Phytomedicine Vol. 4 (4), pp.
359-368, 1997
1997 by Gustav Fischer Verlag
Current Status of Ayurveda in Phytomedicine
S. A. DAHANUKAR and U. M. THAnE
Dept. of Pharmacology, Seth GS Medical College, Parel, Mumbai, India
Introduction
Ayurveda, the science of life, was elucidated in India over
6,000 years ago. It was the first record of scientific medi-
cine in the history of the world. The word "Ayurveda" lit-
erally means knowledge (Veda) of life (Ayu). The aims of
Ayurveda, therefore, are to improve the quality of life and
increase its span. Its major emphasis is on prevention of dis-
ease and promotion of health by strengthening tissues so
that they can withstand exogenous and endogenous stres-
sors. This is achieved by modulating diet and life style, as
well as by the appropriate use of drugs and therapeutic ma-
noeuvres like "Pancbakarma" that restore the equilibrium
of the body (Dahanukar and Thatte, 1989a).
Phytomedicine plays a prominent role in Ayurveda. Over
600 plants are described in original Ayurvedic compendia
like Charaka and Sushruta Samhita. In these texts, plants
are classified into groups based on their effects. One comes
across apparently insignificant groups such as "drugs that
restore the faecal pigment" or "drugs to alleviate hiccups"
but there are also interesting groups such as "drugs that
promote life", "drugs to reduce weight" and "drugs that
delay aging" (Dahanukar and Thatte, 1989b).
The properties of the plants in these compendia are de-
scribed in minute detail. Thus, we read about the alteration
the plant will bring about in the physiology, its site of ac-
tion, ways to facilitate targeting its site of action, dosage
form and route of administration. The specific effects of a
plant on any particular tissue are also described. In every
case the use of the plant revolves around certain basic con-
cepts of health and disease that form the basis of Ayurveda.
Unfortunately, all the information is in Sanskrit, the clas-
sicallanguage of India, which is not easy to interpret. The
Moghul and British invasions did not allow either the lan-
guage or the knowledge to flourish. Consequently, the
properties of the plants described in Ayurveda have not
been meaningfully interpreted in modern scientific lan-
guage nor have they been subjected to verification by rigor-
ous experimental or clinical methodology (Dahanukar &
Thatte, 1989a). Very few Ayurvedic therapies have been
subjected to evaluation keeping the principles of Ayurveda
, Review articles
as the basis for choice of therapy (Paranjpe and Kulkarni,
1995; Satyavati, 1988; Smit et al., 1995).
Our center (Ayurveda Research Center, KEM Hospital,
Mumbai) has been involved in validating the Ayurvedic
principles of health, disease and treatment for a number of
years. We have concentrated on areas where satisfactory
treatment is not available in modern (western orthodox)
medicine. We have also been evaluating the potential of Ay-
urvedic remedies as adjuvants to counteract side effects of
modern therapy and have compared the cost effectiveness
of certain Ayurvedic therapies vis a vis modern therapeutic
schedules. In this article, we discuss briefly some of our
studies that have suggested that Ayurveda (with particular
reference to plants) may play an important role in modern
health care. These include the concept of rasayana, kshara-
sootra, treatment of hemorrhoids and use of vaman (forced
emesis) in bronchial asthma.
Concept of Rasayana
The concept of rasayana interested us as the claims for
this form of therapy are far reaching. In the words of Cha-
raka, "one obtains longevity, regains youth, gets a sharp
memory and intellect and freedom from diseases, gets a lus-
trous complexion and strength of a horse" (Charaka Sam-
hita). Several plants are described as having general rasaya-
na properties. Moreover, specific rasayanas are described to
strengthen specific tissues or organs in an individual.
In order to understand the Ayurvedic rationale underly-
ing the use of rasayanas, one has to appreciate the concept
of health in Ayurveda, which states that the foundation of
health is based on the tripod of dosha (humors), dhatu (tis-
sues) and mala (metabolic end products of these tissues).
These components have to be in equilibrium for the state of
positive health. Seven types of dhatus or tissues are de-
scribed and arranged in a hierarchical fashion. Rasa dhatu,
which has been likened to plasma, is the first; it is followed
by rakta or blood, mamsa or muscle, meda or fatty tissue,
360 S. A. Dahanukar and U. M. Thatte
majja or neural tissue, asthi or osseous tissue and shukra or
germinal tissue. Rasadhatu is the primordial tissue and is
formed by the assimilation of dietary items. The other tis-
sues receive nutrients from the rasadhatu, picking up the
components they need. It is obvious then, that the quality
of the rasadhatu is very important as it would influence the
working of tissues throughout the hierarchy (Dahanukar
and Thatte, 1996).
Drugs that improve the quality of the rasadhatu and
thereby of the entire body are the rasayanas (Thatte and
Dahanukar, 1997). The term rasayana has been split up
into rasa and ayana meaning the path that rasa takes. This
therapy promotes excellent quality rasadhatu, and im-
proves the quality of other tissues as well as of the other
regulators of health like the doshas and mala, leading to a
state of positive health.
Queries
This information on rasayanas raised some questions.
