

29. Liu W, Kato M, Akhand A, et al. The herbal

medicine Sho-saiko-to inhibits the growth of

malignant melanoma cells by up-regulating Fasmediated

apoptosis and arresting cell cycle through

down regulation of cyclin dependent kinases. Int J

Oncol 1998;12:1321-1326.

30. Van Marle J, Aarsen PN, Lind A, et al.

Deglycyrrhizinised liquorice (DGL) and the

renewal of rat stomach epithelium. Eur J

Pharmacol 1981;72:219-225.

31. Goso Y, Ogata Y, Ishihara K, Hotta K. Effects

of traditional herbal medicine on gastric mucin

against ethanol-induced gastric injury in rats. Comp

Biochem Physiol C Pharmacol Toxicol Endocrinol

1996;113:17-21.

32. Tsubota A, Kumada H, Arase Y, et al. Combined

ursodeoxycholic acid and glycyrrhizin therapy for

chronic hepatitis C virus infection: a randomized

controlled trial in 170 patients. Eur J Gastroenterol

Hepatol 1999;11:1077-1083.

33. Iino S, Tango T, Matsushima T, et al. Therapeutic

effects of stronger neo-minophagen C at different

doses on chronic hepatitis and liver cirrhosis.

Hepatol Res 2001;19:31-40.

34. Da Nagao Y, Sata M, Suzuki H, et al. Effectiveness

of glycyrrhizin for oral lichen planus in patients

with chronic HCV infection. J Gastroenterol

1996;31:691-695.

35. Hirabayashi K, Iwata S, Matsumoto H, et al.

Antiviral activities of glycyrrhizin and its modified

compounds against human immunodeficiency

virus type 1 (HIV-1) and Herpes simplex virus

type 1 (HSV-1) in vitro. Chem Pharm Bull (Tokyo)

1991;39:112-115.

36. Pompei R, Pani A, Flore O, et al. Antiviral activity

of glycyrrhizic acid. Experientia 1980;36:304.

37. Aikawa Y, Yoshiike T, Ogawa H. Effect of

glycyrrhizin on pain and HLA-DR antigen

expression on CD8-positive cells in peripheral

blood of herpes zoster patients in comparison with

other antiviral agents. Skin Pharmacol 1990;3:268-

271.

38. Numazaki K, Chiba S. Natural course and trial

of treatment for infantile liver dysfunction

associated with cytomegalovirus infections. In Vivo

1993;7:477-480.

39. Numazaki K. Glycyrrhizin therapy for liver

dysfunction associated with cytomegalovirus

infection in immunocompetent children.

Antimicrobics Infect Dis Newsl 1998;17:70-71.

40. Arase Y, Ikeda K, Murashima N, et al. The long

term efficacy of glycyrrhizin in chronic hepatitis C

patients. Cancer 1997;79:1494-1500.

41. Kumada H. Long-term treatment of chronic

hepatitis C with glycyrrhizin [Stronger Neo-

Minophagen C (SNMC)] for preventing liver

cirrhosis and hepatocellular carcinoma. Oncology

2002;62:94-100.

42. Poswillo D, Partridge M. Management of recurrent

aphthous ulcers. Br Dent J 1984;157:55-57.

43. Das SK, Das V, Gulati AK, Singh VP.

Deglycyrrhizinated liquorice in apthous ulcers. J

Assoc Physicians India 1989;37:647.

44. Loginov AS, Speransky MD, Speranskaya IE,

et al. The effectiveness of carbenoxolone in the

treatment of gastro-duodenal ulcer patients. Scand J

Gastroenterol Suppl 1980;65:85-91.

45. Shibata S. A drug over the millennia:

pharmacognosy, chemistry, and pharmacology of

licorice. Yakugaku Zasshi 2000;120:849-862.

Copyright© 2005 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission. Alternative Medicine Review Volume 10, Number 3 September 2005

Monograph Glycyrrhiza glabra

Alternative Medicine Review u Volume 10, Number 3 u 2005 Page 237

46. Morgan AG, McAdam WA, Pacsoo C,

Darnborough A. Comparison between cimetidine

and Caved-S in the treatment of gastric ulceration,

and subsequent maintenance therapy. Gut

1982;23:545-551.