How was it possible for one plant, with its usual array of
phytochemicals, to produce a variety of effects such as de-
layed aging, improved mental function and freedom from
several diseases, including those caused by infection? If spe-
cific rasayanas are used to strengthen specific tissues,
would they have any organ selectivity as described in Ayur-
veda? How did one rasayana plant differ from the other?
Were there any clues to the pharmacokinetics of the plant?
Interpretation and Hypothesis
The most likely hypothesis explaining the apparently di-
verse actions of rasayanas was that the plants were mod-
ulating an endogenous system of the body, setting into mo-
tion a cascade of events leading to the multiple effects.
With the burgeoning knowledge from the field of psycho-
neuro-immunology as a frame of reference, we devised ex-
periments to attempt to prove this hypothesis. The immune
system has connections to a number of other organs and
can directly or indirectly influence the actions of many oth-
ers, including the brain (Blalock, 1984; Glaser and Kiecolt,
1994). By acting primarily on the components of the im-
eNS
III --------------------------1
Stress I with a regimen combining gentamicin with metronidazole.
I When TC was combined with gentamicin and metronida-
Endocrine sysrem
I zole, mortality fell to 16.6% (p < 0.05) (Dahanukar et al.,
I
II Immune system
I
Infections
Fig. 1. Experimental design based on psycho-neuro-endocrine-im-
mune axis framework.
mune system, such as the macrophages, and activating the
cytokine network, the simple chemical in the herbs could
produce all the actions that have been attributed to them.
The outline of our approach is represented in Fig. 1.
Plants studied
Six rasayana plants were selected for study: Emblica offi-
cinalis (EO, Amla), Tinospora cordifolia Miers (TC, Gudu-
chi), Asparagus racemosus (AR, Shatavari), Withania som-
nifera (WS, Ashwagandha), Terminalia chebula (TCh, Har-
itaki) and Piper longum (PL, Pimpli). These were selected
from a large number of rasayanas because they were speci-
fied to be "ekdravya i.e. they can be given as single entities
II
(Gadre, 1970). We first followed Ayurveda's strictures as to
the part and formulation to be used to verify the concept of
rasayana, and only then pursued the phytochemical aspects
of the plant.
Dose and duration
A dose of 100 mg/kg was selected for initial studies based
on LDso data. All plants were administered orally as total
aqueous extracts for 7 to 15 days.
1. Induced infections
The first set of experiments were performed to test the ef-
ficacy of rasayanas against infections induced both in nor-
mal animals (by caecal ligation or by inducing peritonitis
with E. coli) and in animals that had been immunosup-
pressed. Pretreatment with all rasayanas was effective in
protecting animals to a varying degree from different infec-
tions (Thatte and Dahanukar, 1989).
1.1. Normal animals
1.1.1. Caecal ligation
In the model of mixed infection produced by caecalliga-
tion in rats (Manjrekar et al., 1982), untreated animals
showed a mortality rate of 85% by the fifth day after sur-
gery. Animals (n = 6 per group) treated with AR had a mor-
tality rate of 26% (p < 0.05). Pretreatment with TC re-
duced the mortality to 33 %, comparable to those treated
1988).
1.1.2. E. coli peritonitis: In another set of experiments,
we found that pretreatment of mice (n = 20 each) with AR
(p = 0.002) and TC (p = 0.0004) significantly reduced mor-

tality induced by E. coli peritonitis (Thatte et al., 1987a).
Bacterial clearance was hastened in the TC-treated mice
compared to the control and was associated with activation
of PMN phagocytosis (Thatte et al., 1992).
1.2. Immunosuppressed animals
1.2.1. Cholestasis
Irreversible cholestasis was induced in rats by ligation
and sectioning of the common bile duct (Rege NN, 1996).
This produced a picture of obstructive jaundice that was as-
sociated with significant immunosuppression (Dahanukar
et al., 1990), in four weeks. When E coli (1 x 10 8 organ-
isms) were injected intravenously into control rats (n = 20),
40% died and their blood culture tested positive for the
bacteria. On the other hand, TC-treated (n = 20) rats
showed only 16% mortality, and their blood culture tested
negative for the bacteria.
1.2.2. Cyclophosphamide neutropenia
Mice were made neutropenic with either a single dose
(200 mg/kg, subcutaneous) or three doses (30 rug/kg, intra-
peritoneal) of cyclophosphamide (CP); infections were then
induced with different organisms.
1.2.2.a. S. aureus infection: Three groups (n = 10 each)
were pretreated with AR, TC and WS, while one group
served as an untreated control. On the third day after injec-
tion with CP, hospital strain S. aureus (1 x 10 9 organisms/
mouse) was injected intravenously.
In the control mice the mortality was 75%. This was re-
duced to 50% with both TC and AR and it fell further to
30% with WS. Although this reduction in mortality was
not statistically significant, there was an associated leuco-
cytosis and improved PMN functions in the treated groups
(Thatte and Dahanukar, 1989c).
1.2.2.b. K. pneumoniae sepsis: In this experiment, the ef-
fects of pretreatment with TC were compared against re-
sults with gentamicin-treated and control mice. Infection
was induced through intraperitoneal injection of 1 x 10"
organisms of K. pneumonia. The mice were rendered neu-
tropenic with three doses of 30 mg/kg intraperitoneal cy-
clophosphamide. All control mice died, but all gentamicin-
treated mice survived (p = 0.0005). The survival rate for
mice treated with TC was 70% (p = 0.005).
1.2.2.c. C. albicans infection: Mice (n = 20 per group)
made neutropenic with three doses of cyclophosphamide
showed 42% mortality when treated with TC (p = 0.009)
as compared to 86% in control mice when fungal infection
was induced with intravenous injection of C. albicans. In
the same experimental protocol, animals given fluconazole
were similarly protected (40% mortality; p = 0.009). When
Current Status of Ayurveda in Phytomedicine 361
TC was given in addition to fluconazole, the mortality fell
further to 30% (p = 0.001).
In all three models, there was significant leucocytosis and
blunting of the neutropenia, suggesting that the rasayanas
produced an immunomodulatory effect.
1.2.3. Hemisplenectomy
Mice were immunosuppressed by hemisplenectomy (n =
10/group) and infection induced with either E. coli or S. au-
reus. While the control animals had a mortality of 100%,
none of the TC-treated mice died in the E. coli model (p =
0.0005) and only 20% died (p = 0.001) in the S. aureus
model (Thatte & Dahanukar, 1989).
1.2.4. Surgery
Surgical stress induced by the handling of visceral organs
during a laparotomy also produces immunosuppression.
Intravenous injection of C. albicans led to 58% mortality in
control mice; this was reduced to 14 % in the TC-treated
mice (p = 0.06) (Thatte & Dahanukar, 1989).
2. Immunornodulatory effects
2.1. Myeloprotection
The experiments performed so far indicated that the ra-
sayanas protected animals against infections. The mecha-
nism appeared to be mediated through an immunostimu-
lant effect rather than antibacterial actions. This was con-
firmed by doing in vitro antimicrobial studies. In order to
prove that AR, TC and WS had immunomodulatory ef-
fects, their protective effects against the myelosuppressive
effects of cyclophosphamide were tested in mice (Thatte et
al., 1987b). We found that pre-treatment with all the three
drugs (n = 10 each) induced a significant leucocytosis
(p < 0.001 compared to control) with predominant neutro-
philia (p < 0.001) and abolished neutropenia produced by a
single dose of CP. In a separate study, we compared the ef-
fects of AR and TC with lithium carbonate (100 mg/kg/d
orally, 15d) and glucan (0.45 mg/mouse) against the myelo-
suppressive effects of single (200 mg/kg s.c.) and multiple
doses (30 mg/kg/d, three doses, intraperitoneal) of cyclo-
phosphamide. TC, glucan and lithium carbonate
(p < 0.001) as well as AR to a lesser extent (p < 0.05) pro-
duced leucocytosis with a predominant neutrophilia
(p < 0.001). All drugs prevented to varying degrees the leu-
copenia induced by cyclophosphamide, with AR and TC
comparing favorably with glucan and lithium carbonate
(Thatte et al., 1988a).
2.2. Polymorphonuclear (PMN) and monocyte
function
PMN functions, in terms of phagocytosis and intra-cellu-
lar killing, were stimulated in animals treated with the ra-
362 S. A. Dahanukar and U. M. Thatte

Table 1. Peritoneal macrophagefunction following treatment with
rasayanas.
Groups Macrophage phago (%)
Control 32.1 0.948
TC 68.3 1.25':'
AR 61.25 4.57""
EO 51.7 2.193*
" p < 0.0001; n = 10 each
sayanas as compared to control animals in all experiments
(Thatte and Dahanukar, 1989c). Reticulo-endothelial
system function was assessed using the carbon clearance
method (Heller, 1958) in groups containing ten rats each.
The half life of colloidal carbon decreased from
37.69 5.56 to 25.24:!: 0.65 with IC (p < 0.001), to
17.8 :!: 11.52 with AR (p < 0.01) and to 11.2 :!: 6.9 with EO
(p < 0.001), indicating that the RES was greatly activated
and further proving that rasayanas are immunostimulatory
(Thatte and Dahanukar, in press). The phagocytic functions
of peritoneal and alveolar macrophages were also stimulat-
ed with TC, AR and EO. Some results are depicted in
Table 1.
3. Efficacy against cold immobilization stress
Stress-induced damage was measured using these param-
eters: gastric damage by estimating Evan's Blue leakage
(Thatte et al., 1988b), alterations in plasma steroid levels
by RIA and level of peritoneal macrophage function (phag-
ocytosis and intracellular killing capacity) (Rege and Da-
hanukar, 1993).
As expected, stress increased Evan's Blue leakage into
gastric tissue and gastric contents indicating gastric vascu-
lar mucosal damage. Pre-treatment with all three rasayanas
reduced leakage significantly. Similarly, the stress-induced
rise in plasma steroids and suppression of peritoneal mac-
rophage functions was blunted, as shown in the Table 2
(Dahanukar, 1988; Dahanukar and Thatte, 1988).
We then did an experiment to find out whether macro-
phage activation with the rasayanas was the pivotal step in
their anti-stress effects. We administered lipofundin, a fatty
substance which loads the macrophage and prevents its fur-
ther activation with any of the rasayanas. Cold immobiliza-
tion stress was then induced and all three parameters stud-
ied. Results obtained with TC are shown in Table III. We
see that when the macrophages could not be activated by
TC, anti-stress effect was not manifested, indicating that
the macrophages are key cells in the actions of TC.