47. Morgan AG, Pacsoo C, McAdam WA. Maintenance

therapy: a two year comparison between Caved-

S and cimetidine treatment in the prevention

of symptomatic gastric ulcer recurrence. Gut

1985;26:599-602.

48. Turpie AG, Runcie J, Thomson TJ. Clinical trial of

deglycyrrhizinized liquorice in gastric ulcer. Gut

1969;10:299-302.

49. Glick L. Deglycyrrhizinated liquorice for peptic

ulcer. Lancet 1982;2:817.

50. Peterson WL. Helicobacter pylori and peptic ulcer

disease. N Engl J Med 1991;324:1043-1048.

51. Parsonnet J. Helicobacter pylori in the stomach – a

paradox unmasked. N Engl J Med 1996;335:278-

280.

52. Fukai T, Marumo A, Kaitou K, et al. Anti-

Helicobacter pylori flavonoids from licorice

extract. Life Sci 2002;71:1449-1463.

53. Tewari SN, Wilson AK. Deglycyrrhizinated

liquorice in duodenal ulcer. Practitioner

1973;210:820-823.

54. Kassir ZA. Endoscopic controlled trial of four

drug regimens in the treatment of chronic duodenal

ulceration. Ir Med J 1985;78:153-156.

55. Armanini D, De Palo CB, Mattarello MJ, et al.

Effect of licorice on the reduction of body fat

mass in healthy subjects. J Endocrinol Invest

2003;26:646-650.

56. Armanini D, Mattarello MJ, Fiore C, et al. Licorice

reduces serum testosterone in healthy women.

Steroids 2004;69:763-766.

57. Evans FQ. The rational use of glycyrrhetinic acid in

dermatology. Br J Clin Pract 1958;12:269-274.

58. Amer M, Metwalli M. Topical liquiritin improves

melasma. Int J Dermatol 2000;39:299-301.

59. Takeda H, Ohta K, Niki H, et al. Eosinophilic

peritonitis responding to treatment with

glycyrrhizin. Tokai J Exp Clin Med 1991;16:183-

186.

60. Basso A, Dalla Paola L, Erle G, et al. Licorice

ameliorates postural hypotension caused by

diabetic autonomic neuropathy. Diabetes Care

1994;17:1356.

61. Kolarski V, Petrova-Shopova K, Vasileva E, et al.

Erosive gastritis and gastroduodenitis – clinical,

diagnostic and therapeutic studies. Vutr Boles

1987;26:56-59. [Article in Bulgarian]

62. Chen M, Theander TG, Christensen SB, et al.

Licochalcone A, a new anti-malarial agent, inhibits

in vitro growth of the human malaria parasite

Plasmodium falciparum and protects mice from

P. yoelii infection. Antimicrob Agents Chemother

1994;38:1470-1475.

63. Christensen SB, Ming C, Anderson L, et al. An

antileishmanial chalcone from Chinese licorice

roots. Planta Med 1994;60:121-123.

64. Parle M, Dhingra D, Kulkarni SK. Memorystrengthening

activity of Glycyrrhiza glabra in

exteroceptive and interoceptive behavioral models.

J Med Food 2004;7:462-466.

65. Hoes AW, Grobbee DE, Peet TM, Lubsen J. Do

non-potassium-sparing diuretics increase the risk

of sudden cardiac death in hypertensive patients?

Recent evidence. Drugs 1994;47:711-733.

66. Clyburn EB, DiPette DJ. Hypertension induced

by drugs and other substances. Semin Nephrol

1995;15:72-86.

67. Olukoga A, Donaldson D. Liquorice and its health

implications. J R Soc Health 2000;120:83-89.

68. Stormer FC, Reistad R, Alexander J. Glycyrrhizic

acid in liquorice – evaluation of health hazard.

Food Chem Toxicol 1993;31:303-312.

69. Walker BR, Edwards CR. Licorice-induced

hypertension and syndromes of apparent

mineralocorticoid excess. Endocrinol Metab Clin

North Am 1994;23:359-377.