Thus, we proved the first hypothesis: that rasayanas pro-
duced most of their effects by primarily acting on the im-
mune system.

The definition of rasayanas included three aspects: they

delay aging, strengthen tissues to withstand stress (endoge-
nous and exogenous stressor induced) and give freedom
from disease. Having previously proved that the drugs were
stimulating the immune cells, we also had evidence indicat-
ing they had protective effects against infective stresses.
Seyle's (Seyle, 1946) description of stress and increased
knowledge about the PNI axis (Ader et al., 1995) gave us
a lead. The model of cold immobilization stress (Senay
and Lewis, 1967) gave us a composite model to study the
interaction of the central nervous system, the endocrine
system and end organs like the gut and the immune
system.
Organ selectivity
One of the aspects of rasayanas that is very interesting is
that of organ selectivity. Rasayanas have been described as
having specific affinities for specific organs and although
they may have general tonic effects on all tissues, their abil-
ities to confer maximum protection to particular tissues are
mentioned.
Thus, for example, although EO has to be administered
for 7-10 days prior to the exposure to a stressor to produce
rasayana or adaptogenic effects, the plant can confer gas-
tric cytoprotective effects when given only 1/ 2 h before ex-

Table 2. Anti-stress activity of rasayanas

EBleakage EB leakage Plasma steroid Macrophage
Group (pg/g) (pg/g) (mg/dl) phago (%)
(n = 6) stomach contents
Control 10.18 1.49@ 1.637 0.53@ 2.26 0.37@ 28.6 2.1@
TC 3.869 1.77':' 'f 1.06 0.82 1.77 0.3'f 49.1 1.91""
AR 4.9 0.6':":' 1.9 0.6 2.01 2.5 48.4 2.6""
EO 4.47 0.96>f>f 1.14 0.63 2.17 0.42 42.11 1.72""
Unstressed 4.335 0.54 0.6 0.45 1.34 0.54 34.8 4.6
Note: All rats except those described in the last row were subjected to cold immobilization for 1 h.
@P < 0.01 as compared to unstressed rats;
':. p < 0.05 as compared to stressedcontrols;
"':' p < 0.001 as compared to stressedcontrols.
 Current Status of Ayurveda in Phytomedicine 363

Table 3. Mechanism of antistress action of TC.

EB leakage EB leakage Plasma steroid Macrophage
Group (fig/g) (fig/g) (mg/dl] phago (%)
(n =6) stomach contents

Control 6.46 1.05 1.02 0.82 2.22 036 27.65 1.23

Lipofundin 6.99 3.02 1.52 0.85 3.45 0.3 24.83 0.75
TC 3.861.77'" 1.06 0.82 1.77 0.3':' 49.1 1.91 ,:. ,:.
TC + Lipofundin 6.998 2.46@ 1.39 0.906 3.2 0.967@ 30.66 1.21@@
Note: All animals were subjected to cold immobilization for 1 h.
':. p < 0.05 as compared to control;
':. ':. p < 0.001 as compared to control;
@ p < 0.05 as compared to TC alone;
@@ p < 0.001 as compared to TC alone.

posure. This seems to be related to its direct cytoprotective
effect and unrelated to immunostimulant or rasayana ef-
fect.
The organ preference of rasayanas was further investigat-
ed by exploring the effects of different rasayanas on differ-
ent organs. Ancient compendia mention selective affinity of
a plant for a particular organ and advocate its use in dys-
function of that organ e.g. Tinospora cordifolia is prescrib-
ed for the liver, Emblica officinalis for the gut, especially for
the pancreas, Asparagus racemosus for the stomach and
Piper longum for the lungs.
The cirrhotic changes associated with the disruption of
liver architecture induced by carbon tetrachloride were ar-
rested by concurrent treatment with TC (Rege et aI., 1984).
In untreated animals given caerulin, an electron micro-
graph of the damaged pancreas showed co-localization of
the zymogen granules with lysosomes and clumping of nu-
clear material. On the other hand, the pancreas from ani-
mals pretreated with EO showed nuclear membranes were
undamaged and the zymogen granules were intact. Separ-
ate experiments proved the protective effect of EO on pan-
creatitis in dogs induced by an intra-pancreatic duct injec-
tion of a mixture of bile-blood and trypsin (Thorat et aI.,
1995). Asparagus racemosus protected the stomach irre-
spective of the damaging agent (Ethanol, NSAIDs or
stress). Similarly, Piper longum protected the lungs as evi-
denced by its ability to prevent bleomycin-induced fibrosis.
Concept of vipaka
Ayurveda describes the pharmacology of drugs in some
detail. Modern technology was not available, but physi-
cians used their powers of observation to describe what
happens to a plant when it is used as a medicine. One con-
cept that is described is uipal:a. Plants have different ac-
tions depending on the vipaka they produce.
The vipaka can be put into three general categories ac-
cording to its taste, i.e. madhur (sweet), katu (pungent) and
amla (sour). The rasayanas produce two types of vipaka:
madhur (sweet vipaka) and katu (pungent vipaka). We
compared the effects of rasayanas having these two types of
vipaka on carbon clearance (Heller, 1958) in rats (Thatte
and Dahanukar, 1997). We found that only those rasayanas
that produced madhur vipaka (like Tinospora cordifolia,
Asparagus racemosus, Emblica officinalis, Terminalia che-
bula, Bacopa moniera and Withania somnifera) improved
the carbon clearance, indicating stimulation of the reticu-
loendothelial system. On the other hand rasayanas like
Acarus calamus, Commiphora mukul and Picrorrhiza kur-
roa with katu vipaka either did not activate the RES or pro-
longed carbon clearance, suggesting immunosuppression.
Further, non-rasayana plants with madhur vipaka like
Hemidesmus indicus or Tribulus terrestris or non-rasaya-
nas with katu vipaka like Embelia ribes or Curcuma longa
did not hasten carbon clearance. These results are summar-
ized in Table 4.
Table 4. Vipaka concept of rasayanas
Drug Half life of colloidal
carbon (mins)
Control 37.69 5.56
Asparagus racemosus (madhur, rasayana) 17.8 11.52':-'f
Emblica officinalis (madhur, rasayana) 11.2 6.979'f':-
Withania somnifera (madhur, rasayana) 20.76 8.949'f':-
Terminalia chebula (madhur, rasayana) 18.11 0.88'f'f
Bacopa moniera (madhur, rasayana) 12.11 1.2 'f'f
Acarus calamus (katu, rasayana) 47.156 2.26'-':-
Commiphora muku! (katu, rasayana) 37.375 1O.01N5
Picrorrhiza kurroa (leatu, rasayana) 54.419 21.89':-
Hemidesmus indicus (madhur; non-rasayana) 45.89 20.09 N5
Trtbulus terrestris (madhur, non-rasayana) 45.39 10.98 N5
Plumbago zeylanica (katu, non-rasayanat 42.22 16.1810;5
Embelia ribes tkatu, non-rasayana) 65.32 7.19':-"
Curcuma longa (katu, non-rasayana) 67.06 18.2 'f 'f
P < 0.05 as compared to control;
':. ,,- p < 0.001 as compared to control
Each group has 10 rats. Pretreatment with each of the plants
(aqueous extracts) was given for 2 weeks before carbon clearance
test was performed.
36 4 S. A. Dahanukar and U. M . Th atte
Mechanism of action of rasayanas
In an attempt to investiga te the mechan ism of action o f
one of th e rasayanas, i.e. TC, we studied the proliferat ive
fracti on of th e bone mar ro w of mice by flow cyto rnerry, We
found that compared with norma l mice, th ere was a signif-
icant inc rease in th e proliferati ve fracti on in th e bone mar -
row in mice tr eated with th e TC (Usha, 1995).
Groups of mice (n = 10 eac h) were fed ora lly with either
disti lled wa ter (1 ml) or T C in doses of 25, 50, 100, 200,
400 an d 800 mg/kg bod y weight for a variable period ran g-
ing from 3 to 15 day s, after which the y were sacrificed and
th e bone marrow proliferati ve fra ctions were measured. At
doses of 25 and 50 mg/k g, T C did not induce significant
bon e marrow proliferation even at th e end of 15 days of
treatment. In mice treated with 100 and 200 mg/kg, TC in-
du ced a sta tistically significant (p < 0.0 1) increase in the
proli ferat ive fraction of th e bon e marrow. Th e ma ximum
increase was reac hed at the end of 15 days with 100 mg/kg
and afte r 7 days with 200 mg/kg.
The 400 an d 800 mg/kg dose of T C indu ced bon e mar-
row proliferat ion on th e th ird day. O n th e sevent h day, th e
flow cyto metric profiles showed a peculiar featur e. T here
was a pr e-G. peak which was highl y suggestive of apopt o-
sis. This as pect is discussed in a lat er section.
Throu gh our recent exp erim ents, we have proved th at
some rasayanas activate mon onucl ear cells to produce cy-
tokines like GM-CSF (T ha rte et aI., 1994 ) and IL-l in a
dose-depend ent manner.
T hese results indica te it is possible th at the rasayanas
(particula rly th ose with madhur uipaka th at are ad vocat ed
as ada ptoge ns in Ayurveda ) pri marily activate immune
cells, leading to secretion of cytokines, wh ich in turn act on
mult iple ta rget organs to pr oduce th e myriad effects as-
cribed to these treatments . Our experimental work contin-
ues in thi s direction, in an attempt to demonstrate conclu-
sively th e intricate set of events th at are set into motion
when a rasayana plant is used .
Clinical studies
While we were conducting these experiments, we per-
formed clinical studies using a for mulation of the aqueou s
extract of one of the rasayanas, nam ely Tinospora cordifo-
lia, in immunos uppresse d patient s. Th is was sta nda rdized
and cha rac terized to give a rep roducible HPL C pattern. A
500 mg tabl et was mad e and administered three times a
da y.
Clinical stud ies were co nd ucted af ter ob tai ning approval
of the Eth ics Co mmitt ee of our ins titute . T he safety and to l-
erability of the formul ation were co nfirmed in human vo l-
unt eers .
1. Obstructive jaundice
A depression in neutrophil functio n and an increased
susceptibility to infection wit h resulta nt increase in mor -
talit y has been docum ent ed (Rege et al., 1989 ) in pat ient s
(n = 30 ) with o bstructive jaundice (OJ ). H ence, we initia l-
ly gave T C as an "add-o n" to co nventiona l th erapy in an
open prospective stu dy in pa tients with OJ. Patients re-
ceived the co nvent iona l treatment of Vita min K and anti-
bio tics peri -operatively. TC was given in addition to co n-
ventio na l th erap y for thr ee wee ks pr ior to surgery in one
group of patients, but not to the other. We found th at
th ere was onl y a 25 % mortalit y in the group given T C
co mpa red to a 61 % mortalit y in the pat ients treated con-
vent iona lly (p < 0.01). Th e incidence of infection was als o
reduced fro m 44.4% to 12.5 %. Th e depressed PMN
func tio ns observed before th e ther apy (2 1.2 5 % ph ago-
cytosis an d 18 4. 7% intracellular killing capacity) were
normalized only in pat ien ts receivi ng TC (28.2 5.5%
phagocytosis, p < 0.0 1 and 29.4 7 6.5% ICK, P < 0.00 1)
(Rege et a l., 1993).
Subsequently, we conducted a dou ble-bl ind , placebo-
controlled study in which 30 pat ients we re treated with ei-
th er a placebo or with T C in add ition to th e co nventiona l
th erapy. We fo und th at there was a mort alit y of only
6.25 % in th e TCetreared gro up compared to a 39 % mor -
tality in th e placebo-treat ed gro up (Bapa t et aI., 199 0).
Complications o f jau ndice like infection-rela ted morta l-
ity, rena l dysfun ction , bleeding diathesis and redu ced gut
mo tility improved after administration of TC. Th e treat-
ment with TC also improved th e quality of life.
We decided to further invest igat e th ese as pects in an imals
in order to unravel the mechanism o f action of this no vel
plant . We first simulated a model of OJ in rats and con -
firmed th e clinical findings . We then examined the effects of
TC on th e different complicati on s of OJ.
Effect on endotoxemia: T he comp lications in OJ occur
ma inly du e to th e ingress of endotoxin into the circulatio n
following failure of the prot ective fu nctio ns of th e liver.
We assesse d endo roxernia in ra ts (n = 10-13 per gro up)
by no ting th e percentage of mortal ity in cho lesta tic ani-
mals given a subletha l dose of lead ace ta te (Pain & Bailey,
1986). In this endotoxin bioassay, it was found that mor-
tality was only 30 % in TC-treated (p < 0.05 ) rat s com-
pared to 73.3 % in untreated ra ts, signifying decreased
levels of endo toxin. T C also imp rove d survival by effi-
cient bacterial clear an ce and increased PM N fun ction
(Da hanukar et al., 1994 ).
Effect 011 renal ischemia: Similarly, reno pa thy was as-
sessed by eva lua ting mor ta lity and rena l function in cho les-
rat ic ra ts in who m renal dysf unction ha d been produced by
clamping renal arteries for a sho rt period of time (Rege,
1996 ).
In th is model of renal ischemia 33 % of the TCvrreared
ra ts surv ived upto 7 days wh ile all cho lesta tic rats died by

the second day. In the T C-t reat ed gro ups, BUN levels were
found to be normalized by the end of seven da ys.
Effect on fibrinogen and FDP levels: Risk of DIC was es-
timat ed by stu dying th e abno rma lit ies in plasma fibrin ogen
and fibrin ogen-degradati on pr odu cts (FDP). It was found
that in cho lestatic untreated rats the num ber of a bnormal-
ities was low, whi le in TC-tr eated animals it was normal.
FDP levels were und esirably raised in a significantly high
percent age of unt reat ed anima ls and were lowered by T C.
Thus, TC wa s able to normalize the altered ratio of fibrino-
gen to FDP (Rege, 19 96 ).
Effect on bile flow: Th e effect of TC was evaluated on
bile flow in normal and chol estat ic ani ma ls. Cannulation of
the bile duct was carried out and bile was collected for one
hou r. Cholestatic animals wh o received TC, had a signifi-
cantly higher bile flow (5.33 :!: 2 .1 mllh; p < 0.05) com -
pared to those who did not receive TC (2. 8 :!: 1.3 mllh ).
However, TC did not appear to influence th e bile flow in
norm al anima ls.
Effect on gastric emptying: One of the complicatio ns
of OJ is gastr ic sta sis that increases mo rbidity. We con -
firmed thi s in the exper iment al mod el of 0]. Thus the
gastr ic emptying (GE) in vehicle-treated cholestatic mice
was 10.27:!: 13.22 % , which was significa ntly (p < 0.0 1)
less th an normal (51.9 1 :!: 8.58 % ). Cho lesta tic mice treat ed
with TC showed a significant increase III GE
(50 .28 :!: 30.25%, p < 0.0 1).
These experi mental resu lts confor m th at this rasayana
pla nt no t only activates the immu ne cells of the liver, but al-
so increases bile flow int o the gut. Th e immune cells of the
liver deactivate the end otoxin, while bile salts in the gut ad-
sorb the toxin. This redu ces the movement of the toxin into
the circulation and prevent s the complications associated
with o bstru ctive jaundice.
2. Tuberculosis
Our second clinical trial investigated th e effect of T C on
pulm on ary tubercul osis (T B). A placeb o-controlled ran-
domi zed, doubl e-blind study was ca rrie d out in 50 pat ient s.
Twenty three were given TC an d twenty seven were given
the placebo in addition to usual anti-TB regimen. Radi olog-
ical findings were scored and graded. When these ob serva-
tion s were compared two months later, it was found th at
only 47% of placebo gro up showe d some improveme nt
while 75 % patients of th e T C-treat ed group showe d
marked improvement, und erlining th e potenti al of T C as
an ad juva nt in the therapy of tub erculosis. Anti-TB ther ap y
led to side effects in 40 % patient s in the placebo group but
only 15 % developed side effects in the TC -treated gro up (p
= 0.06 ).
Curre nt Sta tus of Ayurveda in Phytom edicine 36 5
3. Cancer chemo therapy
A placebo-controlled, dou ble-blind randomized study in
collabor at ion with th e Tara Me mo rial Cancer Ho spit al,
M umba i, was cond ucted in fort y pa tients of brea st cancer
to eva luate the efficacy of TC as an adjuvant in cancer
chemotherapy (Methotrexate .;. 5 Fluorouracil + Cyclo -
phosp hamide).
We found rhar the number of patients whose peripheral
WBC counts fell below 3,000/cu mm . were less, i.e. 55%,
in the TC-tr eated group, as compa red to 70% in tho se who
received placebo. Similarl y, in the placebo-treated gro up,
the count fell below 2,000/cu mm . 24 times compared to
on ly 14 times in the TC-treat ed grou p (p =0.03). In the pla-
cebo gro up the count went below 500 cu. mm, four times,
while in the TC group this happened only once.
The patients receiving TC said th ey had improved app e-
tit e and a genera l sense of well-being. Above all, there were
no side effects and no postp onem ent of chemo thera py cy-
cles. T his tri al is ongoing with escalated doses.
TC a nd apoprosis
In the earlier flow cyto metry studies we found th at high
doses of TC led to ap optosis in bon e mar row cells. We did
furt her experi ments to confirm this . Five gro ups of mice (n
= 6 each) were stu died. Th ey includ ed contro l anima ls,
mice given TC 200 mg/kg/d for 7 days, mice given T C 400
mg/kg for 7 days, mice given T C 200 mg/kg for 7 da ys fol-
lowed by a single dose (200 mg/kg subcuta neo us) of cyclo-
phosp hamide (CP), a nd mice given only cyclo phos pha mide
(200 mg/kg subcutaneo us). The bon e marrow cells were
sta ined with acridine or ange and studied under a fluor es-
cent micro scope on the seventh day of therapy in the ani-
mals given TC alone and on the 3rd day after the adminis-
trat ion of CP in the mice given CP after TC.
In the control mice, the apo pto tic index was
18.88 :!: 6.76% . It rema ined un affected in the mice given
T C 200 mg/kg (21.33 8.42%). The apo ptotic index was
significantly (p < 0.0 1) increase d at 400 mg/kg T C (38.39
12.29% ). CP also increased apo ptosis (37.5 :!: 18.11 % , p <
0.05) . On the other hand , when 200 mg/kg T C was given
before CP, the apoptosis was redu ced (18 .79 :!: 4.38 % ,
P < 0.05 ). Th is probab ly explains th e prote ctive effect of
TC agains t CP neutropen ia.
Th e pharmacological pr ofile of TC suggested its utilit y
as an adjuvant in cancer pat ient s. As it increased apo ptosis
in high doses, it was of inte rest to find out wh at effect
the dru g had on malignant cells. For this we chose th e mod -
el of mice with ascitic tum ors ind uced with 5-180 cells. Th e
mice were injected intraperitoneally and the apo ptotic in-
dex studied in ascitic aspira te cells. Surprisingly, the thera-
peut ic dose of TC (200 mg/kg fo r 7 days) increased th e
apo pto tic index (4.48:!: 2.11 % as compared to control
1.337:!: 1.94%, P < 0.05) in the peritoneal cells.
366 S. A. Dahanukar and U. M. Thatte
We could conclude from these experiments that at thera-
peutic doses (100-200 mg/kg), TC-induced apoptosis in
malignant cells, but protected the normal bone marrow
from apoptosis induced by cyclophosphamide.
Other Ayurvedic therapies
Plants play an important role in other Ayurvedic thera-
pies that contribute to modern health care. At the Ayurve-
da Research Centre, we have evaluated certain Ayurvedic
therapies for conditions like fistula-in-ane, piles and asth-
ma. These were preliminary studies where the emphasis
was on broadly evaluating the Ayurvedic therapy for effica-
cy. If found effective the therapy would then be subjected to
detailed pharmacological study of individual constituent
plant. All were clinical studies performed in patients after
taking their written informed consent. The Institutional
Ethics Committee had reviewed and approved all proto-
cols.
Kshara sootra
Sootra is a thread. It is coated with Kshara, which are
cauterizing salts of plants like Acyranthus aspera, latex of
Euphorbia nerifolia and powder of Curcuma longa. This
Ayurvedic medicated thread is used in the management of
fistula-in-ane. Our institute was involved in a multicentric ,
randomized, controlled trial conducted by the Indian
Council of Medical Research on the efficacy of kshara-soo-
tra in management of fistula-in-ano (Shukla et aI., 1994).
Of the total 502 patients studied, 73 were from our hos-
pital. The conclusions drawn from this study were that the
long-term outcome was better with kshara-sootra than fol-
lowing surgery. However, some side effects were noted,
such as burning pain and discharge for 48 hours.
Hence, we continued this study further to investigate
whether a combination of therapies could improve patient
comfort. Another objective was to find out whether plain
thread without kshara is as effective as medicated thread.
this was studied in 63 patients.
The modifications to the original protocol by our group
for patient comfort and safety were the use of intravenous
anaesthesia when the kshara-sootra was put into the fistu-
la, local application of glycerine-magnesium sulfate solu-
tion to reduce local edema and pain, use of herbal laxatives
and use of local herbal ointments.
Our conclusion was this is an effective technique, ideal
for the patient as well as the surgeon, useful for all types of
fistulae. Morbidity was minimal. The procedure did not re-
quire a stay in the hospital and the patient did not have to
lose working days. This would have a great impact on
health economics. We found that kshara is an essential pre-
requisite and nonmedicated thread or plain seton is not ef-
fective (Mohite and Bapat, Personal Communication).
Hemorrhoids
We evaluated the efficacy of Ayurvedic therapy in the
management of hemorrhoids. Fifty patients with hemor-
rhoids were recruited and treated with herbal medications
(systemic and local). We found that this therapy was cura-
tive with less chance of a recurrence, and could be used in
third-degree hemorrhoids. Thus, in cases where surgical
correction is contraindicated, Ayurvedic therapy has a defi-
nite role to play. It reduces the morbidity and the cost re-
markably.
Vaman
Yet another example of how Ayurvedic and modern ther-
apies can be combined for better patient care is Panchahar-
ma, which includes certain procedures to establish homeo-
stasis. Plants again are the mainstay in Panchakarma.
Vaman is one of the Panchakarmas which is used in Ay-
urveda for the treatment of asthma. Vaman is "forced eme-
sis" and is thought to relieve the blockage of channels in the
respiratory system. Plants like Acarus calamus and Glycer-
rhiza glabra are used to induce uaman.
We undertook an open prospective trial in 10 patients in
collaboration with the Department of Chest Medicine. Pa-
tients who had bronchial asthma of more than five years
duration that had been uncontrolled with optimal treat-
ment for more than two years were recruited. Symptom
score, drug score and pulmonary function tests were as-
sessed before and after vaman. A composite symptom score
was assigned to each patient depending on the number of
attacks per week. Drug score was assigned depending on
the number of drugs and the dose required. After uaman,
the symptom score was reduced significantly. This improve-
ment persisted until the end of study, i.e. eight weeks. The
drug score showed the same trend. The ratio of forced ex-
piratory volume (FEV) to forced ventilatory capacity
(FVC%) and PEFR showed improvement at the end of two
weeks and persisted till the end of observation period.
These results suggest that tolerance to ~-stimulants was
reduced, which reflects restoration of the airway respon-
siveness. Thus, a rational combination between two
systems can improve patient care (Thali et aI., 1994).
Cautions
From all these facts, it becomes evident that Ayurveda,
particularly the plants it prescribes, has a very important
role in modern health care. Unfortunately, today Ayurveda
is not practiced in the way it should be, i.e. in accordance
with all its principles.
This is particularly true for plant drugs. Today they are
available as either Ayurvedic formulations or as brand-
name products. The brand-name products are available as

ethical as well as over-the-counter products. Often they are
self prescribed. A very firm conviction in the patient's mind
is that Ayurvedic drugs are safe. Unfortunately, safety is
presumed, not proven. Ayurveda by no means propounds
that all drugs are safe.
In fact, untoward effects like giddiness, and even death
and fetal abnormalities have been described. Adverse ef-
fects due to chronic administration have also been de-
scribed, and contraindications are given (Dahanukar 1991;
Thatte et al., 1993).
Ayurveda has described intricate procedures known as
shodhana for processing potentially toxic substances. In
our studies we have shown that samskaras (procedures) can
detoxify toxic substances like aconite but have to be carried
out in their totality (Thorat and Dahanukar, 1991).
Adverse drug reaction (ADR) monitoring must be done
for Ayurvedic drugs just as is done for modern drugs. With
this in mind, an ADR monitoring cell has been established
at the Ayurveda Research Center. Apart from ADR moni-
toring, the cell carries out surveys on pattern of drug usage
and collects data for interaction with modern drugs.
Sufficient unbiased objective scientific documentation
will allow Ayurveda to be practiced in its truly pristine
form, safely and effectively.
Acknowledgment
The authors gratefully acknowledge the support of Dr. Mrs. P.
M. Pai, Dean, K. E. M. Hospital and the contributions of Dr. R. D.
Bapat, Head, Dept. of Surgery and Gastroenterology Surgical Ser-
vices (GESS) and Dr. N. N. Rege, Assoc. Professor, Dept. of Phar-
macology of Seth G. S. Medical College and K. E. M. Hospital,
Bombay.
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Address
S. A. Dahanukar and U. M. Thatte. Dept of Pharmacology
Seth G.S. Medical College Parel, Mumbai 400012, India.
Fax: (91-22) 4143435